WorldWideScience

Sample records for human tissue transplantation

  1. Some quantitative studies on the transplantation of human tissues into nude mice

    International Nuclear Information System (INIS)

    Zietman, A.; Suit, H.D.; Sedlacek, R.

    1987-01-01

    Quantitative cell transplantation assays (TD/sub 50/) were performed for human tumors xenografted into athymic NCr(nμ/nμ) nude mice. Transplantation assays for FaDu when transplanted into brain and when transplanted into subcutaneous tissues are compared. Effects of immunization are discussed and results are given

  2. Discarded human fetal tissue and cell cultures for transplantation research

    International Nuclear Information System (INIS)

    Hay, R.J.; Phillips, T.; Thompson, A.; Vilner, L.; Cleland, M.; Tchaw-ren Chen; Zabrenetzky, V.

    1999-01-01

    A feasibility study has been performed to explore the utility of various tissues from discarded human abortuses for transplantation and related research. Specifically, aborted fetuses plus parental blood samples and all relevant clinical data were obtained through a local hospital complex. Whenever possible, pancreas, skin and skeletal muscle, heart, liver, kidney, cartilage and lung tissues were removed, dissociated and subfractionated for cryopreservation, characterization and cultivation trials in vitro. Existing protocols for these manipulations were compared and improved upon as required. Clonal culture, cell aggregate maintenance techniques and use of feeder cell populations have been utilized where appropriate to develop quantitative comparative data. Histological and biochemical assays were applied both to evaluate separation/cultivation methods and to identify optimal culture conditions for maintaining functional cells. Immunochemical and molecular biological procedures were applied to study expression of Major Histocompatibility Vomplex (MHC) class 1 and 11 molecules on cell lines derived. Tissue and cell culture populations were examined for infections with bacteria, ftingi, mycoplasma, HIV, CMV, hepatitis B and other viruses. Only 1% of the abortuses tested were virally infected. Cytogenetic analyses confin-ned the normal diploid status in the vast majority (>98%) of lines tested. A total of over 250 abortuses have been obtained and processed. Only 25 were found to be contaminated with bacteria or fungi and unsuitable for further cultivation trials. A total of over 200 cell populations were isolated, characterized and cryopreserved for further study. Included were kidney, lung, liver and epidermal epithelia: cartilage-derived cells from the spine and epiphyses plus myogenic myoblasts. Selected lines have been immortalized using HPV I 6E6/E7 sequences. Epithelia from the liver and pancreas and cardiac myocytes were the most problematic in that initial

  3. Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology.

    Science.gov (United States)

    Sopko, Nikolai A; Matsui, Hotaka; Lough, Denver M; Miller, Devin; Harris, Kelly; Kates, Max; Liu, Xiaopu; Billups, Kevin; Redett, Richard; Burnett, Arthur L; Brandacher, Gerald; Bivalacqua, Trinity J

    2017-04-01

    Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking. Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model. Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1μM cyclosporine A (CsA) or 20nM tacrolimus (FK506) treatment. Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test. Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data. This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology. This report describes a novel ex vivo model of human penile transplantation rejection. Tissue rejection impaired erectile tissue physiology. This report suggests that cyclosporin A might hinder corporal physiology and that other immunosuppressant agents, such as FK506, might be better suited

  4. Should we clone human beings? Cloning as a source of tissue for transplantation.

    Science.gov (United States)

    Savulescu, J

    1999-01-01

    The most publicly justifiable application of human cloning, if there is one at all, is to provide self-compatible cells or tissues for medical use, especially transplantation. Some have argued that this raises no new ethical issues above those raised by any form of embryo experimentation. I argue that this research is less morally problematic than other embryo research. Indeed, it is not merely morally permissible but morally required that we employ cloning to produce embryos or fetuses for the sake of providing cells, tissues or even organs for therapy, followed by abortion of the embryo or fetus. PMID:10226910

  5. Evaluation of two endometriosis models by transplantation of human endometrial tissue fragments and human endometrial mesenchymal cells

    Directory of Open Access Journals (Sweden)

    Mina Jafarabadi

    2017-08-01

    Full Text Available Background: The animal models of endometriosis could be a valuable alternative tool for clarifying the etiology of endometriosis. Objective: In this study two endometriosis models at the morphological and molecular levels was evaluated and compared. Materials and Methods: The human endometrial tissues were cut into small fragments then they were randomly considered for transplantation into γ irradiated mice as model A; or they were isolated and cultured up to fourth passages. 2×106 cultured stromal cells were transplanted into γ irradiated mice subcutaneously as model B. twenty days later the ectopic tissues in both models were studied morphologically by Periodic acid-Schiff and hematoxylin and eosin staining. The expression of osteopontin (OPN and matrix metalloproteinase 2 (MMP2 genes were also assessed using real time RT-PCR. 17-β estradiol levels of mice sera were compared before and after transplantation. Results: The endometrial like glands and stromal cells were formed in the implanted subcutaneous tissue of both endometriosis models. The gland sections per cubic millimeter, the expression of OPN and MMP2 genes and the level of 17-β estradiol were higher in model B than model A (p=0.03. Conclusion: Our observation demonstrated that endometrial mesenchymal stromal cells showed more efficiency to establish endometriosis model than human endometrial tissue fragments.

  6. Survival of human mesenchymal stromal cells from bone marrow and adipose tissue after xenogenic transplantation in immunocompetent mice

    DEFF Research Database (Denmark)

    Niemeyer, P; Vohrer, J; Schmal, H

    2008-01-01

    of the current paper was to evaluate the survival of undifferentiated and osteogenically induced human MSC from different origins after transplantation in immunocompetent mice. METHODS: Human MSC were isolated from bone marrow (BMSC) and adipose tissue (ASC). After cultivation on mineralized collagen, MSC were......INTRODUCTION: Mesenchymal stromal cells (MSC) represent an attractive cell population for tissue engineering purposes. As MSC are described as immunoprivileged, non-autologous applications seem possible. A basic requirement is the survival of MSC after transplantation in the host. The purpose...... transplanted subcutaneously into immunocompetent mice (n=12). Undifferentiated MSC (group A) were compared with osteogenic-induced MSC (group B). Human-specific in situ hybridization and anti-vimentin staining was used to follow MSC after transplantation. Quantitative evaluation of lymphocytes and macrophages...

  7. Results from a horizon scan on risks associated with transplantation of human organs, tissues and cells: from donor to patient.

    Science.gov (United States)

    Herberts, C A; Park, M V D Z; Pot, J W G A; de Vries, C G J C A

    2015-03-01

    The successful transplantation of human materials such as organs, tissues and cells into patients does not only depend on the benefits, but also on the mitigation of risks. To gain insight into recent publications on risks associated with the process of transferring human materials from donor to recipient we performed a horizon scan by reviewing scientific literature and news websites of 2011 on this subject. We found there is ample information on how extended donor criteria, such as donor age, affect the survival rates of organs or patients. Interestingly, gender mismatch does not appear to be a major risk factor in organ rejection. Data on risks of donor tumor transmission was very scarce; however, risk categories for various tumor types have been suggested. In order to avoid rejection, a lot of research is directed towards engineering tissues from a patient's own tissues and cells. Some but not all of these developments have reached the clinic. Developments in the field of stem cell therapy are rapid. However, many hurdles are yet to be overcome before these cells can be applied on a large scale in the clinic. The processes leading to genetic abnormalities in cells differentiated from stem cells need to be identified in order to avoid transplantation of aberrant cells. New insights have been obtained on storage and preservation of human materials, a critical step for success of their clinical use. Likewise, quality management systems have been shown to improve the quality and safety of human materials used for transplantation.

  8. Microsurgical Composite Tissue Transplantation

    Science.gov (United States)

    Serafin, Donald; Georgiade, Nicholas G.

    1978-01-01

    Since 1974, 69 patients with extensive defects have undergone reconstruction by microsurgical composite tissue transplantation. Using this method, donor composite tissue is isolated on its blood supply, removed to a distant recipient site, and the continuity of blood flow re-established by microvascular anastomoses. In this series, 56 patients (81%) were completely successful. There have been eight (12%) failures, primarily in the extremities. There have been five (7%) partial successes, (i.e., a microvascular flap in which a portion was lost requiring a secondary procedure such as a split thickness graft). In those patients with a severely injured lower extremity, the failure rate was the greatest. Most of these were arterial (six of seven). These failures occurred early in the series and were thought to be related to a severely damaged recipient vasculature. This problem has been circumvented by an autogenous interpositional vein graft, permitting more mobility of flap placement. In the upper extremity, all but one case were successful. Early motion was permitted, preventing joint capsular contractures and loss of function. Twenty-three cases in the head and neck region were successful (one partial success). This included two composite rib grafts to the mandible. Prolonged delays in reconstruction following extirpation of a malignancy were avoided. A rapid return to society following complete reconstruction was ensured. Nine patients presented for reconstruction of the breast and thorax following radical mastectomy. All were successfully reconstructed with this new technique except one patient. Its many advantages include immediate reconstruction without delayed procedures and no secondary deformity of the donor site. Healthy, well vascularized tissue can now be transferred to a previously irradiated area with no tissue loss. This new method offers many advantages to older methods of reconstruction. Length of hospital stay and immobilization are reduced. The

  9. GLOBAL CONSULTATION ON ESTABLISHMENT A UNIFIED SURVEILLANCE SYSTEM FOR DONATION AND TRANSPLANTATION OF ORGANS, TISSUES AND CELLS OF HUMAN ORIGIN

    Directory of Open Access Journals (Sweden)

    O. V. Orlova

    2011-01-01

    Full Text Available From from February 7th to 9th 2011, the World Health Organization (WHO, the Italian National Transplant Cen- tre and the EU-funded Project «Vigilance and Surveillance of Substances of Human Origin» joined forces to organise a major global consultation that took place in Bologna, Italy. The scope of the project included organs, tissues and cells for transplantation and for assisted reproduction. The participants represented regulatory and non-regulatory government agencies, professional societies and scientific and clinical specialities from all WHO regions. The meeting explored the work already carried out on-line and agreed on priorities for the future deve- lopment of the Project «Vigilance and Surveillance of Substances of Human Origin». 

  10. Importance of good manufacturing practices in microbiological monitoring in processing human tissues for transplant.

    Science.gov (United States)

    Pianigiani, Elisa; Ierardi, Francesca; Fimiani, Michele

    2013-12-01

    Skin allografts represent an important therapeutic resource in the treatment of severe skin loss. The risk associated with application of processed tissues in humans is very low, however, human material always carries the risk of disease transmission. To minimise the risk of contamination of grafts, processing is carried out in clean rooms where air quality is monitored. Procedures and quality control tests are performed to standardise the production process and to guarantee the final product for human use. Since we only validate and distribute aseptic tissues, we conducted a study to determine what type of quality controls for skin processing are the most suitable for detecting processing errors and intercurrent contamination, and for faithfully mapping the process without unduly increasing production costs. Two different methods for quality control were statistically compared using the Fisher exact test. On the basis of the current study we selected our quality control procedure based on pre- and post-processing tissue controls, operator and environmental controls. Evaluation of the predictability of our control methods showed that tissue control was the most reliable method of revealing microbial contamination of grafts. We obtained 100 % sensitivity by doubling tissue controls, while maintaining high specificity (77 %).

  11. Donor-recipient human leukocyte antigen matching practices in vascularized composite tissue allotransplantation: a survey of major transplantation centers.

    Science.gov (United States)

    Ashvetiya, Tamara; Mundinger, Gerhard S; Kukuruga, Debra; Bojovic, Branko; Christy, Michael R; Dorafshar, Amir H; Rodriguez, Eduardo D

    2014-07-01

    Vascularized composite tissue allotransplant recipients are often highly sensitized to human leukocyte antigens because of multiple prior blood transfusions and other reconstructive operations. The use of peripheral blood obtained from dead donors for crossmatching may be insufficient because of life support measures taken for the donor before donation. No study has been published investigating human leukocyte antigen matching practices in this field. A survey addressing human leukocyte antigen crossmatching methods was generated and sent to 22 vascularized composite tissue allotransplantation centers with active protocols worldwide. Results were compiled by center and compared using two-tailed t tests. Twenty of 22 centers (91 percent) responded to the survey. Peripheral blood was the most commonly reported donor sample for vascularized composite tissue allotransplant crossmatching [78 percent of centers (n=14)], with only 22 percent (n=4) using lymph nodes. However, 56 percent of the 18 centers (n=10) that had performed vascularized composite tissue allotransplantation reported that they harvested lymph nodes for crossmatching. Of responding individuals, 62.5 percent (10 of 16 individuals) felt that lymph nodes were the best donor sample for crossmatching. A slight majority of vascularized composite tissue allotransplant centers that have performed clinical transplants have used lymph nodes for human leukocyte antigen matching, and centers appear to be divided on the utility of lymph node harvest. The use of lymph nodes may offer a number of potential benefits. This study highlights the need for institutional review board-approved crossmatching protocols specific to vascularized composite tissue allotransplantation, and the need for global databases for sharing of vascularized composite tissue allotransplantation experiences.

  12. Regulatory aspects of tissue donation, banking and transplantation in India.

    Science.gov (United States)

    Lobo Gajiwala, Astrid

    2018-05-04

    Amendments to India's Transplantation of Human Organs Act, 1994, have established the legality of tissue donation and transplantation from deceased donors and the conditions under which they are permitted. The amended Act, now known as The Transplantation of Human Organs and Tissues Act, 1994, seeks to prevent the commercialization of tissue donation and to guarantee the safety of indigenous allografts. Registration of tissue banks, compliance with national standards and the appointment of transplant co-ordinators in hospitals registered under the Act are now mandatory. A national registry and Regional and State networks for donation and transplantation of tissues have been introduced. Despite the amendments a few anomalies of the principal Act persist as some of the differences between tissue and organ donation and transplantation have been overlooked. These include the possibility of skin donation in locations other than hospitals; the donation of medical and surgical tissue residues which does not pose any risk to the living donor; the non-requirement for compatibility between donor and recipient; the delayed time factor between tissue donation and transplantation which makes identification of a recipient at the time of donation impossible; and the easy availability of alternatives to tissues which make waiting lists redundant for many tissues. Rules for the implementation of the amended Act were framed in 2014 but like the Act must be adopted by the State health assemblies to become universally applicable in the country.

  13. Pakistan's kidney trade: an overview of the 2007 'Transplantation of Human Organs and Human Tissue Ordinance.' To what extent will it curb the trade?

    Science.gov (United States)

    Raza, Mohsen; Skordis-Worrall, Jolene

    2012-01-01

    Pakistan has the unenviable reputation for being one of the world's leading 'transplant tourism' destinations, largely the buying and selling of kidneys from its impoverished population to rich international patients. After nearly two decades of pressure to formally prohibit the trade, the Government of Pakistan promulgated the 'Transplantation of Human Organs and Human Tissue Ordinance' (THOTO) in 2007. This was then passed by Senate and enshrined in law in March 2010. This paper gives a brief overview of the organ trade within Pakistan and analyses the criteria of THOTO in banning the widespread practise. It then goes on to answer: 'To what extent will THOTO succeed in curbing Pakistan's kidney trade?' This is aided by the use of a comparative case study looking at India's failed organ trade legislation. This paper concludes THOTO has set a strong basis for curbing Pakistan's kidney trade. However, for this to be successfully achieved, it needs to be implemented with strong and sustained political will, strict and efficient enforcement as well as effective monitoring and evaluation. Efforts are needed to tackle both 'supply' and 'demand' factors of Pakistan's kidney trade, with developed countries also having a responsibility to reduce the flow of citizens travelling to Pakistan to purchase a kidney.

  14. Ethical issues in organ and tissue transplantation.

    Science.gov (United States)

    Abouna, George M

    2003-12-01

    Clinical organ transplantation provides a way of giving the gift of life to patients with terminal failure of vital organs, which requires the participation of other fellow human beings and of society by donating organs from deceased or living individuals. The increasing incidence of vital organ failure and the inadequate supply of organs, especially from cadavers, has created a wide gap between organ supply and organ demand, which has resulted in very long waiting times to receive an organ as well as an increasing number of deaths while waiting. These events have raised many ethical, moral and societal issues regarding supply, the methods of organ allocation the use of living donors as volunteers including minors. It has also led to the practice of organ sale by entrepreneurs for financial gains in some parts the world through exploitation of the poor, for the benefit of the wealthy. The current advances in immunology and tissue engineering and the use of animal organs, xenotransplantation, while offering very promising solutions to many of these problems, also raise additional ethical and medical issues, which must be considered by the medical profession as well as society. This review deals with the ethical and moral issues generated by the current advances in organ transplantation, the problem of organ supply versus organ demand and the appropriate allocation of available organs. It deals with the risks and benefits of organ donation from living donors, the appropriate and acceptable methods to increase organ donation from the deceased through the adoption of the principle of 'presumed consent', the right methods of providing acceptable appreciation and compensation for the family of the deceased as well as volunteer and altruistic donors, and the duties and responsibilities of the medical profession and society to help fellow humans. The review also deals with the appropriate and ethically acceptable ways of utilizing the recent advances of stem cell

  15. TRANSPLANTATION AND POTENTIAL IMMORTALITY OF MAMMALIAN TISSUES.

    Science.gov (United States)

    Loeb, L

    1926-06-20

    1. Serial transplantation of tumors made it possible in 1901 and following years to draw the conclusion that various mammalian tissues have potential immortality. Serial transplantations of normal tissues did not succeed at first, because the homoioreaction on the part of the lymphocytes and connective tissue of the host injures the transplant. 2. In continuation of these experiments we found that cartilage of the rat can be transplanted serially to other rats at least for a period of 3 years. At the end of that time great parts of the transplanted cartilage and perichondrium are alive. 3. Not only the cartilage of young rats can be homoiotransplanted, but also the cartilage of very old rats which are nearing the end of life. By using such animals we have been able to obtain cartilage and perichondrium approaching an age of 6 years which is almost double the average age of a rat. 4. We found that cartilage can be homoiotransplanted more readily than other tissues for the following reasons: (a) While in principle the homoioreaction towards cartilage is the same as against other tissues, cartilage elicits this reaction with less intensity; (b) cartilage is better able to resist the invasion of lymphocytes and connective tissue than the majority of other tissues; (c) a gradual adaptation between transplant and host seems to take place in the case of cartilage transplantation, as a result of which the lymphocytic reaction on the part of the host tissue decreases progressively the longer the cartilage is kept in the strange host. 5. At time of examination we not only found living transplanted cartilage tissue, but also perichondrial tissue, which in response to a stimulus apparently originating in the necrotic central cartilage, had been proliferating and replacing it. These results suggest that it may perhaps be possible under favorable conditions to keep cartilage alive indefinitely through serial transplantations. 6. At the same time these experiments permit the

  16. Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells

    DEFF Research Database (Denmark)

    Rolandsson, Sara; Andersson Sjöland, Annika; Brune, Jan C

    2014-01-01

    BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported. This st......BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported...

  17. Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Okura, Hanayuki [The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Saga, Ayami; Soeda, Mayumi [Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Miyagawa, Shigeru; Sawa, Yoshiki [Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Daimon, Takashi [Division of Biostatistics, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Ichinose, Akihiro [Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo (Japan); Matsuyama, Akifumi, E-mail: akifumi-matsuyama@umin.ac.jp [The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo (Japan); RIKEN Program for Drug Discovery and Medical Technology Platforms, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 (Japan)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer We administered human CLCs in a swine model of MI via intracoronary artery. Black-Right-Pointing-Pointer Histological studies demonstrated engraftment of hCLCs into the scarred myocardium. Black-Right-Pointing-Pointer Echocardiography showed rescue of cardiac function in the hCLCs transplanted swine. Black-Right-Pointing-Pointer Transplantation of hCLCs is an effective therapeutics for cardiac regeneration. -- Abstract: Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion of the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1 week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer's solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8 weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8 week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p = 0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of

  18. Transplantation of frozen-thawed ovarian tissue

    DEFF Research Database (Denmark)

    Gellert, S E; Pors, S E; Kristensen, Stine Gry

    2018-01-01

    . CONCLUSION: This study found no indications of sufficient numbers of malignant cells present in the ovarian tissue to cause recurrence of cancer after OTT. Further, it is unlikely that OTC affects the well-being of children born. OTC is now an established method of fertility preservation in Denmark......PURPOSE: The purpose of the study is to review all peer-reviewed published reports of women receiving ovarian tissue transplantation (OTT) with frozen/thawed tissue (OTC) with respect to age, diagnosis, transplantation site, fertility outcome, and potential side effects, including data from all...... women in the Danish program. METHODS: A systematic review of the literature was performed in PubMed combined with results from all patients who had received OTT in Denmark up to December 2017. RESULTS: OTT has been reported from 21 different countries comprising a total of 360 OTT procedures in 318...

  19. The Relationship of a Combination of Human Adipose Tissue-Derived Stem Cells and Frozen Fat with the Survival Rate of Transplanted Fat

    Directory of Open Access Journals (Sweden)

    Ki-Young Ha

    2015-11-01

    Full Text Available BackgroundThe survival rate of grafted fat is difficult to predict, and repeated procedures are frequently required. In this study, the effects of the freezing period of harvested adipose tissue and the addition of human adipose tissue-derived stem cells (ASCs on the process of fat absorption were studied.MethodsAdipose tissue was obtained from patients who underwent a lipoaspirated fat graft. The fat tissue was cryopreserved at -20℃ in a domestic refrigerator. A total of 40 nude mice were used. The mice in the experimental group received three different subcutaneous injections in the back: an injection of fresh fat and ASCs, an injection of fat that had been frozen for one month and ASCs, and an injection of fat that had been frozen for two months and ASCs. The control mice received fat grafts without ASCs. The mice were sacrificed at four or eight weeks after the procedure, and the grafted fat tissues were harvested. The extracted fat was evaluated using photographic analysis, volume measurements, and histological examination.ResultsIn the control group, the fat resorption rates four weeks after transplantation in the grafts of fresh fat, fat that had been frozen for one month, and fat that had been frozen for two months were 21.14%, 22.46%, and 42.56%, respectively. In the experimental group, the corresponding resorption rates were 6.68%, 13.0%, and 33.9%, respectively.ConclusionsASCs can increase the fat graft survival rate. The use of ASCs in fat grafting can reduce the need for repeated fat grafts and provide good long term results.

  20. Enhanced trace element concentrations in tissues of the clam Ruditapes decussatus transplanted to areas influenced by human activities (Ria Formosa, Portugal

    Directory of Open Access Journals (Sweden)

    Maria João Botelho

    2017-06-01

    Full Text Available To examine the extent to which human activities near the Ria Formosa coastal lagoon influence the accumulation of trace elements (TE in Ruditapes decussatus, individuals were transplanted from a natural bank located in the lower lagoon to three sites located in clam growth grounds under the influence of a small city (Faro, a fish farming centre (Olhão and a site near the lagoon inlet (Lavajo. Concentrations were determined in substrate of the clam grounds and in the digestive gland, gills, mantle plus siphons, and remaining tissues of clams in four periods of the year. These measurements were accomplished with the monthly survey of the gametogenic stages, condition index, proteins, glycogen, total lipids, pH and osmolarity of hemolymph. Arsenic, Cu, Mn, V, Cr and Pb were preferentially linked to the digestive gland, while Cd was linked to the gills. TE concentrations in the digestive gland and remaining tissues were higher in winter, most likely reflecting additional inputs associated with rain. The lack of disruptions in biological parameters and the prolonged period of spawning and gonad recovery in clams suggest that the current TE availability in the lagoon has a minor influence on the reproductive cycle and hence on clam production.

  1. Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic Transplantation

    Directory of Open Access Journals (Sweden)

    Yoshinobu Takahashi

    2018-05-01

    Full Text Available Summary: Clinical transplantation of tissue fragments, including islets, faces a critical challenge because of a lack of effective strategies that ensure efficient engraftment through the timely integration of vascular networks. We recently developed a complex organoid engineering method by “self-condensation” culture based on mesenchymal cell-dependent contraction, thereby enabling dissociated heterotypic lineages including endothelial cells to self-organize in a spatiotemporal manner. Here, we report the successful adaptation of this method for generating complex tissues from diverse tissue fragments derived from various organs, including pancreatic islets. The self-condensation of human and mouse islets with endothelial cells not only promoted functionalization in culture but also massively improved post-transplant engraftment. Therapeutically, fulminant diabetic mice were more efficiently treated by a vascularized islet transplant compared with the conventional approach. Given the general limitations of post-transplant vascularization associated with 3D tissue-based therapy, our approach offers a promising means of enhancing efficacy in the context of therapeutic tissue transplantation. : Takahashi et al. report on generating vascularized islet tissue from humans and mice. After transplantation, vascularized islets significantly improve survival of diabetic mice, demonstrating the quick normalization of blood glucose compared with conventional islet transplantation. Keywords: tissue engineering, tissue-based therapy, vascularization, islet transplantation, organoid

  2. Regeneration of rat corpora cavernosa tissue by transplantation of CD133+ cells derived from human bone marrow and placement of biodegradable gel sponge sheet

    Directory of Open Access Journals (Sweden)

    Shogo Inoue

    2017-01-01

    Full Text Available The objective is to develop an easier technique for regenerating corpora cavernosa tissue through transplantation of human bone marrow-derived CD133 + cells into a rat corpora cavernosa defect model. We excised 2 mm × 2 mm squares of the right corpora cavernosa of twenty-three 8-week-old male nude rats. Alginate gel sponge sheets supplemented with 1 × 10 4 CD133 + cells were then placed over the excised area of nine rats. Functional and histological evaluations were carried out 8 weeks later. The mean intracavernous pressure/mean arterial pressure ratio for the nine rats (0.34258 ± 0.0831 was significantly higher than that for eight rats with only the excision (0.0580 ± 0.0831, P = 0.0238 and similar to that for five rats for which the penis was exposed, and there was no excision (0.37228 ± 0.1051, P = 0.8266. Immunohistochemical analysis revealed that the nine fully treated rats had venous sinus-like structures and quantitative reverse transcription polymerase chain reaction analysis of extracts from their alginate gel sponge sheets revealed that the amounts of mRNA encoding the nerve growth factor (NGF, and vascular endothelial growth factor (VEGF were significantly higher than those for rats treated with alginate gel sheets without cell supplementation (NGF: P = 0.0309; VEGF: P < 0.0001. These findings show that transplantation of CD133 + cells accelerates functional and histological recovery in the corpora cavernosa defect model.

  3. Systemic transplantation of human adipose tissue-derived mesenchymal stem cells for the regeneration of irradiation-induced salivary gland damage.

    Directory of Open Access Journals (Sweden)

    Jae-Yol Lim

    Full Text Available OBJECTIVES: Cell-based therapy has been reported to repair or restore damaged salivary gland (SG tissue after irradiation. This study was aimed at determining whether systemic administration of human adipose-derived mesenchymal stem cells (hAdMSCs can ameliorate radiation-induced SG damage. METHODS: hAdMSCs (1 × 10(6 were administered through a tail vein of C3H mice immediately after local irradiation, and then this infusion was repeated once a week for 3 consecutive weeks. At 12 weeks after irradiation, functional evaluations were conducted by measuring salivary flow rates (SFRs and salivation lag times, and histopathologic and immunofluorescence histochemistry studies were performed to assay microstructural changes, apoptosis, and proliferation indices. The engraftment and in vivo differentiation of infused hAdMSCs were also investigated, and the transdifferentiation of hAdMSCs into amylase-producing SG epithelial cells (SGCs was observed in vitro using a co-culture system. RESULTS: The systemic administration of hAdMSCs exhibited improved SFRs at 12 weeks after irradiation. hAdMSC-transplanted SGs showed fewer damaged and atrophied acinar cells and higher mucin and amylase production levels than untreated irradiated SGs. Immunofluorescence TUNEL assays revealed fewer apoptotic cells in the hAdMSC group than in the untreated group. Infused hAdMSCs were detected in transplanted SGs at 4 weeks after irradiation and some cells were found to have differentiated into SGCs. In vitro, a low number of co-cultured hAdMSCs (13%-18% were observed to transdifferentiate into SGCs. CONCLUSION: The findings of this study indicate that hAdMSCs have the potential to protect against irradiation-induced cell loss and to transdifferentiate into SGCs, and suggest that hAdMSC administration should be viewed as a candidate therapy for the treatment of radiation-induced SG damage.

  4. Microautoradiographic studies on distribution of 5α-dihydrotestosterone, cyproterone acetate and oestradiol-17β in human prostatic hyperplasia tissue transplanted to juvenile rats

    International Nuclear Information System (INIS)

    Ruberg, I.; Neumann, F.; Senge, Th.

    1982-01-01

    While maintaining the actual conditions prevailing in benign prostatic hyperplasia (BHP) in man, transplantation of BPH tissue to newborn rats proved a suitable model for examining the distribution of sexual hormones in different tissue compartments of BPH. In combination with the microautoradiographic method, it was possible to demonstrate the residence of the radioactive androgen 5α-=dihydrotestosterone (5α- DHT), the antiandrogen cyproterone acetate (CA) and the oestrogen oestradiol-17β(E 2 ) in the epithelium and/or stroma of human BPH tissue. Quantitative evaluation in the form of a point per area count on photographic pictures yielded a silver grain distribution ratio in epithelium and stroma of 1.3:1 and 1.5:1 for epithelium to stroma after administration of [ 3 H]5α-DHT and [ 3 H]CA administration respectively and 0.5:1 after [ 3 H]E 2 . The high tracer recovery rate throughout the stroma following E 2 administration supports the current view that the stromal proliferation is attributable mainly to oestrogen influences. The relatively high silver particle proportion throughout the stroma following 5α-DHT administration corroborates recent findings which suggest that the exclusive androgen dependency of the glandular epithelium can only be considered in conjunction with an active metabolization of androgens in the stroma. The correspondence in the distribution of the radioactive tracer after [ 3 H]5α-DHT and [ 3 H]CA administration both in the epithelium and stroma suggests that an antagonism may also exist in the stroma. (author)

  5. A rapid radioimmunoassay for insulin suitable for testing pancreatic tissue prior to transplantation

    International Nuclear Information System (INIS)

    Besch, W.; Kohnert, K.-D.; Hahn, H.-J.; Ziegler, M.; Lorenz, D.

    1984-01-01

    One way of diabetes mellitus treatment is the transplantation of insulin-producing tissue. As islet or pancreas transplantation has made progress, testing of the tissue for its vitality, insulin content and insulin secretory response prior to transplantation became necessary. Apart from problems of rejection of allografted tissue, improvement of the patients metabolic control partly depends on the insulin content of the tissue transplanted. It was the aim of the present work to establish a radioimmunoassay which ensures rapid determination of immunoreactive insulin concentrations (IRI) either intracellularly-stored or released upon stimulation of human pancreas or islet with glucose, and to demonstrate the useful application of this assay for the assessment of transplantable tissue. (Auth.)

  6. Current Status and Future Development of Cell Transplantation Therapy for Periodontal Tissue Regeneration

    Science.gov (United States)

    Yoshida, Toshiyuki; Washio, Kaoru; Iwata, Takanori; Okano, Teruo; Ishikawa, Isao

    2012-01-01

    It has been shown that stem cell transplantation can regenerate periodontal tissue, and several clinical trials involving transplantation of stem cells into human patients have already begun or are in preparation. However, stem cell transplantation therapy is a new technology, and the events following transplantation are poorly understood. Several studies have reported side effects and potential risks associated with stem cell transplantation therapy. To protect patients from such risks, governments have placed regulations on stem cell transplantation therapies. It is important for the clinicians to understand the relevant risks and governmental regulations. This paper describes the ongoing clinical studies, basic research, risks, and governmental controls related to stem cell transplantation therapy. Then, one clinical study is introduced as an example of a government-approved periodontal cell transplantation therapy. PMID:22315604

  7. Current Status and Future Development of Cell Transplantation Therapy for Periodontal Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Toshiyuki Yoshida

    2012-01-01

    Full Text Available It has been shown that stem cell transplantation can regenerate periodontal tissue, and several clinical trials involving transplantation of stem cells into human patients have already begun or are in preparation. However, stem cell transplantation therapy is a new technology, and the events following transplantation are poorly understood. Several studies have reported side effects and potential risks associated with stem cell transplantation therapy. To protect patients from such risks, governments have placed regulations on stem cell transplantation therapies. It is important for the clinicians to understand the relevant risks and governmental regulations. This paper describes the ongoing clinical studies, basic research, risks, and governmental controls related to stem cell transplantation therapy. Then, one clinical study is introduced as an example of a government-approved periodontal cell transplantation therapy.

  8. US of tissue banking and transplantation in North America

    International Nuclear Information System (INIS)

    Strong, M.; Moogk, M.

    1999-01-01

    Tissue banking in North America began as surgical bone banking in individual hospitals and progressed to recovery of cadaveric tissues, initially by the United States Navy Tissue Bank and more recently to regional tissue banks throughout North America. The American Association of Tissue Banks was established in 1976 to develop standards for tissue banking and the eventual inspection and accreditation of tissue banks. The gathering of statistics of tissue banking practices was first undertaken in 1992, from accredited tissue banks. The most recent statistics were compiled in 1997 and will be reported at this conference.There are currently 63 accredited tissue banks in North America, 60 in the United States and three in Canada. Overall, tissue donation has increased by 48% during this 5 year reporting time. During the same period, the number of living surgical bone donors has decreased from nearly 3,000 to less than 500. This impact is largely due to the new regulations that have been implemented by the Food and Drug Administration (FDA). There were over 340,000 bone grafts distributed in 1996, an increase of 20% over 1992, 33% were not sterilized, 21% were sterilized using irradiation, and 45% were demineralized. Only 1% were processed using ethylene oxide as a sterilant, a decrease from 15% in 1992. The primary mode of preservation and storage is freeze-drying with 90% of the tissues falling into this category and the rest being frozen. The second largest number of grafts distributed were skin grafts. Total tissue grafts distributed including cornea was 445,417. In January 1998, the FDA Final Rule regarding regulation of tissue banking became effective. The elements of that Final Rule and new tissue banking rules the FDA has proposed will be discussed along with regulations recently published by the Health and Human Services Department relative to organ and tissue donor referrals. Tissue Banking in North America continues to evolve and has become more and more

  9. Repair of radiation injury by transplantation of hemopoietic tissue

    International Nuclear Information System (INIS)

    Smith, L.H.

    1978-01-01

    The following topics are discussed: endogenous repair of tissue by surviving cells; exogenous repair by transplantation of tissue from unirradiated donor; repair of hematopoietic tissue following sublethal exposure or exposure in the LD 1 to LD 100 range; early studies on regeneration of hematopoietic tissue in x-irradiated dogs by giving bone marrow; hypotheses as to how bone marrow injections result in regeneration of blood-forming tissue; effects of rat bone marrow transplants on survival of lethally irradiated mice; and effect of tissue transplants on dose-response curve

  10. Uterine transplantation: Review in human research.

    Science.gov (United States)

    Favre-Inhofer, A; Rafii, A; Carbonnel, M; Revaux, A; Ayoubi, J M

    2018-06-01

    Uterine transplantation is the solution to treat absolute uterine fertility. In this review, we present the historical, medical, technical, psychological and ethical perspectives in human uterine transplantation research. We reviewed the PubMed database following PRISMA guidelines and added data presented by several research teams during the first international congress on uterine transplantation. Copyright © 2018. Published by Elsevier Masson SAS.

  11. Aspectos ético-legais da retirada e transplante de tecidos, órgãos e partes do corpo humano Aspectos ético-legales de la retirada y transplante de tejidos, organos y partes del cuerpo humano Legal-ethical aspects of the removal and transplantation of tissues, organs and parts of the human body

    Directory of Open Access Journals (Sweden)

    Elenice Dias Ribeiro de Paula Lima

    1997-10-01

    Full Text Available As autoras fazem uma análise crítica da legislação em vigor relativa aos transplantes de órgãos, tecidos e partes do corpo humano, e tecem comentários sobre os artigos pertinentes a eles nos respectivos códigos de ética médica e da enfermagem, alertando os profissionais de enfermagem para a necessidade de registrarem as infrações cometidas contra o cliente, à luz desses códigos.Las autoras hacen un analisis crítico de la legislación en vigor referente a los transplantes de órganos, tejidos y partes del cuerpo humano y hacen comentarios sobre los artículos pertinentes a ellos en los respectivos códigos de ética médica y de enfermería, alertando a los profesionales de enfermería sobre la necesidad de registrar las transgresiones hechas contra el cliente, a la luz de esos códigos.The authors analise critically the current legislation related to the transplantation of organs, tissues and parts of the human body, as well as they comment the articles which refer to this topic and which are found in medical and nursing ethical codes, advising nursing professionals to the need of registration of legal infractions attempted against the clients.

  12. Long-term function of ovarian tissue transplants

    Directory of Open Access Journals (Sweden)

    Sherman J. Silber

    2012-12-01

    Full Text Available The long term duration of function of ovarian cortical tissue grafts is reviewed in this paper by describing cases of restoration of fertility by transplant of ovarian cortical tissue from matching donors where the recipient was in need of the transplant due to sterilizing effects of leukemia, premature ovarian failure (POF, and to reflect that it may be possible to postpone the normal time of menopause or to alleviate its symptoms.

  13. Radiation sterilisation of tissue allografts for transplant surgery

    International Nuclear Information System (INIS)

    Phillips, G.O.

    1994-01-01

    The application of ionising radiation to sterilise biological tissues is an extension of their use for the sterilisation of other medical products and pharmaceuticals. This paper describes the effects of radiation on biological tissues, both at the macro- and molecular level. Changes in mechanical and other physical properties can accompany irradiation. These are shown to be due to the glycosamino-glycan component (hyaluronic acid), rather than to the collagen fibrils. Fast reaction methods are used to identify the mechanism of the radiation degradation processes. Methods by which tissues can be protected from these undesirable effects are discussed. The application of radiation sterilisation to human tissues used in transplant surgery is described, and the practical methods of processing given. Such radiation sterilised allografts now have wide application, with more than 500,000 used each year. The IAEA programme in this field has extended the application to 13 countries of the Asia and Pacific Region. Such Tissue Banks are also established with the support of IAEA in Africa and South America. The allografts can now be produced in developing countries in a readily available form, at low cost, and reduce the need for costly imported alternatives. (author). 45 refs., 19 figs., 3 tabs

  14. Public awareness in promotion of tissue transplantation in Malaysia

    International Nuclear Information System (INIS)

    Abd Rani Samsudin; Hasim Mohammad

    1999-01-01

    Malaysia is a developing country in South East Asia with a population of 21 million. The population is multiracial, multicultural and multireligion and it is one of the few countries in the world which possess a multicomplexity way of life among its ethnic groups. The health care system in Malaysia is divided into two main system, i.e. government based or public service and private based health care practice. The idea about organ donation and transplant science has a rise in Malaysia some 30 years ago, and the first historical event of a kidney transplant from a cadaveric donor took place in 1976. 22 years down the line, the first heart transplant was performed in Malaysia. Over the last 22 years between 1976 and 1998 many programmes promoting the idea of organ and tissue transplantation has been came out throughout the country led by government based bodies and non governmental Organisation. In terms of government funding, supporting a transplant programme is not a cheap exercise and this aspect of health care financial burden must be given due consideration by government and non governmental bodies for success of the programme. Besides financial burden, there are the common dilemma of culture and religious barrier for the success of the programme, but this problem has been tackled extremely well by the government. The setting up of two tissue banks in Malaysia in 1991 has further enhanced the idea of organ and tissue transplantation in this country, and the establishment of the national transplant resource centre based at Hospital Kuala Lumpur provides a national coordination service system for both organ and tissue procurement services for the whole country. Organ and tissue donation programme-ne and finally the success of a national transplant programme will certainly depend on the health status and health priorities of the country, the standard of general education, the quality of life style while cultural and religious factors in Malaysia will play a minor

  15. The safety of transplanting cryopreserved ovarian tissue in cancer patients

    DEFF Research Database (Denmark)

    Rosendahl, Mikkel; Greve, Tine; Andersen, Claus Yding

    2013-01-01

    Transplantation of frozen/thawed ovarian tissue from patients with a malignant condition is associated with a risk of re-introduction of the disease as the tissue usually is removed before anti-cancer therapy and may thus contain malignant cells. We review studies investigating the presence...

  16. Experience of nurses in the process of donation of organs and tissues for transplant.

    Science.gov (United States)

    de Moraes, Edvaldo Leal; dos Santos, Marcelo José; Merighi, Miriam Aparecida Barbosa; Massarollo, Maria Cristina Komatsu Braga

    2014-01-01

    to investigate the meaning of the action of nurses in the donation process to maintain the viability of organs and tissues for transplantation. this qualitative study with a social phenomenological approach was conducted through individual interviews with ten nurses of three Organ and Tissue Procurement Services of the city of São Paulo. the experience of the nurses in the donation process was represented by the categories: obstacles experienced in the donation process, and interventions performed. The meaning of the action to maintain the viability of organs and tissues for transplantation was described by the categories: to change paradigms, to humanize the donation process, to expand the donation, and to save lives. knowledge of the experience of the nurses in this process is important for healthcare professionals who work in different realities, indicating strategies to optimize the procurement of organs and tissues for transplantation.

  17. Experience of nurses in the process of donation of organs and tissues for transplant

    Directory of Open Access Journals (Sweden)

    Edvaldo Leal de Moraes

    2014-04-01

    Full Text Available OBJECTIVE: to investigate the meaning of the action of nurses in the donation process to maintain the viability of organs and tissues for transplantation.METHOD: this qualitative study with a social phenomenological approach was conducted through individual interviews with ten nurses of three Organ and Tissue Procurement Services of the city of São Paulo.RESULTS: the experience of the nurses in the donation process was represented by the categories: obstacles experienced in the donation process, and interventions performed. The meaning of the action to maintain the viability of organs and tissues for transplantation was described by the categories: to change paradigms, to humanize the donation process, to expand the donation, and to save lives.FINAL CONSIDERATIONS: knowledge of the experience of the nurses in this process is important for healthcare professionals who work in different realities, indicating strategies to optimize the procurement of organs and tissues for transplantation.

  18. ATP-ase positive cells in human oral mucosa transplanted to nude mice

    DEFF Research Database (Denmark)

    Dabelsteen, E; Kirkeby, S

    1981-01-01

    A model to study the differentiation of human oral epithelium in vivo utilizing transplantation of human tissue to nude mice has been described. Previous studies have described the epithelial cells in this model. In this study we demonstrate that 8 d after transplantation, Langerhans cells, ident......, identified as ATP-ase positive dendritic cells, have almost disappeared from the transplanted epithelium whereas at day 21 after transplantation such cells were abundant. It is suggested that the ATP-ase positive cells which reappear in the transplanted epithelium are of mouse origin....

  19. Bioprinting scale-up tissue and organ constructs for transplantation.

    Science.gov (United States)

    Ozbolat, Ibrahim T

    2015-07-01

    Bioprinting is an emerging field that is having a revolutionary impact on the medical sciences. It offers great precision for the spatial placement of cells, proteins, genes, drugs, and biologically active particles to better guide tissue generation and formation. This emerging biotechnology appears to be promising for advancing tissue engineering toward functional tissue and organ fabrication for transplantation, drug testing, research investigations, and cancer or disease modeling, and has recently attracted growing interest worldwide among researchers and the general public. In this Opinion, I highlight possibilities for the bioprinting scale-up of functional tissue and organ constructs for transplantation and provide the reader with alternative approaches, their limitations, and promising directions for new research prospects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Evaluation of the ovarian reserve in women transplanted with frozen and thawed ovarian cortical tissue

    DEFF Research Database (Denmark)

    Greve, Tine; Schmidt, Kirsten Tryde; Kristensen, Stine Gry

    2012-01-01

    To investigate ovarian reserve and ovarian function in women transplanted with frozen/thawed ovarian tissue.......To investigate ovarian reserve and ovarian function in women transplanted with frozen/thawed ovarian tissue....

  1. The International Registry on Hand and Composite Tissue Transplantation.

    Science.gov (United States)

    Petruzzo, Palmina; Lanzetta, Marco; Dubernard, Jean-Michel; Landin, Luis; Cavadas, Pedro; Margreiter, Raimund; Schneeberger, Stephan; Breidenbach, Warren; Kaufman, Christina; Jablecki, Jerzy; Schuind, Frédéric; Dumontier, Christian

    2010-12-27

    The International Registry on Hand and Composite Tissue Transplantation was founded in May 2002, and the analysis of all cases with follow-up information up to July 2010 is presented here. From September 1998 to July 2010, 49 hands (17 unilateral and 16 bilateral hand transplantations, including 1 case of bilateral arm transplantation) have been reported, for a total of 33 patients. They were 31 men and 2 women (median age 32 years). Time since hand loss ranged from 2 months to 34 years, and in 46% of cases, the level of amputation was at wrist. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, sirolimus, and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was also used in several cases. Follow-up ranges from 1 month to 11 years. One patient died on day 65. Three patients transplanted in the Western countries have lost their graft, whereas until September 2009, seven hand grafts were removed for noncompliance to the immunosuppressive therapy in China. Eighty-five percent of recipients experienced at least one episode of acute rejection within the first year, and they were reversible when promptly treated. Side effects included opportunistic infections, metabolic complications, and malignancies. All patients developed protective sensibility, 90% of them developed tactile sensibility, and 82.3% also developed a discriminative sensibility. Motor recovery enabled patients to perform most daily activities. Hand transplantation is a complex procedure, and its success is based on patient's compliance and his or her careful evaluation before and after transplantation.

  2. [Human brown adipose tissue].

    Science.gov (United States)

    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  3. Uterine Tissue Engineering and the Future of Uterus Transplantation.

    Science.gov (United States)

    Hellström, Mats; Bandstein, Sara; Brännström, Mats

    2017-07-01

    The recent successful births following live donor uterus transplantation are proof-of-concept that absolute uterine factor infertility is a treatable condition which affects several hundred thousand infertile women world-wide due to a dysfunctional uterus. This strategy also provides an alternative to gestational surrogate motherhood which is not practiced in most countries due to ethical, religious or legal reasons. The live donor surgery involved in uterus transplantation takes more than 10 h and is then followed by years of immunosuppressive medication to prevent uterine rejection. Immunosuppression is associated with significant adverse side effects, including nephrotoxicity, increased risk of serious infections, and diabetes. Thus, the development of alternative approaches to treat absolute uterine factor infertility would be desirable. This review discusses tissue engineering principles in general, but also details strategies on how to create a bioengineered uterus that could be used for transplantation, without risky donor surgery and any need for immunosuppression. We discuss scaffolds derived from decellularized organs/tissues which may be recellularized using various types of autologous somatic/stem cells, in particular for uterine tissue engineering. It further highlights the hurdles that lay ahead in developing an alternative to an allogeneic source for uterus transplantation.

  4. Colonic complications following human bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Paulino Martínez Hernández-Magro

    2015-01-01

    Full Text Available Background: Human bone marrow transplantation (BMT becomes an accepted treatment of leukemia, aplastic anemia, immunodeficiency syndromes, and hematologic malignancies. Colorectal surgeons must know how to determine and manage the main colonic complications. Objective: To review the clinical features, clinical and pathological staging of graft vs host disease (GVHD, and treatment of patients suffering with colonic complications of human bone marrow transplantation. Patients and methods: We have reviewed the records of all patients that received an allogeneic bone marrow transplant and were evaluated at our Colon and Rectal Surgery department due to gastrointestinal symptoms, between January 2007 and January 2012. The study was carried out in patients who developed colonic complications, all of them with clinical, histopathological or laboratory diagnosis. Results: The study group was constituted by 77 patients, 43 male and 34 female patients. We identified colonic complications in 30 patients (38.9%; five patients developed intestinal toxicity due to pretransplant chemotherapy (6.4%; graft vs. host disease was present in 16 patients (20%; 13 patients (16.8% developed acute colonic GVHD, and 3 (3.8% chronic GVHD. Infection was identified in 9 patients (11.6%. Conclusions: The three principal colonic complications are the chemotherapy toxicity, GVHD, and superinfection; the onset of symptoms could help to suspect the type of complication (0–20 day chemotherapy toxicity, 20 and more GVHD, and infection could appear in any time of transplantation. Resumo: Experiência: O transplante de medula óssea humana (MOH passou a ser um tratamento adotado para leucemia, anemia aplástica, síndromes de imunodeficiência e neoplasias hematológicas. Cirurgiões colorretais devem saber como determinar e tratar as principais complicações do cólon. Objetivo: Revisar as características clínicas, estadiamentos clínico e patológico da doença do enxerto

  5. Autologous Pancreatic Islet Transplantation in Human Bone Marrow

    Science.gov (United States)

    Maffi, Paola; Balzano, Gianpaolo; Ponzoni, Maurilio; Nano, Rita; Sordi, Valeria; Melzi, Raffaella; Mercalli, Alessia; Scavini, Marina; Esposito, Antonio; Peccatori, Jacopo; Cantarelli, Elisa; Messina, Carlo; Bernardi, Massimo; Del Maschio, Alessandro; Staudacher, Carlo; Doglioni, Claudio; Ciceri, Fabio; Secchi, Antonio; Piemonti, Lorenzo

    2013-01-01

    The liver is the current site of choice for pancreatic islet transplantation, even though it is far from being ideal. We recently have shown in mice that the bone marrow (BM) may be a valid alternative to the liver, and here we report a pilot study to test feasibility and safety of BM as a site for islet transplantation in humans. Four patients who developed diabetes after total pancreatectomy were candidates for the autologous transplantation of pancreatic islet. Because the patients had contraindications for intraportal infusion, islets were infused in the BM. In all recipients, islets engrafted successfully as shown by measurable posttransplantation C-peptide levels and histopathological evidence of insulin-producing cells or molecular markers of endocrine tissue in BM biopsy samples analyzed during follow-up. Thus far, we have recorded no adverse events related to the infusion procedure or the presence of islets in the BM. Islet function was sustained for the maximum follow-up of 944 days. The encouraging results of this pilot study provide new perspectives in identifying alternative sites for islet infusion in patients with type 1 diabetes. Moreover, this is the first unequivocal example of successful engraftment of endocrine tissue in the BM in humans. PMID:23733196

  6. [The legal and ethical aspects of nerve tissue transplantation].

    Science.gov (United States)

    Sramka, M; Rattaj, M

    1992-01-01

    The authors have specified the following criteria for the withdrawal of embryonal tissue at their department: 1) only tissue from dead fetus is allowed to be used in neurotransplantation; 2) embryonal tissue is to be obtained after spontaneous abortions from volunteers or from women asking for artificial abortion; 3) the women should be informed about the curative purposes of embryonal tissue voluntary donorship and they must give a written consent; 4) decision on abortion should be separated from the use of embryonal tissue; 5) women should not know recipients; no payments should be made for tissue; 6) the donor is not permitted to impregnate in order to use embryos for research or clinical purposes; 7) sampling of BWR, HBsAG, anti-HIV, cytomegalovirus, herpes I and II is to be made for serologic examinations and that from the cervix for cultivation and sensitivity, as well as ultrasound verification of a germinal age is done in potential donors; 8) consent should be signed to embryonal brain transplantation by recipient or his legitimate deputy if the recipient is certifiable. The above criteria should protect both the donor and the recipient. The use of embryonal tissue cultures seems to be promising. In addition to legal and ethic problems, immunological problems and problems concerning the aseptic withdrawal of embryonal tissue are falling off.

  7. Histomorphological Evaluation of Fresh Ovarian Tissue Transplanted Into Back Muscles of Balb/C Mice

    Directory of Open Access Journals (Sweden)

    I Amiri

    2011-06-01

    Full Text Available & objectives: Today, different methods for maintaining reproductive capability in young women with cancer are being considered. One of the most prominent of these methods is ovarian tissue transplant. Despite the relative success of this method, the appropriate location and methods of transplantation is still a matter of discussion. The present study evaluated the histomorphology of fresh ovarian tissue transplantation by two methods, inter muscular and intra muscular, in Balb/C mice. Methods & Materials: The study was conducted at Hamedan University of Medical Sciences in 2009. Fresh ovarian tissues from 12-14 day old Balb/C mice were transplanted into back muscles of ovarectomized 6 week old Balb/C mice both intermuscularly and intramuscularly. All transplanted mice received intra-peritoneal injections of a unit of rFSH for 4 weeks, every other day. At the end of the tenth week, all transplant recipient mice were killed and the transplanted ovarian tissues were removed. All samples were assessed for the angiogenesis and viability of follicles. Data were analyzed using SPSS software, using independent t- test. Results: In intermuscular transplanted group, the transplanted tissues were rejected in two cases. In the sections prepared from the other cases, in spite of the presence of some small necrotic areas, the majority of ovarian tissues had a healthy appearance within the primordial, primary, secondary and antral follicles. Apart from a significant reduction in the number of follicles and smaller size of follicles in the transplanted tissue in comparison with control group, no other major differences in morphology, histology, and the process of maturation of ovarian follicles were observed between the transplanted and control groups. Conclusion: Fresh ovarian tissue transplantation into muscles of the back area without basic vascular pedicle has new angiogenesis capabilities, appropriate survival and development of primordial follicles and

  8. Reversal of Type 1 Diabetes in Mice by Brown Adipose Tissue Transplant

    OpenAIRE

    Gunawardana, Subhadra C.; Piston, David W.

    2012-01-01

    Current therapies for type 1 diabetes (T1D) involve insulin replacement or transplantation of insulin-secreting tissue, both of which suffer from numerous limitations and complications. Here, we show that subcutaneous transplants of embryonic brown adipose tissue (BAT) can correct T1D in streptozotocin-treated mice (both immune competent and immune deficient) with severely impaired glucose tolerance and significant loss of adipose tissue. BAT transplants result in euglycemia, normalized gluco...

  9. Random lasing in human tissues

    International Nuclear Information System (INIS)

    Polson, Randal C.; Vardeny, Z. Valy

    2004-01-01

    A random collection of scatterers in a gain medium can produce coherent laser emission lines dubbed 'random lasing'. We show that biological tissues, including human tissues, can support coherent random lasing when infiltrated with a concentrated laser dye solution. To extract a typical random resonator size within the tissue we average the power Fourier transform of random laser spectra collected from many excitation locations in the tissue; we verified this procedure by a computer simulation. Surprisingly, we found that malignant tissues show many more laser lines compared to healthy tissues taken from the same organ. Consequently, the obtained typical random resonator was found to be different for healthy and cancerous tissues, and this may lead to a technique for separating malignant from healthy tissues for diagnostic imaging

  10. Trend Analysis of Organ and Tissue Donation for Transplantation.

    Science.gov (United States)

    Dos Santos, M J; Leal de Moraes, E; Santini Martins, M; Carlos de Almeida, E; Borges de Barros E Silva, L; Urias, V; Silvano Corrêa Pacheco Furtado, M C; Brito Nunes, Á; El Hage, S

    2018-03-01

    The goal of this study was to identify the tendency toward donations of tissue and organs from donors with brain death between 2001 and 2016 as registered by an organ procurement organization in São Paulo City. This quantitative, retrospective, exploratory study encompassed all Tissue and Organ Donation Terms signed between 2001 and 2016. A logistic regression model was applied to verify whether there was an upward or downward trend in donation. After statistical analysis, a significant change trend was identified in skin, bones, valve, vessel, heart, lung, and pancreas donations, indicating an increase in the donation rate through the years. The donation rate did not show changes over the years for donations of liver, kidneys, and corneas. The decision-making process regarding organ and tissue donation is restricted not only to the dilemma of whether to donate but another question then arises as well: which organs and tissues are to be donated? The discrepancy between the authorization for organ donation and the authorization for tissue donation, as well as the option for one or another organ and/or tissue, must be thoroughly examined because these factors directly affect the number of transplants and acquirements effectively accomplished. These factors may be related to explaining to one's relatives aspects of the surgery, body reassembling, and usage of such organs and/or tissues. They may also be related to the lack of knowledge concerning organ donation and the symbolism represented by the organ and/or tissue, among other factors. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. The immunologic considerations in human head transplantation.

    Science.gov (United States)

    Hardy, Mark A; Furr, Allen; Barret, Juan P; Barker, John H

    2017-05-01

    The idea of head transplantation appears at first as unrealistic, unethical, and futile. Here we discuss immunological considerations in human head transplantation. In a separate accompanying article we discuss surgical, ethical, and psychosocial issues concerned in body-to-head transplantation (BHT) [1]. The success of such an unusual allograft, where the donor and the recipient can reject each other, depends on prevention of complex immunologic reactions, especially rejection of the head by the body (graft-vs-host) or probably less likely, the possibility of the head rejecting the total body allograft (host-vs-graft). The technical and immunologic difficulties are enormous, especially since rapid nerve and cord connections and regeneration have not yet been possible to achieve. In this article we begin by briefly reviewing neuro-immunologic issues that may favor BHT such as the blood brain barrier (BBB) and point out its shortcomings. And we touch on the cellular and humoral elements in the brain proper that differ in some respects from those in other organs and in the periphery. Based on recent successes in vascular composite allografts (VCAs), we will elaborate on potential specific advantages and difficulties in BHT of various available immunosuppressive medications already utilized in VCAs. The risk/benefit ratio of these drugs will be emphasized in relation to direct brain toxicity such as seizure disorders, interference, or promotion of nerve regeneration, and potentiation of cerebral viral infections. The final portion of this article will focus on pre-transplant immunologic manipulation of the deceased donor body along with pretreatment of the recipient. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  12. Ninety-five orthotopic transplantations in 74 women of ovarian tissue after cytotoxic treatment in a fertility preservation network: tissue activity, pregnancy and delivery rates.

    Science.gov (United States)

    Van der Ven, H; Liebenthron, J; Beckmann, M; Toth, B; Korell, M; Krüssel, J; Frambach, T; Kupka, M; Hohl, M K; Winkler-Crepaz, K; Seitz, S; Dogan, A; Griesinger, G; Häberlin, F; Henes, M; Schwab, R; Sütterlin, M; von Wolff, M; Dittrich, R

    2016-09-01

    What is the success rate in terms of ovarian activity (menstrual cycles) as well as pregnancy and delivery rates 1 year after orthotopic ovarian transplantations conducted in a three-country network? In 49 women with a follow-up >1 year after transplantation, the ovaries were active in 67% of cases and the pregnancy and delivery rates were 33 and 25%, respectively. Cryopreservation of ovarian tissue in advance of cytotoxic therapies and later transplantation of the tissue is being performed increasingly often, and the total success rates in terms of pregnancy and delivery have been described in case series. However, published case series have not allowed either a more detailed analysis of patients with premature ovarian insufficiency (POI) or calculation of success rates based on the parameter 'tissue activity'. Retrospective analysis of 95 orthotopic transplantations in 74 patients who had been treated for cancer, performed in the FertiPROTEKT network from 2008 to June 2015. Of those 95 transplantations, a first subgroup (Subgroup 1) was defined for further analysis, including 49 women with a follow-up period >1 year after transplantation. Of those 49 women, a second subgroup (Subgroup 5) was further analysed, including 40 women who were transplanted for the first time and who were diagnosed with POI before transplantation. Transplantation was performed in 16 centres and data were transferred to the FertiPROTEKT registry. The transplantations were carried out after oncological treatment had been completed and after a remission period of at least 2 years. Tissue was transplanted orthotopically, either into or onto the residual ovaries or into a pelvic peritoneal pocket. The success rates were defined as tissue activity (menstrual cycles) after 1 year (primary outcome) and as pregnancies and deliveries achieved. The average age of all transplanted 74 women was 31 ± 5.9 years at the time of cryopreservation and 35 ± 5.2 at the time of transplantation. Twenty

  13. Erythropoietin improves the survival of fat tissue after its transplantation in nude mice.

    Directory of Open Access Journals (Sweden)

    Saher Hamed

    Full Text Available BACKGROUND: Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. METHODOLOGY/PRINCIPAL FINDINGS: Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF-treated and phosphate-buffered saline (PBS-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. CONCLUSIONS/SIGNIFICANCE: Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

  14. Erythropoietin improves the survival of fat tissue after its transplantation in nude mice.

    Science.gov (United States)

    Hamed, Saher; Egozi, Dana; Kruchevsky, Danny; Teot, Luc; Gilhar, Amos; Ullmann, Yehuda

    2010-11-15

    Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

  15. A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

    Directory of Open Access Journals (Sweden)

    Matthew E. Brown

    2018-04-01

    Full Text Available Summary: Here, we describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood hematopoietic stem cells (HSCs. Conventional humanized mouse models are made by engrafting human fetal thymus and HSCs into immunocompromised mice. These mice harbor functional human T cells that have matured in the presence of human self-peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more abundant and developmentally mature and allows for creation of up to ∼50-fold more mice per donor compared with fetal tissue models. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. The NeoThy model may provide significant advantages for induced pluripotent stem cell immunogenicity studies, while bypassing the requirement for fetal tissue. : Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo. Keywords: NeoThy, humanized mouse, iPSC, PSC, immunogenicity, transplantation, immunology, hematopoietic stem cells, induced pluripotent stem cells, thymus

  16. Interpretive conundrum on the exclusion criterion of "transplantation with xenografts" for tissue and cell donation.

    Science.gov (United States)

    Cox, Michael A; Brubaker, Scott A

    2012-06-01

    In the context of the EU Directives for human tissues and cells (2004/23/EC, 2006/17/EC and 2006/86/EC) further interest has arisen on the practical application of a few clauses. One such aspect, for the evaluation phase of a potential donor, is the interpretation of the exclusion criterion "transplantation with xenografts." This article outlines the consensus viewpoints regarding the earlier evaluation of the risks related to xenotransplantation and describes the current status of the terminology and recommendations/laws in several healthcare sectors. The application of uniform terminology is encouraged within the healthcare sectors at the international level.

  17. The effect of radiation sterilization on human transplantable bone

    International Nuclear Information System (INIS)

    Triantafyllou, N.; Karatzas, P.

    1974-11-01

    In order to study the effect of radiation sterilization on human transplantable bones, work was carried out on human and bovine bone tissue samples. Factors causing possible alterations in the mechanical structures of the preserved bone allografts were considered to be deep freezing (-35degC), lyophylization, irradiation, or a combination of lyophylization and irradiation. The latter could be shown to lower the mechanical strength of the bone. Crystal lattice of the bone did not show any alterations in x-ray diffraction pattern, following freeze drying and/or irradiation with doses up to 10 Mrad of gamma radiation. Deterioration in mechanical properties is probably due to damage to the organic phase of the bone matrix

  18. Uterus transplantation: Experimental animal models and recent experience in humans

    Directory of Open Access Journals (Sweden)

    Sadık Şahin

    2015-03-01

    Full Text Available Uterus transplantation has been considered as an alternative management modality in the last few years for adoption or gestational surrogacy for women with absence of uterus due to congenital or acquired reasons. Surrogacy is legal in only a few countries because of ethical, social and legal issues. Up to date, a total of 11 uterus transplantation cases have been reported in which uteri were harvested from ten live donors and one donor with brain death. After unsuccessful attempt of first uterus transplantation, many studies have been conducted in animals and these experimental models enabled our knowledge to increase on this topic. First experimental studies were performed in rodents; later uterus transplantation was accomplished in sheep, pigs and rabbits. Recently, researches in non-human primates have led the experience regarding transplantation technique and success to improve. In this review, we reviewed the experimental animal researches in the area of uterus transplantation and recent experience in humans.

  19. CD16(+) monocytes with smooth muscle cell characteristics are reduced in human renal chronic transplant dysfunction

    NARCIS (Netherlands)

    Boersema, M.; van den Born, Joost; van Ark, J.; Harms, Geertruida; Seelen, M. A.; van Dijk, M. C. R. F.; van Goor, H.; Navis, G. J.; Popa, E. R.; Hillebrands, J. L.

    In chronic transplant dysfunction (CTD), persistent (allo)immune-mediated inflammation eventually leads to tissue remodeling including neointima formation in intragraft arteries. We previously showed that recipient-derived neointimal alpha-SMA(+) smooth muscle-like cells are present in human renal

  20. A New Composite Eyeball-Periorbital Transplantation Model in Humans: An Anatomical Study in Preparation for Eyeball Transplantation.

    Science.gov (United States)

    Siemionow, Maria; Bozkurt, Mehmet; Zor, Fatih; Kulahci, Yalcin; Uygur, Safak; Ozturk, Can; Djohan, Risal; Papay, Frank

    2018-04-01

    Vascularized composite allotransplantation offers a new hope for restoration of orbital content and perhaps vision. The aim of this study was to introduce a new composite eyeball-periorbital transplantation model in fresh cadavers in preparation for composite eyeball allotransplantation in humans. The composite eyeball-periorbital transplantation flap borders included the inferior border, outlined by the infraorbital rim; the medial border, created by the nasal dorsum; the lateral border, created by the lateral orbital rim; and the superior border, created by the superior part of the eyebrow. The pedicle of the flap included the facial artery, superficial temporal artery, and external jugular vein. The skin and subcutaneous tissues of the periorbital region were dissected and the bony tissue was reached. A coronal incision was performed and the frontal lobe of the brain was reached by means of frontal osteotomy. Ophthalmic and oculomotor nerves were also included in the flap. After a "box osteotomy" around the orbit, the dissection was completed. Methylene blue and indocyanine green injection (SPY Elite System) was performed to show the integrity of the vascular territories after facial flap harvest. Adequate venous return was observed within the flap after methylene blue dye injection. Laser-assisted indocyanine green angiography identified a well-defined vascular network within the entire composite eyeball-periorbital transplantation flap. For the first time, a novel composite eyeball-periorbital transplantation model in human cadavers was introduced. Good perfusion of the flap confirmed the feasibility of composite eyeball-periorbital transplantation in the clinical setting. Although harvesting of the flap is challenging, it introduces a new option for reconstruction of the periorbital region including the eyeball.

  1. Results from the organ and tissue transplant program in Nuevo Leon, Mexico, 1996 to 2001.

    Science.gov (United States)

    Carbajal, H; Cabriales, H

    2003-12-01

    Before 1996, solid organs from cadaveric donors (CD) did not account for more than 2% of all transplants. The need for more transplants led the state to undergo several legislative, societal, organizational, and infrastructure changes. A descriptive analysis of the evolution of the transplant program in the State of Nuevo León, Mexico, from 1996 to 2001. Trimester reports have been routinely performed since 1996 from the 14 institutions that are licensed to perform organ and tissue transplants in the State of Nuevo León, Mexico. All reports were concentrated and a descriptive analysis is presented herein. From 1996 until 2001, a total of 1457 organ and tissue (OT) transplants have been performed. At the end of this period, there was a 214% increase in the total number of transplants. By 2001, 73% of the program's total of 1457 OT transplants came from cadaveric donors. The state transplant program of Nuevo León has experienced a dramatic growth since 1996. The percent of organs transplanted from cadaveric donors is one of the highest in Mexico. There is still much work to be done at the state and national levels; better epidemiological studies and dialysis registries are needed as well as investment in transplant research.

  2. Differential expression of proteoglycans in tissue remodeling and lymphangiogenesis after experimental renal transplantation in rats.

    Directory of Open Access Journals (Sweden)

    Heleen Rienstra

    Full Text Available BACKGROUND: Chronic transplant dysfunction explains the majority of late renal allograft loss and is accompanied by extensive tissue remodeling leading to transplant vasculopathy, glomerulosclerosis and interstitial fibrosis. Matrix proteoglycans mediate cell-cell and cell-matrix interactions and play key roles in tissue remodeling. The aim of this study was to characterize differential heparan sulfate proteoglycan and chondroitin sulfate proteoglycan expression in transplant vasculopathy, glomerulosclerosis and interstitial fibrosis in renal allografts with chronic transplant dysfunction. METHODS: Renal allografts were transplanted in the Dark Agouti-to-Wistar Furth rat strain combination. Dark Agouti-to-Dark Agouti isografts and non-transplanted Dark Agouti kidneys served as controls. Allograft and isograft recipients were sacrificed 66 and 81 days (mean after transplantation, respectively. Heparan sulfate proteoglycan (collXVIII, perlecan and agrin and chondroitin sulfate proteoglycan (versican expression, as well as CD31 and LYVE-1 (vascular and lymphatic endothelium, respectively expression were (semi- quantitatively analyzed using immunofluorescence. FINDINGS: Arteries with transplant vasculopathy and sclerotic glomeruli in allografts displayed pronounced neo-expression of collXVIII and perlecan. In contrast, in interstitial fibrosis expression of the chondroitin sulfate proteoglycan versican dominated. In the cortical tubular basement membranes in both iso- and allografts, induction of collXVIII was detected. Allografts presented extensive lymphangiogenesis (p<0.01 compared to isografts and non-transplanted controls, which was associated with induced perlecan expression underneath the lymphatic endothelium (p<0.05 and p<0.01 compared to isografts and non-transplanted controls, respectively. Both the magnitude of lymphangiogenesis and perlecan expression correlated with severity of interstitial fibrosis and impaired graft function

  3. Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue due to cancer recurrence

    DEFF Research Database (Denmark)

    Ernst, Emil Hagen; Offersen, Birgitte Vrou; Andersen, Claus Yding

    2013-01-01

    To report on a woman who conceived naturally and had a normal intrauterine pregnancy following transplantation of frozen/thawed ovarian tissue but decided to have an early abortion due to recurrence of breast cancer.......To report on a woman who conceived naturally and had a normal intrauterine pregnancy following transplantation of frozen/thawed ovarian tissue but decided to have an early abortion due to recurrence of breast cancer....

  4. Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Tilahun Alelign

    2018-01-01

    Full Text Available Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy.

  5. Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

    Science.gov (United States)

    Ahmed, Momina M.; Bobosha, Kidist; Tadesse, Yewondwossen; Howe, Rawleigh; Petros, Beyene

    2018-01-01

    Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy. PMID:29693023

  6. Stem Cell Transplants (For Parents)

    Science.gov (United States)

    ... of Transplants Transplantation Recovery Coping Print en español Trasplantes de células madre Stem cells are cells in ... finding a match is called tissue typing (or HLA [human leukocyte antigen] typing). HLA is a protein ...

  7. Composite Tissue Transplant of Hand or Arm: A Health Technology Assessment.

    Science.gov (United States)

    2016-01-01

    Injuries to arms and legs following severe trauma can result in the loss of large regions of tissue, disrupting healing and function and sometimes leading to amputation of the damaged limb. People experiencing amputations of the hand or arm could potentially benefit from composite tissue transplant, which is being performed in some countries. Currently, there are no composite tissue transplant programs in Canada. We conducted a systematic review of the literature, with no restriction on study design, examining the effectiveness and cost-effectiveness of hand and arm transplant. We assessed the overall quality of the clinical evidence with GRADE. We developed a Markov decision analytic model to determine the cost-effectiveness of transplant versus standard care for a healthy adult with a hand amputation. Incremental cost-effectiveness ratios (ICERs) were calculated using a 30-year time horizon. We also estimated the impact on provincial health care costs if these transplants were publicly funded in Ontario. Compared to pre-transplant function, patients' post-transplant function was significantly better. For various reasons, 17% of transplanted limbs were amputated, 6.4% of patients died within the first year after the transplant, and 10.6% of patients experienced chronic rejections. GRADE quality of evidence for all outcomes was very low. In the cost-effectiveness analysis, single-hand transplant was dominated by standard care, with increased costs ($735,647 CAD vs. $61,429) and reduced quality-adjusted life-years (QALYs) (10.96 vs. 11.82). Double-hand transplant also had higher costs compared with standard care ($633,780), but it had an increased effectiveness of 0.17 QALYs, translating to an ICER of $3.8 million per QALY gained. In most sensitivity analyses, ICERs for bilateral hand transplant were greater than $1 million per QALY gained. A hand transplant program would lead to an estimated annual budget impact of $0.9 million to $1.2 million in the next 3 years

  8. Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA nano-sustained release microspheres.

    Science.gov (United States)

    Li, Liqun; Pan, Shengsheng; Ni, Binting; Lin, Yuanshao

    2014-08-01

    Early neovascularization is important for autologous fat transplant survival. SVF cells are ideal seed cells. Both vascular endothelial growth factor (VEGF) and SVF cells can promote neovascularization. However, the half-life (about 50 min) of VEGF is too short to sustain an adequate local concentration. We have investigated whether VEGF-polylactic acid (PLA) nano-sustained release microspheres plus SVF cells can improve neovascularization and survival of transplanted fat tissues. SVF cells were harvested and constructed VEGF-PLA nano-sustained release microspheres in vitro. Human fat tissues was mixed with SVF cells plus VEGF-PLA, SVF cells alone or Dulbecco's modified Eagle's medium as the control. These three mixtures were injected into random sites in 18 nude mice. Two months later, the transplants were weighed and examined histologically; and capillaries were counted to quantify neovascularization. Hematoxylin-eosin (HE) and anti-VEGF stains were applied to reveal cell infiltration. The mean wet weight of fat in the SVF plus VEGF-PLA, SVF alone, and control transplants were 0.18 ± 0.013 g, 0.16 ± 0.015 g, and 0.071 ± 0.12 g, respectively; the differences between groups were statistically significant. More vessels were present in the SVF plus VEGF-PLA transplants than in the other two types. Transplants mixed with SVF cells also had an acceptable density of capillaries. Histological analysis revealed that both the SVF plus VEGF-PLA and SVF alone transplants, but not the control transplants, were composed of adipose tissue, and had less fat necrosis and less fibrosis than control specimens. SVF plus VEGF-PLA transplants had significantly greater capillary density and VEGF expression than the other two transplant groups. Thus transplanted fat tissue survival and quality can be enhanced by the addition of VEGF-PLA nano-sustained release microspheres plus SVF cells. © 2014 International Federation for Cell Biology.

  9. Reversal of Type 1 Diabetes in Mice by Brown Adipose Tissue Transplant

    Science.gov (United States)

    Gunawardana, Subhadra C.; Piston, David W.

    2012-01-01

    Current therapies for type 1 diabetes (T1D) involve insulin replacement or transplantation of insulin-secreting tissue, both of which suffer from numerous limitations and complications. Here, we show that subcutaneous transplants of embryonic brown adipose tissue (BAT) can correct T1D in streptozotocin-treated mice (both immune competent and immune deficient) with severely impaired glucose tolerance and significant loss of adipose tissue. BAT transplants result in euglycemia, normalized glucose tolerance, reduced tissue inflammation, and reversal of clinical diabetes markers such as polyuria, polydipsia, and polyphagia. These effects are independent of insulin but correlate with recovery of the animals’ white adipose tissue. BAT transplants lead to significant increases in adiponectin and leptin, but with levels that are static and not responsive to glucose. Pharmacological blockade of the insulin receptor in BAT transplant mice leads to impaired glucose tolerance, similar to what is seen in nondiabetic animals, indicating that insulin receptor activity plays a role in the reversal of diabetes. One possible candidate for activating the insulin receptor is IGF-1, whose levels are also significantly elevated in BAT transplant mice. Thus, we propose that the combined action of multiple adipokines establishes a new equilibrium in the animal that allows for chronic glycemic control without insulin. PMID:22315305

  10. Total lymphatic irradiation and bone marrow in human heart transplantation

    International Nuclear Information System (INIS)

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-01-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem

  11. Implications of human tissue studies

    International Nuclear Information System (INIS)

    Kathren, R.L.

    1986-10-01

    Through radiochemical analysis of voluntary tissue donations, the United States Transuranium and Uranium Registries are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole body contributions to the Transuranium Registry revealed an inverse proportionality between actinide concentration and bone ash fraction. The analysis of a whole body with a documented 241 Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies of the Registries are designed to evaluate in vivo estimates of actinide deposition with those derived from postmortem tissue analysis, compare results of animal experiments with human data, and reviw histopathologic slides for tissue toxicity that might be attributable to exposure to uranium and the transuranic elements. The implications of these recent findings and other work of the Registries are discussed from the standpoint of their potential impact on biokinetic modeling, internal dose assessment, safety standards, and operational health physics practices

  12. Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue

    DEFF Research Database (Denmark)

    Dolmans, Marie-Madeleine; Luyckx, Valérie; Donnez, Jacques

    2013-01-01

    Ovarian tissue cryopreservation and transplantation is a real option to preserve and restore fertility in young cancer patients. However, there is a concern regarding the possible presence of malignant cells in the ovarian tissue, which could lead to recurrence of the primary disease after reimpl...

  13. Transplantation of embryonic porcine neocortical tissue into newborn rats

    DEFF Research Database (Denmark)

    Castro, Anthony J; Meyer, Morten; Møller Dall, Annette

    2003-01-01

    cavities made in newborn rats. Sacrifice at 3-12.5 weeks posttransplantation revealed healthy looking grafts in several animals. Apparent graft rejection evidenced by areas of necrosis and OX1 reactivity was observed in some of the older transplants. Treatment of nursing mothers or of postweaning newborns...... with cyclosporin A did not appear to promote graft survival. Some transplants grew to extremely large proportions and were characterized by bands of cells and bundles of axons as observed using immunohistochemical staining for pig neurofilament. Neurofilament-positive axons projected from several of the grafts...

  14. Current status and future prospects for cultured limbal tissue transplants in Australia and New Zealand.

    Science.gov (United States)

    Harkin, Damien G; Apel, Andrew J; Di Girolamo, Nick; Watson, Stephanie; Brown, Karl; Daniell, Mark D; McGhee, J Jane; McGhee, Charles N J

    2013-04-01

    Cultured limbal tissue transplants have become widely used over the last decade as a treatment for limbal stem cell deficiency (LSCD). While the number of patients afflicted with LSCD in Australia and New Zealand is considered to be relatively low, the impact of this disease on quality of life is so severe that the potential efficacy of cultured transplants has necessitated investigation. We presently review the basic biology and experimental strategies associated with the use of cultured limbal tissue transplants in Australia and New Zealand. In doing so, we aim to encourage informed discussion on the issues required to advance the use of cultured limbal transplants in Australia and New Zealand. Moreover, we propose that a collaborative network could be established to maintain access to the technology in conjunction with a number of other existing and emerging treatments for eye diseases. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

  15. Human tissue in systems medicine.

    Science.gov (United States)

    Caie, Peter D; Schuur, Klaas; Oniscu, Anca; Mullen, Peter; Reynolds, Paul A; Harrison, David J

    2013-12-01

    Histopathology, the examination of an architecturally artefactual, two-dimensional and static image remains a potent tool allowing diagnosis and empirical expectation of prognosis. Considerable optimism exists that the advent of molecular genetic testing and other biomarker strategies will improve or even replace this ancient technology. A number of biomarkers already add considerable value for prediction of whether a treatment will work. In this short review we argue that a systems medicine approach to pathology will not seek to replace traditional pathology, but rather augment it. Systems approaches need to incorporate quantitative morphological, protein, mRNA and DNA data. A significant challenge for clinical implementation of systems pathology is how to optimize information available from tissue, which is frequently sub-optimal in quality and amount, and yet generate useful predictive models that work. The transition of histopathology to systems pathophysiology and the use of multiscale data sets usher in a new era in diagnosis, prognosis and prediction based on the analysis of human tissue. © 2013 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.

  16. The significance of monitoring sex hormones levels after ovarian tissue auto-transplantation

    International Nuclear Information System (INIS)

    Wang Qiuwei; Xu Peizhen; Yu Bin; Zhou Hong

    2003-01-01

    Objective: To evaluate the significance of monitoring serum sex hormones levels after ovarian tissue auto-transplantation. Methods: Twenty-five patients with stage IV recurrent endometriosis after one or two times of conservative surgeries underwent radical surgery. Their ovarian tissue fragments were transplanted to greater omentum. Serum follicle-stimulation hormone (FSH), Luteinizing hormone (LH) and estradiol (E 2 ) levels were measured monthly since fourth month post-operatively. After E 2 was increased, based body temperature was measured and vaginal hormone cytology was examined weekly for maturation index (MI) to assess the ovulatory phase and luteal phase in those with viable ovarian tissues. Serum levels of FSH, LH and E 2 in ovulatory phase and luteal phase were determined 20 women with viable ovarian tissues for three cycles as well as in 20 normal sexually mature women and 20 operative menopausal women. Results: There were 12 cases who had increasing of E 2 at four months post operatively and 8 cases more at six months. The other 5 cases with low serum E 2 levels and high FSH and LH levels at 12 months were designated as failures. The survival rate of transplanted ovarian tissue was 80.0%. There were no significant differences of the serum FSH, LH and E 2 levels in ovulatory phase and luteal phase between women with viable grafted ovarian tissues and normal sexually mature women. Conclusion: Monitoring of sex hormones is a good means to assess the viability of the transplanted ovarian tissue fragments

  17. Advancing biomaterials of human origin for tissue engineering

    Science.gov (United States)

    Chen, Fa-Ming; Liu, Xiaohua

    2015-01-01

    Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for

  18. SUITABILITY OF CORNEAL TISSUE FOR TRANSPLANTATION PROCURED FROM HANGING CASES

    Directory of Open Access Journals (Sweden)

    Rekha Gyanchand

    2017-06-01

    Full Text Available BACKGROUND Requirement of donor cornea is essential to target the corneal blind. The best method to procure such corneas is from any major hospitals, which has a mortuary facility. The eye donation with hanging as the cause of death is very common in a mortuary setup. Some factors that are concerning regarding corneas procured from death due to hanging is the prolonged exposure of the cornea at the time of death, the exact time of death is not known, most of the cadavers are refrigerated for investigations as these arrive at the mortuary usually at night. Due to these reasons, the corneal surgeons are hesitant to use corneas procured from death due to hanging for corneal transplantation. Analysing these corneas would contribute to a great extent to the donor cornea pool in providing sight to the corneal blind, especially as majority are young individuals who commit suicide by hanging. In this study, the donor corneas were analysed with regards to corneal epithelial defect, endothelial cell morphology and utilisation of these corneas for transplantation. The aim of the HCRP study is to analyse the effect of death due to hanging on donor cornea. 1. Corneal epithelial status. 2. Corneal endothelial cell morphology. 3. Utilisation of corneas for transplantation. MATERIALS AND METHODS Donor corneas from 22 donors who died due to hanging were procured from hospital mortuary. All the 44 corneas were transplanted. Various parameters like demography, death to enucleation time, cadaver preservation in cold storage, endothelial cell density and utilisation of cornea for transplantation were noted. Design- Retrospective study. Statistical Analysis- Descriptive statistics, Pearson and Spearman correlation and Chi-square test were used to test the hypotheses. RESULTS Out of the 44 corneas analysed, 75% of the donors were refrigerated as a part of medicolegal investigations protocol. The average DTP time was 12 hours in refrigerated group and 5 hours in non

  19. Anaemia and fever in kidney transplant. The role of human parvovirus B19

    Directory of Open Access Journals (Sweden)

    Yanet Parodis López

    2017-03-01

    We report the case of a 65 year-old man with a history of deceased donor renal transplant in September 2014. At 38 days after the transplant, the patient presented progressive anaemia that was resistant to erythropoiesis-stimulating agents. At 64 days after transplant, hyperthermia occurred with progressive deterioration of the patient's general condition. The viral serology and the first blood PCR for human parvovirus B19 were both negative. At 4 months and 19 days after, a bone marrow biopsy was conducted, showing giant erythroblasts with nuclear viral inclusions that were compatible with parvovirus; a PCR in the tissue confirmed the diagnosis. A second blood PCR was positive for parvovirus. After treatment with intravenous immunoglobulin and the temporary discontinuation of mycophenolate mofetil, a complete remission of the disease occurred, although the blood PCR for parvovirus B19 remained positive, so monitoring is necessary for future likely recurrence.

  20. Status quo of management of the human tissue banks in Taiwan.

    Science.gov (United States)

    Chou, Ching-Pang; Chou, Szu-Cheng; Chen, Ying-Hua; Chen, Yu-Hsuan; Lee, Ming-Shin

    2017-03-01

    As the technologies associated with transplantation and biological tissue engineering continue to advance, human cells and tissues form an integral part to the practice of regenerative medicine. The patient's use of tissues entails the risk of introducing, transmitting and spreading communicable diseases. To prevent such risk and to ensure that the human organs, tissues and cells remain intact and functional after being handled and processed, the transplanted tissues must be subject to good management standards through all stages of collection, screening, processing, storage and distribution as the safety of the users is of the utmost importance. On February 2009, the government of Taiwan promulgated the Regulations for Administration on Human Organ Bank that requires all human tissues banks to adhere to the Good Tissue Practice for Human Organ, Tissue and Cell in terms of establishment and operation in order to cope with the international management trend and the development and management need of the domestic industry. Six years have passed since the law became effective. This article seeks to introduce the current management mechanism and status quo of management of human tissue banks in Taiwan. We also conducted statistical analysis of the data relating to the tissue banks to identify potential risks and the room for improvement. The study concludes that human tissue banks in Taiwan are on the right track with their management practice, leading to a state of steady development and progress.

  1. Nanotechnology as an adjunct tool for transplanting engineered cells and tissues.

    Science.gov (United States)

    Borlongan, Cesar V; Masuda, Tadashi; Walker, Tiffany A; Maki, Mina; Hara, Koichi; Yasuhara, Takao; Matsukawa, Noriyuki; Emerich, Dwaine F

    2007-11-01

    Laboratory and clinical studies have provided evidence of feasibility, safety and efficacy of cell transplantation to treat a wide variety of diseases characterized by tissue and cell dysfunction ranging from diabetes to spinal cord injury. However, major hurdles remain and limit pursuing large clinical trials, including the availability of a universal cell source that can be differentiated into specific cellular phenotypes, methods to protect the transplanted allogeneic or xenogeneic cells from rejection by the host immune system, techniques to enhance cellular integration of the transplant within the host tissue, strategies for in vivo detection and monitoring of the cellular implants, and new techniques to deliver genes to cells without eliciting a host immune response. Finding ways to circumvent these obstacles will benefit considerably from being able to understand, visualize, and control cellular interactions at a sub-micron level. Cutting-edge discoveries in the multidisciplinary field of nanotechnology have provided us a platform to manipulate materials, tissues, cells, and DNA at the level of and within the individual cell. Clearly, the scientific innovations achieved with nanotechnology are a welcome strategy for enhancing the generally encouraging results already achieved in cell transplantation. This review article discusses recent progress in the field of nanotechnology as a tool for tissue engineering, gene therapy, cell immunoisolation, and cell imaging, highlighting its direct applications in cell transplantation therapy.

  2. [Early human transplants: 60th anniversary of the first successful kidney transplants].

    Science.gov (United States)

    Gentili, Marc E

    2015-11-01

    First kidney transplant attempts begin with the 20th century: improving vascular sutures, understanding the phenomena of rejection or tolerance, then progress in HLA groups enable early success in the second half of the century. Definition of brain death, use of corticosteroids, radiotherapy and prime immunosuppressors promote the development of transplants. Discover of cyclosporine in the 1980s, and legislative developments augur a new era. Many advances are arising: use of stem cells from the donor, enhancement of Maastricht 3 donor or living donation. Finally organ transplantation remains an immense human adventure, but also scientific and ethic. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  3. Lung-Derived Microscaffolds Facilitate Diabetes Reversal after Mouse and Human Intraperitoneal Islet Transplantation.

    Science.gov (United States)

    Abualhassan, Nasser; Sapozhnikov, Lena; Pawlick, Rena L; Kahana, Meygal; Pepper, Andrew R; Bruni, Antonio; Gala-Lopez, Boris; Kin, Tatsuya; Mitrani, Eduardo; Shapiro, A M James

    2016-01-01

    There is a need to develop three-dimensional structures that mimic the natural islet tissue microenvironment. Endocrine micro-pancreata (EMPs) made up of acellular organ-derived micro-scaffolds seeded with human islets have been shown to express high levels of key beta-cell specific genes and secrete quantities of insulin per cell similar to freshly isolated human islets in a glucose-regulated manner for more than three months in vitro. The aim of this study was to investigate the capacity of EMPs to restore euglycemia in vivo after transplantation of mouse or human islets in chemically diabetic mice. We proposed that the organ-derived EMPs would restore the extracellular components of the islet microenvironment, generating favorable conditions for islet function and survival. EMPs seeded with 500 mouse islets were implanted intraperitoneally into streptozotocin-induced diabetic mice and reverted diabetes in 67% of mice compared to 13% of controls (p = 0.018, n = 9 per group). Histological analysis of the explanted grafts 60 days post-transplantation stained positive for insulin and exhibited increased vascular density in a collagen-rich background. EMPs were also seeded with human islets and transplanted into the peritoneal cavity of immune-deficient diabetic mice at 250 islet equivalents (IEQ), 500 IEQ and 1000 IEQ. Escalating islet dose increased rates of normoglycemia (50% of the 500 IEQ group and 75% of the 1000 IEQ group, n = 3 per group). Human c-peptide levels were detected 90 days post-transplantation in a dose-response relationship. Herein, we report reversal of diabetes in mice by intraperitoneal transplantation of human islet seeded on EMPs with a human islet dose as low as 500 IEQ.

  4. Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

    Science.gov (United States)

    Peterson, Christopher W; Wang, Jianbin; Deleage, Claire; Reddy, Sowmya; Kaur, Jasbir; Polacino, Patricia; Reik, Andreas; Huang, Meei-Li; Jerome, Keith R; Hu, Shiu-Lok; Holmes, Michael C; Estes, Jacob D; Kiem, Hans-Peter

    2018-04-01

    Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP) model of latent infection using simian/human immunodeficiency virus (SHIV) and combination antiretroviral therapy (cART) in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs) persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05), relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.

  5. Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

    Directory of Open Access Journals (Sweden)

    Christopher W Peterson

    2018-04-01

    Full Text Available Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP model of latent infection using simian/human immunodeficiency virus (SHIV and combination antiretroviral therapy (cART in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05, relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.

  6. The Role of Tissue-Resident Donor T Cells in Rejection of Clinical Face Transplants

    Science.gov (United States)

    2017-10-01

    cells contribute to VCA rejection, and that pathogenic T cells (both donor and recipient-derived) are detectable in blood during rejection to serve as...AWARD NUMBER: W81XWH-16-1-0760 TITLE: The role of tissue-resident donor T cells in rejection of clinical face transplants PRINCIPAL...AND SUBTITLE The role of tissue-resident donor T cells in rejection of clinical face transplants 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1

  7. Evidence of the Association Between Psychology and Tissue and Organ Transplantation in Brazil.

    Science.gov (United States)

    Silva, J D A; Ariente, L C; Roza, B A; Mucci, S

    2016-09-01

    The addition of psychologists to organ transplant teams is still new in Brazil. In seeking the efficient performance of this professional, the knowledge of the scientific production and the development of research in the area is fundamental. In this sense, this study aims to survey the Brazilian scientific research that has investigated the psychologic aspects involved in tissue and organ transplantation. A literature narrative review was performed with the use of the "Transplante AND Psicologia" descriptors in the Biblioteca Virtual em Saúde and the CAPES Journal Portal. Fifty-three articles were found, of which 22 met the inclusion criteria: publications dating from 2000 to 2014 and the main topic of interest of the studies being quality of life, followed by organ donation. The instruments used most frequently were interviews developed by the researchers and the SF-36 Quality of Life Questionnaire. Recent Brazilian studies on the association between psychology and transplantation are still scarce, possibly because of the recent addition of psychologists to transplantation teams. Therefore, it is suggested that more scientific research is made in the area and that the objects of study are more varied, to ensure adequacy of the psychologist to meet the specific demands of organ and tissue transplantation process. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Liver Transplantation in the Mouse: Insights Into Liver Immunobiology, Tissue Injury and Allograft Tolerance

    Science.gov (United States)

    Yokota, Shinichiro; Yoshida, Osamu; Ono, Yoshihiro; Geller, David A.; Thomson, Angus W.

    2016-01-01

    The surgically-demanding mouse orthotopic liver transplant model was first described in 1991. It has proved a powerful research tool for investigation of liver biology, tissue injury, the regulation of alloimmunity and tolerance induction and the pathogenesis of specific liver diseases. Liver transplantation in mice has unique advantages over transplantation of the liver in larger species, such as the rat or pig, since the mouse genome is well-characterized and there is much greater availability of both genetically-modified animals and research reagents. Liver transplant experiments using various transgenic or gene knockout mice has provided valuable mechanistic insights into the immuno- and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in regulation of tissue injury and promotion of liver transplant tolerance provide new potential targets for therapeutic intervention to control adverse inflammatory responses/ immune-mediated events in the hepatic environment and systemically. Conclusion: Orthotopic liver transplantation in the mouse is a valuable model for gaining improved insights into liver biology, immunopathology and allograft tolerance that may result in therapeutic innovation in liver and other diseases. PMID:26709949

  9. The role of allofibroblasts transplantation in cartilaginous tissue regeneration process

    OpenAIRE

    Khadjibaev Аbdukhakim Muminovich; Tilyakov Akbar Buriyevich; Magrupov Bokhodir Asadullaevich; Urazmetova Maisa Dmitriyevna; Ubaydullaev Bobur Sabirovich

    2017-01-01

    Aim of investigation. Ground of embryonal allofibroblasts in the process of cartilaginous tissue regeneration. Material and methods. Investigation is based on the study the results of stimulation cartilaginous tissue regeneration process in the conditions of embryonal allofibroblasts application in 24 experimental sexually mature rabbits in which the model of symphysis pubis rupture with its following recovery have been used. Pieces of cartilaginous tissue have been fixed in 10% neutral forma...

  10. The first woman to give birth to two children following transplantation of frozen/thawed ovarian tissue

    DEFF Research Database (Denmark)

    Ernst, Erik; Bergholdt, Stinne; Jørgensen, Jan Stener

    2010-01-01

    Worldwide eight children have been born as a result of transplanting frozen/thawed ovarian tissue. Two of these children were born in Denmark following transport of the ovarian tissue for a period of 5 h prior to cryopreservation. One of these women, who was originally transplanted with six pieces...

  11. Generation of a transplantable erythropoietin-producer derived from human mesenchymal stem cells.

    Science.gov (United States)

    Yokoo, Takashi; Fukui, Akira; Matsumoto, Kei; Ohashi, Toya; Sado, Yoshikazu; Suzuki, Hideaki; Kawamura, Tetsuya; Okabe, Masataka; Hosoya, Tatsuo; Kobayashi, Eiji

    2008-06-15

    Differentiation of autologous stem cells into functional transplantable tissue for organ regeneration is a promising regenerative therapeutic approach for cancer, diabetes, and many human diseases. Yet to be established, however, is differentiation into tissue capable of producing erythropoietin (EPO), which has a critical function in anemia. We report a novel EPO-producing organ-like structure (organoid) derived from human mesenchymal stem cells. Using our previously established relay culture system, a human mesenchymal stem cell-derived, human EPO-competent organoid was established in rat omentum. The organoid-derived levels of human EPO increased in response to anemia induced by rapid blood withdrawal. In addition, the presence of an organoid in rats suppressed for native (rat) EPO production enhanced recovery from anemia when compared with control animals lacking the organoid. Together these results confirmed the generation of a stem cell-derived organoid that is capable of producing EPO and sensitive to physiological regulation.

  12. Pre-transplantation specification of stem cells to cardiac lineage for regeneration of cardiac tissue.

    Science.gov (United States)

    Mayorga, Maritza; Finan, Amanda; Penn, Marc

    2009-03-01

    Myocardial infarction (MI) is a lead cause of mortality in the Western world. Treatment of acute MI is focused on restoration of antegrade flow which inhibits further tissue loss, but does not restore function to damaged tissue. Chronic therapy for injured myocardial tissue involves medical therapy that attempts to minimize pathologic remodeling of the heart. End stage therapy for chronic heart failure (CHF) involves inotropic therapy to increase surviving cardiac myocyte function or mechanical augmentation of cardiac performance. Not until the point of heart transplantation, a limited resource at best, does therapy focus on the fundamental problem of needing to replace injured tissue with new contractile tissue. In this setting, the potential for stem cell therapy has garnered significant interest for its potential to regenerate or create new contractile cardiac tissue. While to date adult stem cell therapy in clinical trials has suggested potential benefit, there is waning belief that the approaches used to date lead to regeneration of cardiac tissue. As the literature has better defined the pathways involved in cardiac differentiation, preclinical studies have suggested that stem cell pretreatment to direct stem cell differentiation prior to stem cell transplantation may be a more efficacious strategy for inducing cardiac regeneration. Here we review the available literature on pre-transplantation conditioning of stem cells in an attempt to better understand stem cell behavior and their readiness in cell-based therapy for myocardial regeneration.

  13. The donor management algorithm in transplantation of a composite facial tissue allograft.. First experience in Russia

    Directory of Open Access Journals (Sweden)

    V. V. Uyba

    2016-01-01

    Full Text Available In the period from 2005 to December 2015, 37 transplantations of vascularized composite facial tissue allografts (VCAs were performed in the world. A vascularized composite tissue allotransplantation has been recognized as a solid organ transplantation rather than a special kind of tissue transplantation. The recent classification of composite tissue allografts into the category of donor organs gave rise to a number of organizational, ethical, legal, technical, and economic problems. In May 2015, the first successful transplantation of a composite facial tissue allograft was performed in Russia. The article describes our experience of multiple team interactions at donor management stage when involved in the identification, conditioning, harvesting, and delivering donor organs to various hospitals. A man, aged 51 years old, diagnosed with traumatic brain injury became a donor after the diagnosis of brain deathhad been made, his death had been ascertained, and the requested consent for organ donation had been obtained from relatives. At donor management stage, a tracheostomy was performed and a posthumous facial mask was molded. The "face first, concurrent completion" algorithm was chosen for organ harvesting and facial VCA procurement; meanwhile, the facial allograft was procured as the "full face" category. The total surgery duration from the incision to completing the procurement (including that of solid organs made 8 hours 20 minutes. Immediately after the procurement, the facial VCA complex was sent to the St. Petersburg clinic by medical aircraft transportation, and was there transplanted 9 hours later. Donor kidneys were transported to Moscow bycivil aviation and transplanted 17 and 20 hours later. The authors believe that this clinical case report demonstrates the feasibility and safety of multiple harvesting of solid organs and a vascularized composite facial tissue allograft. However, this kind of surgery requires an essential

  14. Variation in alternative splicing across human tissues

    OpenAIRE

    Yeo, Gene; Holste, Dirk; Kreiman, Gabriel; Burge, Christopher B

    2004-01-01

    Background: Alternative pre-mRNA splicing (AS) is widely used by higher eukaryotes to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically aligned expressed sequence tags (ESTs) derived from libraries of cDNAs from different tissues. Results: Controlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most p...

  15. West Nile Virus RNA in Tissues from Donor Associated with Transmission to Organ Transplant Recipients

    Centers for Disease Control (CDC) Podcasts

    2013-11-19

    William Hale reads an abridged version of the Emerging Infectious Diseases’ dispatch, West Nile Virus RNA in Tissues from Donor Associated with Transmission to Organ Transplant Recipients.  Created: 11/19/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/21/2013.

  16. Proteomic analysis of tyrosine phosphorylation during human liver transplantation

    Directory of Open Access Journals (Sweden)

    Boutros Tarek

    2007-01-01

    Full Text Available Abstract Background Ischemia-reperfusion (I/R causes a dramatic reprogramming of cell metabolism during liver transplantation and can be linked to an alteration of the phosphorylation level of several cellular proteins. Over the past two decades, it became clear that tyrosine phosphorylation plays a pivotal role in a variety of important signalling pathways and was linked to a wide spectrum of diseases. Functional profiling of the tyrosine phosphoproteome during liver transplantation is therefore of great biological significance and is likely to lead to the identification of novel targets for drug discovery and provide a basis for novel therapeutic strategies. Results Using liver biopsies collected during the early phases of organ procurement and transplantation, we aimed at characterizing the global patterns of tyrosine phosphorylation during hepatic I/R. A proteomic approach, based on the purification of tyrosine phosphorylated proteins followed by their identification using mass spectrometry, allowed us to identify Nck-1, a SH2/SH3 adaptor, as a potential regulator of I/R injury. Using immunoblot, cell fractionation and immunohistochemistry, we demonstrate that Nck-1 phosphorylation, expression and localization were affected in liver tissue upon I/R. In addition, mass spectrometry identification of Nck-1 binding partners during the course of the transplantation also suggested a dynamic interaction between Nck-1 and actin during I/R. Conclusion Taken together, our data suggest that Nck-1 may play a role in I/R-induced actin reorganization, which was previously reported to be detrimental for the hepatocytes of the transplanted graft. Nck-1 could therefore represent a target of choice for the design of new organ preservation strategies, which could consequently help to reduce post-reperfusion liver damages and improve transplantation outcomes.

  17. Experience of nurses in the process of donation of organs and tissues for transplant

    OpenAIRE

    Moraes,Edvaldo Leal de; Santos,Marcelo José dos; Merighi,Miriam Aparecida Barbosa; Massarollo,Maria Cristina Komatsu Braga

    2014-01-01

    OBJECTIVE: to investigate the meaning of the action of nurses in the donation process to maintain the viability of organs and tissues for transplantation.METHOD: this qualitative study with a social phenomenological approach was conducted through individual interviews with ten nurses of three Organ and Tissue Procurement Services of the city of São Paulo.RESULTS: the experience of the nurses in the donation process was represented by the categories: obstacles experienced in the donation proce...

  18. Ionization radiation in sterilization of the tissue transplants

    International Nuclear Information System (INIS)

    Uhrynowska-Tyszkiewicz, I.; Kaminski, A.

    2007-01-01

    Established in 1963, the Central Tissue Bank in Warsaw is a multi-tissue bank located in the Department of Transplantology of the Medical University in Warsaw. Allografts such as bone, cartilage, tendons, ligaments, sclera, skin and amnion are preserved mainly by deep-freezing and/or lyophilization and subsequently radiation-sterilized with a dose of 35 kGy with gamma rays in a 60 Co source (at the Institute of Applied Radiation Chemistry in Lodz) or with electron beam 10 MeV accelerator (at the Institute of Nuclear Chemistry and Technology in Warsaw). This is the oldest working tissue bank in the world, which for almost 40 years now has routinely used ionizing radiation for sterilization of tissue allografts

  19. Anaemia and fever in Kidney transplant. The role of human parvovirus B19.

    Science.gov (United States)

    Parodis López, Yanet; Santana Estupiñán, Raquel; Marrero Robayna, Silvia; Gallego Samper, Roberto; Henríquez Palop, Fernando; Rivero Vera, José Carlos; Camacho Galán, Rafael; Pena López, María José; Sablón González, Nery; González Cabrera, Fayna; Oliva Dámaso, Elena; Vega Díaz, Nicanor; Rodríguez Pérez, José Carlos

    Infections remain an issue of particular relevance in renal transplant patients, particularly viral infections. Human parvovirus B19 infection causes severe refractory anaemia, pancytopenia and thrombotic microangiopathy. Its presence is recognized by analysing blood polymerase chain reaction (PCR) and by the discovery of typical giant proerythroblasts in the bone marrow. We report the case of a 65 year-old man with a history of deceased donor renal transplant in September 2014. At 38 days after the transplant, the patient presented progressive anaemia that was resistant to erythropoiesis-stimulating agents. At 64 days after transplant, hyperthermia occurred with progressive deterioration of the patient's general condition. The viral serology and the first blood PCR for human parvovirus B19 were both negative. At 4 months and 19 days after, a bone marrow biopsy was conducted, showing giant erythroblasts with nuclear viral inclusions that were compatible with parvovirus; a PCR in the tissue confirmed the diagnosis. A second blood PCR was positive for parvovirus. After treatment with intravenous immunoglobulin and the temporary discontinuation of mycophenolate mofetil, a complete remission of the disease occurred, although the blood PCR for parvovirus B19 remained positive, so monitoring is necessary for future likely recurrence. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Effect of transplantation of muscle tissue in rats from the same litter on total number of flavins and FAD

    Directory of Open Access Journals (Sweden)

    S. N. Kobylnik

    2015-01-01

    Full Text Available Riboflavin is a member of redox enzymes involved in fatty acid oxidation and energy generation. Important role of this vitamin is in reproductive function. Exchange of transformation of riboflavin in animal tissues and cells of microorganisms include reactions that lead to synthesis and subsequent collapse of FMN and FAD. It is involved in enhancing antitumor activity of many anticancer drugs, as well as activation of the immune system to kill tumor cells. Issues of transport of riboflavin and its derivatives in animals have been studied enough. Investigations of changes of the balance of riboflavin and its metabolites in muscular tissues before transplantation in rats from one litter and at operation without replanting were conducted, based on the Udenfriend method of flavin determination. Transplantation in the experiment was carried out on white non-linear male rats weighing 180–300 g. Animals were taken out of the experiment by passing electric current through the medulla. Belly muscular tissue was taken from donor rats of the same litter, and that tissue was sewn to homological muscular tissue of the recipient. The same procedure was carried out with femoral muscular tissue. In the course of operation without replanting the same manipulations have been made except for transplantation stage (for determination of the effect of surgical intervention. Tissue not subject to any surgical intervention served as a control. Parameters of the study were measured on the first, third and seventh days after transplantation. Transplantation of muscular tissue caused no changes in total flavin amount. Content of RF + FMN after transplantation of muscular tissue in rats of the same litter decreased in femoral muscular tissue of the recipient. Transplantation of muscular tissues in rats from the same litter lead to increase in FAD amount in femoral muscular tissue of the donor and recipient on the third day of the experiment. Transplantation of femoral

  1. Cryobanking of human ovarian tissue

    DEFF Research Database (Denmark)

    Ernst, Erik; Andersen, Anders Nyboe; Andersen, Claus Yding

    2014-01-01

    Cryopreservation of ovarian tissue is one way of preserving fertility in young women with a malignant disease or other disorders that require gonadotoxic treatment. The purpose of the study was to explore how many women remained interested in continued cryostorage of their ovarian tissue beyond...... an initial 5-year period. Between 1999 and 2006, a total of 201 girls and young women had one ovary cryopreserved for fertility preservation in Denmark. One hundred of these met our inclusion criteria, which included a follow-up period of at least 5 years, and were mailed a questionnaire. The response rate...... women with ovarian tissue cryobanked requested continued cryostorage after an initial period of at least 5 years. The main reason for requesting disposal was successful completion of a family....

  2. Long-term duration of function of ovarian tissue transplants

    DEFF Research Database (Denmark)

    Andersen, Claus; Silber, Sherman J; Berghold, Stinne Holm

    2012-01-01

    These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had frozen ovarian...... or to alleviate its symptoms. These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had...

  3. The necessity of strengthening the cooperation between tissue banks and organ transplant organizations at national, regional, and international levels.

    Science.gov (United States)

    Morales Pedraza, Jorge

    2013-12-01

    The donation of tissues and organs increases significantly when tissue banks and organ transplant organizations work together in the procurement of organs and tissues at donor sources (hospitals, coroners system, organ procurement agencies, and funeral homes, among others). To achieve this important goal, national competent health authorities should considered the establishment of a mechanism that promote the widest possible cooperation between tissue banks and organ transplant organizations with hospitals, research medical institutions, universities, and other medical institutions and facilities. One of the issues that can facilitate this cooperation is the establishment of a coding and traceability system that could identify all tissues and organs used in transplant activities carried out in any country. The promotion of national, regional, and international cooperation between tissue banks and organ transplant organizations would enable the sharing of relevant information that could be important for medical practice and scientific studies carried out by many countries, particularly for those countries with a weak health care system.

  4. Hand transplantation and vascularized composite tissue allografts in orthopaedics and traumatology.

    Science.gov (United States)

    Schuind, F

    2010-05-01

    Composite tissue allograft (CTA) is defined as heterologous transplantation of a complex comprising skin and subcutaneous, neurovascular and mesenchymal tissue. Such techniques allow complex reconstruction using matched tissue, without donor site morbidity. The potential indications in orthopaedics-traumatology could in the future be more frequent than the present indications of heart, lung, liver, kidney and pancreas transplantation. International clinical experience clearly demonstrates the feasibility of CTA, both surgically and immunologically. However, immunosuppression remains indispensable, exposing the patient to risks that are not acceptable for purely functional surgery, except in very particular indications. The main hope for the future lies in induction of graft-specific tolerance. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  5. Human papilloma virus infection in female kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Shirin Ghazizadeh

    2011-01-01

    Full Text Available The objective of this study was to evaluate the incidence of genital human papilloma virus (HPV infection and cervical intra-epithelial lesions in transplanted patients. Cervical Papanicolaou (Pap smear/HPV test and colposcopic examinations were performed in 58 patients who were candidates for renal transplant surgery; these tests were repeated one year later. Their age range was 26-53 years (mean, 37.2 years. Hypertension was the most common cause of renal insufficiency (34.4%, while in 41.4% of the patients, the causative pathology was unknown. In 24.1% of the patients, there was no history of dialysis, i.e. they had pre-emptive transplantation. The mean duration of marriage (years since first intercourse was 16.2 years (range, 1-35. Coitus interruptus was the most common contraceptive method used (37.9%, followed by tubal ligation and condom (10.3% and 6.9%, respectively. All patients had negative Pap tests and normal gynecologic exam before undergoing transplantation. The Pap test remained normal after transplant surgery, although the HPV test became positive in four patients (6.9%. There were five cases of white epithelium on colposcopy, but biopsy showed normal metaplasia. Two cases of extensive anogenital warts were treated by CO 2 laser, and one patient had recurrent warts, which responded well to second laser surgery. None of the study patients had squamous intra-epithelial lesions (SIL or vulvar intra-epithelial neoplasia. Our study suggests that screening with HPV and Pap test should be performed before transplant surgery and should be repeated at regular intervals in order to avoid irreversible situations such as high-grade SILs, which are difficult to treat. Avoiding high-risk sexual relations in this group of patients is highly recommended.

  6. Concise Review: Bioprinting of Stem Cells for Transplantable Tissue Fabrication.

    Science.gov (United States)

    Leberfinger, Ashley N; Ravnic, Dino J; Dhawan, Aman; Ozbolat, Ibrahim T

    2017-10-01

    Bioprinting is a quickly progressing technology, which holds the potential to generate replacement tissues and organs. Stem cells offer several advantages over differentiated cells for use as starting materials, including the potential for autologous tissue and differentiation into multiple cell lines. The three most commonly used stem cells are embryonic, induced pluripotent, and adult stem cells. Cells are combined with various natural and synthetic materials to form bioinks, which are used to fabricate scaffold-based or scaffold-free constructs. Computer aided design technology is combined with various bioprinting modalities including droplet-, extrusion-, or laser-based bioprinting to create tissue constructs. Each bioink and modality has its own advantages and disadvantages. Various materials and techniques are combined to maximize the benefits. Researchers have been successful in bioprinting cartilage, bone, cardiac, nervous, liver, and vascular tissues. However, a major limitation to clinical translation is building large-scale vascularized constructs. Many challenges must be overcome before this technology is used routinely in a clinical setting. Stem Cells Translational Medicine 2017;6:1940-1948. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  7. Tracking fusion of human mesenchymal stem cells after transplantation to the heart.

    Science.gov (United States)

    Freeman, Brian T; Kouris, Nicholas A; Ogle, Brenda M

    2015-06-01

    Evidence suggests that transplanted mesenchymal stem cells (MSCs) can aid recovery of damaged myocardium caused by myocardial infarction. One possible mechanism for MSC-mediated recovery is reprogramming after cell fusion between transplanted MSCs and recipient cardiac cells. We used a Cre/LoxP-based luciferase reporter system coupled to biophotonic imaging to detect fusion of transplanted human pluripotent stem cell-derived MSCs to cells of organs of living mice. Human MSCs, with transient expression of a viral fusogen, were delivered to the murine heart via a collagen patch. At 2 days and 1 week later, living mice were probed for bioluminescence indicative of cell fusion. Cell fusion was detected at the site of delivery (heart) and in distal tissues (i.e., stomach, small intestine, liver). Fusion was confirmed at the cellular scale via fluorescence in situ hybridization for human-specific and mouse-specific centromeres. Human cells in organs distal to the heart were typically located near the vasculature, suggesting MSCs and perhaps MSC fusion products have the ability to migrate via the circulatory system to distal organs and engraft with local cells. The present study reveals previously unknown migratory patterns of delivered human MSCs and associated fusion products in the healthy murine heart. The study also sets the stage for follow-on studies to determine the functional effects of cell fusion in a model of myocardial damage or disease. Mesenchymal stem cells (MSCs) are transplanted to the heart, cartilage, and other tissues to recover lost function or at least limit overactive immune responses. Analysis of tissues after MSC transplantation shows evidence of fusion between MSCs and the cells of the recipient. To date, the biologic implications of cell fusion remain unclear. A newly developed in vivo tracking system was used to identify MSC fusion products in living mice. The migratory patterns of fusion products were determined both in the target organ (i

  8. NCI’s Cooperative Human Tissue Network

    Science.gov (United States)

    Quality biospecimens are a foundational resource for cancer research. One of NCI’s longest running biospecimen programs is the Cooperative Human Tissue Network, a resource mainly for basic discovery and early translational research.

  9. Construction of retroviral recombinant containing human tissue ...

    African Journals Online (AJOL)

    USER

    2010-03-29

    Mar 29, 2010 ... Recombinant retroviral vector containing human tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) gene was ..... heavy metal ions, the protein could be express in an .... involves adhesion, degradation and movement. To.

  10. FAMILY CONSENT FOR ORGAN OR TISSUE REMOVAL FROM A DECEASED PERSON FOR TRANSPLANTATION PURPOSES IN THE REPUBLIC OF CROATIA

    Directory of Open Access Journals (Sweden)

    Tomislav Nedić

    2017-04-01

    Full Text Available The Republic of Croatia is a country with the system of presumed consent donation of organs and tissues after death, where the consent of the family, according to law, is not one of the conditions for organ or tissue removal for transplantation purposes. However, the consent is a condition required by the Codex of Medical Ethics and Deontology. The author primary proposes harmonization of the Codex with current legislation. Accordingly, this paper primarily analyses the typology of the Codex, ethical issues and ethical and positivist reasons to harmonize the Codex with current legislation. Furthermore, although the author in the first place considers that the Codex should be in line with legislation, he also considers the provision of family consent for organ and tissue removal itself flawed and poorly developed. In this regard, the author considers the comparative legislation and judgments of the European Court of Human Rights, analyses current provisions of the Codex in the part of the removal and transplantation of organs and tissues from deceased persons, states the facts that the Codex should contain so as to make the mechanism of family consent for organ and tissue removal and donation after death more effective. In fact, if the author’s original proposal for harmonization of the Codex with the current legislation is not accepted, a more detailed and precise elaboration of the mentioned current provisions of the Codex will be suggested. This will include exact definition of the family and relatives, exact deadlines and ways of informing the family, but also refining the concept of “ethical“ according to the Codex in part of the organ and tissue donation and removal from the deceased person.

  11. Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats

    International Nuclear Information System (INIS)

    Rodrigues, L.P.; Iglesias, D.; Nicola, F.C.; Steffens, D.; Valentim, L.; Witczak, A.; Zanatta, G.; Achaval, M.; Pranke, P.; Netto, C.A.

    2011-01-01

    Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 10 6 cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 10 6 cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation

  12. Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, L.P. [Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Iglesias, D. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Nicola, F.C. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Steffens, D. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Valentim, L.; Witczak, A.; Zanatta, G. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Achaval, M. [Departamento de Ciências Morfológicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Pranke, P. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Netto, C.A. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil)

    2011-12-23

    Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 10{sup 6} cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 10{sup 6} cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation.

  13. Salisphere derived c-Kit+ cell transplantation restores tissue homeostasis in irradiated salivary gland

    International Nuclear Information System (INIS)

    Nanduri, Lalitha S.Y.; Lombaert, Isabelle M.A.; Zwaag, Marianne van der; Faber, Hette; Brunsting, Jeanette F.; Os, Ronald P. van; Coppes, Robert P.

    2013-01-01

    Introduction: During radiotherapy salivary glands of head and neck cancer patients are unavoidably co-irradiated, potentially resulting in life-long impairment. Recently we showed that transplantation of salisphere-derived c-Kit expressing cells can functionally regenerate irradiated salivary glands. This study aims to select a more potent subpopulation of c-Kit + cells, co-expressing stem cell markers and to investigate whether long-term tissue homeostasis is restored after stem cell transplantation. Methods and results: Salisphere derived c-Kit + cells that co-expressed CD24 and/or CD49f markers, were intra-glandularly injected into 15 Gy irradiated submandibular glands of mice. Particularly, c-Kit + /CD24 + /CD49f + cell transplanted mice improved saliva production (54.59 ± 11.1%) versus the irradiated control group (21.5 ± 8.7%). Increase in expression of cells with differentiated duct cell markers like, cytokeratins (CK8, 18, 7 and 14) indicated functional recovery of this compartment. Moreover, ductal stem cell marker expression like c-Kit, CD133, CD24 and CD49f reappeared after transplantation indicating long-term functional maintenance potential of the gland. Furthermore, a normalization of vascularization as indicated by CD31 expression and reduction of fibrosis was observed, indicative of normalization of the microenvironment. Conclusions: Our results show that stem cell transplantation not only rescues hypo-salivation, but also restores tissue homeostasis of the irradiated gland, necessary for long-term maintenance of adult tissue

  14. Family perspectives on organ and tissue donation for transplantation: a principlist analysis.

    Science.gov (United States)

    Dos Santos, Marcelo José; Feito, Lydia

    2017-01-01

    The family interview context is permeated by numerous ethical issues which may generate conflicts and impact on organ donation process. This study aims to analyze the family interview process with a focus on principlist bioethics. This exploratory, descriptive study uses a qualitative approach. The speeches were collected using the following prompt: "Talk about the family interview for the donation of organs and tissues for transplantation, from the preparation for the interview to the decision of the family to donate or not." For the treatment of qualitative data, we chose the method of content analysis and categorical thematic analysis. The study involved 18 nurses who worked in three municipal organ procurement organizations in São Paulo, Brazil, and who conducted family interviews for organ donation. Ethical considerations: The data were collected after approval of the study by the Research Ethics Committee of the School of Nursing of the University of São Paulo. The results were classified into four categories and three subcategories. The categories are the principles adopted by principlist bioethics. The principles of autonomy, beneficence, non-maleficence, and justice permeate the family interview and reveal their importance in the organs and tissues donation process for transplantation. The analysis of family interviews for the donation of organs and tissues for transplantation with a focus on principlist bioethics indicates that the process involves many ethical considerations. The elucidation of these aspects contributes to the discussion, training, and improvement of professionals, whether nurses or not, who work in organ procurement organizations and can improve the curriculum of existing training programs for transplant coordinators who pursue ethics in donation and transplantation as their foundation.

  15. Integrity of the oral tissues in patients with solid-organ transplants.

    Science.gov (United States)

    Rojas, Gonzalo; Bravo, Loreto; Cordero, Karina; Sepúlveda, Luis; Elgueta, Leticia; Díaz, Juan Carlos; Urzúa, Blanca; Morales, Irene

    2012-01-01

    The relationship between the use of immunosuppressants in solid-organ transplant patients and oral tissue abnormalities has been recognized. The objective of this study was to determine the state of oral tissue integrity in renal, heart, and liver transplant patients who are on continuous medical and dental control. Forty patients of both sexes were clinically evaluated at the Clinical Hospital of the University of Chile to identify pathologies of oral mucosa, gingival enlargement (GE), decayed, missing, filled teeth (DMFT) index, and salivary flow. The average age of the transplant subjects was 49.4 years, and the age range was 19 to 69 years. Most subjects maintained a good level of oral hygiene, and the rate mean of DMFT was 14.7. The degree of involvement of the oral mucosa and GE was low (10%). Unlike other studies, the frequency of oral mucosal diseases and GE was low despite the fact that these patients were immunosuppressed. Care and continuous monitoring seem to be of vital importance in maintaining the oral health of transplant patients.

  16. Integrity of the Oral Tissues in Patients with Solid-Organ Transplants

    Directory of Open Access Journals (Sweden)

    Gonzalo Rojas

    2012-01-01

    Full Text Available The relationship between the use of immunosuppressants in solid-organ transplant patients and oral tissue abnormalities has been recognized. The objective of this study was to determine the state of oral tissue integrity in renal, heart, and liver transplant patients who are on continuous medical and dental control. Forty patients of both sexes were clinically evaluated at the Clinical Hospital of the University of Chile to identify pathologies of oral mucosa, gingival enlargement (GE, decayed, missing, filled teeth (DMFT index, and salivary flow. The average age of the transplant subjects was 49.4 years, and the age range was 19 to 69 years. Most subjects maintained a good level of oral hygiene, and the rate mean of DMFT was 14.7. The degree of involvement of the oral mucosa and GE was low (10%. Unlike other studies, the frequency of oral mucosal diseases and GE was low despite the fact that these patients were immunosuppressed. Care and continuous monitoring seem to be of vital importance in maintaining the oral health of transplant patients.

  17. Pattern of leukemia induction in BC3F1 mice transplanted with irradiated lymphohemopoietic tissues

    International Nuclear Information System (INIS)

    Covelli, V.; Di Majo, V.; Bassani, B.; Metalli, P.; Silini, G.

    1982-01-01

    (C57BL/Cne X C3H/Cne)F 1 male mice spontaneously develop reticulum cell sarcoma (RCS) with an average final incidence of 56%; neither myeloid leukemia (ML) nor thymic lymphoma (TL) has been observed in intact animals. X rays (4Gy, 250 kV) induce a few cases of ML but no TL. In increasing the dose to 6 Gy, we observed a few cases of TL, no ML, and a drastic reduction (8%) of RCS. The same dose of 6 Gy fractionated into four weekly doses of 1.5 Gy induced 24% of TL. By transplanting cells into appropriately preirradiated (4 Gy) syngeneic recipients we found evidence that four weekly doses of 1.5 Gy to donor animals caused an excess of ML and drastic changes of both TL and RCS incidences and rates in recipients as a function of time postirradiation at which the lymphohemopoietic tissues are transplanted. Furthermore, the same transplanted animals showed an evident acceleration of time of appearance of RCS and an enhanced incidence of NL; the latter effect is significant 10 days after the last X-ray fraction, but not thereafter. These data are in line with the hypothesis that committed cells for these two types of systemic tumors may be present among the irradiated transplanted tissues

  18. Neuroprotective effect of transplanted human embryonic stem cell-derived neural precursors in an animal model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Michal Aharonowiz

    Full Text Available BACKGROUND: Multiple sclerosis (MS is an immune mediated demyelinating disease of the central nervous system (CNS. A potential new therapeutic approach for MS is cell transplantation which may promote remyelination and suppress the inflammatory process. METHODS: We transplanted human embryonic stem cells (hESC-derived early multipotent neural precursors (NPs into the brain ventricles of mice induced with experimental autoimmune encephalomyelitis (EAE, the animal model of MS. We studied the effect of the transplanted NPs on the functional and pathological manifestations of the disease. RESULTS: Transplanted hESC-derived NPs significantly reduced the clinical signs of EAE. Histological examination showed migration of the transplanted NPs to the host white matter, however, differentiation to mature oligodendrocytes and remyelination were negligible. Time course analysis of the evolution and progression of CNS inflammation and tissue injury showed an attenuation of the inflammatory process in transplanted animals, which was correlated with the reduction of both axonal damage and demyelination. Co-culture experiments showed that hESC-derived NPs inhibited the activation and proliferation of lymph node-derived T cells in response to nonspecific polyclonal stimuli. CONCLUSIONS: The therapeutic effect of transplantation was not related to graft or host remyelination but was mediated by an immunosuppressive neuroprotective mechanism. The attenuation of EAE by hESC-derived NPs, demonstrated here, may serve as the first step towards further developments of hESC for cell therapy in MS.

  19. Bone tissue engineering with human mesenchymal stem cell sheets constructed using magnetite nanoparticles and magnetic force.

    Science.gov (United States)

    Shimizu, Kazunori; Ito, Akira; Yoshida, Tatsuro; Yamada, Yoichi; Ueda, Minoru; Honda, Hiroyuki

    2007-08-01

    An in vitro reconstruction of three-dimensional (3D) tissues without the use of scaffolds may be an alternative strategy for tissue engineering. We have developed a novel tissue engineering strategy, termed magnetic force-based tissue engineering (Mag-TE), in which magnetite cationic liposomes (MCLs) with a positive charge at the liposomal surface, and magnetic force were used to construct 3D tissue without scaffolds. In this study, human mesenchymal stem cells (MSCs) magnetically labeled with MCLs were seeded onto an ultra-low attachment culture surface, and a magnet (4000 G) was placed on the reverse side. The MSCs formed multilayered sheet-like structures after a 24-h culture period. MSCs in the sheets constructed by Mag-TE maintained an in vitro ability to differentiate into osteoblasts, adipocytes, or chondrocytes after a 21-day culture period using each induction medium. Using an electromagnet, MSC sheets constructed by Mag-TE were harvested and transplanted into the bone defect in the crania of nude rats. Histological observation revealed that new bone surrounded by osteoblast-like cells was formed in the defect area 14 days after transplantation with MSC sheets, whereas no bone formation was observed in control rats without the transplant. These results indicated that Mag-TE could be used for the transplantation of MSC sheets using magnetite nanoparticles and magnetic force, providing novel methodology for bone tissue engineering.

  20. The postischemic environment differentially impacts teratoma or tumor formation after transplantation of human embryonic stem cell-derived neural progenitors

    DEFF Research Database (Denmark)

    Seminatore, Christine; Polentes, Jerome; Ellman, Ditte

    2010-01-01

    Risk of tumorigenesis is a major obstacle to human embryonic and induced pluripotent stem cell therapy. Likely linked to the stage of differentiation of the cells at the time of implantation, formation of teratoma/tumors can also be influenced by factors released by the host tissue. We have...... analyzed the relative effects of the stage of differentiation and the postischemic environment on the formation of adverse structures by transplanted human embryonic stem cell-derived neural progenitors....

  1. Clonality evaluation in human tissues

    Directory of Open Access Journals (Sweden)

    Villamizar-Rivera, Nicolás

    2015-07-01

    Full Text Available Malignant proliferations are usually clonal. While most times the biological potential can be established through routine pathologic and clinical examinations, some cases are difficult to classify. Moreover, in some situations there are dominant clones whose analysis is important, such as in autoimmune diseases and immunodeficiency. This paper presents in an understandable way the main techniques for the study of clonality, namely: evaluation of gene rearrangements of antigen receptor, and evaluation of human antigen receptor gene.

  2. Human dental pulp cell culture and cell transplantation with an alginate scaffold.

    Science.gov (United States)

    Kumabe, Shunji; Nakatsuka, Michiko; Kim, Gi-Seup; Jue, Seong-Suk; Aikawa, Fumiko; Shin, Je-Won; Iwai, Yasutomo

    2006-02-01

    Many studies on tissue stem cells have been conducted in the field of regenerative medicine, and some studies have indicated that cultured dental pulp mesenchymal cells secrete dentin matrix. In the present study we used alginate as a scaffold to transplant subcultured human dental pulp cells subcutaneously into the backs of nude mice. We found that when beta-glycerophosphate was added to the culture medium, dentin sialophosphoprotein mRNA coding dentin sialoprotein (DSP) was expressed. An increase in alkaline phosphatase, which is an early marker for odontoblast differentiation, was also demonstrated. At 6 weeks after implantation the subcutaneous formation of radio-opaque calcified bodies was observed in situ. Immunohistochemical and fine structure studies identified expression of type I collagen, type III collagen, and DSP in the mineralizing transplants. Isolated odontoblast-like cells initiated dentin-like hard tissue formation and scattered autolyzing apoptotic cells were also observed in the transplants. The study showed that subcultured dental pulp cells actively differentiate into odontoblast-like cells and induce calcification in an alginate scaffold.

  3. Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

    NARCIS (Netherlands)

    Geuken, Erwin; Visser, Dorien; Kuipers, Folkert; Blokzijl, Hans; Leuvenink, Henri G. D.; de Jong, Koert P.; Peeters, Paul M. J. G.; Jansen, Peter L. M.; Slooff, Maarten J. H.; Gouw, Annette S. H.; Porte, Robert J.

    2004-01-01

    BACKGROUND/AIMS: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. METHODS: In 28 liver transplant recipients, bile samples were collected daily

  4. Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

    NARCIS (Netherlands)

    Geuken, E; Visser, D; Kuipers, F; Blokzijl, H; Leuvenink, HGD; de Jong, KP; Peeters, PMJG; Jansen, PLM; Slooff, MJH; Gouw, ASH; Porte, RJ

    2004-01-01

    Background/Aims: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. Methods: In 28 liver transplant recipients, bile samples were collected daily

  5. Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus.

    Science.gov (United States)

    Carlsson, Per-Ola; Espes, Daniel; Sedigh, Amir; Rotem, Avi; Zimerman, Baruch; Grinberg, Helena; Goldman, Tali; Barkai, Uriel; Avni, Yuval; Westermark, Gunilla T; Carlbom, Lina; Ahlström, Håkan; Eriksson, Olof; Olerud, Johan; Korsgren, Olle

    2017-12-29

    Macroencapsulation devices provide the dual possibility of immunoprotecting transplanted cells while also being retrievable, the latter bearing importance for safety in future trials with stem cell-derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets into patients with type 1 diabetes. Four patients were transplanted with 1-2 βAir devices, each containing 155 000-180 000 islet equivalents (ie, 1800-4600 islet equivalents per kg body weight), and monitored for 3-6 months, followed by the recovery of devices. Implantation of the βAir device was safe and successfully prevented immunization and rejection of the transplanted tissue. However, although beta cells survived in the device, only minute levels of circulating C-peptide were observed with no impact on metabolic control. Fibrotic tissue with immune cells was formed in capsule surroundings. Recovered devices displayed a blunted glucose-stimulated insulin response, and amyloid formation in the endocrine tissue. We conclude that the βAir device is safe and can support survival of allogeneic islets for several months, although the function of the transplanted cells was limited (Clinicaltrials.gov: NCT02064309). © 2018 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.

  6. Adenovirus 36 DNA in human adipose tissue.

    Science.gov (United States)

    Ponterio, E; Cangemi, R; Mariani, S; Casella, G; De Cesare, A; Trovato, F M; Garozzo, A; Gnessi, L

    2015-12-01

    Recent studies have suggested a possible correlation between obesity and adenovirus 36 (Adv36) infection in humans. As information on adenoviral DNA presence in human adipose tissue are limited, we evaluated the presence of Adv36 DNA in adipose tissue of 21 adult overweight or obese patients. Total DNA was extracted from adipose tissue biopsies. Virus detection was performed using PCR protocols with primers against specific Adv36 fiber protein and the viral oncogenic E4orf1 protein nucleotide sequences. Sequences were aligned with the NCBI database and phylogenetic analyses were carried out with MEGA6 software. Adv36 DNA was found in four samples (19%). This study indicates that some individuals carry Adv36 in the visceral adipose tissue. Further studies are needed to determine the specific effect of Adv36 infection on adipocytes, the prevalence of Adv36 infection and its relationship with obesity in the perspective of developing a vaccine that could potentially prevent or mitigate infection.

  7. Tissue-specific methylation of human insulin gene and PCR assay for monitoring beta cell death.

    Directory of Open Access Journals (Sweden)

    Mohamed I Husseiny

    Full Text Available The onset of metabolic dysregulation in type 1 diabetes (T1D occurs after autoimmune destruction of the majority of pancreatic insulin-producing beta cells. We previously demonstrated that the DNA encoding the insulin gene is uniquely unmethylated in these cells and then developed a methylation-specific PCR (MSP assay to identify circulating beta cell DNA in streptozotocin-treated mice prior to the rise in blood glucose. The current study extends to autoimmune non-obese diabetic (NOD mice and humans, showing in NOD mice that beta cell death occurs six weeks before the rise in blood sugar and coincides with the onset of islet infiltration by immune cells, demonstrating the utility of MSP for monitoring T1D. We previously reported unique patterns of methylation of the human insulin gene, and now extend this to other human tissues. The methylation patterns of the human insulin promoter, intron 1, exon 2, and intron 2 were determined in several normal human tissues. Similar to our previous report, the human insulin promoter was unmethylated in beta cells, but methylated in all other tissues tested. In contrast, intron 1, exon 2 and intron 2 did not exhibit any tissue-specific DNA methylation pattern. Subsequently, a human MSP assay was developed based on the methylation pattern of the insulin promoter and human islet DNA was successfully detected in circulation of T1D patients after islet transplantation therapy. Signal levels of normal controls and pre-transplant samples were shown to be similar, but increased dramatically after islet transplantation. In plasma the signal declines with time but in whole blood remains elevated for at least two weeks, indicating that association of beta cell DNA with blood cells prolongs the signal. This assay provides an effective method to monitor beta cell destruction in early T1D and in islet transplantation therapy.

  8. Modular tissue engineering for the vascularization of subcutaneously transplanted pancreatic islets.

    Science.gov (United States)

    Vlahos, Alexander E; Cober, Nicholas; Sefton, Michael V

    2017-08-29

    The transplantation of pancreatic islets, following the Edmonton Protocol, is a promising treatment for type I diabetics. However, the need for multiple donors to achieve insulin independence reflects the large loss of islets that occurs when islets are infused into the portal vein. Finding a less hostile transplantation site that is both minimally invasive and able to support a large transplant volume is necessary to advance this approach. Although the s.c. site satisfies both these criteria, the site is poorly vascularized, precluding its utility. To address this problem, we demonstrate that modular tissue engineering results in an s.c. vascularized bed that enables the transplantation of pancreatic islets. In streptozotocin-induced diabetic SCID/beige mice, the injection of 750 rat islet equivalents embedded in endothelialized collagen modules was sufficient to restore and maintain normoglycemia for 21 days; the same number of free islets was unable to affect glucose levels. Furthermore, using CLARITY, we showed that embedded islets became revascularized and integrated with the host's vasculature, a feature not seen in other s.c. Collagen-embedded islets drove a small (albeit not significant) shift toward a proangiogenic CD206 + MHCII - (M2-like) macrophage response, which was a feature of module-associated vascularization. While these results open the potential for using s.c. islet delivery as a treatment option for type I diabetes, the more immediate benefit may be for the exploration of revascularized islet biology.

  9. Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.

    Directory of Open Access Journals (Sweden)

    Anabel S de la Garza-Rodea

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSCs are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs are capable of extensive proliferation without showing chromosomal aberrations. Large numbers of hMSCs can thus be acquired from small samples of easily obtainable tissues like fat and bone marrow. MSCs can contribute to regeneration indirectly by secretion of cytokines or directly by differentiation into specialized cell types. The latter mechanism requires their long-term acceptance by the recipient. Although MSCs do not elicit immune responses in vitro, animal studies have revealed that allogeneic and xenogeneic MSCs are rejected. METHODOLOGY/PRINCIPAL FINDINGS: We aim to overcome MSC immune rejection through permanent down-regulation of major histocompatibility complex (MHC class I proteins on the surface of these MHC class II-negative cells through the use of viral immune evasion proteins. Transduction of hMSCs with a retroviral vector encoding the human cytomegalovirus US11 protein resulted in strong inhibition of MHC class I surface expression. When transplanted into immunocompetent mice, persistence of the US11-expressing and HLA-ABC-negative hMSCs at levels resembling those found in immunodeficient (i.e., NOD/SCID mice could be attained provided that recipients' natural killer (NK cells were depleted prior to cell transplantation. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate the potential utility of herpesviral immunoevasins to prevent rejection of xenogeneic MSCs. The observation that down-regulation of MHC class I surface expression renders hMSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make hMSCs non-immunogenic and thereby universally transplantable.

  10. Modulation of human allogeneic and syngeneic pluripotent stem cells and immunological implications for transplantation.

    Science.gov (United States)

    Sackett, S D; Brown, M E; Tremmel, D M; Ellis, T; Burlingham, W J; Odorico, J S

    2016-04-01

    Tissues derived from induced pluripotent stem cells (iPSCs) are a promising source of cells for building various regenerative medicine therapies; from simply transplanting cells to reseeding decellularized organs to reconstructing multicellular tissues. Although reprogramming strategies for producing iPSCs have improved, the clinical use of iPSCs is limited by the presence of unique human leukocyte antigen (HLA) genes, the main immunologic barrier to transplantation. In order to overcome the immunological hurdles associated with allogeneic tissues and organs, the generation of patient-histocompatible iPSCs (autologous or HLA-matched cells) provides an attractive platform for personalized medicine. However, concerns have been raised as to the fitness, safety and immunogenicity of iPSC derivatives because of variable differentiation potential of different lines and the identification of genetic and epigenetic aberrations that can occur during the reprogramming process. In addition, significant cost and regulatory barriers may deter commercialization of patient specific therapies in the short-term. Nonetheless, recent studies provide some evidence of immunological benefit for using autologous iPSCs. Yet, more studies are needed to evaluate the immunogenicity of various autologous and allogeneic human iPSC-derived cell types as well as test various methods to abrogate rejection. Here, we present perspectives of using allogeneic vs. autologous iPSCs for transplantation therapies and the advantages and disadvantages of each related to differentiation potential, immunogenicity, genetic stability and tumorigenicity. We also review the current literature on the immunogenicity of syngeneic iPSCs and discuss evidence that questions the feasibility of HLA-matched iPSC banks. Finally, we will discuss emerging methods of abrogating or reducing host immune responses to PSC derivatives. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The world's first human-to-human heart transplant at Groote Schuur ...

    African Journals Online (AJOL)

    The world's first human-to-human heart transplant at Groote Schuur Hospital: 50 years later. Johan Brink, Tim Pennel, Karen Seele, Peter Zilla. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO ...

  12. Ovarian tissue cryopreservation in girls undergoing haematopoietic stem cell transplant: experience of a single centre.

    Science.gov (United States)

    Biasin, E; Salvagno, F; Berger, M; Nesi, F; Quarello, P; Vassallo, E; Evangelista, F; Marchino, G L; Revelli, A; Benedetto, C; Fagioli, F

    2015-09-01

    Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.

  13. Viscoelastic Properties of Human Tracheal Tissues.

    Science.gov (United States)

    Safshekan, Farzaneh; Tafazzoli-Shadpour, Mohammad; Abdouss, Majid; Shadmehr, Mohammad B

    2017-01-01

    The physiological performance of trachea is highly dependent on its mechanical behavior, and therefore, the mechanical properties of its components. Mechanical characterization of trachea is key to succeed in new treatments such as tissue engineering, which requires the utilization of scaffolds which are mechanically compatible with the native human trachea. In this study, after isolating human trachea samples from brain-dead cases and proper storage, we assessed the viscoelastic properties of tracheal cartilage, smooth muscle, and connective tissue based on stress relaxation tests (at 5% and 10% strains for cartilage and 20%, 30%, and 40% for smooth muscle and connective tissue). After investigation of viscoelastic linearity, constitutive models including Prony series for linear viscoelasticity and quasi-linear viscoelastic, modified superposition, and Schapery models for nonlinear viscoelasticity were fitted to the experimental data to find the best model for each tissue. We also investigated the effect of age on the viscoelastic behavior of tracheal tissues. Based on the results, all three tissues exhibited a (nonsignificant) decrease in relaxation rate with increasing the strain, indicating viscoelastic nonlinearity which was most evident for cartilage and with the least effect for connective tissue. The three-term Prony model was selected for describing the linear viscoelasticity. Among different models, the modified superposition model was best able to capture the relaxation behavior of the three tracheal components. We observed a general (but not significant) stiffening of tracheal cartilage and connective tissue with aging. No change in the stress relaxation percentage with aging was observed. The results of this study may be useful in the design and fabrication of tracheal tissue engineering scaffolds.

  14. [Subcutaneous transplants of juvenile rat testicular tissues continue to develop and secret androgen in adult rats].

    Science.gov (United States)

    Yu, Zhou; Wang, Tong; Cui, Jiangbo; Song, Yajuan; Ma, Xianjie; Su, Yingjun; Peng, Pai

    2017-12-01

    Objective To explore the effects of subcutaneous microenvironment of adult rats on survival, development and androgen secretion of Leydig cells of transplanted juvenile rat testis. Methods Healthy adult SD rats were randomly divided into control group, sham group, castrated group and non-castrated group. Rats in the control group were kept intact, no testis was transplanted subcutaneously after adult recipients were castrated in the sham group; 5-7-day juvenile rat testes were transplanted subcutaneously in the castrated group, with one testis per side; Testes resected from juvenile rats were directly transplanted subcutaneously on both sides of the recipients in the non-castrated group. The grafts were obtained and weighed 4 weeks later. Then the histological features of the grafts were examined by HE staining; the expression and distribution of hydroxysteroid 17-beta dehydrogenase 1 (HSD-17β1) were investigated by immunohistochemistry; and the serum androgen level was determined by ELISA. Results The average mass of grafts obtained from the castrated group was significantly higher than that of the non-castrated group. Immunohistochemistry indicated that Leydig cells were visible in the tissues from both the castrated and non-castrated groups, but the number of HSD-17β1-posotive cells in the castrated group was larger than that in the non-castrated group. ELISA results showed that the serum androgen level was higher in the control group and non-castrated group than in the sham group and castrated group, and compared with the sham group, the serum androgen level in the castrated group was significantly higher. Conclusion The juvenile rat testis subcutaneously transplanted could further develop under the adult recipient rat skin, and the Leydig cells of grafts harbored the ability to produce and secret androgen.

  15. Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem cells.

    Science.gov (United States)

    Saito, Taku; Yano, Fumiko; Mori, Daisuke; Kawata, Manabu; Hoshi, Kazuto; Takato, Tsuyoshi; Masaki, Hideki; Otsu, Makoto; Eto, Koji; Nakauchi, Hiromitsu; Chung, Ung-il; Tanaka, Sakae

    2015-01-01

    Induced pluripotent stem cells (iPSCs) are a promising cell source for cartilage regenerative medicine. Meanwhile, the risk of tumorigenesis should be considered in the clinical application of human iPSCs (hiPSCs). Here, we report in vitro chondrogenic differentiation of hiPSCs and maturation of the differentiated hiPSCs through transplantation into mouse knee joints. Three hiPSC clones showed efficient chondrogenic differentiation using an established protocol for human embryonic stem cells. The differentiated hiPSCs formed hyaline cartilage tissues at 8 weeks after transplantation into the articular cartilage of NOD/SCID mouse knee joints. Although tumors were not observed during the 8 weeks after transplantation, an immature teratoma had developed in one mouse at 16 weeks. In conclusion, hiPSCs are a potent cell source for regeneration of hyaline articular cartilage. However, the risk of tumorigenesis should be managed for clinical application in the future.

  16. Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain.

    Science.gov (United States)

    Li, Xiaowei; Tzeng, Stephany Y; Liu, Xiaoyan; Tammia, Markus; Cheng, Yu-Hao; Rolfe, Andrew; Sun, Dong; Zhang, Ning; Green, Jordan J; Wen, Xuejun; Mao, Hai-Quan

    2016-04-01

    Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The importance of ethic in the field of human tissue banking.

    Science.gov (United States)

    Morales Pedraza, Jorge; Herson, Marisa Roma

    2012-03-01

    A tissue bank is accountable before the community in fulfilling the expectations of tissue donors, their families and recipients. The expected output from the altruistic donation is that safe and high quality human tissue grafts will be provided for the medical treatment of patients. Thus, undertakings of tissue banks have to be not only authorised and audited by national competent health care authorities, but also comply with a strong ethical code, a code of practices and ethical principles. Ethical practice in the field of tissue banking requires the setting of principles, the identification of possible deviations and the establishment of mechanisms that will detect and hinder abuses that may occur during the procurement, processing and distribution of human tissues for transplantation. The opinions and suggestions manifested by the authors in this paper may not be necessarily a reflection of those within the institutions or community they are linked to.

  18. In utero transplantation of human bone marrow-derived multipotent mesenchymal stem cells in mice.

    Science.gov (United States)

    Chou, Shiu-Huey; Kuo, Tom K; Liu, Ming; Lee, Oscar K

    2006-03-01

    Mesenchymal stem cells (MSCs) are multipotent cells that can be isolated from human bone marrow and possess the potential to differentiate into progenies of embryonic mesoderm. However, current evidence is based predominantly on in vitro experiments. We used a murine model of in utero transplantation (IUT) to study the engraftment capabilities of human MSCs. MSCs were obtained from bone marrow by negative immunoselection and limiting dilution, and were characterized by flow cytometry and by in vitro differentiation into osteoblasts, chondrocytes, and adipocytes. MSCs were transplanted into fetal mice at a gestational age of 14 days. Engraftment of human MSCs was determined by flow cytometry, polymerase chain reaction, and fluorescence in situ hybridization (FISH). MSCs engrafted into tissues originating from all three germ layers and persisted for up to 4 months or more after delivery, as evidenced by the expression of the human-specific beta-2 microglobulin gene and by FISH for donor-derived cells. Donor-derived CD45+ cells were detectable in the peripheral blood of recipients, suggesting the participation of MSCs in hematopoiesis at the fetal stage. This model can further serve to evaluate possible applications of MSCs. Copyright 2006 Orthopaedic Research Society.

  19. Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site

    Directory of Open Access Journals (Sweden)

    Andrew R. Pepper

    2017-06-01

    Full Text Available Beta-cell replacement therapy is an effective means to restore glucose homeostasis in select humans with autoimmune diabetes. The scarcity of “healthy” human donor pancreata restricts the broader application of this effective curative therapy. “β-Like” cells derived from human embryonic stem cells (hESC, with the capacity to secrete insulin in a glucose-regulated manner, have been developed in vitro, with limitless capacity for expansion. Here we report long-term diabetes correction in mice transplanted with hESC-derived pancreatic endoderm cells (PECs in a prevascularized subcutaneous site. This advancement mitigates chronic foreign-body response, utilizes a device- and growth factor-free approach, facilitates in vivo differentiation of PECs into glucose-responsive insulin-producing cells, and reliably restores glycemic control. Basal and stimulated human C-peptide secretion was detected throughout the study, which was abolished upon graft removal. Recipient mice demonstrated physiological clearance of glucose in response to metabolic challenge and safely retrieved grafts contained viable glucose regulatory cells.

  20. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant.

    Science.gov (United States)

    Bartz, Christoph; Meixner, Miriam; Giesemann, Petra; Roël, Giulietta; Bulwin, Grit-Carsta; Smink, Jeske J

    2016-11-15

    Cell-based therapies such as autologous chondrocyte implantation are promising therapeutic approaches to treat cartilage defects to prevent further cartilage degeneration. To assure consistent quality of cell-based therapeutics, it is important to be able to predict the biological activity of such products. This requires the development of a potency assay, which assesses a characteristic of the cell transplant before implantation that can predict its cartilage regeneration capacity after implantation. In this study, an ex vivo human cartilage repair model was developed as quality assessment tool for potency and applied to co.don's chondrosphere product, a matrix-associated autologous chondrocyte implant (chondrocyte spheroids) that is in clinical use in Germany. Chondrocyte spheroids were generated from 14 donors, and implanted into a subchondral cartilage defect that was manually generated in human articular cartilage tissue. Implanted spheroids and cartilage tissue were co-cultured ex vivo for 12 weeks to allow regeneration processes to form new tissue within the cartilage defect. Before implantation, spheroid characteristics like glycosaminoglycan production and gene and protein expression of chondrogenic markers were assessed for each donor sample and compared to determine donor-dependent variation. After the co-cultivation, histological analyses showed the formation of repair tissue within the cartilage defect, which varied in amount for the different donors. In the repair tissue, aggrecan protein was expressed and extra-cellular matrix cartilage fibers were present, both indicative for a cartilage hyaline-like character of the repair tissue. The amount of formed repair tissue was used as a read-out for regeneration capacity and was correlated with the spheroid characteristics determined before implantation. A positive correlation was found between high level of aggrecan protein expression in spheroids before implantation and a higher regeneration potential

  1. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant

    Directory of Open Access Journals (Sweden)

    Christoph Bartz

    2016-11-01

    Full Text Available Abstract Background Cell-based therapies such as autologous chondrocyte implantation are promising therapeutic approaches to treat cartilage defects to prevent further cartilage degeneration. To assure consistent quality of cell-based therapeutics, it is important to be able to predict the biological activity of such products. This requires the development of a potency assay, which assesses a characteristic of the cell transplant before implantation that can predict its cartilage regeneration capacity after implantation. In this study, an ex vivo human cartilage repair model was developed as quality assessment tool for potency and applied to co.don’s chondrosphere product, a matrix-associated autologous chondrocyte implant (chondrocyte spheroids that is in clinical use in Germany. Methods Chondrocyte spheroids were generated from 14 donors, and implanted into a subchondral cartilage defect that was manually generated in human articular cartilage tissue. Implanted spheroids and cartilage tissue were co-cultured ex vivo for 12 weeks to allow regeneration processes to form new tissue within the cartilage defect. Before implantation, spheroid characteristics like glycosaminoglycan production and gene and protein expression of chondrogenic markers were assessed for each donor sample and compared to determine donor-dependent variation. Results After the co-cultivation, histological analyses showed the formation of repair tissue within the cartilage defect, which varied in amount for the different donors. In the repair tissue, aggrecan protein was expressed and extra-cellular matrix cartilage fibers were present, both indicative for a cartilage hyaline-like character of the repair tissue. The amount of formed repair tissue was used as a read-out for regeneration capacity and was correlated with the spheroid characteristics determined before implantation. A positive correlation was found between high level of aggrecan protein expression in spheroids

  2. Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia

    Directory of Open Access Journals (Sweden)

    Liyuan Chen

    2018-03-01

    Full Text Available Background: Fat deposition is associated with peripheral arterial disease. Adipose tissue has recently been implicated in vascular remodeling and angiogenic activity. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice.Methods: After 14 weeks of high-fat diet (HFD-fed mice, unilateral hind limb ischemia was performed. Subcutaneous white adipose tissue (WAT and brown adipose tissue (BAT fat pads were harvested from normal EGFP mice, and subcutaneously transplanted over the region of the adductor muscles of HFD mice. Blood flow was measured using Laser Doppler Scanner. Vascular density, macrophages infiltration, and macrophage polarization were examined by RT-qPCR, and immunohistochemistry.Results: We found that the transplantation of WAT derived from normal mice improved functional blood flow in HFD-fed mice compared to mice transplanted with BAT and sham-treated mice. WAT transplantation increased the recruitment of pericytes associated with nascent blood vessels, but did not affect capillary formation. Furthermore, transplantation of WAT ameliorated HFD-induced insulin resistance, M2 macrophage predominance and the release of arteriogenic factors in ischemic muscles. Mice receiving WAT also displayed a marked reduction in several proinflammatory cytokines. In contrast, mice transplanted with BAT were glucose intolerant and demonstrated increased IL-6 levels in ischemic muscles.Conclusion: These results indicate that transplantation of adipose tissue elicits improvements in blood perfusion and beneficial effects on systemic glucose homeostasis and could be a promising therapeutic option for the treatment of diabetic peripheral arterial disease.

  3. Maturation and function of human embryonic stem cell-derived pancreatic progenitors in macroencapsulation devices following transplant into mice.

    Science.gov (United States)

    Bruin, Jennifer E; Rezania, Alireza; Xu, Jean; Narayan, Kavitha; Fox, Jessica K; O'Neil, John J; Kieffer, Timothy J

    2013-09-01

    Islet transplantation is a promising cell therapy for patients with diabetes, but it is currently limited by the reliance upon cadaveric donor tissue. We previously demonstrated that human embryonic stem cell (hESC)-derived pancreatic progenitor cells matured under the kidney capsule in a mouse model of diabetes into glucose-responsive insulin-secreting cells capable of reversing diabetes. However, the formation of cells resembling bone and cartilage was a major limitation of that study. Therefore, we developed an improved differentiation protocol that aimed to prevent the formation of off-target mesoderm tissue following transplantation. We also examined how variation within the complex host environment influenced the development of pancreatic progenitors in vivo. The hESCs were differentiated for 14 days into pancreatic progenitor cells and transplanted either under the kidney capsule or within Theracyte (TheraCyte, Laguna Hills, CA, USA) devices into diabetic mice. Our revised differentiation protocol successfully eliminated the formation of non-endodermal cell populations in 99% of transplanted mice and generated grafts containing >80% endocrine cells. Progenitor cells developed efficiently into pancreatic endocrine tissue within macroencapsulation devices, despite lacking direct contact with the host environment, and reversed diabetes within 3 months. The preparation of cell aggregates pre-transplant was critical for the formation of insulin-producing cells in vivo and endocrine cell development was accelerated within a diabetic host environment compared with healthy mice. Neither insulin nor exendin-4 therapy post-transplant affected the maturation of macroencapsulated cells. Efficient differentiation of hESC-derived pancreatic endocrine cells can occur in a macroencapsulation device, yielding glucose-responsive insulin-producing cells capable of reversing diabetes.

  4. Successful pregnancy in a woman previously suffering from β-thalassaemia following transplantation of ovarian tissue cryopreserved before puberty

    DEFF Research Database (Denmark)

    Matthews, Sara J; Picton, Helen M; Ernst, Erik

    2018-01-01

    Ovarian tissue removed from a nine year old girl suffering from thalassemia was kept deep- frozen for 14 years before being transplanted back to the now adult woman. Subsequently, she conceived following IVF treatment and delivered a healthy baby where the oocyte derived from the transplanted...... tissue. This is the first woman worldwide to have a baby where the ovarian tissue was frozen pre-pubertally and expand the therapeutic options for rare genetic diseases like thalassemia and girls who suffer from childhood cancer....

  5. Establishing the role of pre-implantation genetic diagnosis with human leucocyte antigen typing: what place do "saviour siblings" have in paediatric transplantation?

    Science.gov (United States)

    Samuel, G N; Strong, K A; Kerridge, I; Jordens, C F C; Ankeny, R A; Shaw, P J

    2009-04-01

    Not all children in need of a haematopoietic stem cell transplant have a suitable relative or unrelated donor available. Recently, in vitro fertilisation (IVF) with pre-implantation genetic diagnosis (PGD) for human leucocyte antigen (HLA) tissue typing has been used to selectively transfer an IVF embryo in order to produce a child who may provide umbilical cord blood for transplantation to an ill sibling. Such children are sometimes called "saviour siblings". To examine the published clinical and epidemiological evidence relevant to the use of this technology, with the aim of clarifying those situations where IVF and PGD for HLA typing should be discussed with parents of an ill child. A critical analysis of published literature on comparative studies of umbilical cord blood versus other sources of stem cells for transplantation; comparative studies of matched unrelated donor versus matched related donor transplantation; and the likelihood of finding an unrelated stem cell donor. IVF and PGD for HLA typing is only applicable when transplantation is non-urgent and parents are of reproductive age. Discussions regarding this technology may be appropriate where no suitable related or unrelated donor is available for a child requiring a transplant, or where no suitable related donor is available and transplantation is only likely to be entertained with a matched sibling donor. Discussion may also be considered in the management of any child lacking a matched related donor who requires a non-urgent transplant or may require a transplant in the future.

  6. Beta adrenergic receptors in human cavernous tissue

    Energy Technology Data Exchange (ETDEWEB)

    Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

    1985-04-01

    Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

  7. Preliminary study of coconut water for graft tissues preservation in transplantation

    Directory of Open Access Journals (Sweden)

    Jorge Miguel Schettino César

    Full Text Available OBJECTIVE: to verify the effectiveness of coconut water in preserving tissues for transplant. METHODS: Fifty male Wistar rats were randomly distributed in five groups, according to the following preservation solutions for tissue grafts: Group 1: Lactated Ringer; Group 2: Belzer solution; Group 3: mature coconut water; Group 4: green coconut water; Group 5: modified coconut water. In Group 5, the green coconut water has been modified like the Belzer solution. From each animal we harvasted the spleen, ovaries and skin of the back segment. These tissues were preserved for six hours in one of the solutions. Then, the grafts were reimplanted. The recovery of the function of the implanted tissues was assessed 90 days after surgery, by splenic scintigraphy and blood exame. The implanted tissues were collected for histopathological examination. RESULTS: The serum levels did not differ among groups, except for the animals in Group 5, which showed higher levels of IgG than Group 1, and differences in relation to FSH between groups 1 and 2 (p <0.001, 4 and 2 (p = 0.03 and 5 and 2 (p = 0.01. The splenic scintigraphy was not different between groups. The ovarian tissue was better preserved in mature coconut water (p <0.007. CONCLUSION: the coconut water-based solutions preserves spleen, ovary, and rat skin for six hours, maintaining their normal function.

  8. Mining the human urine proteome for monitoring renal transplant injury

    Energy Technology Data Exchange (ETDEWEB)

    Sigdel, Tara K.; Gao, Yuqian; He, Jintang; Wang, Anyou; Nicora, Carrie D.; Fillmore, Thomas L.; Shi, Tujin; Webb-Robertson, Bobbie-Jo; Smith, Richard D.; Qian, Wei-Jun; Salvatierra, Oscar; Camp, David G.; Sarwal, Minnie M.

    2016-06-01

    The human urinary proteome reflects systemic and inherent renal injury perturbations and can be analyzed to harness specific biomarkers for different kidney transplant injury states. 396 unique urine samples were collected contemporaneously with an allograft biopsy from 396 unique kidney transplant recipients. Centralized, blinded histology on the graft was used to classify matched urine samples into categories of acute rejection (AR), chronic allograft nephropathy (CAN), BK virus nephritis (BKVN), and stable graft (STA). Liquid chromatography–mass spectrometry (LC-MS) based proteomics using iTRAQ based discovery (n=108) and global label-free LC-MS analyses of individual samples (n=137) for quantitative proteome assessment were used in the discovery step. Selected reaction monitoring (SRM) was applied to identify and validate minimal urine protein/peptide biomarkers to accurately segregate organ injury causation and pathology on unique urine samples (n=151). A total of 958 proteins were initially quantified by iTRAQ, 87% of which were also identified among 1574 urine proteins detected in LC-MS validation. 103 urine proteins were significantly (p<0.05) perturbed in injury and enriched for humoral immunity, complement activation, and lymphocyte trafficking. A set of 131 peptides corresponding to 78 proteins were assessed by SRM for their significance in an independent sample cohort. A minimal set of 35 peptides mapping to 33 proteins, were modeled to segregate different injury groups (AUC =93% for AR, 99% for CAN, 83% for BKVN). Urinary proteome discovery and targeted validation identified urine protein fingerprints for non-invasive differentiation of kidney transplant injuries, thus opening the door for personalized immune risk assessment and therapy.

  9. Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase

    Directory of Open Access Journals (Sweden)

    Silvia Baldari

    2016-07-01

    Full Text Available Short-term persistence of transplanted cells during early post-implant period limits clinical efficacy of cell therapy. Poor cell survival is mainly due to the harsh hypoxic microenvironment transplanted cells face at the site of implantation and to anoikis, driven by cell adhesion loss. We evaluated the hypothesis that viral-mediated expression of a gene conferring hypoxia resistance to cells before transplant could enhance survival of grafted cells in early stages after implant. We used adipose tissue as cell source because it consistently provides high yields of adipose-tissue-derived stromal and vascular cells (ASCs, suitable for regenerative purposes. Luciferase positive cells were transduced with lentiviral vectors expressing either green fluorescent protein as control or human manganese superoxide dismutase (SOD2. Cells were then exposed in vitro to hypoxic conditions, mimicking cell transplantation into an ischemic site. Cells overexpressing SOD2 displayed survival rates significantly greater compared to mock transduced cells. Similar results were also obtained in vivo after implantation into syngeneic mice and assessment of cell engraftment by in vivo bioluminescent imaging. Taken together, these findings suggest that ex vivo gene transfer of SOD2 into ASCs before implantation confers a cytoprotective effect leading to improved survival and engraftment rates, therefore enhancing cell therapy regenerative potential.

  10. Improvement of Heart Failure by Human Amniotic Mesenchymal Stromal Cell Transplantation in Rats.

    Science.gov (United States)

    Razavi Tousi, Seyed Mohammad Taghi; Faghihi, Mahdieh; Nobakht, Maliheh; Molazem, Mohammad; Kalantari, Elham; Darbandi Azar, Amir; Aboutaleb, Nahid

    2016-07-06

    Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells (hAMSCs) in rats with heart failure (HF). Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups (7 rats each) as 1- Control 2- Heart Failure (HF) 3- Sham 4- Culture media 5- Stem Cell Transplantation (SCT). Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3×10 6 cells in 150 µl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done. Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 ± 9% to 81/25 ± 6/05% in SCT group (p value < 0.001). Fraction shortening in HF group was increased from 27/53 ± 8/58% into 45/55 ± 6/91% in SCT group (p value < 0.001). Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group (p value < 0.001) compared with the animals in the HF group. Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters.

  11. Histomorphology of the Olfactory Mucosa and Spinal Tissue Sparing Following Transplantation in the Partial Spinal Cord Injury in Rats

    Directory of Open Access Journals (Sweden)

    H Delaviz

    2011-01-01

    Full Text Available Introduction & Objective: Nowadays, cellular and tissues transplant has become the focus of attention for spinal cord injury. It has been shown olfactory nerve cells or olfactory mucosa whi have more efficient on nervous tissue repair and they have been more studied in experimental study. Furthermore, they were used in a few clinical centers for spinal defect. But mucosa tissue and spinal tissue have different structure and there is doubt about the integration of mucosa tissue in nervous tissue. Thus, in this research the morphology and the effect of the fetal olfactory mucosa (FOM on spinal tissue sparing were studied after transplanted into the spinal cord hemisection in rats. Materials & Methods: This experimental study was conducted at Iran University of Medical Sciences in 2008. Of thirty eight female Sprague-Dawley (200-250g rats twenty- eight were spinally hemisected at the L1 spinal level and were randomized into two groups of 14 animals. Treatment group received FOM graft and the control group received fetal respiratory mucosa graft (FRM. The other animals received surgical procedure without spinal cord injury as a sham group. The morphology of the transplant region and spinal tissue sparing was examined histological eight weeks after transplantation. The collected data was analyzed by the SPSS software using ANOVA and the morphology of the transplant region were studied by light microscope. Results: Histological study showed that the both mucosa tissues could not integrate with the parenchyma of the spinal tissue. Although the FOM were fused more than the FRM with the host tissue but clear boundary was seen at the graft–host interface. The mean spinal tissue sparing of the treatment group increased a little compare to the control but a significant difference was not apparent whereas, the spinal tissue sparing in treatment and control groups compare to the sham group decreased significantly (P < 0.05. Conclusion: Transplantation of

  12. TRANSPLANTATION

    African Journals Online (AJOL)

    stage ... renal artery thrombosis, renal vein thrombosis, ureteric leak or stenosis ... alternative organ source for patients with end-stage renal disease. Kidney ... status.27,28 Post-transplant acute tubular necrosis is caused by ischaemic injury to the ...

  13. Tissue integrity is essential for ectopic implantation of human endometrium in the chicken chorioallantoic membrane.

    Science.gov (United States)

    Nap, Annemiek W; Groothuis, Patrick G; Demir, Ayse Y; Maas, Jacques W M; Dunselman, Gerard A J; de Goeij, Anton F P M; Evers, Johannes L H

    2003-01-01

    Not all women with patent tubes develop clinically manifest endometriosis. Quality and quantity of endometrium in retrograde menstruation may be the determining factor in the development of the disease. We hypothesize that retrograde shedding of endometrial fragments with preserved integrity facilitates implantation of endometrium in ectopic locations, resulting in endometriotic lesion development. We evaluate the impact of tissue integrity on the success of endometriosis-like lesion development in the chicken embryo chorioallantoic membrane (CAM) model. Menstrual and non-menstrual (cyclic) endometrium were collected by biopsy, and either minced or enzymatically dispersed. Spontaneously shed menstrual effluent was collected by a menstrual cup, and cells and tissue were isolated. We evaluated whether infiltration or lesion formation in the CAM occurred after transplantation of endometrium onto the CAM. Transplantation of biopsied menstrual and cyclic endometrium fragments, and of endometrium fragments >1 mm(3) isolated from menstrual effluent, resulted in lesion formation. Transplantation of endometrial cells isolated from menstrual effluent did not lead to lesion formation. After transplantation of digested biopsied cyclic endometrium, infiltration in the CAM but no lesions were observed. In the CAM assay, integrity of tissue architecture determines success of implantation of human endometrium in ectopic locations.

  14. Preliminary study of coconut water for graft tissues preservation in transplantation.

    Science.gov (United States)

    César, Jorge Miguel Schettino; Petroianu, Andy; Vasconcelos, Leonardo de Souza; Cardoso, Valbert Nascimento; Mota, Luciene das Graças; Barbosa, Alfredo José Afonso; Soares, Cristina Duarte Vianna; de Oliveira, Amanda Lima

    2015-01-01

    to verify the effectiveness of coconut water in preserving tissues for transplant. Fifty male Wistar rats were randomly distributed in five groups, according to the following preservation solutions for tissue grafts: Group 1: Lactated Ringer; Group 2: Belzer solution; Group 3: mature coconut water; Group 4: green coconut water; Group 5: modified coconut water. In Group 5, the green coconut water has been modified like the Belzer solution. From each animal we harvested the spleen, ovaries and skin of the back segment. These tissues were preserved for six hours in one of the solutions. Then, the grafts were reimplanted. The recovery of the function of the implanted tissues was assessed 90 days after surgery, by splenic scintigraphy and blood exam. The implanted tissues were collected for histopathological examination. The serum levels did not differ among groups, except for the animals in Group 5, which showed higher levels of IgG than Group 1, and differences in relation to FSH between groups 1 and 2 (p coconut water (p coconut water-based solutions preserves spleen, ovary, and rat skin for six hours, maintaining their normal function.

  15. Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after transplantation into adult unconditioned mice.

    Science.gov (United States)

    Allers, Carolina; Sierralta, Walter D; Neubauer, Sonia; Rivera, Francisco; Minguell, José J; Conget, Paulette A

    2004-08-27

    The use of mesenchymal stem cells (MSC) for cell therapy relies on their capacity to engraft and survive long-term in the appropriate target tissue(s). Animal models have demonstrated that the syngeneic or xenogeneic transplantation of MSC results in donor engraftment into the bone marrow and other tissues of conditioned recipients. However, there are no reliable data showing the fate of human MSC infused into conditioned or unconditioned adult recipients. In the present study, the authors investigated, by using imaging, polymerase chain reaction (PCR), and in situ hybridization, the biodistribution of human bone marrow-derived MSC after intravenous infusion into unconditioned adult nude mice. As assessed by imaging (gamma camera), PCR, and in situ hybridization analysis, the authors' results demonstrate the presence of human MSC in bone marrow, spleen, and mesenchymal tissues of recipient mice. These results suggest that human MSC transplantation into unconditioned recipients represents an option for providing cellular therapy and avoids the complications associated with drugs or radiation conditioning.

  16. [The clinical use of cryopreserved human skin allografts for transplantation].

    Science.gov (United States)

    Martínez-Flores, Francisco; Chacón-Gómez, María; Madinaveitia-Villanueva, Juan Antonio; Barrera-Lopez, Araceli; Aguirre-Cruz, Lucinda; Querevalu-Murillo, Walter

    2015-01-01

    The biological recovery of human skin allografts is the gold standard for preservation in Skin Banks. However, there is no worldwide consensus about specific allocation criteria for preserved human skin allografts with living cells. A report is presented on the results of 5 years of experience of using human skin allografts in burned patient in the Skin and Tissue Bank at the "Instituto Nacional de Rehabilitacion" The human skin allografts were obtained from multi-organ donors. processed and preserved at -80 °C for 12 months. Allocation criteria were performed according to blood type match, clinical history, and burned body surface. Up to now, the Skin and Tissue Bank at 'Instituto Nacional de Rehabilitacion" has processed and recovered 125,000 cm(2) of human skin allografts. It has performed 34 surgical implants on 21 burned patients. The average of burn body surface was 59.2%. More than two-thirds (67.7%) of recipients of skin allografts were matched of the same to type blood of the donor, and 66.6% survived after 126 days hospital stay. It is proposed to consider recipient's blood group as allocation criteria to assign tissue; and use human skin allografts on patiens affected with burns over 30% of body surface (according the "rule of the 9"). Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  17. Adult Tissue-Derived Stem Cells and Tolerance Induction in Nonhuman Primates for Vascularized Composite Allograft Transplantation

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-2-0042 TITLE: Adult Tissue-Derived Stem Cells and Tolerance Induction in Nonhuman Primates for Vascularized Composite...2017 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2016 - 29 Sep 2017 4. TITLE AND SUBTITLE Adult Tissue-Derived Stem Cells and Tolerance Induction...Distribution Unlimited 13. SUPPLEMENTARY NOTES The utilization of adult derived adipose stem cells administration in composite tissue transplantation

  18. BMP4 Expression Following Stem Cells from Human Exfoliated Deciduous and Carbonate Apatite Transplantation on Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    Tania Saskianti

    2018-04-01

    Full Text Available Background: Alveolar bone defects in children still have a high incidence. Conventional bone graft technique that has been used as a defect therapy is still not effective, so new techniques with tissue engineering approach are needed. Bone Morphogenetic Protein 4 (BMP4 as one of the indicators of osteogenic differentiation has not been widely studied, especially in the transplantation with combination of Stem Cells from Human Exfoliated Deciduous (SHED and carbonate apatite. Aim and Objectives: This research aimed to determine the expression of BMP4 after SHED and carbonate apatite transplantation on Rattus norvegicus. Material and Methods: The combinations of SHED and carbonate apatite were transplanted on alveolar bone defects of 4 rats (Rattus norvegicus as the treatment groups and another 4 rats were transplanted with carbonate apatite as the control groups. After 21 days, staining with Hematoxylin Eosin (HE and Immunohistochemistry (IHC BMP4 was performed. Results: BMP4 expression in the treatment groups was significantly higher when compared to the control groups. Discussion: Carbonate apatite has low crystallization rate and high osteoconductivity that produce more osteoblasts and increased BMP4 expression. Conclusion: The transplantation of SHED and carbonate apatite increased BMP4 expression as an indicator of osteogenic differentiation in rats.

  19. Using non-human primates to benefit humans: research and organ transplantation.

    Science.gov (United States)

    Shaw, David; Dondorp, Wybo; de Wert, Guido

    2014-11-01

    Emerging biotechnology may soon allow the creation of genetically human organs inside animals, with non-human primates (henceforth simply "primates") and pigs being the best candidate species. This prospect raises the question of whether creating organs in primates in order to then transplant them into humans would be more (or less) acceptable than using them for research. In this paper, we examine the validity of the purported moral distinction between primates and other animals, and analyze the ethical acceptability of using primates to create organs for human use.

  20. UWB pulse propagation into human tissues

    International Nuclear Information System (INIS)

    Cavagnaro, Marta; Pittella, Erika; Pisa, Stefano

    2013-01-01

    In this paper the propagation of a UWB pulse into a layered model of the human body is studied to characterize absorption and reflection of the UWB signal due to the different body tissues. Several time behaviours for the incident UWB pulse are considered and compared with reference to the feasibility of breath and heartbeat activity monitoring. Results show that if the UWB source is placed far from the human body, the reflection coming from the interface between air and skin can be used to detect the respiratory activity. On the contrary, if the UWB source is placed close to the human body, a small reflection due to the interface between the posterior lung wall and the bone, which is well distanced in time from the reflections due to the first layers of the body model, can be used to detect lung and heart changes associated with the cardio-respiratory activity. (paper)

  1. Hepatic tissue environment in NEMO-deficient mice critically regulates positive selection of donor cells after hepatocyte transplantation.

    Directory of Open Access Journals (Sweden)

    Michaela Kaldenbach

    Full Text Available BACKGROUND: Hepatocyte transplantation (HT is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. METHODS: Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa. RESULTS: Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. CONCLUSION: This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and

  2. Allogeneic transplantation of programmable cells of monocytic origin (PCMO) improves angiogenesis and tissue recovery in critical limb ischemia (CLI): a translational approach.

    Science.gov (United States)

    Berndt, Rouven; Hummitzsch, Lars; Heß, Katharina; Albrecht, Martin; Zitta, Karina; Rusch, Rene; Sarras, Beke; Bayer, Andreas; Cremer, Jochen; Faendrich, Fred; Groß, Justus

    2018-04-27

    Employing growth factor-induced partial reprogramming in vitro, peripheral human blood monocytes can acquire a state of plasticity along with expression of various markers of pluripotency. These so-called programmable cells of monocytic origin (PCMO) hold great promise in regenerative therapies. The aim of this translational study was to explore and exploit the functional properties of PCMO for allogeneic cell transplantation therapy in critical limb ischemia (CLI). Using our previously described differentiation protocol, murine and human monocytes were differentiated into PCMO. We examined paracrine secretion of pro-angiogenic and tissue recovery-associated proteins under hypoxia and induction of angiogenesis by PCMO in vitro. Allogeneic cell transplantation of PCMO was performed in a hind limb ischemia mouse model in comparison to cell transplantation of native monocytes and a placebo group. Moreover, we analyzed retrospectively four healing attempts with PCMO in patients with peripheral artery disease (PAD; Rutherford classification, stage 5 and 6). Statistical analysis was performed by using one-way ANOVA, Tukey's test or the Student's t test, p < 0.05. Cell culture experiments revealed good resilience of PCMO under hypoxia, enhanced paracrine release of pro-angiogenic and tissue recovery-associated proteins and induction of angiogenesis in vitro by PCMO. Animal experiments demonstrated significantly enhanced SO 2 saturation, blood flow, neoangiogenesis and tissue recovery after treatment with PCMO compared to treatment with native monocytes and placebo. Finally, first therapeutic application of PCMO in humans demonstrated increased vascular collaterals and improved wound healing in patients with chronic CLI without exaggerated immune response, malignant processes or extended infection after 12 months. In all patients minor and/or major amputations of the lower extremity could be avoided. In summary, PCMO improve angiogenesis and tissue recovery in chronic

  3. Safety profile and long-term engraftment of human CD31+ blood progenitors in bone tissue engineering.

    Science.gov (United States)

    Zigdon-Giladi, Hadar; Elimelech, Rina; Michaeli-Geller, Gal; Rudich, Utai; Machtei, Eli E

    2017-07-01

    Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. hEPCs were isolated from peripheral blood, cultured and characterized. β tricalcium phosphate scaffold (βTCP, control) or 10 6 hEPCs loaded onto βTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  4. Long-term persistence of human donor alveolar macrophages in lung transplant recipients

    DEFF Research Database (Denmark)

    Eguíluz-Gracia, Ibon; Schultz, Hans Henrik Lawaetz; Sikkeland, Liv I. B.

    2016-01-01

    and life span of human AMFs is scarce. METHODS: To follow the origin and longevity of AMFs in patients with lung transplantation for more than 100 weeks, we obtained transbronchial biopsies from 10 gender-mismatched patients with lung transplantation. These were subjected to combined in situ hybridisation...... transplantation we found that recipient monocytes seeded the alveoli early after transplantation, and showed subsequent phenotypical changes consistent with differentiation into proliferating mature AMFs. This resulted in a stable mixed chimerism between donor and recipient AMFs throughout the 2-year period...

  5. Donor transplant programme

    International Nuclear Information System (INIS)

    Abu Bakar Sulaiman

    1999-01-01

    The transplantation of organs and tissues from one human to another human has become an essential and well established form of therapy for many types of organ and tissue failure. In Malaysia, kidney, cornea and bone marrow transplantation are well established. Recently, liver, bone and heart transplanation have been performed. Unfortunately, because of the lack of cadaveric organ donation, only a limited number of solid organ transplantation have been performed. The cadaveric organ donor rate in Malaysia is low at less than one per million population. The first tissue transplanted in Malaysia was the cornea which was performed in the early 1970s. At that time and even now the majority of corneas came from Sri Lanka. The first kidney transplant was performed in 1975 from a live related donor. The majority of the 629 kidney transplants done at Hospital Kuala Lumpur to date have been from live related donors. Only 35 were from cadaver donors. Similarly, the liver transplantation programme which started in 1995 are from live related donors. A more concerted effort has been made recently to increase the awareness of the public and the health professionals on organ and tissue donation. This national effort to promote organ and tissue donation seems to have gathered momentum in 1997 with the first heart transplant successfully performed at the National Heart Institute. The rate of cadaveric donors has also increased from a previous average of I to 2 per year to 6 per year in the last one year. These developments are most encouraging and may signal the coming of age of our transplantati on programme. The Ministry of Health in conjunction with various institutions, organizations and professional groups, have taken a number of proactive measures to facilitate the development of the cadaveric organ donation programme. Efforts to increase public awareness and to overcome the negative cultural attitude towards organ donation have been intensified. Equally important are efforts

  6. MRI-tracking of transplanted human ASC in a SCID mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Siegmund, Birte J.; Kasten, Annika [Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center (Germany); Kühn, Jens-Peter [Institute of Diagnostic Radiology and Neuroradiology, Greifswald University Medical Center (Germany); Winter, Karsten [Institute of Anatomy, Faculty of Medicine, University of Leipzig (Germany); Grüttner, Cordula [Micromod Partikeltechnologie GmbH, Rostock (Germany); Frerich, Bernhard, E-mail: bernhard.frerich@med.uni-rostock.de [Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center (Germany)

    2017-04-01

    Background: Regarding strategies improving the efficacy of stem cell transplantation in adipose tissue engineering, cell tracking might be useful. Here we report the in vivo tracking of adipose tissue derived stem cells (ASC) by means of nanoparticle labeling and magnetic resonance imaging (MRI). Here we report the in vivo tracking of adipose tissue derived stromal cells (ASC) by means of nanoparticle labeling and magnetic resonance imaging (MRI). Materials and methods: Human ASC were amplified and labeled with two types of magnetic nanoparticles (MNP), BNF starch and nanomag®-D-spio. Adipose tissue constructs were fabricated by seeding collagen scaffolds with labeled and unlabeled ASCs. Constructs were implanted subcutaneously in the back of severe combined immunodeficient (SCID) mice (n =69, group 1: control with cells w/o label, group 2: BNF starch labeled cells, group 3: nanomag®-D-spio labeled cells). MRI scans were performed at 24 hours, four, twelve and 28 days and four months in a 7.1 T animal device. Explanted constructs were analyzed histomorphometrically. Results: MRI scans showed high contrast of the labeled cells in t2-tse-sequence compared to unlabeled controls. Loss of volume of the implants was observed over time due to partial loss for transplanted cells without significant difference (level of significance p<0.017). Compared to histomorphometry, there was found a positiv correlations in measurement of implant size with a significant at day four (correlation coefficient =0.643; p=0.024) and day twelve (correlation coefficient =0.687; p=0.010). Additional Prussian blue stain showed iron in all implants. Significant differences between the three groups (significance level p<0.017) were found after twelve days between control group and group 3 (p=0.008) and after 28 days between control group and group 2 and 3 (p=0.011). Conclusion: Both MNPs might be suitable for tracking of ASC in vivo and show long term stability over 4 months. - Highlights:

  7. Fractionation parameters for human tissues and tumors

    International Nuclear Information System (INIS)

    Thames, H.D.; Turesson, I.; Bogaert, W. van den

    1989-01-01

    Time-dose factors such as fractionation sensitivity (α/β) can sometimes be estimated from clinical data, when there is a wide variation in dose, fraction size, treatment time, etc. This report summarizes estimates of fractionation parameters derived from clinical results. Consistent with the animal data, α/β is higher for acutely responding than for late-responding normal tissues. While many human tumors seem to be characterized by high α/β values, there are exceptions (e.g. melanomas). Repair kinetics may be slower in human than in rodent skin and mucosa, but there are no hard and fast estimates of the repair halftime. Regeneration in head and neck tumors is equivalent to a daily dose of 1 Gy or less, while in the mucosa it is equivalent to approximately 1.8 Gy/day. (author)

  8. Vitrification and xenografting of human ovarian tissue.

    Science.gov (United States)

    Amorim, Christiani Andrade; Dolmans, Marie-Madeleine; David, Anu; Jaeger, Jonathan; Vanacker, Julie; Camboni, Alessandra; Donnez, Jacques; Van Langendonckt, Anne

    2012-11-01

    To assess the efficiency of two vitrification protocols to cryopreserve human preantral follicles with the use of a xenografting model. Pilot study. Gynecology research unit in a university hospital. Ovarian biopsies were obtained from seven women aged 30-41 years. Ovarian tissue fragments were subjected to one of three cryopreservation protocols (slow freezing, vitrification protocol 1, and vitrification protocol 2) and xenografted for 1 week to nude mice. The number of morphologically normal follicles after cryopreservation and grafting and fibrotic surface area were determined by histologic analysis. Apoptosis was assessed by the TUNEL method. Morphometric analysis of TUNEL-positive surface area also was performed. Follicle proliferation was evaluated by immunohistochemistry. After xenografting, a difference was observed between the cryopreservation procedures applied. According to TUNEL analysis, both vitrification protocols showed better preservation of preantral follicles than the conventional freezing method. Moreover, histologic evaluation showed a significantly higher proportion of primordial follicles in vitrified (protocol 2)-warmed ovarian tissue than in frozen-thawed tissue. The proportion of growing follicles and fibrotic surface area was similar in all groups. Vitrification procedures appeared to preserve not only the morphology and survival of preantral follicles after 1 week of xenografting, but also their ability to resume folliculogenesis. In addition, vitrification protocol 2 had a positive impact on the quiescent state of primordial follicles after xenografting. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Isolation of primary human hepatocytes from normal and diseased liver tissue: a one hundred liver experience.

    Directory of Open Access Journals (Sweden)

    Ricky H Bhogal

    2011-03-01

    Full Text Available Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples.

  10. Function of skeletal muscle tissue formed after myoblast transplantation into irradiated mouse muscles.

    Science.gov (United States)

    Wernig, A; Zweyer, M; Irintchev, A

    2000-01-15

    1. Pretreatment of muscles with ionising radiation enhances tissue formation by transplanted myoblasts but little is known about the effects on muscle function. We implanted myoblasts from an expanded, male-donor-derived, culture (i28) into X-ray irradiated (16 Gy) or irradiated and damaged soleus muscles of female syngeneic mice (Balb/c). Three to 6 months later the isometric contractile properties of the muscles were studied in vitro, and donor nuclei were visualised in muscle sections with a Y chromosome-specific DNA probe. 2. Irradiated sham-injected muscles had smaller masses than untreated solei and produced less twitch and tetanic force (all by about 18 %). Injection of 106 myoblasts abolished these deficiencies and innervation appeared normal. 3. Cryodamage of irradiated solei produced muscle remnants with few (1-50) or no fibres. Additional myoblast implantation led to formation of large muscles (25 % above normal) containing numerous small-diameter fibres. Upon direct electrical stimulation, these muscles produced considerable twitch (53 % of normal) and tetanic forces (35 % of normal) but innervation was insufficient as indicated by weak nerve-evoked contractions and elevated ACh sensitivity. 4. In control experiments on irradiated muscles, reinnervation was found to be less complete after botulinum toxin paralysis than after nerve crush indicating that proliferative arrest of irradiated Schwann cells may account for the observed innervation deficits. 5. Irradiation appears to be an effective pretreatment for improving myoblast transplantation. The injected cells can even produce organised contractile tissue replacing whole muscle. However, impaired nerve regeneration limits the functional performance of the new muscle.

  11. Radioimmunoassay of renin in human renal tissues

    International Nuclear Information System (INIS)

    Wowra, B.

    1981-01-01

    A method has been developed to quantitatively determine renin in human kidney tissue. The angiotensin I split off angiotensinogs by renin was radioimmunologically determined. The renin-renin substrate reaction rate followed a saturation kinetics, as it increased the larger the substrate content in the incubation medium until it acquired a maximum value; the reaction rate decreased with substrate concentrations over 40 mg/ml incubation medium. The discontinuance of the renin reaction after incubation by adding acid, boiling and neutralizing again, gave highest renin values. The RIA scattering was 8.3% for double determination of the same sample, for the determination in different RIA additions 7.0%. The detection limit was 20 pg angiotensin I. A direct comparison of radioimmunoassay and bioassay exhibited a very significant agreement of both methods, where the radioimmunologically measured renin values were on average four times larger than those obtained using biological technique. The definition of the so-called normal values for absolute and specific renin concentration in human kidney tissue enabled one to assess the renin values in various syndromes. (orig./MG) [de

  12. Transplanted human pancreatic islets after long-term insulin independence

    DEFF Research Database (Denmark)

    Muller, Y D; Gupta, Shashank; Morel, P

    2013-01-01

    Long-term insulin independence after islets of Langerhans transplantation is rarely achieved. The aims of this study were to identify the histological and immunological features of islets transplanted in a type 1 diabetic patient who died of a cerebral hemorrhage after >13 years insulin independe...

  13. 86 successful births and 9 ongoing pregnancies worldwide in women transplanted with frozen-thawed ovarian tissue

    DEFF Research Database (Denmark)

    Jensen, Annette Klüver; Macklon, Kirsten Tryde; Fedder, Jens

    2017-01-01

    Purpose: This study aims to make an account of the children born following transplantation of frozen-thawed ovarian tissue worldwide with specific focus on the perinatal outcome of the children. Furthermore, perinatal outcome of seven deliveries (nine children) from Denmark is reported. Methods...

  14. Safety considerations for transplanting cryopreserved ovarian tissue to restore fertility in female patients who have recovered from Ewing's sarcoma

    DEFF Research Database (Denmark)

    Sørensen, Stine D; Greve, Tine; Wielenga, Vera Timmermans

    2014-01-01

    ovarian tissue, potentially causing recrudescence of the original cancer after transplantation. The risk of EWS metastasizing to the ovary is probably low but has not been studied in great detail. This review describes the available evidence on the risk of malignant cell contamination in the ovaries...

  15. Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

    Directory of Open Access Journals (Sweden)

    Cindy J.M. Loomans

    2018-03-01

    Full Text Available Summary: Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi, express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC, and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue. Endocrine lineage markers were detected upon in vitro differentiation. Engrafted organoids differentiated toward insulin-positive (INS+ cells, and circulating human C-peptide was detected upon glucose challenge 1 month after transplantation. Engrafted ALDHhi cells formed INS+ cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential. : In the context of β cell replacement therapy for diabetes, de Koning and colleagues describe a 3D culture platform that supports ex vivo expansion of human pancreatic tissue as organoids. These organoids harbor a subpopulation of ALDHhi cells that display proliferative capacity and can differentiate to an endocrine fate. Keywords: pancreas, organoid, human, ALDH, endocrine differentiation, beta cells, insulin, progenitor, fetal, diabetes

  16. Storage effect on viability and biofunctionality of human adipose tissue-derived stromal cells.

    Science.gov (United States)

    Falah, Mizied; Rayan, Anwar; Srouji, Samer

    2015-09-01

    In our recent studies, the transplantation of human adipose tissue-derived stromal cells (ASCs) has shown promise for treatment of diseases related to bone and joint disorders. For the current clinical applications, ASCs were formulated and suspended in PlasmaLyte A supplemented with heparin, glucose and human serum albumin, balanced to pH 7.4 with sodium bicarbonate. This cell solution constitutes 20% of the overall transplanted mixture and is supplemented with hyaluronic acid (60%) and OraGraft particles (20%). We intended to investigate the effect of this transplantation mixture on the viability and biofunctionality of ASCs in bone formation. Freshly harvested cells were resuspended and incubated in the indicated mixture for up to 48 h at 4°C. Cell viability was assessed using trypan blue and AlamarBlue, and cell functionality was determined by quantifying their adhesion rate in vitro and bone formation in an ectopic mouse model. More than 80% of the ASCs stored in the transplantation mixture were viable for up to 24 h. Cell viability beyond 24 h in storage decreased to approximately 50%. In addition, an equal degree of bone formation was observed between the cells transplanted following incubation in transplantation mixture for up to 24 h and zero-time non-incubated cells (control). The viability and functionality of ASCs stored in the presented formulation will make such cell therapy accessible to larger and more remote populations. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  17. Registry of Hospital das Clínicas of the University of São Paulo Medical School: first official solid organ and tissue transplantation report - 2008

    Directory of Open Access Journals (Sweden)

    Estela Azeka

    2009-02-01

    Full Text Available OBJECTIVE: The aim of this study was to report a single center experience of organ and tissue transplantation INTRODUCTION: This is the first report of organ and tissue transplantation at the Hospital das Clínicas of the University of Sao Paulo Medical School. METHODS: We collected data from each type of organ transplantation from 2002 to 2007. The data collected were patient characteristics and actuarial survival Kaplan-Meier curves at 30 days, one year, and five years RESULTS: There were a total of 3,321 transplants at our institution and the 5-year survival curve ranged from 53% to 88%. CONCLUSION: This report shows that solid organ and tissue transplants are feasible within the institution and allow us to expect that the quality of transplantation will improve in the future.

  18. Assessment of human MAPCs for stem cell transplantation and cardiac regeneration after myocardial infarction in SCID mice.

    Science.gov (United States)

    Dimomeletis, Ilias; Deindl, Elisabeth; Zaruba, Marc; Groebner, Michael; Zahler, Stefan; Laslo, Saskia M; David, Robert; Kostin, Sawa; Deutsch, Markus A; Assmann, Gerd; Mueller-Hoecker, Josef; Feuring-Buske, Michaela; Franz, Wolfgang M

    2010-11-01

    Clinical studies suggest that transplantation of total bone marrow (BM) after myocardial infarction (MI) is feasible and potentially effective. However, focusing on a defined BM-derived stem cell type may enable a more specific and optimized treatment. Multilineage differentiation potential makes BM-derived multipotent adult progenitor cells (MAPCs) a promising stem cell pool for regenerative purposes. We analyzed the cardioregenerative potential of human MAPCs in a murine model of myocardial infarction. Human MAPCs were selected by negative depletion of CD45(+)/glycophorin(+) BM cells and plated on fibronectin-coated dishes. In vitro, stem cells were analyzed by reverse transcription polymerase chain reaction. In vivo, we transplanted human MAPCs (5 × 10(5)) by intramyocardial injection after MI in severe combined immunodeficient (SCID) beige mice. Six and 30 days after the surgical procedure, pressure-volume relationships were investigated in vivo. Heart tissues were analyzed immunohistochemically. Reverse transcription polymerase chain reaction experiments on early human MAPC passages evidenced an expression of Oct-4, a stem cell marker indicating pluripotency. In later passages, cardiac markers (Nkx2.5, GATA4, MLC-2v, MLC-2a, ANP, cTnT, cTnI,) and smooth muscle cell markers (SMA, SM22α) were expressed. Transplantation of human MAPCs into the ischemic border zone after MI resulted in an improved cardiac function at day 6 (ejection fraction, 26% vs 20%) and day 30 (ejection fraction, 30% vs 23%). Confirmation of human MAPC marker vimentin in immunohistochemistry demonstrated that human MAPC integrated in the peri-infarct region. The proliferation marker Ki67 was absent in immunohistochemistry and teratoma formation was not found, indicating no tumorous potential of transplanted human MAPCs in the tumor-sensitive SCID model. Transplantation of human MAPCs after MI ameliorates myocardial function, which may be explained by trophic effects of human MAPCs. Lack of

  19. Therapeutic effects of human multilineage-differentiating stress enduring (MUSE cell transplantation into infarct brain of mice.

    Directory of Open Access Journals (Sweden)

    Tomohiro Yamauchi

    Full Text Available Bone marrow stromal cells (BMSCs are heterogeneous and their therapeutic effect is pleiotropic. Multilineage-differentiating stress enduring (Muse cells are recently identified to comprise several percentages of BMSCs, being able to differentiate into triploblastic lineages including neuronal cells and act as tissue repair cells. This study was aimed to clarify how Muse and non-Muse cells in BMSCs contribute to functional recovery after ischemic stroke.Human BMSCs were separated into stage specific embryonic antigen-3-positive Muse cells and -negative non-Muse cells. Immunodeficient mice were subjected to permanent middle cerebral artery occlusion and received transplantation of vehicle, Muse, non-Muse or BMSCs (2.5×104 cells into the ipsilateral striatum 7 days later.Motor function recovery in BMSC and non-Muse groups became apparent at 21 days after transplantation, but reached the plateau thereafter. In Muse group, functional recovery was not observed for up to 28 days post-transplantation, but became apparent at 35 days post-transplantation. On immunohistochemistry, only Muse cells were integrated into peri-infarct cortex and differentiate into Tuj-1- and NeuN-expressing cells, while negligible number of BMSCs and non-Muse cells remained in the peri-infarct area at 42 days post-transplantation.These findings strongly suggest that Muse cells and non-Muse cells may contribute differently to tissue regeneration and functional recovery. Muse cells may be more responsible for replacement of the lost neurons through their integration into the peri-infarct cortex and spontaneous differentiation into neuronal marker-positive cells. Non-Muse cells do not remain in the host brain and may exhibit trophic effects rather than cell replacement.

  20. Transplantation of Xenopus laevis tissues to determine the ability of motor neurons to acquire a novel target.

    Directory of Open Access Journals (Sweden)

    Karen L Elliott

    Full Text Available The evolutionary origin of novelties is a central problem in biology. At a cellular level this requires, for example, molecularly resolving how brainstem motor neurons change their innervation target from muscle fibers (branchial motor neurons to neural crest-derived ganglia (visceral motor neurons or ear-derived hair cells (inner ear and lateral line efferent neurons. Transplantation of various tissues into the path of motor neuron axons could determine the ability of any motor neuron to innervate a novel target. Several tissues that receive direct, indirect, or no motor innervation were transplanted into the path of different motor neuron populations in Xenopus laevis embryos. Ears, somites, hearts, and lungs were transplanted to the orbit, replacing the eye. Jaw and eye muscle were transplanted to the trunk, replacing a somite. Applications of lipophilic dyes and immunohistochemistry to reveal motor neuron axon terminals were used. The ear, but not somite-derived muscle, heart, or liver, received motor neuron axons via the oculomotor or trochlear nerves. Somite-derived muscle tissue was innervated, likely by the hypoglossal nerve, when replacing the ear. In contrast to our previous report on ear innervation by spinal motor neurons, none of the tissues (eye or jaw muscle was innervated when transplanted to the trunk. Taken together, these results suggest that there is some plasticity inherent to motor innervation, but not every motor neuron can become an efferent to any target that normally receives motor input. The only tissue among our samples that can be innervated by all motor neurons tested is the ear. We suggest some possible, testable molecular suggestions for this apparent uniqueness.

  1. Simultaneous Transplantation of Fetal Ventral Mesencephalic Tissue and Encapsulated Genetically Modified Cells Releasing GDNF in a Hemi-Parkinsonian Rat Model of Parkinson’s Disease

    DEFF Research Database (Denmark)

    Perez-Bouza, Alberto; Di Santo, Stefano; Seiler, Stefanie

    2017-01-01

    Transplantation of fetal ventral mesencephalic (VM) neurons for Parkinson's disease (PD) is limited by poor survival and suboptimal integration of grafted tissue into the host brain. In a 6-OHDA rat model of PD we investigated the feasibility of simultaneous transplantation of rat fetal VM tissue...... between groups were observed for the number of surviving TH-ir neurons or graft volume. In conclusion, our findings demonstrate that simultaneous transplantation of fetal VM tissue and encapsulated GDNF-releasing cells is feasible and support the graft survival and function. Pre-treatment of donor tissue...

  2. The case for applying tissue engineering methodologies to instruct human organoid morphogenesis.

    Science.gov (United States)

    Marti-Figueroa, Carlos R; Ashton, Randolph S

    2017-05-01

    Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i.e. 100's of microns to millimeters), the organoids' morphology, cytoarchitecture, and cellular composition are non-biomimetic and variable. The current lack of control over in vitro organoid morphogenesis at the microscale induces aberrations at the macroscale, which impedes realization of the technology's potential to reproducibly form anatomically correct human tissue units that could serve as optimal human in vitro models and even transplants. Here, we review tissue engineering methodologies that could be used to develop powerful approaches for instructing multiscale, 3-D human organoid morphogenesis. Such technological mergers are critically needed to harness organoid morphogenesis as a tool for engineering functional human tissues with biomimetic anatomy and physiology. Human PSC-derived 3-D organoids are revolutionizing the biomedical sciences. They enable the study of development and disease within patient-specific genetic backgrounds and unprecedented biomimetic tissue microenvironments. However, their uncontrolled, spontaneous morphogenesis at the microscale yields inconsistences in macroscale organoid morphology, cytoarchitecture, and cellular composition that limits their standardization and application. Integration of tissue engineering methods with organoid derivation protocols could allow us to harness their potential by instructing standardized in vitro morphogenesis

  3. Enhancing human islet transplantation by localized release of trophic factors from PLG scaffolds.

    Science.gov (United States)

    Hlavaty, K A; Gibly, R F; Zhang, X; Rives, C B; Graham, J G; Lowe, W L; Luo, X; Shea, L D

    2014-07-01

    Islet transplantation represents a potential cure for type 1 diabetes, yet the clinical approach of intrahepatic delivery is limited by the microenvironment. Microporous scaffolds enable extrahepatic transplantation, and the microenvironment can be designed to enhance islet engraftment and function. We investigated localized trophic factor delivery in a xenogeneic human islet to mouse model of islet transplantation. Double emulsion microspheres containing exendin-4 (Ex4) or insulin-like growth factor-1 (IGF-1) were incorporated into a layered scaffold design consisting of porous outer layers for islet transplantation and a center layer for sustained factor release. Protein encapsulation and release were dependent on both the polymer concentration and the identity of the protein. Proteins retained bioactivity upon release from scaffolds in vitro. A minimal human islet mass transplanted on Ex4-releasing scaffolds demonstrated significant improvement and prolongation of graft function relative to blank scaffolds carrying no protein, and the release profile significantly impacted the duration over which the graft functioned. Ex4-releasing scaffolds enabled better glycemic control in animals subjected to an intraperitoneal glucose tolerance test. Scaffolds releasing IGF-1 lowered blood glucose levels, yet the reduction was insufficient to achieve euglycemia. Ex4-delivering scaffolds provide an extrahepatic transplantation site for modulating the islet microenvironment to enhance islet function posttransplant. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. Coefficient of Friction of Human Corneal Tissue.

    Science.gov (United States)

    Wilson, Tawnya; Aeschlimann, Rudolf; Tosatti, Samuele; Toubouti, Youssef; Kakkassery, Joseph; Osborn Lorenz, Katherine

    2015-09-01

    A novel property evaluation methodology was used to determine the elusive value for the human corneal coefficient of friction (CoF). Using a microtribometer on 28 fresh human donor corneas with intact epithelia, the CoF was determined in 4 test solutions (≥5 corneas/solution): tear-mimicking solution (TMS) in borate-buffered saline (TMS-PS), TMS in phosphate-buffered saline (TMS-PBS), TMS with HEPES-buffered saline (TMS-HEPES), and tear-like fluid in PBS (TLF-PBS). Mean (SD) CoF values ranged from 0.006 to 0.015 and were 0.013 (0.010) in TMS-PS, 0.006 (0.003) in TMS-PBS, 0.014 (0.005) in TMS-HEPES, and 0.015 (0.009) in TLF-PBS. Statistically significant differences were shown for TMS-PBS versus TLF (P = 0.0424) and TMS-PBS versus TMS-HEPES (P = 0.0179), but not for TMS-PBS versus TMS-PS (P = 0.2389). Successful measurement of the fresh human corneal tissue CoF was demonstrated, with values differing in the evaluated buffer solutions, within this limited sample size.

  5. Sustainability of Routine Notification and Request legislation on eye bank tissue supply and corneal transplantation wait times in Canada.

    Science.gov (United States)

    Lee, Kenneth; Boimer, Corey; Hershenfeld, Samantha; Sharpen, Linda; Slomovic, Allan R

    2011-10-01

    To assess whether provinces with Routine Notification and Request (RNR) legislation have sustained increases in corneal tissue supply and decreases in wait times for corneal transplantation surgery. Cross-sectional survey of Canadian corneal transplant (CT) surgeons and eye banks. Canadian CT surgeons and representatives from the 10 Canadian eye banks. Voluntary and anonymous surveys were distributed between July and October 2009. Eligible CT surgeons were defined as ophthalmologists who practice in Canada; currently perform Penetrating keratoplasty (PKP), Deep anterior lamellar keratoplasty (DALK), Deep lamellar endothelial keratoplasty (DLEK), Descemet stripping endothelial keratoplasty (DSEK), or Descemet membrane endothelial keratoplasty (DMEK); and have obtained tissues from a Canadian eye bank. From 2006 to 2009, for provinces with RNR legislation and where data are available, mean wait times from date of diagnosis to date of CT surgery have increased: in Ontario, from 31 ± 34 weeks to 36 ± 27 weeks; in British Columbia, from 39 ± 20 weeks to 42 ± 35 weeks; in Manitoba, from 32 ± 23 weeks to 49 ± 36 weeks. In addition, the amount of corneal tissue in RNR provinces suitable for transplant, with the exception of British Columbia, has declined between 2006 and 2008: in Ontario, 1186 tissues to 999 tissues (16% decline); in Manitoba, 92 tissues to 83 tissues (10% decline); in New Brunswick, 129 tissues to 98 tissues (24% decline). Although initially effective, RNR legislation has not sustained an increase in corneal tissue availability nor has it shortened wait times in most provinces. Incorporation of community hospitals into the RNR catchment, improved enforcement, and continued education of hospital staff regarding the RNR process may be effective in making this legislation more sustainable in the long term. Copyright © 2011 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  6. Detection of acute renal allograft rejection by analysis of renal tissue proteomics in rat models of renal transplantation

    Directory of Open Access Journals (Sweden)

    Dai Yong

    2008-01-01

    Full Text Available At present, the diagnosis of renal allograft rejection requires a renal biopsy. Clinical management of renal transplant patients would be improved if rapid, noninvasive and reliable biomarkers of rejection were available. This study is designed to determine whether such protein biomarkers can be found in renal-graft tissue proteomic approach. Orthotopic kidney transplantations were performed using Fisher (F344 or Lewis rats as donors and Lewis rats as recipients. Hence, there were two groups of renal transplant models: one is allograft (from F344 to Lewis rats; another is syngrafts (from Lewis to Lewis rats serving as control. Renal tissues were collected 3, 7 and 14 days after transplantation. As many as 18 samples were analyzed by 2-D Electrophoresis and mass spectrometry (MALDI-TOF-TOF-MS. Eleven differentially expressed proteins were identified between groups. In conclusion, proteomic technology can detect renal tissue proteins associated with acute renal allograft rejection. Identification of these proteins as diagnostic markers for rejection in patients′ urine or sera may be useful and non-invasive, and these proteins might serve as novel therapeutic targets that also help to improve the understanding of mechanism of renal rejection.

  7. Expanding the Tissue Toolbox : Deriving Colon Tissue from Human Pluripotent Stem Cells

    NARCIS (Netherlands)

    Bruens, Lotte; Snippert, Hugo J.G.

    2017-01-01

    Organoid technology holds great potential for disease modeling and regenerative medicine. In this issue of Cell Stem Cell, Múnera et al. (2017) establish the generation of pluripotent stem cell-derived colon organoids that upon transplantation in mice, resembling human colon to a large extent,

  8. Polarized spectral features of human breast tissues through wavelet ...

    Indian Academy of Sciences (India)

    Abstract. Fluorescence characteristics of human breast tissues are investigated through wavelet transform and principal component analysis (PCA). Wavelet transform of polar- ized fluorescence spectra of human breast tissues is found to localize spectral features that can reliably differentiate different tissue types.

  9. Three-dimensional bioprinting of stem-cell derived tissues for human regenerative medicine.

    Science.gov (United States)

    Skeldon, Gregor; Lucendo-Villarin, Baltasar; Shu, Wenmiao

    2018-07-05

    Stem cell technology in regenerative medicine has the potential to provide an unlimited supply of cells for drug testing, medical transplantation and academic research. In order to engineer a realistic tissue model using stem cells as an alternative to human tissue, it is essential to create artificial stem cell microenvironment or niches. Three-dimensional (3D) bioprinting is a promising tissue engineering field that offers new opportunities to precisely place stem cells within their niches layer-by-layer. This review covers bioprinting technologies, the current development of 'bio-inks' and how bioprinting has already been applied to stem-cell culture, as well as their applications for human regenerative medicine. The key considerations for bioink properties such as stiffness, stability and biodegradation, biocompatibility and printability are highlighted. Bioprinting of both adult and pluriopotent stem cells for various types of artificial tissues from liver to brain has been reviewed. 3D bioprinting of stem-cell derived tissues for human regenerative medicine is an exciting emerging area that represents opportunities for new research, industries and products as well as future challenges in clinical translation.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. © 2018 The Author(s).

  10. 2010 Great Lakes Human Health Fish Tissue Study Fish Tissue Data Dictionary

    Science.gov (United States)

    The Office of Science and Technology (OST) is providing the fish tissue results from the 2010 Great Lakes Human Health Fish Tissue Study (GLHHFTS). This document includes the “data dictionary” for Mercury, PFC, PBDE and PCBs.

  11. Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions.

    Science.gov (United States)

    Gan, Lu; Duan, Hua; Xu, Qian; Tang, Yi-Qun; Li, Jin-Jiao; Sun, Fu-Qing; Wang, Sha

    2017-05-01

    Intrauterine adhesion (IUA) is a common uterine cavity disease characterized by the unsatisfactory regeneration of damaged endometria. Recently, stem cell transplantation has been proposed to promote the recovery process. Here we investigated whether human amniotic mesenchymal stromal cells (hAMSCs), a valuable resource for transplantation therapy, could improve endometrial regeneration in rodent IUA models. Forty female Sprague-Dawley rats were randomly assigned to five groups: normal, sham-operated, mechanical injury, hAMSC transplantation, and negative control group. One week after intervention and transplantation, histological analyses were performed, and immunofluorescent and immunohistochemical expression of cell-specific markers and messenger RNA expression of cytokines were measured. Thicker endometria, increased gland numbers and fewer fibrotic areas were found in the hAMSC transplantation group compared with the mechanical injury group. Engraftment of hAMSCs was detected by the presence of anti-human nuclear antigen-positive cells in the endometrial glands of the transplantation uteri. Transplantation of hAMSCs significantly decreased messenger RNA levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and increased those of anti-inflammatory cytokines (basic fibroblast growth factor, and interleukin-6) compared with the injured uterine horns. Immunohistochemical expression of endometrial epithelial cells was revealed in specimens after hAMSC transplantation, whereas it was absent in the mechanically injured uteri. hAMSC transplantation promotes endometrial regeneration after injury in IUA rat models, possibly due to immunomodulatory properties. These cells provide a more easily accessible source of stem cells for future research into the impact of cell transplantation on damaged endometria. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  12. Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by 19F- and diffusion-MRI

    Science.gov (United States)

    Bible, Ellen; Dell’Acqua, Flavio; Solanky, Bhavana; Balducci, Anthony; Crapo, Peter; Badylak, Stephen F.; Ahrens, Eric T.; Modo, Michel

    2012-01-01

    Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metal-based 1H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a 19F-MRI contrast agent can adequately monitor the distribution of transplanted cells, whilst allowing an evaluation of the lesion cavity and the formation of new tissue on 1H-MRI scans. Twenty percent of cells labeled with the 19F-agent were of host origin, potentially reflecting the re-uptake of label from dead transplanted cells. Both T2- and diffusion-weighted MRI scans indicated that transplantation of hNSCs suspended in a gel form of a xenogeneic extracellular matrix (ECM) bioscaffold resulted in uniformly distributed cells throughout the lesion cavity. However, diffusion MRI indicated that the injected materials did not yet establish diffusion barriers (i.e. cellular network, fiber tracts) normally found within striatal tissue. The ECM bioscaffold therefore provides an important support to hNSCs for the creation of de novo tissue and multi-nuclei MRI represents an adept method for the visualization of some aspects of this process. However, significant developments of both the transplantation paradigm, as well as regenerative imaging, are required to successfully create new tissue in the lesion cavity and to monitor this process non-invasively. PMID:22244696

  13. Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by (19)F- and diffusion-MRI.

    Science.gov (United States)

    Bible, Ellen; Dell'Acqua, Flavio; Solanky, Bhavana; Balducci, Anthony; Crapo, Peter M; Badylak, Stephen F; Ahrens, Eric T; Modo, Michel

    2012-04-01

    Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metal-based (1)H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a (19)F-MRI contrast agent can adequately monitor the distribution of transplanted cells, whilst allowing an evaluation of the lesion cavity and the formation of new tissue on (1)H-MRI scans. Twenty percent of cells labeled with the (19)F agent were of host origin, potentially reflecting the re-uptake of label from dead transplanted cells. Both T(2)- and diffusion-weighted MRI scans indicated that transplantation of hNSCs suspended in a gel form of a xenogeneic extracellular matrix (ECM) bioscaffold resulted in uniformly distributed cells throughout the lesion cavity. However, diffusion MRI indicated that the injected materials did not yet establish diffusion barriers (i.e. cellular network, fiber tracts) normally found within striatal tissue. The ECM bioscaffold therefore provides an important support to hNSCs for the creation of de novo tissue and multi-nuclei MRI represents an adept method for the visualization of some aspects of this process. However, significant developments of both the transplantation paradigm, as well as regenerative imaging, are required to successfully create new tissue in the lesion cavity and to monitor this process non-invasively. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Plastic compressed collagen as a novel carrier for expanded human corneal endothelial cells for transplantation.

    Directory of Open Access Journals (Sweden)

    Hannah J Levis

    Full Text Available Current treatments for reversible blindness caused by corneal endothelial cell failure involve replacing the failed endothelium with donor tissue using a one donor-one recipient strategy. Due to the increasing pressure of a worldwide donor cornea shortage there has been considerable interest in developing alternative strategies to treat endothelial disorders using expanded cell replacement therapy. Protocols have been developed which allow successful expansion of endothelial cells in vitro but this approach requires a supporting material that would allow easy transfer of cells to the recipient. We describe the first use of plastic compressed collagen as a highly effective, novel carrier for human corneal endothelial cells. A human corneal endothelial cell line and primary human corneal endothelial cells retained their characteristic cobblestone morphology and expression of tight junction protein ZO-1 and pump protein Na+/K+ ATPase α1 after culture on collagen constructs for up to 14 days. Additionally, ultrastructural analysis suggested a well-integrated endothelial layer with tightly opposed cells and apical microvilli. Plastic compressed collagen is a superior biomaterial in terms of its speed and ease of production and its ability to be manipulated in a clinically relevant manner without breakage. This method provides expanded endothelial cells with a substrate that could be suitable for transplantation allowing one donor cornea to potentially treat multiple patients.

  15. Ethical tissue: a not-for-profit model for human tissue supply.

    Science.gov (United States)

    Adams, Kevin; Martin, Sandie

    2011-02-01

    Following legislative changes in 2004 and the establishment of the Human Tissue Authority, access to human tissues for biomedical research became a more onerous and tightly regulated process. Ethical Tissue was established to meet the growing demand for human tissues, using a process that provided ease of access by researchers whilst maintaining the highest ethical and regulatory standards. The establishment of a licensed research tissue bank entailed several key criteria covering ethical, legal, financial and logistical issues being met. A wide range of stakeholders, including the HTA, University of Bradford, flagged LREC, hospital trusts and clinical groups were also integral to the process.

  16. High-Yield Purification, Preservation, and Serial Transplantation of Human Satellite Cells

    Directory of Open Access Journals (Sweden)

    Steven M. Garcia

    2018-03-01

    Full Text Available Summary: Investigation of human muscle regeneration requires robust methods to purify and transplant muscle stem and progenitor cells that collectively constitute the human satellite cell (HuSC pool. Existing approaches have yet to make HuSCs widely accessible for researchers, and as a result human muscle stem cell research has advanced slowly. Here, we describe a robust and predictable HuSC purification process that is effective for each human skeletal muscle tested and the development of storage protocols and transplantation models in dystrophin-deficient and wild-type recipients. Enzymatic digestion, magnetic column depletion, and 6-marker flow-cytometric purification enable separation of 104 highly enriched HuSCs per gram of muscle. Cryostorage of HuSCs preserves viability, phenotype, and transplantation potential. Development of enhanced and species-specific transplantation protocols enabled serial HuSC xenotransplantation and recovery. These protocols and models provide an accessible system for basic and translational investigation and clinical development of HuSCs. : Garcia and colleagues report methods for efficient purification of satellite cells from human skeletal muscle. They use their approaches to demonstrate stem cell functions of endogenous satellite cells and to make human satellite cells accessible for sharing among researchers. Keywords: human satellite cell purification, serial transplantation, satellite cell cryopreservation

  17. Tissue-based map of the human proteome

    DEFF Research Database (Denmark)

    Uhlén, Mathias; Fagerberg, Linn; Hallström, Björn M.

    2015-01-01

    Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transc...

  18. Growth curves of three human malignant tumors transplanted to nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Nielsen, A; Visfeldt, J

    1980-01-01

    Experimental growth data for three human malignant tumors transplanted to nude mice of BALB/c origin are analyzed statistically in order to investigate whether they can be described according to the Gompertz function. The aim is to set up unequivocal standards for planned therapeutic experiments...... as a standard, e.g. in therapeutic experiments. The course of tumor growth is independent of the size of the transplant, and whether tumors are transplanted in the right or left or both flanks of the recipient mice. Furthermore, the growth does not vary in a systematic way with the number of passages in nude...

  19. Transplantation of Human Skin-Derived Mesenchymal Stromal Cells Improves Locomotor Recovery After Spinal Cord Injury in Rats.

    Science.gov (United States)

    Melo, Fernanda Rosene; Bressan, Raul Bardini; Forner, Stefânia; Martini, Alessandra Cadete; Rode, Michele; Delben, Priscilla Barros; Rae, Giles Alexander; Figueiredo, Claudia Pinto; Trentin, Andrea Gonçalves

    2017-07-01

    Spinal cord injury (SCI) is a devastating neurologic disorder with significant impacts on quality of life, life expectancy, and economic burden. Although there are no fully restorative treatments yet available, several animal and small-scale clinical studies have highlighted the therapeutic potential of cellular interventions for SCI. Mesenchymal stem cells (MSCs)-which are conventionally isolated from the bone marrow-recently emerged as promising candidates for treating SCI and have been shown to provide trophic support, ameliorate inflammatory responses, and reduce cell death following the mechanical trauma. Here we evaluated the human skin as an alternative source of adult MSCs suitable for autologous cell transplantation strategies for SCI. We showed that human skin-derived MSCs (hSD-MSCs) express a range of neural markers under standard culture conditions and are able to survive and respond to neurogenic stimulation in vitro. In addition, using histological analysis and behavioral assessment, we demonstrated as a proof-of-principle that hSD-MSC transplantation reduces the severity of tissue loss and facilitates locomotor recovery in a rat model of SCI. Altogether, the study provides further characterization of skin-derived MSC cultures and indicates that the human skin may represent an attractive source for cell-based therapies for SCI and other neurological disorders. Further investigation is needed to elucidate the mechanisms by which hSD-MSCs elicit tissue repair and/or locomotor recovery.

  20. Effects of three different types of antifreeze proteins on mouse ovarian tissue cryopreservation and transplantation.

    Directory of Open Access Journals (Sweden)

    Jaewang Lee

    Full Text Available Ovarian tissue (OT cryopreservation is effective in preserving fertility in cancer patients who have concerns about fertility loss due to cancer treatment. However, the damage incurred at different steps during the cryopreservation procedure may cause follicular depletion; hence, preventing chilling injury would help maintain ovarian function.This study was designed to investigate the beneficial effects of different antifreeze proteins (AFPs on mouse ovarian tissue cryopreservation and transplantation.Ovaries were obtained from 5-week-old B6D2F1 mice, and each ovary was cryopreserved using two-step vitrification and four-step warming procedures. In Experiment I, ovaries were randomly allocated into fresh, vitrification control, and nine experimental groups according to the AFP type (FfIBP, LeIBP, type III and concentration (0.1, 1, 10 mg/mL used. After vitrification and warming, 5,790 ovarian follicles were evaluated using histology and TUNEL assays, and immunofluorescence for τH2AX and Rad51 was used to detect DNA double-strand breaks (DSBs and repair (DDR, respectively. In Experiment II, 20 mice were randomly divided into two groups: one where the vitrification and warming media were supplemented with 10 mg/mL LeIBP, and the other where media alone were used (control. Ovaries were then autotransplanted under both kidney capsules 7 days after vitrification together with the addition of 10 mg/mL LeIBP in the vitrification-warming media. After transplantation, the ovarian follicles, the percentage of apoptotic follicles, the extent of the CD31-positive area, and the serum FSH levels of the transplanted groups were compared.In Experiment I, the percentage of total grade 1 follicles was significantly higher in the 10 mg/mL LeIBP group than in the vitrification control, while all AFP-treated groups had significantly improved grade 1 primordial follicle numbers compared with those of the vitrification control. The number of apoptotic (TUNEL

  1. Cadmium Concentration in Human Autopsy Tissues.

    Science.gov (United States)

    Lech, Teresa; Sadlik, Józefa K

    2017-10-01

    The concentration of cadmium in human tissues obtained on the basis of autopsies of non-poisoned Polish people (n = 150), aged from 1 to 80 years, examined between 1990 and 2010, is presented. The following values were found in wet digested samples by flame atomic absorption spectrometry (FAAS) (mean ± SD, median, and range, μg/g of wet weight): brain 0.020 ± 0.031, 0.084, 0-0.120 (n = 41); stomach 0.148 ± 0.195, 0.084, 0-1.25 (n = 89); small intestine 0.227 ± 0.231, 0.130, 0-0.830 (n = 39); liver 1.54 ± 1.55, 1.01, 0.015-9.65 (n = 99); kidney 16.0 ± 13.2, 14.0, 0.62-61.3 (n = 91); lung 0.304 ± 0.414, 0.130, 0-1.90 (n = 25); and heart 0.137 ± 0.107, 0.140, 0.017-0.250 (n = 4). Additionally, results (n = 13 people, aged from 2 to 83 years, 63 samples) obtained by inductively coupled plasma optical emission spectrometry (ICP OES) between 2010 and 2015 are given. The obtained data on Cd concentration in the human body can be used to estimate the amounts occurring in "healthy" people and those occurring in cases of chronic or acute poisonings with Cd compounds, which are examined for forensic purposes or to assess environmental exposure levels.

  2. Treated of type 1 diabetes mellitus in non-obese diabetic mice by transplantation of allogeneic bone marrow and pancreatic tissue

    International Nuclear Information System (INIS)

    Yasumizu, R.; Sugiura, K.; Iwai, H.

    1987-01-01

    Non-obese diabetic (NOD) mice provide a model for type 1 diabetes mellitus. We previously showed that allogeneic bone marrow transplantation (ABMT) can prevent and treat insulitis and overt diabetes in NOD mice. However, ABMT alone could not be used to treat overt diabetes in NOD mice whose islets had been completely destroyed. To provide insulin-producing cells, pancreatic tissue from newborn mice was grafted under the renal capsules in combination with ABMT. The aims of concomitant ABMT are as follows. (i) It induces immunological tolerance to the donor-type major histocompatibility complex determinants and permits the host to accept subsequent pancreatic allografts from the bone marrow donor. (ii) ABMT replaces abnormal stem cells with normal stem cells. After transplantation of bone marrow plus newborn pancreas, NOD mice showed reduction of the glycosuria and a normal response in the glucose-tolerance test. Immunohistological study revealed the presence of clustered insulin-containing beta cells in the grafted pancreatic transplants. ABMT may become a viable treatment of established type 1 diabetes mellitus in humans

  3. Transplantation of Bioprinted Tissues and Organs: Technical and Clinical Challenges and Future Perspectives.

    Science.gov (United States)

    Ravnic, Dino J; Leberfinger, Ashley N; Koduru, Srinivas V; Hospodiuk, Monika; Moncal, Kazim K; Datta, Pallab; Dey, Madhuri; Rizk, Elias; Ozbolat, Ibrahim T

    2017-07-01

    : Three-dimensional (3D) bioprinting is a revolutionary technology in building living tissues and organs with precise anatomic control and cellular composition. Despite the great progress in bioprinting research, there has yet to be any clinical translation due to current limitations in building human-scale constructs, which are vascularized and readily implantable. In this article, we review the current limitations and challenges in 3D bioprinting, including in situ techniques, which are one of several clinical translational models to facilitate the application of this technology from bench to bedside. A detailed discussion is made on the technical barriers in the fabrication of scalable constructs that are vascularized, autologous, functional, implantable, cost-effective, and ethically feasible. Clinical considerations for implantable bioprinted tissues are further expounded toward the correction of end-stage organ dysfunction and composite tissue deficits.

  4. Transcriptomics resources of human tissues and organs

    DEFF Research Database (Denmark)

    Uhlén, Mathias; Hallström, Björn M.; Lindskog, Cecilia

    2016-01-01

    a framework for defining the molecular constituents of the human body as well as for generating comprehensive lists of proteins expressed across tissues or in a tissue-restricted manner. Here, we review publicly available human transcriptome resources and discuss body-wide data from independent genome......Quantifying the differential expression of genes in various human organs, tissues, and cell types is vital to understand human physiology and disease. Recently, several large-scale transcriptomics studies have analyzed the expression of protein-coding genes across tissues. These datasets provide...

  5. Bone Density, Microarchitecture, and Tissue Quality Long-term After Kidney Transplant.

    Science.gov (United States)

    Pérez-Sáez, María José; Herrera, Sabina; Prieto-Alhambra, Daniel; Nogués, Xavier; Vera, María; Redondo-Pachón, Dolores; Mir, Marisa; Güerri, Roberto; Crespo, Marta; Díez-Pérez, Adolfo; Pascual, Julio

    2017-06-01

    Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry is used to assess bone health in kidney transplant recipients (KTR). Trabecular bone score and in vivo microindentation are novel techniques that directly measure trabecular microarchitecture and mechanical properties of bone at a tissue level and independently predict fracture risk. We tested the bone status of long-term KTR using all 3 techniques. Cross-sectional study including 40 KTR with more than 10 years of follow-up and 94 healthy nontransplanted subjects as controls. Bone mineral density was measured at lumbar spine and the hip. Trabecular bone score was measured by specific software on the dual-energy x-ray absorptiometry scans of lumbar spine in 39 KTR and 77 controls. Microindentation was performed at the anterior tibial face with a reference-point indenter device. Bone measurements were standardized as percentage of a reference value, expressed as bone material strength index (BMSi) units. Multivariable (age, sex, and body mass index-adjusted) linear regression models were fitted to study the association between KTR and BMD/BMSi/trabecular bone score. Bone mineral density was lower at lumbar spine (0.925 ± 0.15 vs 0.982 ± 0.14; P = 0.025), total hip (0.792 ± 0.14 vs 0.902 ± 0.13; P bone score was borderline lower (1.21 ± 0.14 vs 1.3 ± 0.15; adjusted P = 0.072) in KTR. Despite persistent decrease in BMD, trabecular microarchitecture and tissue quality remain normal in long-term KTR, suggesting important recovery of bone health.

  6. Detection of human leukocyte antigen compatibility and antibodies in liver transplantation in China

    Institute of Scientific and Technical Information of China (English)

    Xue-Qin Meng; Xuan Zhang; Jun Fan; Lin Zhou; Bing Hao; Xiao-Ming Chen; Wei-Hang Ma; Shu-Sen Zheng

    2009-01-01

    BACKGROUND: The exact roles of human leukocyte antigen (HLA) compatibility, HLA antibodies and underlying diseases in acute rejection of liver transplants are not clear. Moreover, cytomegalovirus (CMV) infection, one of the most common infections after transplantation, is related to HLA genotype and the incidence of acute rejection. METHODS: Since there are controversial reports, we analyzed the impact of HLA matching, HLA antibodies and underlying diseases in 38 liver transplant recipients in China, and assessed the association of CMV infection and HLA compatibility. RESULTS: The frequency of no HLA compatibility was high in patients without antigenemia (P=0.019). All 17 patients with HLA-A matching developed antigenemia (P0.05). In patients with acute rejection, no differences were found in the incidence of acute rejection in transplants for hepatitis B, tumors, or combined hepatitis B and tumors (P>0.05).CONCLUSIONS: There are fewer acute rejections in transplants with more HLA compatibilities. Speciifc investigations of underlying diseases and HLA typing may be necessary in liver transplantation. The mechanisms of CMV infection and HLA matching should be further studied. HLA before transplantation should be examined for the prevention of acute rejection and CMV infection.

  7. Survival of Free and Encapsulated Human and Rat Islet Xenografts Transplanted into the Mouse Bone Marrow

    Science.gov (United States)

    Meier, Raphael P. H.; Seebach, Jörg D.; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H.; Muller, Yannick D.

    2014-01-01

    Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation. PMID:24625569

  8. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

    Directory of Open Access Journals (Sweden)

    Raphael P H Meier

    Full Text Available Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow and 10 days (kidney capsule. Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

  9. Phenylalanine kinetics in human adipose tissue.

    OpenAIRE

    Coppack, S W; Persson, M; Miles, J M

    1996-01-01

    Very little is known about the regulation of protein metabolism in adipose tissue. In this study systemic, adipose tissue, and forearm phenylalanine kinetics were determined in healthy postabsorptive volunteers before and during a 2-h glucose infusion (7 mg.kg-1.min-1). [3H]Phenylalanine was infused and blood was sampled from a radial artery, a subcutaneous abdominal vein, and a deep forearm vein. Adipose tissue and forearm blood flow were measured with 133Xe and plethysmography, respectively...

  10. Detection of acute renal allograft rejection by analysis of Renal TissueProteomics in rat models of renal transplantation

    International Nuclear Information System (INIS)

    Dai, Y.; Lv, T.; Wang, K.; Li, D.; Huang, Y.; Liu, J.

    2008-01-01

    At present, the diagnosis of renal allograft rejection requires a renalbiopsy. Clinical management of renal transplant patients would be improved ifrapid, noninvasive and reliable biomarkers of rejection were available. Thisstudy is designed to determine whether such protein biomarkers can be foundin renal graft tissue proteomic approach. Orthotopic kidney transplantationswere performed using Fisher (F344) or Lewis rats as donors and Lewis rats asrecipients. Hence, there were two groups of renal transplant models: one isallograft (from F344 to Lewis rats); another is syngrafts (from Lewis toLewis rats) serving as control. Renal tissues were collected 3, 7 and 14 daysafter transplantation. As many 18 samples were analyzed by 2-DElectrophoresis and mass spectrometry (MALDI-TOF-TOF-MS). Elevendifferentially expressed proteins were identified between groups. Inconclusion, proteomic technology can detect renal tissue proteins associatedwith acute renal allograft rejection. Identification of these proteins asdiagnostic markers for rejection in patient's urine or sera may be useful andnon-invasive, and these proteins might serve as novel therapeutic targetsthat also help to improve the understanding of mechanisms of renal rejection.(author)

  11. Redifferentiation of insulin-secreting cells after in vitro expansion of adult human pancreatic islet tissue

    International Nuclear Information System (INIS)

    Lechner, Andreas; Nolan, Anna L.; Blacken, Robyn A.; Habener, Joel F.

    2005-01-01

    Cellular replacement therapy holds promise for the treatment of diabetes mellitus but donor tissue is severely limited. Therefore, we investigated whether insulin-secreting cells could be differentiated in vitro from a monolayer of cells expanded from human donor pancreatic islets. We describe a three-step culture protocol that allows for the efficient generation of insulin-producing cell clusters from in vitro expanded, hormone-negative cells. These clusters express insulin at levels of up to 34% that of average freshly isolated human islets and secrete C-peptide upon membrane depolarization. They also contain cells expressing the other major islet hormones (glucagon, somatostatin, and pancreatic polypeptide). The source of the newly differentiated endocrine cells could either be indigenous stem/progenitor cells or the proliferation-associated dedifferentiation and subsequent redifferentiation of mature endocrine cells. The in vitro generated cell clusters may be efficacious in providing islet-like tissue for transplantation into diabetic recipients

  12. Advanced biomaterial strategies to transplant preformed micro-tissue engineered neural networks into the brain

    Science.gov (United States)

    Harris, J. P.; Struzyna, L. A.; Murphy, P. L.; Adewole, D. O.; Kuo, E.; Cullen, D. K.

    2016-02-01

    Objective. Connectome disruption is a hallmark of many neurological diseases and trauma with no current strategies to restore lost long-distance axonal pathways in the brain. We are creating transplantable micro-tissue engineered neural networks (micro-TENNs), which are preformed constructs consisting of embedded neurons and long axonal tracts to integrate with the nervous system to physically reconstitute lost axonal pathways. Approach. We advanced micro-tissue engineering techniques to generate micro-TENNs consisting of discrete populations of mature primary cerebral cortical neurons spanned by long axonal fascicles encased in miniature hydrogel micro-columns. Further, we improved the biomaterial encasement scheme by adding a thin layer of low viscosity carboxymethylcellulose (CMC) to enable needle-less insertion and rapid softening for mechanical similarity with brain tissue. Main results. The engineered architecture of cortical micro-TENNs facilitated robust neuronal viability and axonal cytoarchitecture to at least 22 days in vitro. Micro-TENNs displayed discrete neuronal populations spanned by long axonal fasciculation throughout the core, thus mimicking the general systems-level anatomy of gray matter—white matter in the brain. Additionally, micro-columns with thin CMC-coating upon mild dehydration were able to withstand a force of 893 ± 457 mN before buckling, whereas a solid agarose cylinder of similar dimensions was predicted to withstand less than 150 μN of force. This thin CMC coating increased the stiffness by three orders of magnitude, enabling needle-less insertion into brain while significantly reducing the footprint of previous needle-based delivery methods to minimize insertion trauma. Significance. Our novel micro-TENNs are the first strategy designed for minimally invasive implantation to facilitate nervous system repair by simultaneously providing neuronal replacement and physical reconstruction of long-distance axon pathways in the brain

  13. The use of animal tissues alongside human tissue: Cultural and ethical considerations.

    Science.gov (United States)

    Kaw, Anu; Jones, D Gareth; Zhang, Ming

    2016-01-01

    Teaching and research facilities often use cadaveric material alongside animal tissues, although there appear to be differences in the way we handle, treat, and dispose of human cadaveric material compared to animal tissue. This study sought to analyze cultural and ethical considerations and provides policy recommendations on the use of animal tissues alongside human tissue. The status of human and animal remains and the respect because of human and animal tissues were compared and analyzed from ethical, legal, and cultural perspectives. The use of animal organs and tissues is carried out within the context of understanding human anatomy and function. Consequently, the interests of human donors are to be pre-eminent in any policies that are enunciated, so that if any donors find the presence of animal remains unacceptable, the latter should not be employed. The major differences appear to lie in differences in our perceptions of their respective intrinsic and instrumental values. Animals are considered to have lesser intrinsic value and greater instrumental value than humans. These differences stem from the role played by culture and ethical considerations, and are manifested in the resulting legal frameworks. In light of this discussion, six policy recommendations are proposed, encompassing the nature of consent, respect for animal tissues as well as human remains, and appropriate separation of both sets of tissues in preparation and display. © 2015 Wiley Periodicals, Inc.

  14. Transplanted Human Umbilical Cord Mesenchymal Stem Cells Facilitate Lesion Repair in B6.Fas Mice

    Directory of Open Access Journals (Sweden)

    Guang-ping Ruan

    2014-01-01

    Full Text Available Background. Systemic lupus erythematosus (SLE is a multisystem disease that is characterized by the appearance of serum autoantibodies. No effective treatment for SLE currently exists. Methods. We used human umbilical cord mesenchymal stem cell (H-UC-MSC transplantation to treat B6.Fas mice. Results. After four rounds of cell transplantation, we observed a statistically significant decrease in the levels of mouse anti-nuclear, anti-histone, and anti-double-stranded DNA antibodies in transplanted mice compared with controls. The percentage of CD4+CD25+Foxp3+ T cells in mouse peripheral blood significantly increased after H-UC-MSC transplantation. Conclusions. The results showed that H-UC-MSCs could repair lesions in B6.Fas mice such that all of the relevant disease indicators in B6.Fas mice were restored to the levels observed in normal C57BL/6 mice.

  15. Porcine endogenous retroviral nucleic acid in peripheral tissues is associated with migration of porcine cells post islet transplant.

    Science.gov (United States)

    Binette, Tanya M; Seeberger, Karen L; Lyon, James G; Rajotte, Ray V; Korbutt, Gregory S

    2004-07-01

    Porcine islets represent an alternative source of insulin-producing tissue, however, porcine endogenous retrovirus (PERV) remains a concern. In this study, SCID mice were transplanted with nonencapsulated (non-EC), microencapsulated (EC) or macroencapsulated (in a TheraCyte trade mark device) neonatal porcine islets (NPIs), and peripheral tissues were screened for presence of viral DNA and mRNA. To understand the role of an intact immune system in PERV incidence, mice with established NPI grafts were reconstituted with splenocytes. Peripheral tissues were screened for PERV and porcine DNA using PCR. Tissues with positive DNA were analyzed for PERV mRNA using RT-PCR. No significant difference was observed between non-EC and EC transplants regarding presence of PERV or porcine-specific DNA or mRNA. In reconstituted animals, little PERV or porcine DNA, and no PERV mRNA was detected. No PERV or porcine-specific DNA was observed in animals implanted with a TheraCyte trade mark device. In conclusion, an intact immune system significantly lowered the presence of PERV. Microencapsulation of islets did not alter PERV presence, however, macroencapsulation in the TheraCyte device did. Lower PERV incidence coincided with lower porcine DNA in peripheral tissues, linking the presence of PERV to migration of porcine cells.

  16. Incorporating placental tissue in cord blood banking for stem cell transplantation.

    Science.gov (United States)

    Teofili, Luciana; Silini, Antonietta R; Bianchi, Maria; Valentini, Caterina Giovanna; Parolini, Ornella

    2018-06-01

    Human term placenta is comprised of various tissues from which different cell populations can be obtained, including hematopoietic stem cells and mesenchymal stem/stromal cells (MSCs). Areas covered: This review will discuss the possibility to incorporate placental tissue cells in cord blood banking. It will discuss general features of human placenta, with a brief review of the immune cells at the fetal-maternal interface and the different cell populations isolated from placenta, with a particular focus on MSCs. It will address the question as to why placenta-derived MSCs should be banked with their hematopoietic counterparts. It will discuss clinical trials which are studying safety and efficacy of placenta tissue-derived MSCs in selected diseases, and preclinical studies which have proven their therapeutic properties in other diseases. It will discuss banking of umbilical cord blood and raise several issues for improvement, and the applications of cord blood cells in non-malignant disorders. Expert Commentary: Umbilical cord blood banking saves lives worldwide. The concomitant banking of non-hematopoietic cells from placenta, which could be applied therapeutically in the future, alone or in combination to their hematopoietic counterparts, could exploit current banking processes while laying the foundation for clinical trials exploring placenta-derived cell therapies in regenerative medicine.

  17. In vivo transplantation of neurosphere-like bodies derived from the human postnatal and adult enteric nervous system: a pilot study.

    Directory of Open Access Journals (Sweden)

    Susan Hetz

    Full Text Available Recent advances in the in vitro characterization of human adult enteric neural progenitor cells have opened new possibilities for cell-based therapies in gastrointestinal motility disorders. However, whether these cells are able to integrate within an in vivo gut environment is still unclear. In this study, we transplanted neural progenitor-containing neurosphere-like bodies (NLBs in a mouse model of hypoganglionosis and analyzed cellular integration of NLB-derived cell types and functional improvement. NLBs were propagated from postnatal and adult human gut tissues. Cells were characterized by immunohistochemistry, quantitative PCR and subtelomere fluorescence in situ hybridization (FISH. For in vivo evaluation, the plexus of murine colon was damaged by the application of cationic surfactant benzalkonium chloride which was followed by the transplantation of NLBs in a fibrin matrix. After 4 weeks, grafted human cells were visualized by combined in situ hybridization (Alu and immunohistochemistry (PGP9.5, GFAP, SMA. In addition, we determined nitric oxide synthase (NOS-positive neurons and measured hypertrophic effects in the ENS and musculature. Contractility of treated guts was assessed in organ bath after electrical field stimulation. NLBs could be reproducibly generated without any signs of chromosomal alterations using subtelomere FISH. NLB-derived cells integrated within the host tissue and showed expected differentiated phenotypes i.e. enteric neurons, glia and smooth muscle-like cells following in vivo transplantation. Our data suggest biological effects of the transplanted NLB cells on tissue contractility, although robust statistical results could not be obtained due to the small sample size. Further, it is unclear, which of the NLB cell types including neural progenitors have direct restoring effects or, alternatively may act via 'bystander' mechanisms in vivo. Our findings provide further evidence that NLB transplantation can be

  18. Route of delivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Wang FJ

    2015-12-01

    Full Text Available Mesenchymal stromal cells (MSCs have shown promise as treatment for graft-versus-host disease (GvHD following allogeneic bone marrow transplantation (alloBMT. Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs were injected via carotid artery (IA or tail vein (TV into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole–body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments.

  19. Effect of human leukocyte antigen-C and -DQ matching on pediatric heart transplant graft survival.

    Science.gov (United States)

    Butts, Ryan J; Savage, Andrew J; Nietert, Paul J; Kavarana, Minoo; Moussa, Omar; Burnette, Ali L; Atz, Andrew M

    2014-12-01

    A higher degree of human leukocyte antigen (HLA) matching at the A, B, and DR loci has been associated with improved long-term survival after pediatric heart transplantation in multiple International Society for Heart and Lung Transplantation registry reports. The aim of this study was to investigate the association of HLA matching at the C and DQ loci with pediatric graft survival. The United Network of Organ Sharing database was queried for isolated heart transplants that occurred from 1988 to 2012 with a recipient age of 17 or younger and at least 1 postoperative follow-up encounter. When HLA matching at the C or DQ loci were analyzed, only transplants with complete typing of donor and recipient at the respective loci were included. Transplants were divided into patients with at least 1 match at the C locus (C-match) vs no match (C-no), and at least 1 match at the DQ (DQ-match) locus vs no match (DQ-no). Primary outcome was graft loss. Univariate analysis was performed with the log-rank test. Cox regression analysis was performed with the following patient factors included in the model: recipient age, ischemic time; recipient on ventilator, extracorporeal membrane oxygenation, ventricular assist device, or inotropes at transplant; recipient serum bilirubin and creatinine closest to transplant, ratio of donor weight to recipient weight, underlying cardiac diagnosis, crossmatch results, transplant year, and HLA matching at the A, B, and DR loci. Complete typing at the C locus occurred in 2,429 of 4,731 transplants (51%), and complete typing at the DQ locus occurred in 3,498 of 4,731 transplants (74%). Patient factors were similar in C-match and C-no, except for year of transplant (median year, 2007 [interquartile range, 1997-2010] vs year 2005 [interquartile range, 1996-2009], respectively; p = 0.03) and the degree of HLA matching at the A, B, and DR loci (high level of HLA matching in 11.9% vs 3%, respectively; p HLA matching at the C locus or the DQ locus

  20. Human technology after cardiac epigenesis. Artificial heart versus cardiac transplantation.

    Science.gov (United States)

    Losman, J G

    1977-09-24

    Cardiovascular disease is the chief cause of death in technologically advanced countries and accounts for more than 50% of all deaths in the USA. For a patient with end-stage cardiac failure the only treatment presently available is organ replacement, either by transplantation or by the use of a mechanical heart. Transplantation has demonstrated its value: survival of more than 8 years and restoration of a normal quality of life to patients who were in end-stage cardiac decompensation. However, the prospect of routine clinical application of an artificial heart remains distant. The development of a totally implantable artificial heart still presents a series of challenging engineering problems with regard to strict constraints of size, weight, blood-material compatibility, adaptability of output to demand, efficiency and reliability of the power supply, and safety if nuclear fuel is used. The totally artificial heart is presently not an alternative to the cardiac allograft, but could provide short-term support for patients awaiting cardiac transplantation.

  1. Automated processing of human bone marrow grafts for transplantation.

    Science.gov (United States)

    Zingsem, J; Zeiler, T; Zimmermanm, R; Weisbach, V; Mitschulat, H; Schmid, H; Beyer, J; Siegert, W; Eckstein, R

    1993-01-01

    Prior to purging or cryopreservation, we concentrated 21 bone marrow (BM) harvests using a modification of the 'grancollect-protocol' of the Fresenius AS 104 cell separator with the P1-Y set. Within 40-70 min, the initial marrow volume of 1,265 ml (+/- 537 ml) was processed two to three times. A mean of 47% (+/- 21%) of the initial mononuclear cells was recovered in a mean volume of 128 ml (+36 ml). The recovery of clonogenic cells, measured by CFU-GM assays, was 68% (+/- 47%). Red blood cells in the BM concentrates were reduced to 7% (+/- 4%) of the initial number. The procedure was efficient and yielded a BM cell fraction suitable for purging, cryopreservation and transplantation. At this time, 10 of the 21 patients whose BM was processed using this technique have been transplanted. Seven of these 10 patients have been grafted using the BM alone. Three of the 10 patients showed reduced cell viability and colony growth in the thawed BM samples, and therefore obtained BM and peripheral blood-derived stem cells. All transplanted patients showed an evaluable engraftment, achieving 1,000 granulocytes per microliter of peripheral blood in a mean of 18 days.

  2. Isolation and characterization of human salivary gland cells for stem cell transplantation to reduce radiation-induced hyposalivation

    International Nuclear Information System (INIS)

    Feng Jielin; Zwaag, Marianne van der; Stokman, Monique A.; Os, Ronald van; Coppes, Robert P.

    2009-01-01

    Background: Recently, we showed that transplantation of 100-300 c-Kit + stem cells isolated from cultured salispheres ameliorates radiation-damage in murine salivary glands. The aim of this study is to optimize and translate these findings from mice to man. Methods: Mouse and human non-malignant parotid and submandibular salivary gland tissue was collected and enzymatically digested. The remaining cell suspension was cultured according to our salisphere culture method optimized for murine salispheres. Salisphere cells were tested using 3D matrix culturing for their in vitro stem cell characteristics such as the potential to differentiate into tissue specific cell types. Several potential mouse and human salivary gland stem cells were selected using FACS. Results: In human salivary gland, c-Kit + cells were only detected in excretory ducts as shown previously in mice. From both human parotid and submandibular gland cell suspensions salispheres could be grown, which when placed in 3D culture developed ductal structures and mucin-expressing acinar-like cells. Moreover, cells dispersed from primary salispheres were able to form secondary spheres in matrigel, a procedure that could be repeated for at least seven passages. Approximately 3000 c-Kit + cells could be isolated from primary human salispheres per biopsy. Conclusion: Human salivary glands contain a similar 'putative' stem cell population as rodents, expressing c-kit and capable of in vitro differentiation and self-renewal. In the future, these cells may have the potential to reduce radiotherapy-induced salivary gland dysfunction in patients.

  3. Transplante cardíaco humano: experiência inicial Human cardiac transplant: initial experience

    Directory of Open Access Journals (Sweden)

    Noedir A. G Stolf

    1986-12-01

    Full Text Available No Instituto do Coração, de março de 1985 a fevereiro de 1986,11 pacientes foram submetidos a transplante cardíaco ortotópico. Eram todos do sexo masculino, com idade variando de 39 a 54 anos; 6 com cardiopatia isquémica, 4 com cardiomiopatia dilatada e um com cardiomiopatia chagásica. Foi realizado estudo hemodinâmico através de catéter de Swan-Ganz, no pré-operatório, no pós-operatório, após estabilização na unidade de recuperação, e trinta ou mais dias após o transplante. Os dados mostram melhora progressiva em relação ao índice cardíaco, pressão em artéria pulmonar, pressão de capilar pulmonar, resistência vascular pulmonar e resistência vascular sistêmica. Três dos 11 pacientes apresentaram disfunção renal transitória no pós-operatório imediato e que regrediram até o 15º dia, enquanto que 2 pacientes apresentaram aumento moderado da creatinina plasmática. Apenas 3 pacientes não apresentaram qualquer episódio de rejeição; nos demais, esses episódios foram um diagnóstico histológico sem repercussões clínicas. Complicações infecciosas ocorreram em 9 pacientes e foram de fácil controle clínico. No pós-operatório tardio, a hipertensão esteve presente em 8 pacientes, sendo mais acentuada em 2 deles. Não houve óbitos, nesta série de pacientes; todos estão assintomáticos e os 6 primeiros estão trabalhando.At the Instituto do Cora��ão, University of São Paulo Medical School, 11 patients were submitted to heart transplantation from march 1985 up to february 1986. All were male, with ages of 39-59 years, 6 with coronary heart disease, 4 with dilated cardiomyopathy and 1 with Chagas cardiomyopathy. The patients were studied hemodynamically with a Swan-Ganz catheter pre-operatively, at the arrival in the intensive care unit, in the first postoperative day and 30 or more days after the transplant. The data showed that there was a progressive increase of cardiac index and decreases of

  4. Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue

    DEFF Research Database (Denmark)

    Donnez, Jacques; Dolmans, Marie-Madeleine; Pellicer, Antonio

    2013-01-01

    Aggressive chemotherapy/radiotherapy and bone marrow transplantation can cure >90% of girls and young women affected by disorders requiring such treatment. However, the ovaries are very sensitive to cytotoxic drugs, especially to alkylating agents. Several options are currently available...

  5. Human normal tissue reactions in radiotherapy

    International Nuclear Information System (INIS)

    Taniike, Keiko

    1990-01-01

    Acute and late normal tissue reactions in radiotherapy have not been considered to be major problems with conventional fractionation. But they may cause certain problems when newer schedules such as hyperfractionation or accelerated fractionation are used. In opposing parallel radiotherapy, the dose fractionation of skin or subcutaneous connective tissue are different between in one portal and two portals daily. So we examined acute skin erythema and late connective tissue fibrosis in the two groups (one and two portals) of the patients with uterus cancer. Acute skin erythema and late connective tissue fibrosis were slightly stronger in case of one portal daily. In relation to the anatomical site of skin, acute skin erythema was stronger at the buttocks than the lower abdomen, but late fibrosis was reverse to that. So the degree of acute skin erythema did not predict the degree of late connective tissue fibrosis. The number of Time Dose Fractionation Factor could roughly estimate the degree of erythema and fibrosis. Late fibrosis in 36 fractions increased with an increase of abdominal thickness, but acute erythema did not. (author)

  6. Dissociation between peripheral blood chimerism and tolerance to hindlimb composite tissue transplants: preferential localization of chimerism in donor bone.

    Science.gov (United States)

    Rahhal, Dina N; Xu, Hong; Huang, Wei-Chao; Wu, Shengli; Wen, Yujie; Huang, Yiming; Ildstad, Suzanne T

    2009-09-27

    Mixed chimerism induces donor-specific tolerance to composite tissue allotransplants (CTAs). In the present studies, we used a nonmyeloablative conditioning approach to establish chimerism and promote CTA acceptance. Wistar Furth (RT1A(u)) rats were conditioned with 600 to 300 cGy total body irradiation (TBI, day-1), and 100 x 10(6) T-cell-depleted ACI (RT1A(abl)) bone marrow cells were transplanted on day 0, followed by a 11-day course of tacrolimus and one dose of antilymphocyte serum (day 10). Heterotopic osteomyocutaneous flap transplantation was performed 4 to 6 weeks after bone marrow transplantation. Mixed chimerism was initially achieved in almost all recipients, but long-term acceptance of CTA was only achieved in rats treated with 600 cGy TBI. When anti-alphabeta-T-cell receptor (TCR) monoclonal antibody (mAb) (day-3) was added into the regimens, donor chimerism was similar to recipients preconditioned without anti-alphabeta-TCR mAb. However, the long-term CTA survival was significantly improved in chimeras receiving more than or equal to 300 cGy TBI plus anti-alphabeta-TCR mAb. Higher levels of donor chimerism were associated with CTA acceptance. The majority of flap acceptors lost peripheral blood chimerism within 6 months. However, donor chimerism persisted in the transplanted bone at significantly higher levels compared with other hematopoietic compartments. The compartment donor chimerism may be responsible for the maintenance of tolerance to CTA. Long-term acceptors were tolerant to a donor skin graft challenge even in the absence of peripheral blood chimerism. Mixed chimerism established by nonmyeloablative conditioning induces long-term acceptance of CTA, which is associated with persistent chimerism preferentially in the transplanted donor bone.

  7. Human leukocyte antigens in indigenous (mapuche) people in a regional renal transplantation program in chile.

    Science.gov (United States)

    Droguett, M A; Oyarzún, M J; Alruiz, P; Jerez, V; Mezzano, S; Ardiles, L

    2005-10-01

    An active regional transplantation program established in the southern region of Chile has allowed the incorporation of ethnic minorities particularly Mapuche living in this geographic area in the development of a histocompatibility database. To identify possible differences in the human leukocyte (HLA) antigen distribution in Chilean Mapuche compared with non-Mapuche, we reviewed 442 HLA tissue-typing studies. Seventy-eight of 309 recipients (25%) and 18 of 133 donors (13%) were Mapuche. Among recipients, Mapuche people showed a significantly higher frequency of the HLA antigens, A28, B16, DR4, and DR8, and a lower one for A19, B15, and DR1 (P Mapuche individuals. A particularly higher frequency of the haplotype A28, -B16, -DR4 was also evidenced in Mapuche. Besides, these recipients showed a higher frequency of the allele -DR4 when compared with Mapuche donors. A greater frequency of some histocompatibility antigens in patients with chronic renal disease might be attributed to allelic concentration due to a high index of endogamy, but a possible association with the development of progressive renal disease cannot be ignored, especially when a higher prevalence of DR4 was observed among Mapuche recipients.

  8. Transplantation of Human Dental Pulp-Derived Stem Cells or Differentiated Neuronal Cells from Human Dental Pulp-Derived Stem Cells Identically Enhances Regeneration of the Injured Peripheral Nerve.

    Science.gov (United States)

    Ullah, Imran; Park, Ju-Mi; Kang, Young-Hoon; Byun, June-Ho; Kim, Dae-Geon; Kim, Joo-Heon; Kang, Dong-Ho; Rho, Gyu-Jin; Park, Bong-Wook

    2017-09-01

    Human dental mesenchymal stem cells isolated from the dental follicle, pulp, and root apical papilla of extracted wisdom teeth have been known to exhibit successful and potent neurogenic differentiation capacity. In particular, human dental pulp-derived stem cells (hDPSCs) stand out as the most prominent source for in vitro neuronal differentiation. In this study, to evaluate the in vivo peripheral nerve regeneration potential of hDPSCs and differentiated neuronal cells from DPSCs (DF-DPSCs), a total of 1 × 10 6 hDPSCs or DF-hDPSCs labeled with PKH26 tracking dye and supplemented with fibrin glue scaffold and collagen tubulization were transplanted into the sciatic nerve resection (5-mm gap) of rat models. At 12 weeks after cell transplantation, both hDPSC and DF-hDPSC groups showed notably increased behavioral activities and higher muscle contraction forces compared with those in the non-cell transplanted control group. In immunohistochemical analysis of regenerated nerve specimens, specific markers for angiogenesis, axonal fiber, and myelin sheath increased in both the cell transplantation groups. Pretransplanted labeled PKH26 were also distinctly detected in the regenerated nerve tissues, indicating that transplanted cells were well-preserved and differentiated into nerve cells. Furthermore, no difference was observed in the nerve regeneration potential between the hDPSC and DF-hDPSC transplanted groups. These results demonstrate that dental pulp tissue is an excellent stem cell source for nerve regeneration, and in vivo transplantation of the undifferentiated hDPSCs could exhibit sufficient and excellent peripheral nerve regeneration potential.

  9. Increasing Human Neural Stem Cell Transplantation Dose Alters Oligodendroglial and Neuronal Differentiation after Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Katja M. Piltti

    2017-06-01

    Full Text Available Multipotent human central nervous system-derived neural stem cells transplanted at doses ranging from 10,000 (low to 500,000 (very high cells differentiated predominantly into the oligodendroglial lineage. However, while the number of engrafted cells increased linearly in relationship to increasing dose, the proportion of oligodendrocytic cells declined. Increasing dose resulted in a plateau of engraftment, enhanced neuronal differentiation, and increased distal migration caudal to the transplantation sites. Dose had no effect on terminal sensory recovery or open-field locomotor scores. However, total human cell number and decreased oligodendroglial proportion were correlated with hindlimb girdle coupling errors. Conversely, greater oligodendroglial proportion was correlated with increased Ab step pattern, decreased swing speed, and increased paw intensity, consistent with improved recovery. These data suggest that transplant dose, and/or target niche parameters can regulate donor cell engraftment, differentiation/maturation, and lineage-specific migration profiles.

  10. Engineering Human Neural Tissue by 3D Bioprinting.

    Science.gov (United States)

    Gu, Qi; Tomaskovic-Crook, Eva; Wallace, Gordon G; Crook, Jeremy M

    2018-01-01

    Bioprinting provides an opportunity to produce three-dimensional (3D) tissues for biomedical research and translational drug discovery, toxicology, and tissue replacement. Here we describe a method for fabricating human neural tissue by 3D printing human neural stem cells with a bioink, and subsequent gelation of the bioink for cell encapsulation, support, and differentiation to functional neurons and supporting neuroglia. The bioink uniquely comprises the polysaccharides alginate, water-soluble carboxymethyl-chitosan, and agarose. Importantly, the method could be adapted to fabricate neural and nonneural tissues from other cell types, with the potential to be applied for both research and clinical product development.

  11. Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

    Science.gov (United States)

    Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

    2017-01-01

    Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

  12. Identification of human tissue cross-presenting dendritic cells

    OpenAIRE

    Haniffa, Muzlifah; Collin, Matthew; Ginhoux, Florent

    2013-01-01

    Dendritic cells (DCs) are a heterogeneous group of functionally specialized antigen-presenting cells. We recently characterized the human tissue cross-presenting DCs and aligned the human and mouse DC subsets. Our findings will facilitate the translation of murine DC studies to the human setting and aid the design of DC-based vaccine strategies for infection and cancer immunotherapy.

  13. Extensive Loss of Islet Mass Beyond the First Day After Intraportal Human Islet Transplantation in a Mouse Model.

    Science.gov (United States)

    Liljebäck, Hanna; Grapensparr, Liza; Olerud, Johan; Carlsson, Per-Ola

    2016-01-01

    Clinical islet transplantation is characterized by a progressive deterioration of islet graft function, which renders many patients once again dependent on exogenous insulin administration within a couple of years. In this study, we aimed to investigate possible engraftment factors limiting the survival and viability of experimentally transplanted human islets beyond the first day after their transplantation to the liver. Human islets were transplanted into the liver of nude mice and characterized 1 or 30 days after transplantation by immunohistochemistry. The factors assessed were endocrine mass, cellular death, hypoxia, vascular density and amyloid formation in the transplanted islets. One day posttransplantation, necrotic cells, as well as apoptotic cells, were commonly observed. In contrast to necrotic death, apoptosis rates remained high 1 month posttransplantation, and the total islet mass was reduced by more than 50% between 1 and 30 days posttransplantation. Islet mass at 30 days posttransplantation correlated negatively to apoptotic death. Vascular density within the transplanted islets remained less than 30% of that in native human islets up to 30 days posttransplantation and was associated with prevailing hypoxia. Amyloid formation was rarely observed in the 1-day-old transplants, but was commonly observed in the 30-day-old islet transplants. We conclude that substantial islet cell death occurs beyond the immediate posttransplantation phase, particularly through apoptotic events. Concomitant low vascularization with prevailing hypoxia and progressive amyloid development was observed in the human islet grafts. Strategies to improve engraftment at the intraportal site or change of implantation site in the clinical setting are needed.

  14. Chapter 8. Ionisation radiation and human organism. Radioactivity of human tissues

    International Nuclear Information System (INIS)

    Toelgyessy, J.; Harangozo, M.

    2000-01-01

    This is a chapter of textbook of radioecology for university students. In this chapter authors deal with ionisation radiation and human organism as well as with radioactivity of human tissues. Chapter consists of next parts: (1) Radiation stress of human organism; (2) Radioactivity of human tissues and the factors influencing radioactive contamination; (3) Possibilities of decreasing of radiation stress

  15. Preliminary Examination of X-ray Scattering from Human Tissues

    International Nuclear Information System (INIS)

    Desouky, O.S.; Wilkinson, S.; Hall, C.; Rogers, K.; Round, A.

    2008-01-01

    Small Angle x-ray scattering (SAXS) and wide angle x-ray scattering (WAXS) patterns have been recorded from different human soft tissues using x-ray synchrotron radiation.Pathological breast, normal kidney and lung tissues show SAXS peaks at q-values equal to 0.291 nm -1 and 0.481 nm -1 (d 21.6 nm and d =13. nm) which are the 3 r d and 5 t h order of the well known axial D-spacing of collagen fibrils. The diffraction is particularly intense in the meridional direction indicating some febrile alignment. In contrast, the normal tissue of brain, liver and heart shows diffuse scatter.The wide-angle coherent scattering from normal human tissues of brain, liver, heart, lung, and kidney is typical of that for amorphous materials. The scatter of the healthy adipose breast tissue shows a sharp peak at momentum transfer 1.24 nm -1 (d= 0.417 nm). The data of the other tissues appears to consist of a broad scattering peak. The two scattering regimes succeed in differentiating between the two major components of breast tissue, collagen and adipose tissue. The results of this study suggest that the soft tissues may have scattering patterns that are characteristics for the particular tissue types and tissue disease state. These results indicate that it may be possible use the coherent scattering as a diagnostic tool

  16. The Human Figure Drawing with Donor and Nondonor Siblings of Pediatric Bone Marrow Transplant Patients.

    Science.gov (United States)

    Packman, Wendy L.; Beck, Vanessa L.; VanZutphen, Kelly H.; Long, Janet K.; Spengler, Gisele

    2003-01-01

    There is little research on the psychological impact of bone marrow transplantation (BMT) on family members. This study uses the Human Figure Drawing (HFD) to measure siblings' emotional distress toward BMT. Among the siblings, feelings of isolation, anger, depression, anxiety, and low self-esteem emerged as major themes. Findings indicate the…

  17. Human dental pulp stem cells transplantation combined with treadmill training in rats after traumatic spinal cord injury

    Directory of Open Access Journals (Sweden)

    F.C. Nicola

    2016-01-01

    Full Text Available Spinal cord injury (SCI is a disabling condition resulting in deficits of sensory and motor functions, and has no effective treatment. Considering that protocols with stem cell transplantation and treadmill training have shown promising results, the present study evaluated the effectiveness of stem cells from human exfoliated deciduous teeth (SHEDs transplantation combined with treadmill training in rats with experimental spinal cord injury. Fifty-four Wistar rats were spinalized using NYU impactor. The rats were randomly distributed into 5 groups: Sham (laminectomy with no SCI, n=10; SCI (laminectomy followed by SCI, n=12; SHEDs (SCI treated with SHEDs, n=11; TT (SCI treated with treadmill training, n=11; SHEDs+TT (SCI treated with SHEDs and treadmill training; n=10. Treatment with SHEDs alone or in combination with treadmill training promoted functional recovery, reaching scores of 15 and 14, respectively, in the BBB scale, being different from the SCI group, which reached 11. SHEDs treatment was able to reduce the cystic cavity area and glial scar, increase neurofilament. Treadmill training alone had no functional effectiveness or tissue effects. In a second experiment, the SHEDs transplantation reduced the TNF-α levels in the cord tissue measured 6 h after the injury. Contrary to our hypothesis, treadmill training either alone or in combination, caused no functional improvement. However, SHEDs showed to be neuroprotective, by the reduction of TNF-α levels, the cystic cavity and the glial scar associated with the improvement of motor function after SCI. These results provide evidence that grafted SHEDs might be an effective therapy to spinal cord lesions, with possible anti-inflammatory action.

  18. Human dental pulp stem cells transplantation combined with treadmill training in rats after traumatic spinal cord injury.

    Science.gov (United States)

    Nicola, F C; Rodrigues, L P; Crestani, T; Quintiliano, K; Sanches, E F; Willborn, S; Aristimunha, D; Boisserand, L; Pranke, P; Netto, C A

    2016-08-08

    Spinal cord injury (SCI) is a disabling condition resulting in deficits of sensory and motor functions, and has no effective treatment. Considering that protocols with stem cell transplantation and treadmill training have shown promising results, the present study evaluated the effectiveness of stem cells from human exfoliated deciduous teeth (SHEDs) transplantation combined with treadmill training in rats with experimental spinal cord injury. Fifty-four Wistar rats were spinalized using NYU impactor. The rats were randomly distributed into 5 groups: Sham (laminectomy with no SCI, n=10); SCI (laminectomy followed by SCI, n=12); SHEDs (SCI treated with SHEDs, n=11); TT (SCI treated with treadmill training, n=11); SHEDs+TT (SCI treated with SHEDs and treadmill training; n=10). Treatment with SHEDs alone or in combination with treadmill training promoted functional recovery, reaching scores of 15 and 14, respectively, in the BBB scale, being different from the SCI group, which reached 11. SHEDs treatment was able to reduce the cystic cavity area and glial scar, increase neurofilament. Treadmill training alone had no functional effectiveness or tissue effects. In a second experiment, the SHEDs transplantation reduced the TNF-α levels in the cord tissue measured 6 h after the injury. Contrary to our hypothesis, treadmill training either alone or in combination, caused no functional improvement. However, SHEDs showed to be neuroprotective, by the reduction of TNF-α levels, the cystic cavity and the glial scar associated with the improvement of motor function after SCI. These results provide evidence that grafted SHEDs might be an effective therapy to spinal cord lesions, with possible anti-inflammatory action.

  19. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  20. Scaffold-assisted cartilage tissue engineering using infant chondrocytes from human hip cartilage.

    Science.gov (United States)

    Kreuz, P C; Gentili, C; Samans, B; Martinelli, D; Krüger, J P; Mittelmeier, W; Endres, M; Cancedda, R; Kaps, C

    2013-12-01

    Studies about cartilage repair in the hip and infant chondrocytes are rare. The aim of our study was to evaluate the use of infant articular hip chondrocytes for tissue engineering of scaffold-assisted cartilage grafts. Hip cartilage was obtained from five human donors (age 1-10 years). Expanded chondrocytes were cultured in polyglycolic acid (PGA)-fibrin scaffolds. De- and re-differentiation of chondrocytes were assessed by histological staining and gene expression analysis of typical chondrocytic marker genes. In vivo, cartilage matrix formation was assessed by histology after subcutaneous transplantation of chondrocyte-seeded PGA-fibrin scaffolds in immunocompromised mice. The donor tissue was heterogenous showing differentiated articular cartilage and non-differentiated tissue and considerable expression of type I and II collagens. Gene expression analysis showed repression of typical chondrocyte and/or mesenchymal marker genes during cell expansion, while markers were re-induced when expanded cells were cultured in PGA-fibrin scaffolds. Cartilage formation after subcutaneous transplantation of chondrocyte loaded PGA-fibrin scaffolds in nude mice was variable, with grafts showing resorption and host cell infiltration or formation of hyaline cartilage rich in type II collagen. Addition of human platelet rich plasma (PRP) to cartilage grafts resulted robustly in formation of hyaline-like cartilage that showed type II collagen and regions with type X collagen. These results suggest that culture of expanded and/or de-differentiated infant hip cartilage cells in PGA-fibrin scaffolds initiates chondrocyte re-differentiation. The heterogenous donor tissue containing immature chondrocytes bears the risk of cartilage repair failure in vivo, which may be possibly overcome by the addition of PRP. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  1. Human tissue models in cancer research: looking beyond the mouse.

    Science.gov (United States)

    Jackson, Samuel J; Thomas, Gareth J

    2017-08-01

    Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of 'non-animal human tissue' models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models. © 2017. Published by The Company of Biologists Ltd.

  2. Human umbilical cord blood mononuclear cell transplantation for delayed encephalopathy after carbon monoxide intoxication

    Directory of Open Access Journals (Sweden)

    Gong D

    2013-08-01

    Full Text Available Dianrong Gong,1 Haiyan Yu,1 Weihua Wang,2 Haixin Yang,1 Fabin Han1,21Department of Neurology, 2Centre for Stem Cells and Regenerative Medicine, Liaocheng People's Hospital, The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of ChinaAbstract: Stem cell transplantation is one of the potential treatments for neurological disorders. Since human umbilical cord stem cells have been shown to provide neuroprotection and promote neural regeneration, we have attempted to transplant the human umbilical cord blood mononuclear cells (hUCB-MNCs to treat patients with delayed encephalopathy after carbon monoxide intoxication (DEACOI. The hUCB-MNCs were isolated from fresh umbilical cord blood and were given to patients subarachnoidally. Physical examinations, mini-mental state examination scores, and computed tomography scans were used to evaluate the improvement of symptoms, signs, and pathological changes of the patient's brain before and after hUCB-MNC transplantation. A total of 12 patients with DEACOI were treated with hUCB-MNCs in this study. We found that most of the patients have shown significant improvements in movement, behavior, and cognitive function, and improved brain images in 1–4 months from the first transplantation of hUCB-MNCs. None of these patients have been observed to have any severe adverse effects. Our study suggests that the hUCB-MNC transplantation may be a safe and effective treatment for DEACOI. Further studies and clinical trials with more cases, using more systematic scoring methods, are needed to evaluate brain structural and functional improvements in patients with DEACOI after hUCB-MNC therapy.Keywords: human umbilical cord blood mononuclear cells, transplantation, delayed encephalopathy after carbon monoxide intoxication, MMSE

  3. Advancing biomaterials of human origin for tissue engineering

    OpenAIRE

    Chen, Fa-Ming; Liu, Xiaohua

    2015-01-01

    Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking in...

  4. Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused 3D Porous Polymer Scaffold for Liver Tissue Engineering

    DEFF Research Database (Denmark)

    Hemmingsen, Mette; Muhammad, Haseena Bashir; Mohanty, Soumyaranjan

    A huge shortage of liver organs for transplantation has motivated the research field of tissue engineering to develop bioartificial liver tissue and even a whole liver. The goal of NanoBio4Trans is to create a vascularized bioartificial liver tissue, initially as a liver-support system. Due...... to limitations of primary hepatocytes regarding availability and maintenance of functionality, stem cells and especially human induced pluripotent stem cells (hIPS cells) are an attractive cell source for liver tissue engineering. The aim of this part of NanoBio4Trans is to optimize culture and hepatic...... differentiation of hIPS-derived definitive endoderm (DE) cells in a 3D porous polymer scaffold built-in a perfusable bioreactor. The use of a microfluidic bioreactor array enables the culture of 16 independent tissues in one experimental run and thereby an optimization study to be performed....

  5. Injury Response of Resected Human Brain Tissue In Vitro

    NARCIS (Netherlands)

    Verwer, Ronald W. H.; Sluiter, Arja A.; Balesar, Rawien A.; Baaijen, Johannes C.; de Witt Hamer, Philip C.; Speijer, Dave; Li, Yichen; Swaab, Dick F.

    2015-01-01

    Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by

  6. Bone marrow stromal cells elicit tissue sparing after acute but not delayed transplantation into the contused adult rat thoracic spinal cord.

    NARCIS (Netherlands)

    Tewarie, R.D.; Hurtado, A.; Ritfeld, G.J.; Rahiem, S.T.; Wendell, D.F.; Barroso, M.M.; Grotenhuis, J.A.; Oudega, M.

    2009-01-01

    Bone marrow stromal cells (BMSC) transplanted into the contused spinal cord may support repair by improving tissue sparing. We injected allogeneic BMSC into the moderately contused adult rat thoracic spinal cord at 15 min (acute) and at 3, 7, and 21 days (delayed) post-injury and quantified tissue

  7. Fertility preservation and refreezing of transplanted ovarian tissue-a potential new way of managing patients with low risk of malignant cell recurrence

    DEFF Research Database (Denmark)

    Kristensen, Stine Gry; Giorgione, Veronica; Humaidan, Peter

    2017-01-01

    OBJECTIVE: To report the first successful refreezing of ovarian tissue recovered more than 3 years after transplantation in a woman previously treated for early-stage ovarian cancer. DESIGN: Evaluation of cryopreserved and grafted ovarian tissue. SETTING: University hospital. PATIENT(S): A 23-yea...

  8. Regeneration of skull bones in adult rabbits after implantation of commercial osteoinductive materials and transplantation of a tissue-engineering construct.

    Science.gov (United States)

    Volkov, A V; Alekseeva, I S; Kulakov, A A; Gol'dshtein, D V; Shustrov, S A; Shuraev, A I; Arutyunyan, I V; Bukharova, T B; Rzhaninova, A A; Bol'shakova, G B; Grigor'yan, A S

    2010-10-01

    We performed a comparative study of reparative osteogenesis in rabbits with experimental critical defects of the parietal bones after implantation of commercial osteoinductive materials "Biomatrix", "Osteomatrix", "BioOss" in combination with platelet-rich plasma and transplantation of a tissue-engineering construct on the basis of autogenic multipotent stromal cells from the adipose tissue predifferentiated in osteogenic direction. It was found that experimental reparative osteogenesis is insufficiently stimulated by implantation materials and full-thickness trepanation holes were not completely closed. After transplantation of the studied tissue-engineering construct, the defect was filled with full-length bone regenerate (in the center of the regenerate and from the maternal bone) in contrast to control and reference groups, where the bone tissue was formed only on the side of the maternal bone. On day 120 after transplantation of the tissue-engineering construct, the percent of newly-formed bone tissue in the regenerate was 24% (the total percent of bone tissue in the regenerate was 39%), which attested to active incomplete regenerative process in contrast to control and reference groups. Thus, the study demonstrated effective regeneration of the critical defects of the parietal bones in rabbits 120 days after transplantation of the tissue-engineering construct in contrast to commercial osteoplastic materials for directed bone regeneration.

  9. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    Science.gov (United States)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  10. Periodontal regeneration in swine after cell injection and cell sheet transplantation of human dental pulp stem cells following good manufacturing practice.

    Science.gov (United States)

    Hu, Jingchao; Cao, Yu; Xie, Yilin; Wang, Hua; Fan, Zhipeng; Wang, Jinsong; Zhang, Chunmei; Wang, Jinsong; Wu, Chu-Tse; Wang, Songlin

    2016-09-09

    Periodontitis, one of the most prevalent infectious diseases in humans, results in the destruction of tooth-supporting tissues. The purpose of the present study is to evaluate the effect of cell injection and cell sheet transplantation on periodontal regeneration in a swine model. In the present study, human dental pulp stem cells (hDPSCs) were transplanted into a swine model for periodontal regeneration. Twelve miniature pigs were used to generate periodontitis with bone defects of 5 mm in width, 7 mm in length, and 3 mm in depth. hDPSCs were obtained for bone regeneration using cell injection or cell sheet transplantation. After 12 weeks, clinical, radiological, and histological assessments of regenerated periodontal tissues were performed to compare periodontal regeneration treated with xenogeneic cell injection and cell sheet implantation. Our study showed that translating hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. After 12 weeks, both the hDPSC sheet treatment and hDPSC injection significantly improved periodontal tissue healing clinically in comparison with the control group. The volume of regenerative bone in the hDPSC sheet group (52.7 ± 4.1 mm(3)) was significantly larger than in the hDPSC injection group (32.4 ± 5.1 mm(3)) (P cell sheet transplantation significantly regenerated periodontal bone in swine. The hDPSC sheet had more bone regeneration capacity compared with hDPSC injection.

  11. Browning of Subcutaneous White Adipose Tissue in Humans

    OpenAIRE

    Sidossis, Labros S.; Porter, Craig; Saraf, Manish K.; Børsheim, Elisabet; Radhakrishnan, Ravi S.; Chao, Tony; Ali, Arham; Chondronikola, Maria; Mlcak, Ronald; Finnerty, Celeste C.; Hawkins, Hal K.; Toliver-Kinsky, Tracy; Herndon, David N.

    2015-01-01

    Since the presence of brown adipose tissue (BAT) was confirmed in adult humans, BAT has become a therapeutic target for obesity and insulin resistance. We examined whether human subcutaneous white adipose tissue (sWAT) can adopt a BAT-like phenotype using a clinical model of prolonged and severe adrenergic stress. sWAT samples were collected from severely burned and healthy individuals. A subset of burn victims were prospectively followed during their acute hospitalization. Browning of sWAT w...

  12. Neuronal regeneration in injured rat spinal cord after human dental pulp derived neural crest stem cell transplantation.

    Science.gov (United States)

    Kabatas, S; Demir, C S; Civelek, E; Yilmaz, I; Kircelli, A; Yilmaz, C; Akyuva, Y; Karaoz, E

    2018-01-01

    This study aimed to analyze the effect of human Dental Pulp-Neural Crest Stem Cells (hDP-NCSCs) delivery on lesion site after spinal cord injury (SCI), and to observe the functional recovery after transplantation. Neural Crest Stem Cells (NCSCs) were isolated from human Dental Pulp (hDP). The experimental rat population was divided into four groups (n = 6/24). Their behavioral motility was scored regularly. After 4-weeks, rats were sacrificed, and their spinal cords were examined for Green Fluorescent Protein (GFP) labeled hDP-NCSCs by immunofluorescence (IF) staining. In early post-injury (p.i) period, the ultrastructure of spinal cord tissue was preserved in Group 4. The majority of cells forming the ependymal region around the central canal were found to be hDP-NCSCs. While the grey-and-white-matter around the ependymal region was composed of e.g. GFP cells, with astrocytic-like appearance. The scores showed significant motor recovery in hind limb functions in Group 4. However, no obvious change was observed in other groups. Cells e.g., mesenchymal (Vimentin+) which express GFP+ cells in the gray-and-white-matter around the ependymal region could indicate the potential to self-renewal and plasticity. Thus, transplantation of hDP-NCSCs might be an effective strategy to improve functional recovery following spinal cord trauma (Fig. 10, Ref. 32).

  13. Microwave non-contact imaging of subcutaneous human body tissues.

    Science.gov (United States)

    Kletsov, Andrey; Chernokalov, Alexander; Khripkov, Alexander; Cho, Jaegeol; Druchinin, Sergey

    2015-10-01

    A small-size microwave sensor is developed for non-contact imaging of a human body structure in 2D, enabling fitness and health monitoring using mobile devices. A method for human body tissue structure imaging is developed and experimentally validated. Subcutaneous fat tissue reconstruction depth of up to 70 mm and maximum fat thickness measurement error below 2 mm are demonstrated by measurements with a human body phantom and human subjects. Electrically small antennas are developed for integration of the microwave sensor into a mobile device. Usability of the developed microwave sensor for fitness applications, healthcare, and body weight management is demonstrated.

  14. Arthroscopic Meniscal Allograft Transplantation With Soft-Tissue Fixation Through Bone Tunnels.

    Science.gov (United States)

    Spalding, Tim; Parkinson, Ben; Smith, Nick A; Verdonk, Peter

    2015-10-01

    Meniscal allograft transplantation improves clinical outcomes for patients with symptomatic meniscus-deficient knees. We describe an established arthroscopic technique for meniscal allograft transplantation without the need for bone fixation of the meniscal horns. After preparation of the meniscal bed, the meniscus is parachuted into the knee through a silicone cannula and the meniscal horns are fixed with sutures through bone tunnels. The body of the meniscus is then fixed with a combination of all-inside and inside-out sutures. This technique is reliable and reproducible and has clinical outcomes comparable with those of bone plug fixation techniques.

  15. Lipolysis in human adipose tissue during exercise

    DEFF Research Database (Denmark)

    Lange, Kai Henrik Wiborg; Lorentsen, Jeanne; Isaksson, Fredrik

    2002-01-01

    exercise), as well as during non-steady-state (onset of exercise and early exercise) experimental settings. Fourteen healthy women [age: 74 +/- 1 (SE) yr] were studied at rest and during 60-min continuous bicycling at 60% of peak O(2) uptake. Calculated and measured subcutaneous abdominal adipose tissue...... venous glycerol concentrations increased substantially from rest to exercise but were similar both at rest and during later stages of exercise. In contrast, during the initial approximately 40 min of exercise, calculated glycerol concentration was significantly lower (approximately 40%) than measured...... and continuous prolonged exercise. However, during shorter periods of exercise (

  16. Safety of Cultivated Limbal Epithelial Stem Cell Transplantation for Human Corneal Regeneration

    Directory of Open Access Journals (Sweden)

    J. Behaegel

    2017-01-01

    Full Text Available Ex vivo cultivated limbal stem cell transplantation is a promising technique for the treatment of limbal stem cell deficiency. While the results of the clinical trials have been extensively reported since the introduction of the technique in 1997, little has been reported regarding the potential health risks associated with production processes and transplantation techniques. Culture procedures require the use of animal and/or human-derived products, which carry the potential of introducing toxic or infectious agents through contamination with known or unknown additives. Protocols vary widely, and the risks depend on the local institutional methods. Good manufacturing practice and xeno-free culture protocols could reduce potential health risks but are not yet a common practice worldwide. In this review, we focus on the safety of both autologous- and allogeneic-cultivated limbal stem cell transplantation, with respect to culture processes, surgical approaches, and postoperative strategies.

  17. Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease

    OpenAIRE

    Shroff, Geeta

    2016-01-01

    Case series Patient: Male, 42 ? Female, 30 Final Diagnosis: Human embryonic stem cells showed good therapeutic potential for treatment of multiple sclerosis with lyme disease Symptoms: Fatigue ? weakness in limbs Medication: ? Clinical Procedure: Human embryonic stem cells transplantation Specialty: Transplantology Objective: Rare disease Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause dela...

  18. Construction of Anterior Hemi-Corneal Equivalents Using Nontransfected Human Corneal Cells and Transplantation in Dog Models.

    Science.gov (United States)

    Xu, Bin; Song, Zhan; Fan, Tingjun

    2017-11-01

    Tissue-engineered human anterior hemi-cornea (TE-aHC) is a promising equivalent for treating anterior lamellar keratopathy to surmount the severe shortage of donated corneas. This study was intended to construct a functional TE-aHC with nontransfected human corneal stromal (ntHCS) and epithelial (ntHCEP) cells using acellular porcine corneal stromata (aPCS) as a carrier scaffold, and evaluate its biological functions in a dog model. To construct a TE-aHC, ntHCS cells were injected into an aPCS scaffold and cultured for 3 days; then, ntHCEP cells were inoculated onto the Bowman's membrane of the scaffold and cultured for 5 days under air-liquid interface condition. After its morphology and histological structure were characterized, the constructed TE-aHC was transplanted into dog eyes via lamellar keratoplasty. The corneal transparency, thickness, intraocular pressure, epithelial integrity, and corneal regeneration were monitored in vivo, and the histological structure and histochemical property were examined ex vivo 360 days after surgery, respectively. The results showed that the constructed TE-aHC was highly transparent and composed of a corneal epithelium of 7-8 layer ntHCEP cells and a corneal stroma of regularly aligned collagen fibers and well-preserved glycosaminoglycans with sparsely distributed ntHCS cells, mimicking a normal anterior hemi-cornea (aHC). Moreover, both ntHCEP and ntHCS cells maintained positive expression of their marker and functional proteins. After transplantation into dog eyes, the constructed TE-aHC acted naturally in terms of morphology, structure and inherent property, and functioned well in maintaining corneal clarity, thickness, normal histological structure, and composition in dog models by reconstructing a normal aHC, which could be used as a promising aHC equivalent in corneal regenerative medicine and aHC disorder therapy. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  19. Birth and death of human β-cells in pancreas from cadaver donors, autopsies, surgical specimens, and islets transplanted into mice

    Science.gov (United States)

    Caballero, Francisco; Siniakowicz, Karolina; Jennifer-Hollister-Lock; Duran, Luisa; Katsuta, Hitoshi; Yamada, Takatsugu; Lei, Ji; Deng, Shaoping; Westermark, Gunilla T.; Markmann, James; Bonner-Weir, Susan; Weir, Gordon C.

    2013-01-01

    There is great interest in the potential of the human endocrine pancreas for regeneration by β-cell replication or neogenesis. Our aim was to explore this potential in adult human pancreases and in both islet and exocrine tissue transplanted into mice. The design was to examine pancreases obtained from cadaver donors, autopsies and fresh surgical specimens and compare these findings with those obtained from islet and duct tissue grafted into the kidney. Islets and exocrine tissue were transplanted into normoglycemic ICR/SCID mice and studied 4 and 14 wk later. β-cell replication as assessed by double staining for insulin and Ki67 was 0.22 ± 0.03 % at 4 wk and 0.13 ± 0.03 % at 14 wk. In contrast, no evidence of β-cell replication could be found in 11 cadaver donor and 10 autopsy pancreases. However, Ki67 staining of β-cells in frozen sections obtained at surgery was comparable to that found in transplanted islets. Evidence for neogenesis in transplanted pancreatic exocrine tissue was supported by finding β-cells within the duct epithelium, and the presence of cells double stained for insulin and cytokeratin 19 (CK19). However, β-cells within the ducts never constituted more than 1% of the CK19 positive cells. With confocal microscopy, 7 of 12 examined cells expressed both markers, consistent with a neogeneic process. Mice with grafts containing islet or exocrine tissue were treated with various combinations exendin-4, gastrin and epidermal growth factor; none increased β-cell replication or stimulated neogenesis. In summary, human β-cells replicate at a low level in islets transplanted into mice and in surgical pancreatic frozen sections but rarely in cadaver donor or autopsy pancreases. The absence of β-cell replication in many adult cadaver or autopsy pancreases could, in part, be an artifact of the postmortem state. Thus, it appears that adult human β-cells maintain a low level of turnover through replication and neogenesis. PMID:23321263

  20. Birth and death of human β-cells in pancreases from cadaver donors, autopsies, surgical specimens, and islets transplanted into mice.

    Science.gov (United States)

    Caballero, Francisco; Siniakowicz, Karolina; Hollister-Lock, Jennifer; Duran, Luisa; Katsuta, Hitoshi; Yamada, Takatsugu; Lei, Ji; Deng, Shaoping; Westermark, Gunilla T; Markmann, James; Bonner-Weir, Susan; Weir, Gordon C

    2014-02-01

    There is great interest in the potential of the human endocrine pancreas for regeneration by β-cell replication or neogenesis. Our aim was to explore this potential in adult human pancreases and in both islet and exocrine tissue transplanted into mice. The design was to examine pancreases obtained from cadaver donors, autopsies, and fresh surgical specimens and compare these findings with those obtained from islet and duct tissue grafted into the kidney. Islets and exocrine tissue were transplanted into normoglycemic ICR-SCID mice and studied 4 and 14 weeks later. β-Cell replication, as assessed by double staining for insulin and Ki67, was 0.22 ± 0.03% at 4 weeks and 0.13 ± 0.03% at 14 weeks. In contrast, no evidence of β-cell replication could be found in 11 cadaver donor and 10 autopsy pancreases. However, Ki67 staining of β-cells in frozen sections obtained at surgery was comparable to that found in transplanted islets. Evidence for neogenesis in transplanted pancreatic exocrine tissue was supported by finding β-cells within the duct epithelium and the presence of cells double stained for insulin and cytokeratin 19 (CK19). However, β-cells within the ducts never constituted more than 1% of the CK19-positive cells. With confocal microscopy, 7 of 12 examined cells expressed both markers, consistent with a neogeneic process. Mice with grafts containing islet or exocrine tissue were treated with various combinations of exendin-4, gastrin, and epidermal growth factor; none increased β-cell replication or stimulated neogenesis. In summary, human β-cells replicate at a low level in islets transplanted into mice and in surgical pancreatic frozen sections, but rarely in cadaver donor or autopsy pancreases. The absence of β-cell replication in many adult cadaver or autopsy pancreases could, in part, be an artifact of the postmortem state. Thus, it appears that adult human β-cells maintain a low level of turnover through replication and neogenesis.

  1. Mechanical properties of human atherosclerotic intima tissue.

    Science.gov (United States)

    Akyildiz, Ali C; Speelman, Lambert; Gijsen, Frank J H

    2014-03-03

    Progression and rupture of atherosclerotic plaques in coronary and carotid arteries are the key processes underlying myocardial infarctions and strokes. Biomechanical stress analyses to compute mechanical stresses in a plaque can potentially be used to assess plaque vulnerability. The stress analyses strongly rely on accurate representation of the mechanical properties of the plaque components. In this review, the composition of intima tissue and how this changes during plaque development is discussed from a mechanical perspective. The plaque classification scheme of the American Heart Association is reviewed and plaques originating from different vascular territories are compared. Thereafter, an overview of the experimental studies on tensile and compressive plaque intima properties are presented and the results are linked to the pathology of atherosclerotic plaques. This overview revealed a considerable variation within studies, and an enormous dispersion between studies. Finally, the implications of the dispersion in experimental data on the clinical applications of biomechanical plaque modeling are presented. Suggestions are made on mechanical testing protocol for plaque tissue and on using a standardized plaque classification scheme. This review identifies the current status of knowledge on plaque mechanical properties and the future steps required for a better understanding of the plaque type specific material properties. With this understanding, biomechanical plaque modeling may eventually provide essential support for clinical plaque risk stratification. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. The Long Road from the Kidney Bazaar: A Commentary on Pakistan’s Progress Towards Self-sufficiency in Organ Transplantation

    OpenAIRE

    Martin, Dominique E.

    2011-01-01

    The dark history of transplant tourism in Pakistan demonstrates the hazards of unregulated cross-border markets in human organs. Trading on existing national and international social inequities, ‘transplant tourism’ offers dubious benefits for transplant recipients and attractive profits to those facilitating the industry at the expense of the world’s poor. The impact of Pakistan’s 2007 Transplantation of Human Organs and Tissue Ordinance and the sustained efforts of transplant professionals ...

  3. Geometry Modeling Program Implementation of Human Hip Tissue

    Directory of Open Access Journals (Sweden)

    WANG Mo-nan

    2017-10-01

    Full Text Available Abstract:Aiming to design a simulate software of human tissue modeling and analysis,Visual Studio 2010 is selected as a development tool to develop a 3 D reconstruction software of human tissue with language C++.It can be used alone. It also can be a module of the virtual surgery systems. The system includes medical image segmentation modules and 3 D reconstruction modules,and can realize the model visualization. This software system has been used to reconstruct hip muscles,femur and hip bone accurately. The results show these geometry models can simulate the structure of hip tissues.

  4. Geometry Modeling Program Implementation of Human Hip Tissue

    Directory of Open Access Journals (Sweden)

    WANG Monan

    2017-04-01

    Full Text Available Aiming to design a simulate software of human tissue modeling and analysis,Visual Studio 2010 is selected as a development tool to develop a 3 D reconstruction software of human tissue with language C++.It can be used alone. It also can be a module of the virtual surgery systems. The system includes medical image segmentation modules and 3 D reconstruction modules,and can realize the model visualization. This software system has been used to reconstruct hip muscles,femur and hip bone accurately. The results show these geometry models can simulate the structure of hip tissues.

  5. Ethical issues of transplanting organs from transgenic animals into human beings.

    Science.gov (United States)

    Behnam Manesh, Shima; Omani Samani, Reza; Behnam Manesh, Shayan

    2014-01-01

    One of the most important applications of transgenic animals for medical purposes is to transplant their organs into human's body, an issue which has caused a lot of ethical and scientific discussions. we can divide the ethical arguments to two comprehensive groups; the first group which is known as deontological critiques (related to the action itself regardless of any results pointing the human or animal) and the second group, called the consequentialist critiques (which are directly pointing the consequences of the action). The latter arguments also can be divided to two subgroups. In the first one which named anthropocentrism, just humankind has inherent value in the moral society, and it studies the problem just from a human-based point of view while in second named, biocentrism all the living organism have this value and it deals specially with the problem from the animal-based viewpoint. In this descriptive-analytic study, ethical issues were retrieved from books, papers, international guidelines, thesis, declarations and instructions, and even some weekly journals using keywords related to transgenic animals, organ, and transplantation. According to the precautionary principle with the strong legal and ethical background, due to lack of accepted scientific certainties about the safety of the procedure, in this phase, transplanting animal's organs into human beings have the potential harm and danger for both human and animals, and application of this procedure is unethical until the safety to human will be proven.

  6. Vibrational Micro-Spectroscopy of Human Tissues Analysis: Review.

    Science.gov (United States)

    Bunaciu, Andrei A; Hoang, Vu Dang; Aboul-Enein, Hassan Y

    2017-05-04

    Vibrational spectroscopy (Infrared (IR) and Raman) and, in particular, micro-spectroscopy and micro-spectroscopic imaging have been used to characterize developmental changes in tissues, to monitor these changes in cell cultures and to detect disease and drug-induced modifications. The conventional methods for biochemical and histophatological tissue characterization necessitate complex and "time-consuming" sample manipulations and the results are rarely quantifiable. The spectroscopy of molecular vibrations using mid-IR or Raman techniques has been applied to samples of human tissue. This article reviews the application of these vibrational spectroscopic techniques for analysis of biological tissue published between 2005 and 2015.

  7. Human tissue models in cancer research: looking beyond the mouse

    Directory of Open Access Journals (Sweden)

    Samuel J. Jackson

    2017-08-01

    Full Text Available Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of ‘non-animal human tissue’ models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models.

  8. Disseminated Soft Tissue Infection and Sepsis with Stenotrophomonas maltophilia in a Bone Marrow Transplant Patient

    Directory of Open Access Journals (Sweden)

    Jeffrey H Lipton

    1996-01-01

    Full Text Available A 32-year-old female presented with aplastic anemia and subsequently underwent a one-antigen mismatched bone marrow transplant from her brother. She failed to engraft and a second graft was attempted. Protracted neutropenia of three months’ duration despite the use of broad spectrum antibiotics occurred. Stenotrophomonas (Xanthomonas maltophilia metastatic cellulitis developed that did not respond to appropriate antibiotics.

  9. Functional Characterization of Preadipocytes Derived from Human Periaortic Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Diana Vargas

    2017-01-01

    Full Text Available Adipose tissue can affect the metabolic control of the cardiovascular system, and its anatomic location can affect the vascular function differently. In this study, biochemical and phenotypical characteristics of adipose tissue from periaortic fat were evaluated. Periaortic and subcutaneous adipose tissues were obtained from areas surrounding the ascending aorta and sternotomy incision, respectively. Adipose tissues were collected from patients undergoing myocardial revascularization or mitral valve replacement surgery. Morphological studies with hematoxylin/eosin and immunohistochemical assay were performed in situ to quantify adipokine expression. To analyze adipogenic capacity, adipokine expression, and the levels of thermogenic proteins, adipocyte precursor cells were isolated from periaortic and subcutaneous adipose tissues and induced to differentiation. The precursors of adipocytes from the periaortic tissue accumulated less triglycerides than those from the subcutaneous tissue after differentiation and were smaller than those from subcutaneous adipose tissue. The levels of proteins involved in thermogenesis and energy expenditure increased significantly in periaortic adipose tissue. Additionally, the expression levels of adipokines that affect carbohydrate metabolism, such as FGF21, increased significantly in mature adipocytes induced from periaortic adipose tissue. These results demonstrate that precursors of periaortic adipose tissue in humans may affect cardiovascular events and might serve as a target for preventing vascular diseases.

  10. Legal Issues Related to Donation of Organs, Tissues and Cells of Human Origin

    Directory of Open Access Journals (Sweden)

    Gabriela Mironov

    2010-06-01

    Full Text Available Scientific developments, positive changes in attitude of the man and the new legal framework allow the donation of organs, tissues and cells of human origin. In this context it is necessary to clarifywhether the donation covered by the special law is, legally, one and the same as that covered by the Romanian Civil Code in force and qualified the successor’s right to accept or reject late withdrawals for transplantation. The right to life and physical integrity is personal patrimony; it is a subjective civil right that has no economic content and it cannot be measured in money. Consequently, the content of these rights can not be expressed in money, the property does not belong to their owner. Given the above view, "the right of disposal" to donation of organs, tissues and cells of human origin is an attribute of ownership, right to life and physical integrity, as a personal right that is an intimate attribute patrimonial related to the person’s right to dispose of his body as it wishes, within the law. Addressing these issues it is necessary to clarify the legal consequences of donating organs, tissues and cells of human origin, considering that medical activities are becoming more numerous.

  11. A family of hyperelastic models for human brain tissue

    Science.gov (United States)

    Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

    2017-09-01

    Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

  12. Comparative in silico profiling of epigenetic modifiers in human tissues.

    Science.gov (United States)

    Son, Mi-Young; Jung, Cho-Rok; Kim, Dae-Soo; Cho, Hyun-Soo

    2018-04-06

    The technology of tissue differentiation from human pluripotent stem cells has attracted attention as a useful resource for regenerative medicine, disease modeling and drug development. Recent studies have suggested various key factors and specific culture methods to improve the successful tissue differentiation and efficient generation of human induced pluripotent stem cells. Among these methods, epigenetic regulation and epigenetic signatures are regarded as an important hurdle to overcome during reprogramming and differentiation. Thus, in this study, we developed an in silico epigenetic panel and performed a comparative analysis of epigenetic modifiers in the RNA-seq results of 32 human tissues. We demonstrated that an in silico epigenetic panel can identify epigenetic modifiers in order to overcome epigenetic barriers to tissue-specific differentiation.

  13. Effects of fluid dynamic stress on fracturing of cell-aggregated tissue during purification for islets of Langerhans transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Shintaku, H; Kawano, S [Department of Mechanical Science and Bioengineering, Graduate School of Engineering Science, Osaka University, Machikaneyama-cho, Toyonaka, Osaka 560-8531 (Japan); Okitsu, T [Transplantation Unit, Kyoto University Hospital, Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Matsumoto, S [Baylor Research Institute Islet Cell Laboratory, 1400 Eight Avenue, Fort Worth, TX 76104 (United States); Suzuki, T; Kanno, I; Kotera, H [Department of Microengineering, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501 (Japan)], E-mail: shintaku@me.es.osaka-u.ac.jp

    2008-06-07

    Among clinical treatments for type 1 diabetes mellitus, the transplantation of islets of Langerhans to the portal vein of the hepar is a commonly used treatment for glucose homeostasis. Islet purification using the density gradient of a solution in a centrifuge separator is required for safety and efficiency. In the purification, the number of tissues to be transplanted is reduced by removing the acinar tissue and gathering the islet from the digest of pancreas. However, the mechanical effects on the fracture of islets in the centrifuge due to fluid dynamic stress are a serious problem in the purification process. In this study, a preliminary experiment using a cylindrical rotating viscometer with a simple geometry is conducted in order to systematically clarify the effect of fluid dynamic stress on the fracture of islets. The effects of fluid dynamic stress on the islet configuration is quantitatively measured for various flow conditions, and a predictive fracture model is developed based on the experimental results. Furthermore, in the practical purification process in the COBE (Gambro BCT), which is widely used in clinical applications, we perform a numerical analysis of the fluid dynamic stress based on Navier-Stokes equations to estimate the stress conditions for islets. Using the fracture model and numerical analysis, the islet fracture characteristics using the COBE are successfully investigated. The results obtained in this study provide crucial information for the purification of islets by centrifuge in practical and clinical applications.

  14. Effects of fluid dynamic stress on fracturing of cell-aggregated tissue during purification for islets of Langerhans transplantation

    International Nuclear Information System (INIS)

    Shintaku, H; Kawano, S; Okitsu, T; Matsumoto, S; Suzuki, T; Kanno, I; Kotera, H

    2008-01-01

    Among clinical treatments for type 1 diabetes mellitus, the transplantation of islets of Langerhans to the portal vein of the hepar is a commonly used treatment for glucose homeostasis. Islet purification using the density gradient of a solution in a centrifuge separator is required for safety and efficiency. In the purification, the number of tissues to be transplanted is reduced by removing the acinar tissue and gathering the islet from the digest of pancreas. However, the mechanical effects on the fracture of islets in the centrifuge due to fluid dynamic stress are a serious problem in the purification process. In this study, a preliminary experiment using a cylindrical rotating viscometer with a simple geometry is conducted in order to systematically clarify the effect of fluid dynamic stress on the fracture of islets. The effects of fluid dynamic stress on the islet configuration is quantitatively measured for various flow conditions, and a predictive fracture model is developed based on the experimental results. Furthermore, in the practical purification process in the COBE (Gambro BCT), which is widely used in clinical applications, we perform a numerical analysis of the fluid dynamic stress based on Navier-Stokes equations to estimate the stress conditions for islets. Using the fracture model and numerical analysis, the islet fracture characteristics using the COBE are successfully investigated. The results obtained in this study provide crucial information for the purification of islets by centrifuge in practical and clinical applications

  15. Commercialization of human organs for transplantation intervivos under the perspective of the social bioethics

    Directory of Open Access Journals (Sweden)

    Fernando Hellmann

    2012-12-01

    Full Text Available Buying and selling human organs for transplants from living donors has been discussed worldwide in the bioethical debate and it is becoming a public health problem. This essay discusses, in light of the Social Bioethics, arguments used to justify such practices, which are related to the common good, moral plurality, autonomy and individual freedom. Such justificatory aspects assume liberal and utilitarian characteristics. They present the possibility of double standard, do not consider social vulnerability, and harm dignity and human rights by evidencing an apology to the market laws. Thus, the justifications for buying and selling human organs for transplantations intervivos eventually turn the body, or part of it, into a commodity.

  16. Genetic effects on gene expression across human tissues

    NARCIS (Netherlands)

    Battle, Alexis; Brown, Christopher D.; Engelhardt, Barbara E.; Montgomery, Stephen B.; Aguet, François; Ardlie, Kristin G.; Cummings, Beryl B.; Gelfand, Ellen T.; Getz, Gad; Hadley, Kane; Handsaker, Robert E.; Huang, Katherine H.; Kashin, Seva; Karczewski, Konrad J.; Lek, Monkol; Li, Xiao; MacArthur, Daniel G.; Nedzel, Jared L.; Nguyen, Duyen T.; Noble, Michael S.; Segrè, Ayellet V.; Trowbridge, Casandra A.; Tukiainen, Taru; Abell, Nathan S.; Balliu, Brunilda; Barshir, Ruth; Basha, Omer; Bogu, Gireesh K.; Brown, Andrew; Castel, Stephane E.; Chen, Lin S.; Chiang, Colby; Conrad, Donald F.; Cox, Nancy J.; Damani, Farhan N.; Davis, Joe R.; Delaneau, Olivier; Dermitzakis, Emmanouil T.; Eskin, Eleazar; Ferreira, Pedro G.; Frésard, Laure; Gamazon, Eric R.; Garrido-Martín, Diego; Gewirtz, Ariel D. H.; Gliner, Genna; Gloudemans, Michael J.; Guigo, Roderic; Hall, Ira M.; Han, Buhm; He, Yuan

    2017-01-01

    Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression

  17. Ethical Issues of Transplanting Organs from Transgenic Animals into Human Beings

    Science.gov (United States)

    Behnam Manesh, Shima; Omani Samani, Reza; Behnam Manesh, Shayan

    2014-01-01

    One of the most important applications of transgenic animals for medical purposes is to transplant their organs into human’s body, an issue which has caused a lot of ethical and scientific discussions. we can divide the ethical arguments to two comprehensive groups; the first group which is known as deontological critiques (related to the action itself regardless of any results pointing the human or animal) and the second group, called the consequentialist critiques (which are directly pointing the consequences of the action). The latter arguments also can be divided to two subgroups. In the first one which named anthropocentrism, just humankind has inherent value in the moral society, and it studies the problem just from a human-based point of view while in second named, biocentrism all the living organism have this value and it deals specially with the problem from the animal-based viewpoint. In this descriptive-analytic study, ethical issues were retrieved from books, papers, international guidelines, thesis, declarations and instructions, and even some weekly journals using keywords related to transgenic animals, organ, and transplantation. According to the precautionary principle with the strong legal and ethical background, due to lack of accepted scientific certainties about the safety of the procedure, in this phase, transplanting animal’s organs into human beings have the potential harm and danger for both human and animals, and application of this procedure is unethical until the safety to human will be proven. PMID:25383334

  18. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tissue culture media for human ex vivo tissue and cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture...

  19. Histological study on the effect of transplanted human umbilical cord ...

    African Journals Online (AJOL)

    ways to manage heart failure by replacing damaged cardiac muscle with healthy tissue. This study aimed at examining .... sodium phosphate buffer, pH 7.4 at room temperature. Specimens were dehydrated in ascending grades of cold ethanol and ..... been shown to express angiogenic growth factors in a paracrine way to ...

  20. Immunolocalization of transforming growth factor alpha in normal human tissues

    DEFF Research Database (Denmark)

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

  1. Human Adipose Tissue Derived Stem Cells Promote Liver Regeneration in a Rat Model of Toxic Injury

    Directory of Open Access Journals (Sweden)

    Eva Koellensperger

    2013-01-01

    Full Text Available In the light of the persisting lack of donor organs and the risks of allotransplantations, the possibility of liver regeneration with autologous stem cells from adipose tissue (ADSC is an intriguing alternative. Using a model of a toxic liver damage in Sprague Dawley rats, generated by repetitive intraperitoneal application of retrorsine and allyl alcohol, the ability of human ADSC to support the restoration of liver function was investigated. A two-thirds hepatectomy was performed, and human ADSC were injected into one remaining liver lobe in group 1 (n = 20. Injection of cell culture medium performed in group 2 (n = 20 served as control. Cyclosporine was applied to achieve immunotolerance. Blood samples were drawn weekly after surgery to determine liver-correlated blood values. Six and twelve weeks after surgery, animals were sacrificed and histological sections were analyzed. ADSC significantly raised postoperative albumin (P < 0.017, total protein (P < 0.031, glutamic oxaloacetic transaminase (P < 0.001, and lactate dehydrogenase (P < 0.04 levels compared to injection of cell culture medium alone. Transplanted cells could be found up to twelve weeks after surgery in histological sections. This study points towards ADSC being a promising alternative to hepatocyte or liver organ transplantation in patients with severe liver failure.

  2. Human natural killer cell development in secondary lymphoid tissues

    Science.gov (United States)

    Freud, Aharon G.; Yu, Jianhua; Caligiuri, Michael A.

    2014-01-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34+CD45RA+ hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field. PMID:24661538

  3. Mechanized syringe homogenization of human and animal tissues.

    Science.gov (United States)

    Kurien, Biji T; Porter, Andrew C; Patel, Nisha C; Kurono, Sadamu; Matsumoto, Hiroyuki; Scofield, R Hal

    2004-06-01

    Tissue homogenization is a prerequisite to any fractionation schedule. A plethora of hands-on methods are available to homogenize tissues. Here we report a mechanized method for homogenizing animal and human tissues rapidly and easily. The Bio-Mixer 1200 (manufactured by Innovative Products, Inc., Oklahoma City, OK) utilizes the back-and-forth movement of two motor-driven disposable syringes, connected to each other through a three-way stopcock, to homogenize animal or human tissue. Using this method, we were able to homogenize human or mouse tissues (brain, liver, heart, and salivary glands) in 5 min. From sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and a matrix-assisted laser desorption/ionization time-of-flight mass spectrometric enzyme assay for prolidase, we have found that the homogenates obtained were as good or even better than that obtained used a manual glass-on-Teflon (DuPont, Wilmington, DE) homogenization protocol (all-glass tube and Teflon pestle). Use of the Bio-Mixer 1200 to homogenize animal or human tissue precludes the need to stay in the cold room as is the case with the other hands-on homogenization methods available, in addition to freeing up time for other experiments.

  4. Pancreatic Islet Cell Transplantation

    Science.gov (United States)

    Warnock, Garth L.; Rajotte, Ray V.

    1992-01-01

    Transplantation of insulin-producing tissue offers a physiologic approach to restoration of glycemic control. Whereas transplantation of vascularized pancreatic grafts has recently achieved encouraging results, pancreatic islet cell transplantation holds the promise of low morbidity and reduced requirements for agressive immunosuppression for recipients. Islet cell transplantation was recently demonstrated to induce euglycemia with insulin independence. Imagesp1656-a PMID:21221366

  5. Ovarian tissue cryopreservation and transplantation among alternatives for fertility preservation in the Nordic countries

    DEFF Research Database (Denmark)

    Rodriguez-Wallberg, Kenny A; Tanbo, Tom; Tinkanen, Helena

    2016-01-01

    cryopreservation to be experimental. In Iceland, embryo cryopreservation is the only option for fertility preservation. Most centers use slow-freezing methods for ovarian tissue cryopreservation. Most patients selected for ovarian tissue cryopreservation were newly diagnosed with cancer and the tissue...

  6. Stem and stromal cell reconstitution of lethally irradiated mice following transplantation of hematopoietic tissue from donors of various ages

    International Nuclear Information System (INIS)

    Schmidt, C.M.; Doran, G.A.; Crouse, D.A.; Sharp, J.G.

    1987-01-01

    If the limited life span of hematopoietic tissues in vitro is due to a finite proliferative capacity of individual stem cells, one might expect tissues of young donors to possess a greater proliferative capacity and to contain a larger population of primitive stem cells than those of older donors. To test this hypothesis, we used 12- and 8-day spleen colony formation (CFU-s) to assay more and less primitive stem cell subpopulations of three murine hematopoietic tissues: fetal liver (FL) and weanling (WBM) and adult (ABM) bone marrow. Subsequently, the same assays and a stromal cell assay were performed on the bone marrow from groups of lethally irradiated mice reconstituted with these tissues. Comparison of the CFU-s content of the donor tissues revealed that FL contained a significantly greater proportion of primitive stem cells as evidenced by a (Day 12):(Day 8) CFU-s ratio of 3.0 +/- 1.0 as compared to 0.9 +/- 0.1 for WBM and ABM. In addition, at 21 weeks post-transplantation the CFU-s/femur values of the FL reconstituted group were significantly greater than those of the ABM and WBM reconstituted groups. These results suggest that fetal hematopoietic tissue contains a greater proportion of primitive stem cells and has a greater proliferative potential than hematopoietic tissue from older donors. No differences were seen in stromal cell reconstitution of the three experimental groups. In all cases, assayable fibroblast colony forming cells (CFU-f) remained at 20-40% of control values, even at 21 weeks postreconstitution

  7. Astrocyte calcium signal and gliotransmission in human brain tissue.

    Science.gov (United States)

    Navarrete, Marta; Perea, Gertrudis; Maglio, Laura; Pastor, Jesús; García de Sola, Rafael; Araque, Alfonso

    2013-05-01

    Brain function is recognized to rely on neuronal activity and signaling processes between neurons, whereas astrocytes are generally considered to play supportive roles for proper neuronal function. However, accumulating evidence indicates that astrocytes sense and control neuronal and synaptic activity, indicating that neuron and astrocytes reciprocally communicate. While this evidence has been obtained in experimental animal models, whether this bidirectional signaling between astrocytes and neurons occurs in human brain remains unknown. We have investigated the existence of astrocyte-neuron communication in human brain tissue, using electrophysiological and Ca(2+) imaging techniques in slices of the cortex and hippocampus obtained from biopsies from epileptic patients. Cortical and hippocampal human astrocytes displayed spontaneous Ca(2+) elevations that were independent of neuronal activity. Local application of transmitter receptor agonists or nerve electrical stimulation transiently elevated Ca(2+) in astrocytes, indicating that human astrocytes detect synaptic activity and respond to synaptically released neurotransmitters, suggesting the existence of neuron-to-astrocyte communication in human brain tissue. Electrophysiological recordings in neurons revealed the presence of slow inward currents (SICs) mediated by NMDA receptor activation. The frequency of SICs increased after local application of ATP that elevated astrocyte Ca(2+). Therefore, human astrocytes are able to release the gliotransmitter glutamate, which affect neuronal excitability through activation of NMDA receptors in neurons. These results reveal the existence of reciprocal signaling between neurons and astrocytes in human brain tissue, indicating that astrocytes are relevant in human neurophysiology and are involved in human brain function.

  8. Polychlorinated naphthalenes in human adipose tissue from New York, USA

    International Nuclear Information System (INIS)

    Kunisue, Tatsuya; Johnson-Restrepo, Boris; Hilker, David R.; Aldous, Kenneth M.; Kannan, Kurunthachalam

    2009-01-01

    Polychlorinated naphthalenes (PCNs) are persistent, bioaccumulative, and toxic contaminants. Prior to this study, the occurrence of PCNs in human adipose tissues from the USA has not been analyzed. Here, we have measured concentrations of PCNs in human adipose tissue samples collected in New York City during 2003-2005. Concentrations of PCNs were in the range of 61-2500 pg/g lipid wt. in males and 21-910 pg/g lipid wt. in females. PCN congeners 52/60 (1,2,3,5,7/1,2,4,6,7) and 66/67 (1,2,3,4,6,7/1,2,3,5,6,7) were predominant, collectively accounting for 66% of the total PCN concentrations. Concentrations of PCNs in human adipose tissues were 2-3 orders of magnitude lower than the previously reported concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Concentrations of PCNs were not correlated with PCB concentrations. The contribution of PCNs to dioxin-like toxic equivalents (TEQs) in human adipose tissues was estimated to be <1% of the polychlorinated dibenzo-p-dioxin/dibenzofuran (PCDD/F)-TEQs. - Polychlorinated naphthalenes have been measured in human adipose tissues from the USA for the first time

  9. Predicting Tissue-Specific Enhancers in the Human Genome

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Loots, Gabriela G.; Nobrega, Marcelo A.; Ovcharenko, Ivan

    2006-07-01

    Determining how transcriptional regulatory signals areencoded in vertebrate genomes is essential for understanding the originsof multi-cellular complexity; yet the genetic code of vertebrate generegulation remains poorly understood. In an attempt to elucidate thiscode, we synergistically combined genome-wide gene expression profiling,vertebrate genome comparisons, and transcription factor binding siteanalysis to define sequence signatures characteristic of candidatetissue-specific enhancers in the human genome. We applied this strategyto microarray-based gene expression profiles from 79 human tissues andidentified 7,187 candidate enhancers that defined their flanking geneexpression, the majority of which were located outside of knownpromoters. We cross-validated this method for its ability to de novopredict tissue-specific gene expression and confirmed its reliability in57 of the 79 available human tissues, with an average precision inenhancer recognition ranging from 32 percent to 63 percent, and asensitivity of 47 percent. We used the sequence signatures identified bythis approach to assign tissue-specific predictions to ~;328,000human-mouse conserved noncoding elements in the human genome. Byoverlapping these genome-wide predictions with a large in vivo dataset ofenhancers validated in transgenic mice, we confirmed our results with a28 percent sensitivity and 50 percent precision. These results indicatethe power of combining complementary genomic datasets as an initialcomputational foray into the global view of tissue-specific generegulation in vertebrates.

  10. Characterization of muscarinic receptor subtypes in human tissues

    International Nuclear Information System (INIS)

    Giraldo, E.; Martos, F.; Gomez, A.; Garcia, A.; Vigano, M.A.; Ladinsky, H.; Sanchez de La Cuesta, F.

    1988-01-01

    The affinities of selective, pirenzepine and AF-DX 116, and classical, N-methylscopolamine and atropine, muscarinic cholinergic receptor antagonists were investigated in displacement binding experiments with [ 3 H]Pirenzepine and [ 3 H]N-methylscopolamine in membranes from human autoptic tissues (forebrain, cerebellum, atria, ventricle and submaxillary salivary glands). Affinity estimates of N-methylscopolamine and atropine indicated a non-selective profile. Pirenzepine showed differentiation between the M 1 neuronal receptor of the forebrain and the receptors in other tissues while AF-DX 116 clearly discriminated between muscarinic receptors of heart and glands. The results in human tissues confirm the previously described selectivity profiles of pirenzepine and AF-DX 116 in rat tissues. These findings thus reveal the presence also in man of three distinct muscarinic receptor subtypes: the neuronal M 1 , the cardiac M 2 and the glandular M 3

  11. Tissue engineering and surgery: from translational studies to human trials

    Directory of Open Access Journals (Sweden)

    Vranckx Jan Jeroen

    2017-06-01

    Full Text Available Tissue engineering was introduced as an innovative and promising field in the mid-1980s. The capacity of cells to migrate and proliferate in growth-inducing medium induced great expectancies on generating custom-shaped bioconstructs for tissue regeneration. Tissue engineering represents a unique multidisciplinary translational forum where the principles of biomaterial engineering, the molecular biology of cells and genes, and the clinical sciences of reconstruction would interact intensively through the combined efforts of scientists, engineers, and clinicians. The anticipated possibilities of cell engineering, matrix development, and growth factor therapies are extensive and would largely expand our clinical reconstructive armamentarium. Application of proangiogenic proteins may stimulate wound repair, restore avascular wound beds, or reverse hypoxia in flaps. Autologous cells procured from biopsies may generate an ‘autologous’ dermal and epidermal laminated cover on extensive burn wounds. Three-dimensional printing may generate ‘custom-made’ preshaped scaffolds – shaped as a nose, an ear, or a mandible – in which these cells can be seeded. The paucity of optimal donor tissues may be solved with off-the-shelf tissues using tissue engineering strategies. However, despite the expectations, the speed of translation of in vitro tissue engineering sciences into clinical reality is very slow due to the intrinsic complexity of human tissues. This review focuses on the transition from translational protocols towards current clinical applications of tissue engineering strategies in surgery.

  12. Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: a combined gene therapy-cell transplantation approach.

    Science.gov (United States)

    Jabbarzadeh, Ehsan; Starnes, Trevor; Khan, Yusuf M; Jiang, Tao; Wirtel, Anthony J; Deng, Meng; Lv, Qing; Nair, Lakshmi S; Doty, Steven B; Laurencin, Cato T

    2008-08-12

    One of the fundamental principles underlying tissue engineering approaches is that newly formed tissue must maintain sufficient vascularization to support its growth. Efforts to induce vascular growth into tissue-engineered scaffolds have recently been dedicated to developing novel strategies to deliver specific biological factors that direct the recruitment of endothelial cell (EC) progenitors and their differentiation. The challenge, however, lies in orchestration of the cells, appropriate biological factors, and optimal factor doses. This study reports an approach as a step forward to resolving this dilemma by combining an ex vivo gene transfer strategy and EC transplantation. The utility of this approach was evaluated by using 3D poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for bone tissue engineering applications. Our goal was achieved by isolation and transfection of adipose-derived stromal cells (ADSCs) with adenovirus encoding the cDNA of VEGF. We demonstrated that the combination of VEGF releasing ADSCs and ECs results in marked vascular growth within PLAGA scaffolds. We thereby delineate the potential of ADSCs to promote vascular growth into biomaterials.

  13. Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: A combined gene therapy–cell transplantation approach

    Science.gov (United States)

    Jabbarzadeh, Ehsan; Starnes, Trevor; Khan, Yusuf M.; Jiang, Tao; Wirtel, Anthony J.; Deng, Meng; Lv, Qing; Nair, Lakshmi S.; Doty, Steven B.; Laurencin, Cato T.

    2008-01-01

    One of the fundamental principles underlying tissue engineering approaches is that newly formed tissue must maintain sufficient vascularization to support its growth. Efforts to induce vascular growth into tissue-engineered scaffolds have recently been dedicated to developing novel strategies to deliver specific biological factors that direct the recruitment of endothelial cell (EC) progenitors and their differentiation. The challenge, however, lies in orchestration of the cells, appropriate biological factors, and optimal factor doses. This study reports an approach as a step forward to resolving this dilemma by combining an ex vivo gene transfer strategy and EC transplantation. The utility of this approach was evaluated by using 3D poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for bone tissue engineering applications. Our goal was achieved by isolation and transfection of adipose-derived stromal cells (ADSCs) with adenovirus encoding the cDNA of VEGF. We demonstrated that the combination of VEGF releasing ADSCs and ECs results in marked vascular growth within PLAGA scaffolds. We thereby delineate the potential of ADSCs to promote vascular growth into biomaterials. PMID:18678895

  14. Combined spectroscopic imaging and chemometric approach for automatically partitioning tissue types in human prostate tissue biopsies

    Science.gov (United States)

    Haka, Abigail S.; Kidder, Linda H.; Lewis, E. Neil

    2001-07-01

    We have applied Fourier transform infrared (FTIR) spectroscopic imaging, coupling a mercury cadmium telluride (MCT) focal plane array detector (FPA) and a Michelson step scan interferometer, to the investigation of various states of malignant human prostate tissue. The MCT FPA used consists of 64x64 pixels, each 61 micrometers 2, and has a spectral range of 2-10.5 microns. Each imaging data set was collected at 16-1 resolution, resulting in 512 image planes and a total of 4096 interferograms. In this article we describe a method for separating different tissue types contained within FTIR spectroscopic imaging data sets of human prostate tissue biopsies. We present images, generated by the Fuzzy C-Means clustering algorithm, which demonstrate the successful partitioning of distinct tissue type domains. Additionally, analysis of differences in the centroid spectra corresponding to different tissue types provides an insight into their biochemical composition. Lastly, we demonstrate the ability to partition tissue type regions in a different data set using centroid spectra calculated from the original data set. This has implications for the use of the Fuzzy C-Means algorithm as an automated technique for the separation and examination of tissue domains in biopsy samples.

  15. Engineered human broncho-epithelial tissue-like assemblies

    Science.gov (United States)

    Goodwin, Thomas J. (Inventor)

    2012-01-01

    Three-dimensional human broncho-epithelial tissue-like assemblies (TLAs) are produced in a rotating wall vessel (RWV) with microcarriers by coculturing mesenchymal bronchial-tracheal cells (BTC) and bronchial epithelium cells (BEC). These TLAs display structural characteristics and express markers of in vivo respiratory epithelia. TLAs are useful for screening compounds active in lung tissues such as antiviral compounds, cystic fibrosis treatments, allergens, and cytotoxic compounds.

  16. Scheduled transplantation of human umbilical cord blood to severe combined immunodeficient mice

    International Nuclear Information System (INIS)

    Wu Jianqiu; Yang Yunfang; Jin Zhijun; Cai Jianming; Yang Rujun; Xiang Yingsong

    2000-01-01

    Objective: To explore a new method for developing the efficiency of human umbilical cord blood (UCB) cells engraftment, and further understand the growth characteristic of hematopoietic stem cells (HSC) in vivo. Methods: Sublethally irradiated severe combined immunodeficient (SCID) mice were transplanted i.v. with UCB cells which had been cryo-preserved at -80 degree C. The human cells in recipient mice were detected by flow cytometry and CFU-GM assay. Results: In contrast to the single transplantation, scheduled engraftment of similar numbers of UCB cells resulted in a proportionally obvious increase in the percentages of CD45 + , CD34 + cells produced in SCID mouse bone marrow (BM). When the donor cells were reduced to 20 percent, an identical reconstitution of both hematopoietic and part of immunologic functions was achieved. Conclusion: Scheduled engraftment improves the repopulating ability of HSC, which would provide a novel way for clinical cord blood engraftment in adult objects

  17. Amyloid Deposition in Transplanted Human Pancreatic Islets: A Conceivable Cause of Their Long-Term Failure

    Directory of Open Access Journals (Sweden)

    Arne Andersson

    2008-01-01

    Full Text Available Following the encouraging report of the Edmonton group, there was a rejuvenation of the islet transplantation field. After that, more pessimistic views spread when long-term results of the clinical outcome were published. A progressive loss of the β-cell function meant that almost all patients were back on insulin therapy after 5 years. More than 10 years ago, we demonstrated that amyloid deposits rapidly formed in human islets and in mouse islets transgenic for human IAPP when grafted into nude mice. It is, therefore, conceivable to consider amyloid formation as one potential candidate for the long-term failure. The present paper reviews attempts in our laboratories to elucidate the dynamics of and mechanisms behind the formation of amyloid in transplanted islets with special emphasis on the impact of long-term hyperglycemia.

  18. Association of human cytomegalovirus viremia with human leukocyte antigens in liver transplantation recipients

    Institute of Scientific and Technical Information of China (English)

    Jianhua Hu; Jun Fan; Xueqin Meng; Hong Zhao; Xuan Zhang; Hainv Gao; Meifang Yang; Yadan Ma; Minhuan Li; Weihang Ma

    2011-01-01

    Human cytomegalovirus (HCMV) reactivation is a common complication after liver transplantation (LT).Here, we investigated whether human leukocyte antigen (HLA)-matching was related to HCMV infection and subsequent graft failure after LT for hepatitis B virus cirrhosis. This retrospective study reviewed 91 LT recipients.All the patients were grouped according to HLA-A, HLA-B, and HLA-DR locus matching. Clinical data were collected, including complete HLA-typing, HCMV viremia, graft failure, and the time of HCMV viremia.HLA typing was performed using a sequence-specific primer-polymerase chain reaction kit. HCMV was detected by pp65 antigenemia using a commercial kit.The incidence of HCMV infection post-LT was 81.32%.Graft failure was observed in 16 of 91 (17.6%) patients during the 4-year study. The incidence of HCMV viremia was 100% (5/5), 91.4% (32/35), and 72.5% (37/51) in HLA-A two locus, one locus, and zero locus compatibility,respectively. Nevertheless, the degree of the HLA-A,HLA-B, or HLA-DR match did not influence the time of HCMV viremia, graft failure, or the time of graft failure after a diagnosis of HCMV viremia (all P> 0.05). An interesting discovery was that the risk of HCMV viremia tended to be higher in patients with better HLA-A compatibility. Graft failure, time of HCMV viremia, and graft failure after a diagnosis of HCMV viremia appear to be independent of HLA allele compatibility.

  19. Impact of Skeletal Muscle Mass Index, Intramuscular Adipose Tissue Content, and Visceral to Subcutaneous Adipose Tissue Area Ratio on Early Mortality of Living Donor Liver Transplantation.

    Science.gov (United States)

    Hamaguchi, Yuhei; Kaido, Toshimi; Okumura, Shinya; Kobayashi, Atsushi; Shirai, Hisaya; Yagi, Shintaro; Kamo, Naoko; Okajima, Hideaki; Uemoto, Shinji

    2017-03-01

    Skeletal muscle depletion has been shown to be an independent risk factor for poor survival in various diseases. However, in surgery, the significance of other body components including visceral and subcutaneous adipose tissue remains unclear. This retrospective study included 250 adult patients undergoing living donor liver transplantation (LDLT) between January 2008 and April 2015. Using preoperative plain computed tomography imaging at the third lumbar vertebra level, skeletal muscle mass, muscle quality, and visceral adiposity were evaluated by the skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral to subcutaneous adipose tissue area ratio (VSR), respectively. The cutoff values of these parameters were determined for men and women separately using the data of 657 healthy donors for LDLT between 2005 and 2016. Impact of these parameters on outcomes after LDLT was analyzed. VSR was significantly correlated with patient age (P = 0.041), neutrophil-lymphocyte ratio (P mass index (P normal group. On multivariate analysis, low SMI (hazard ratio [HR], 2.367, P = 0.002), high IMAC (HR, 2.096, P = 0.004), and high VSR (HR, 2.213, P = 0.003) were identified as independent risk factors for death after LDLT. Preoperative visceral adiposity, as well as low muscularity, was closely involved with posttransplant mortality.

  20. The Human Tissue Act 2004 and the child donor.

    Science.gov (United States)

    Baston, Jenny

    2009-05-01

    In 2001, the inquiry panel appointed to investigate the removal, retention and disposal of human organs and tissues at the Royal Liverpool Children's Hospital published its report. The panel's recommendations led to a new approach to consent for organ removal and storage under the new Human Tissue Act 2004. For child bone marrow donors, the new consent process requires all donor children or their parent to undergo a separate assessment before the bone marrow donation. They must be assessed by an accredited assessor who will submit a recommendation to the Human Tissue Authority for consideration. The unfortunate circumstances highlighted in the inquiry have led to changes to law, practice and culture that are benefiting other children and families.

  1. Factors associated with anti-human leukocyte antigen antibodies in patients supported with continuous-flow devices and effect on probability of transplant and post-transplant outcomes

    DEFF Research Database (Denmark)

    Alba, Ana C; Tinckam, Kathryn; Foroutan, Farid

    2015-01-01

    BACKGROUND: One major disadvantage of ventricular assist device (VAD) therapy is the development of human-leukocyte antigen (HLA) antibodies. We aimed to identify factors associated with HLA antibodies during continuous flow (CF)-VAD support and assess the effect on transplant probability...

  2. Metabolism of nitrogen-13 labelled ammonia in different conditions in dogs, human volunteers and transplant patients

    International Nuclear Information System (INIS)

    Bormans, G.; Maes, A.; Langendries, W.; Nuyts, J.; Vrolix, M.; Vanhaecke, J.; Schiepers, C.; Roo, M. de; Mortelmans, L.; Verbruggen, A.

    1995-01-01

    To investigate the rate of metabolism of nitrogen-13 labelled ammonia ( 13 NH 3 ) in different conditions, we have determined the relative amount of unchanged 13 NH 3 in the blood of dogs, volunteers and transplant patients at different times following injection. In dogs, the determinations were made under basal conditions, during adenosine administration and after coronary occlusion. The results show that adenosine administration increases the metabolic rate whereas coronary occlusion does not affect 13 NH 3 metabolism. For both human volunteers and transplant patients the metabolic rate of 13 NH 3 was assessed under basal conditions and during adenosine administration. 13 NH 3 metabolism proceeds faster in transplant patients than in volunteers under both conditions. Adenosine administration causes a faster 13 NH 3 turnover in volunteers but not in transplant patients. Application of individual metabolite correction resulted in a 16% decrease in the calculated blood flow compared to uncorrected values. A smaller difference (5%) was observed between correction with mean metabolite values and individually acquired metabolite values. (orig.)

  3. Tissue sparing, behavioral recovery, supraspinal axonal sparing/regeneration following sub-acute glial transplantation in a model of spinal cord contusion.

    Science.gov (United States)

    Barbour, Helen R; Plant, Christine D; Harvey, Alan R; Plant, Giles W

    2013-09-27

    It has been shown that olfactory ensheathing glia (OEG) and Schwann cell (SCs) transplantation are beneficial as cellular treatments for spinal cord injury (SCI), especially acute and sub-acute time points. In this study, we transplanted DsRED transduced adult OEG and SCs sub-acutely (14 days) following a T10 moderate spinal cord contusion injury in the rat. Behaviour was measured by open field (BBB) and horizontal ladder walking tests to ascertain improvements in locomotor function. Fluorogold staining was injected into the distal spinal cord to determine the extent of supraspinal and propriospinal axonal sparing/regeneration at 4 months post injection time point. The purpose of this study was to investigate if OEG and SCs cells injected sub acutely (14 days after injury) could: (i) improve behavioral outcomes, (ii) induce sparing/regeneration of propriospinal and supraspinal projections, and (iii) reduce tissue loss. OEG and SCs transplanted rats showed significant increased locomotion when compared to control injury only in the open field tests (BBB). However, the ladder walk test did not show statistically significant differences between treatment and control groups. Fluorogold retrograde tracing showed a statistically significant increase in the number of supraspinal nuclei projecting into the distal spinal cord in both OEG and SCs transplanted rats. These included the raphe, reticular and vestibular systems. Further pairwise multiple comparison tests also showed a statistically significant increase in raphe projecting neurons in OEG transplanted rats when compared to SCs transplanted animals. Immunohistochemistry of spinal cord sections short term (2 weeks) and long term (4 months) showed differences in host glial activity, migration and proteoglycan deposits between the two cell types. Histochemical staining revealed that the volume of tissue remaining at the lesion site had increased in all OEG and SCs treated groups. Significant tissue sparing was

  4. Size and spatial orientation of uterine tissue transplants on the peritoneum crucially determine the growth and cyst formation of endometriosis-like lesions in mice.

    Science.gov (United States)

    Körbel, Christina; Menger, Michael D; Laschke, Matthias W

    2010-10-01

    In many studies in rodents, intraperitoneal endometriosis-like lesions are surgically induced by syngeneic or autologous transplantation of uterine tissue samples, which are sutured to the abdominal wall. However, until now the surgical techniques have not been standardized, and we address this issue here. Uterine tissue samples were transplanted to the peritoneum of C57BL/6 mice (four study groups, n = 7 each). Using non-invasive high-resolution ultrasound imaging over a period of 4 weeks, we analyzed growth characteristics and cyst formation of the endometriosis-like lesions which developed, in relation to mode of transplantation (syngeneic versus autologous), type of tissue fixed adjacent to the peritoneum (endometrium versus perimetrium), and size of tissue transplanted (2 versus 3 mm). Immunohistochemical analysis was also performed. When the perimetrium, with underlying myometrium, was sutured next to the host peritoneum the endometriosis-like lesions which developed exhibited a higher growth rate (Pendometriosis-like lesions. Our study demonstrates that size and spatial orientation of peritoneally fixed uterine tissue samples crucially determine growth and cyst formation of endometriotic lesions in mice. These findings should improve the standardization and reliability of future studies, performed in the frequently used mouse model of surgically induced endometriosis.

  5. Storing live embryonic and adult human cartilage grafts for transplantation using a joint simulating device.

    Science.gov (United States)

    Cohen, I; Robinson, D; Cohen, N; Nevo, Z

    2000-11-01

    Cartilage transplantation as a means to replace damaged articular surfaces is of interest. A major obstacle is the long-term preservation of cartilage grafts. The commonly used technique of freezing the grafts inevitably leads to cellular death. The current study compares the technique to an innovative approach using a pulsed-pressure perfusion system termed a joint simulating device (JSD), intended to simulate intra-articular mechanical forces. Human articular cartilage explants were harvested from both embryonic epiphyseal tissue and femoral heads of elderly women (over 70 years of age) undergoing a partial joint replacement (hemi-arthroplasty) and were divided in two groups: half of the samples were incubated in the JSD while the remaining half were grown in static culture within tissue culture plates. After 10 days all samples were evaluated for: (a) cell vitality as assessed by image analysis and XTT assay; (b) biosynthetic activity as expressed by radioactive sulfate incorporation into glycosaminoglycans (GAG's); and (c) proteoglycan content as assessed by alcian blue staining intensity. A 10-fold increase in sulfate incorporation in samples held in the JSD compared to the static culture group was observed in embryonic cartilage. In adult cartilage culture in the JSD elevated sulfate incorporation by threefold as compared to static culture. Central necrosis was observed in specimens grown in the static culture plates, while it did not occur in the samples held in the JSD. Cell vitality as assessed by XTT assay was significantly better in the JSD group as compared to static culture. The difference was more pronounced in the embryonic specimens as compared to adult cartilage. The specimens cultured within the JSD retained proteoglycans significantly better than those cultured in static culture. Maintenance of cartilage specimens in a JSD was highly effective in keeping the vitality of cartilage explants in vitro over a 10-day period. A possible future

  6. Simultaneous bone marrow and composite tissue transplantation in rats treated with nonmyeloablative conditioning promotes tolerance1

    Science.gov (United States)

    Xu, Hong; Ramsey, Deborah M.; Wu, Shengli; Bozulic, Larry D.; Ildstad, Suzanne T.

    2012-01-01

    Background Approaches to safely induce tolerance in vascularized composite allotransplantation (VCA) with chimerism through bone marrow transplantation (BMT) are currently being pursued. However, the VCA were historically performed sequentially after donor chimerism was established. Delayed VCA is not clinically applicable due to the time constraints associated with procurement from deceased donors. A more clinically relevant approach to perform both the BMT and VCA simultaneously was evaluated. Methods WF (RT1Au) rats were treated with a short course of immunosuppressive therapy (anti-αβ-TCR mAb, FK-506, and anti-lymphocyte serum). One day prior to BMT, rats were treated with varying doses of total body irradiation (TBI) followed by transplantation of heterotopic osteomyocutaneous flaps from hind limbs of ACI (RT1Aabl) rats. Results 80% of rats conditioned with 300 cGy TBI and 40% of rats receiving 400 cGy TBI accepted the VCA. Mixed chimerism was detected in peripheral blood at one month post-VCA, but chimerism was lost in all transplant recipients by 4 months. The majority of peripheral donor cells originated from the BMT and not the VCA. Acceptors of VCA were tolerant of a donor skin graft challenge and no anti-donor antibodies were detectable, suggesting a central deletional mechanism for tolerance. Regulatory T cells (Treg) from spleens of acceptors more potently suppressed lymphocyte proliferation than Treg from rejectors in the presence of donor stimulator cells. Conclusions These studies suggest that simultaneous BMT and VCA may establish indefinite allograft survival in rats through Treg-mediated suppression and thymic deletion of alloreactive T cells. PMID:23250336

  7. The ethics of human cadaver organ transplantation: a biologist's viewpoint.

    Science.gov (United States)

    Emson, H E

    1987-01-01

    The rights of the various individuals involved in decision-making in cadaver organ donation are considered, and there is discussion of the relation of human cadavers to the planetary biomass. I conclude that the rights of the potential recipient should outweigh those of the other parties concerned and that education and legislation should recognise and promote this. PMID:3669037

  8. Non-invasive in-vivo imaging of stem cells after transplantation in cardiovascular tissue

    DEFF Research Database (Denmark)

    Mathiasen, Anders Bruun; Kastrup, Jens

    2013-01-01

    Stem cell therapy for degenerative diseases, including ischemic heart disease is now a clinical reality. In the search for the optimal cell type for each patient category, many different stem cell subpopulations have been used. In addition, different cell processing procedures and delivery methods......, migration and efficacy of the transplanted cells. Great effort is being made in finding new and better imaging techniques for different imaging modalities, and much have already been learned. But there are still many unanswered questions. In this review, we give an overview of the imaging modalities used...

  9. Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.

    Science.gov (United States)

    Hubbard, Dallin; Enda, Michael; Bond, Tanner; Moghaddam, Seyyed Pouya Hadipour; Conarton, Josh; Scaife, Courtney; Volckmann, Eric; Ghandehari, Hamidreza

    2015-11-02

    Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2 models innately lack mucous barriers, and rat isolated intestinal tissue has been shown to overestimate human permeability. This study is the first report of transport of PAMAM dendrimers across isolated human intestinal epithelium. It was observed that FITC labeled G4-NH2 and G3.5-COOH PAMAM dendrimers at 1 mM concentration do not have a statistically higher permeability compared to free FITC controls in isolated human jejunum and colonic tissues. Mannitol permeability was increased at 10 mM concentrations of G3.5-COOH and G4-NH2 dendrimers. Significant histological changes in human colonic and jejunal tissues were observed at G3.5-COOH and G4-NH2 concentrations of 10 mM implying that dose limiting toxicity may occur at similar concentrations in vivo. The permeability through human isolated intestinal tissue in this study was compared to previous rat and Caco-2 permeability data. This study implicates that PAMAM dendrimer oral drug delivery may be feasible, but it may be limited to highly potent drugs.

  10. The family interview in the process of donating organs and tissues for transplantation: perceptions of potential donors' relatives.

    Science.gov (United States)

    dos Santos, M J; Massarollo, M C K B; de Moraes, E L

    2014-01-01

    The family interview is a complex phase of the organ donation process because it involves aspects of the interviewer, the interviewee, the interview location, and ethical and legal issues. However, there are few publications on this phase of the donation process. This study aimed to reveal the meaning assigned to the interview phase, in the process of donating organs and tissues for transplantation, by the families of potential donors. We performed a qualitative study of the phenomenologic aspect, within the modality "structure situated phenomena." The study included the participation of 10 families. After analyzing the interviews, the meaning of the interview was unveiled by the family members. The statements revealed that the family interview is considered to be an important step for warnings, clarifications, and encouraging families to think about the possibility of donating to save and/or improve the quality of life of people in need for a transplant, and that studies contribute to the technical and scientific qualification of the interviewer as well as stimulate discussion among health professionals to improve the interviewing process. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Formation of tissue factor activity following incubation of recombinant human tissue factor apoprotein with plasma lipoproteins

    International Nuclear Information System (INIS)

    Sakai, T.; Kisiel, W.

    1990-01-01

    Incubation of recombinant human tissue factor apoprotein (Apo-TF) with human plasma decreased the recalcified clotting time of this plasma in a time-and dose-dependent manner suggesting relipidation of the Apo-TF by plasma lipoproteins. Incubation of Apo-TF with purified preparations of human very low density, low density and high density lipoproteins resulted in tissue factor activity in a clotting assay. The order of effectiveness was VLDL greater than LDL much greater than HDL. Tissue factor activity generated by incubation of a fixed amount of Apo-TF with plasma lipoproteins was lipoprotein concentration-dependent and saturable. The association of Apo-TF with lipoprotein particles was supported by gel filtration studies in which 125 I-Apo-TF coeluted with the plasma lipoprotein in the void volume of a Superose 6 column in the presence and absence of calcium ions. In addition, void-volume Apo-TF-lipoprotein fractions exhibited tissue factor activity. These results suggest that the factor VIII-bypassing activity of bovine Apo-TF observed in a canine hemophilic model may be due, in part, to its association with plasma lipoproteins and expression of functional tissue factor activity

  12. Regenerative Medicine, Disease Modelling, and Drug Discovery in Human Pluripotent Stem Cell-Derived Kidney Tissue

    Directory of Open Access Journals (Sweden)

    Navin Gupta

    2017-08-01

    Full Text Available The multitude of research clarifying critical factors in embryonic organ development has been instrumental in human stem cell research. Mammalian organogenesis serves as the archetype for directed differentiation protocols, subdividing the process into a series of distinct intermediate stages that can be chemically induced and monitored for the expression of stage-specific markers. Significant advances over the past few years include established directed differentiation protocols of human embryonic stem cells and human induced pluripotent stem cells (hiPSC into human kidney organoids in vitro. Human kidney tissue in vitro simulates the in vivo response when subjected to nephrotoxins, providing a novel screening platform during drug discovery to facilitate identification of lead candidates, reduce developmental expenditures, and reduce future rates of drug-induced acute kidney injury. Patient-derived hiPSC, which bear naturally occurring DNA mutations, may allow for modelling of human genetic diseases to enable determination of pathological mechanisms and screening for novel therapeutics. In addition, recent advances in genome editing with clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 enable the generation of specific mutations to study genetic disease, with non-mutated lines serving as an ideal isogenic control. The growing population of patients with end-stage kidney disease is a worldwide healthcare problem, with high morbidity and mortality rates, that warrants the discovery of novel forms of renal replacement therapy. Coupling the outlined advances in hiPSC research with innovative bioengineering techniques, such as decellularised kidney and three-dimensional printed scaffolds, may contribute to the development of bioengineered transplantable human kidney tissue as a means of renal replacement therapy.

  13. Anti-tumor effects of 125I radioactive particles implantation on transplantated tumor model of human breast cancer cells in nude mice

    International Nuclear Information System (INIS)

    Xiao Zhongdi; Liang Chunlin; Zhang Guoli; Jing Yue; Zhang Yucheng; Gai Baodong

    2011-01-01

    Objective: To study the anti-tumor effects of 125 I radioactive particles implantation on transplantated tumor model of human breast cancer cells in nude mice and clarify their anti-tumor mechanisms. Methods 120 nude mice transplantated with human breast cancer cells MCF-7 were randomly divided into 3 groups (n=40): 125 I radioactive particles implanted group, non-radioactive particles implanted group and non-particles implanted group. The articles were implanted into mice according to Pairs system principle. The expressions of Fas mRNA and protein and the activaties of caspase-3 and caspase-8 enzyme were detected by RT-PCR and Western blotting. The changes of cell cycle were detected by flow cytometry. Results: Compared with non-radioactive particles implanted group and non-particles implanted group, the size of cancer tissues in 125 I radioactive particles implanted group was reduced significantly (P 0 /G 1 phase was significantly increased (P 125 I radioactive particles into transplantated tumor model of human breast cancer cells can kill tumor cells, inhibit the growth cycle of tumor cells and induce the apoptosis of tumor cells in nude mice. (authors)

  14. Pancreatic islet transplantation

    Directory of Open Access Journals (Sweden)

    Corrêa-Giannella Maria

    2009-09-01

    Full Text Available Abstract Background No formulation of exogenous insulin available to date has yet been able to mimic the physiological nictemeral rhythms of this hormone, and despite all engineering advancements, the theoretical proposal of developing a mechanical replacement for pancreatic β cell still has not been reached. Thus, the replacement of β cells through pancreas and pancreatic islet transplantation are the only concrete alternatives for re-establishing the endogenous insulin secretion in type 1 diabetic patients. Since only 1 to 1.5% of the pancreatic mass corresponds to endocrine tissue, pancreatic islets transplantation arises as a natural alternative. Data from the International Islet Transplant Registry (ITR from 1983 to December 2000 document a total of 493 transplants performed around the world, with progressively worse rates of post-transplant insulin independence. In 2000, the "Edmonton Protocol" introduced several modifications to the transplantation procedure, such as the use of a steroid-free immunosuppression regimen and transplantation of a mean islet mass of 11,000 islet equivalents per kilogram, which significantly improved 1-year outcomes. Although the results of a 5-year follow-up in 65 patients demonstrated improvement in glycemic instability in a significant portion of them, only 7.5% of the patients have reached insulin independence, indicating the need of further advances in the preservation of the function of transplanted islet. In addition to the scarcity of organs available for transplantation, islets transplantation still faces major challenges, specially those related to cell loss during the process of islet isolation and the losses related to the graft site, apoptosis, allorejection, autoimmunity, and immunosuppression. The main strategies to optimize islet transplantation aim at improving all these aspects. Conclusion Human islet transplantation should be regarded as an intervention that can decrease the frequency of

  15. Transplantation of neuronal-primed human bone marrow mesenchymal stem cells in hemiparkinsonian rodents.

    Directory of Open Access Journals (Sweden)

    Melissa L M Khoo

    Full Text Available Bone marrow-derived human mesenchymal stem cells (hMSCs have shown promise in in vitro neuronal differentiation and in cellular therapy for neurodegenerative disorders, including Parkinson' disease. However, the effects of intracerebral transplantation are not well defined, and studies do not agreed on the optimal neuronal differentiation method. Here, we investigated three growth factor-based neuronal differentiation procedures (using FGF-2/EGF/PDGF/SHH/FGF-8/GDNF, and found all to be capable of eliciting an immature neural phenotype, in terms of cell morphology and gene/protein expression. The neuronal-priming (FGF-2/EGF method induced neurosphere-like formation and the highest NES and NR4A2 expression by hMSCs. Transplantation of undifferentiated and neuronal-primed hMSCs into the striatum and substantia nigra of 6-OHDA-lesioned hemiparkinsonian rats revealed transient graft survival of 7 days, despite the reported immunosuppressive properties of MSCs and cyclosporine-immunosuppression of rats. Neither differentiation of hMSCs nor induction of host neurogenesis was observed at injection sites, and hMSCs continued producing mesodermal fibronectin. Strategies for improving engraftment and differentiation post-transplantation, such as prior in vitro neuronal-priming, nigral and striatal grafting, and co-transplantation of olfactory ensheathing cells that promote neural regeneration, were unable to provide advantages. Innate inflammatory responses (Iba-1-positive microglia/macrophage and GFAP-positive astrocyte activation and accumulation were detected around grafts within 7 days. Our findings indicate that growth factor-based methods allow hMSC differentiation toward immature neuronal-like cells, and contrary to previous reports, only transient survival and engraftment of hMSCs occurs following transplantation in immunosuppressed hemiparkinsonian rats. In addition, suppression of host innate inflammatory responses may be a key factor for

  16. Transplantation of human umbilical cord-derived mesenchymal stems cells for the treatment of Becker muscular dystrophy in affected pedigree members.

    Science.gov (United States)

    Li, Pang; Cui, Kai; Zhang, Bo; Wang, Zhendan; Shen, Yangyang; Wang, Xiangyu; Zhang, Jianbo; Tong, Feng; Li, Sheng

    2015-04-01

    The regeneration of muscle tissue has been achieved using multipotent mesenchymal stem cells in mouse models of injured skeletal muscle. In the present study, the utility of multipotent human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in the treatment of Becker muscular dystrophy (BMD), a genetic disease where muscle tissue fails to regenerate, was examined in members from a pedigree affected by BMD. The disease status was evaluated in 4 affected pedigree members (II1, II2, II3 and III2; aged 50, 46, 42 and 6 years, respectively). The transplantation of the hUC‑MSCs (performed on 3 patients, I2, II3 and III2) was performed by infusion with an intravenous drip over a 30‑min period, and the patients were evaluated at 1, 3, 4 and 12 weeks following the procedure. The evaluation was based on physical characteristics, as well as on molecular testing for serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels and a histological examination of muscle biopsies. The patients suffered no adverse reactions in response to the transplantation of the hUC‑MSCs. At 1 week following transplantation all 3 patients showed improvement in the muscle force of the limbs, muscle size and daily activity. The walking gait of patient III2 had improved by 1 week post-transplantation and reached a normal status by 12 weeks. Serum CK and LDH levels were decreased relative to the baseline levels. A histological examination of muscle biopsies displayed no obvious tissue regeneration. In conclusion, the treatment of patients with BMD using hUC-MSCs was safe and of therapeutic benefit that lasted for up to 12 weeks. hUC-MSCs are, therefore, a potential cell therapy-based treatment option for patients with muscular dystrophies.

  17. Human adipose-derived stem cell spheroid treated with photobiomodulation irradiation accelerates tissue regeneration in mouse model of skin flap ischemia.

    Science.gov (United States)

    Park, In-Su; Chung, Phil-Sang; Ahn, Jin Chul; Leproux, Anais

    2017-11-01

    Skin flap grafting is a form of transplantation widely used in plastic surgery. However, ischemia/reperfusion injury is the main factor which reduces the survival rate of flaps following grafting. We investigated whether photobiomodulation (PBM) precondition prior to human adipose-derived stromal cell (hASC) spheroid (PBM-spheroid) transplantation improved skin tissue functional recovery by the stimulation of angiogenesis and tissue regeneration in skin flap of mice. The LED had an emission wavelength peaked at 660 ± 20 nm (6 J/cm 2 , 10 mW/cm 2 ). The expression of angiogenic growth factors in PBM-spheroid hASCs was much greater than that of not-PBM-treated spheroid or monolayer-cultured hASCs. From immunochemical staining analysis, the hASCs of PBM-spheroid were CD31 + , KDR + , and CD34 + , whereas monolayer-cultured hASCs were negative for these markers. To evaluate the therapeutic effect of hASC PBM-spheroid in vivo, PBS, monolayer-cultured hASCs, and not-PBM-spheroid were transplanted into a skin flap model. The animals were observed for 14 days. The PBM-spheroid hASCs transplanted into the skin flap ischemia differentiated into endothelial cells and remained differentiated. Transplantation of PBM-spheroid hASCs into the skin flap ischemia significantly elevated the density of vascular formations through angiogenic factors released by the skin flap ischemia and enhanced tissue regeneration at the lesion site. Consistent with these results, the transplantation of PBM-spheroid hASCs significantly improved functional recovery compared with PBS, monolayer-cultured hASCs, and not-PBM-spheroid treatment. These findings suggest that transplantation of PBM-spheroid hASCs may be an effective stem cell therapy for the treatment of skin flap ischemia.

  18. Generation of Scaffoldless Hyaline Cartilaginous Tissue from Human iPSCs

    Directory of Open Access Journals (Sweden)

    Akihiro Yamashita

    2015-03-01

    Full Text Available Defects in articular cartilage ultimately result in loss of joint function. Repairing cartilage defects requires cell sources. We developed an approach to generate scaffoldless hyaline cartilage from human induced pluripotent stem cells (hiPSCs. We initially generated an hiPSC line that specifically expressed GFP in cartilage when teratoma was formed. We optimized the culture conditions and found BMP2, transforming growth factor β1 (TGF-β1, and GDF5 critical for GFP expression and thus chondrogenic differentiation of the hiPSCs. The subsequent use of scaffoldless suspension culture contributed to purification, producing homogenous cartilaginous particles. Subcutaneous transplantation of the hiPSC-derived particles generated hyaline cartilage that expressed type II collagen, but not type I collagen, in immunodeficiency mice. Transplantation of the particles into joint surface defects in immunodeficiency rats and immunosuppressed mini-pigs indicated that neocartilage survived and had potential for integration into native cartilage. The immunodeficiency mice and rats suffered from neither tumors nor ectopic tissue formation. The hiPSC-derived cartilaginous particles constitute a viable cell source for regenerating cartilage defects.

  19. Generation of scaffoldless hyaline cartilaginous tissue from human iPSCs.

    Science.gov (United States)

    Yamashita, Akihiro; Morioka, Miho; Yahara, Yasuhito; Okada, Minoru; Kobayashi, Tomohito; Kuriyama, Shinichi; Matsuda, Shuichi; Tsumaki, Noriyuki

    2015-03-10

    Defects in articular cartilage ultimately result in loss of joint function. Repairing cartilage defects requires cell sources. We developed an approach to generate scaffoldless hyaline cartilage from human induced pluripotent stem cells (hiPSCs). We initially generated an hiPSC line that specifically expressed GFP in cartilage when teratoma was formed. We optimized the culture conditions and found BMP2, transforming growth factor β1 (TGF-β1), and GDF5 critical for GFP expression and thus chondrogenic differentiation of the hiPSCs. The subsequent use of scaffoldless suspension culture contributed to purification, producing homogenous cartilaginous particles. Subcutaneous transplantation of the hiPSC-derived particles generated hyaline cartilage that expressed type II collagen, but not type I collagen, in immunodeficiency mice. Transplantation of the particles into joint surface defects in immunodeficiency rats and immunosuppressed mini-pigs indicated that neocartilage survived and had potential for integration into native cartilage. The immunodeficiency mice and rats suffered from neither tumors nor ectopic tissue formation. The hiPSC-derived cartilaginous particles constitute a viable cell source for regenerating cartilage defects. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

    Science.gov (United States)

    Reeves, Daniel B; Peterson, Christopher W; Kiem, Hans-Peter; Schiffer, Joshua T

    2017-07-01

    Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact

  1. Translational neuropharmacology: the use of human isolated gastrointestinal tissues.

    Science.gov (United States)

    Sanger, G J; Broad, J; Kung, V; Knowles, C H

    2013-01-01

    Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age, gender, genetic background and disease. Here, these are discussed with reference to neuromuscular and neurosecretory functions of the human gastrointestinal (GI) tract. Tissues are obtained after informed consent, in collaboration with surgeons (surgical techniques help minimize variables) and pathologists. Given the difficulties of directly recording from human myenteric neurones (embedded between muscle layers), enteric motor nerve functions are studied by measuring muscle contractions/relaxations evoked by electrical stimulation of intrinsic nerves; responses are regionally dependent, often involving cholinergic and nitrergic phenotypes. Enteric sensory functions can be studied by evoking the peristaltic reflex, involving enteric sensory and motor nerves, but this has rarely been achieved. As submucosal neurones are more accessible (after removing the mucosa), direct neuronal recordings are possible. Neurosecretory functions are studied by measuring changes in short-circuit current across the mucosa. For all experiments, basic questions must be addressed. Because tissues are from patients, what are the controls and the influence of disease? How long does it take before function fully recovers? What is the impact of age- and gender-related differences? What is the optimal sample size? Addressing these and other questions minimizes variability and raises the scientific credibility of human tissue research. Such studies also reduce animal use. Further, the many differences between animal and human GI functions also means that human tissue research must question the ethical validity of using strains of animals with unproved translational significance. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  2. Tissue localization of human trefoil factors 1, 2, and 3

    DEFF Research Database (Denmark)

    Madsen, Jens; Nielsen, Ole; Tornøe, Ida

    2007-01-01

    Trefoil factors (TTFs) are small, compact proteins coexpressed with mucins in the gastrointestinal tract. Three trefoil factors are known in mammals: TFF1, TFF2, and TFF3. They are implicated to play diverse roles in maintenance and repair of the gastrointestinal channel. We compared the expression...... pattern of the three trefoil factors analyzing mRNA from a panel of 20 human tissues by conventional reverse transcriptase (RT) PCR and, in addition, by real-time PCR. These findings were supported by immunohistochemical analysis of paraffin-embedded human tissues using rabbit polyclonal antibodies raised...... against these factors. TFF1 showed highest expression in the stomach and colon, whereas TFF2 and TFF3 showed highest expression in stomach and colon, respectively. All three TFFs were found in the ducts of pancreas. Whereas TFF2 was found to be restricted to these two tissues, the structurally more...

  3. Tissue distribution of human acetylcholinesterase and butyrylcholinesterase messenger RNA

    Energy Technology Data Exchange (ETDEWEB)

    Jbilo, O.; Barteles, C.F.; Chatonnet, A.; Toutant, J.P.; Lockridge, O.

    1994-12-31

    Tissue distribution of human acetyicholinesterase and butyryicholinesterase messenger RNA. 1 Cholinesterase inhibitors occur naturally in the calabar bean (eserine), green potatoes (solanine), insect-resistant crab apples, the coca plant (cocaine) and snake venom (fasciculin). There are also synthetic cholinesterase inhibitors, for example man-made insecticides. These inhibitors inactivate acetyicholinesterase and butyrylcholinesterase as well as other targets. From a study of the tissue distribution of acetylcholinesterase and butyrylcholinesterase mRNA by Northern blot analysis, we have found the highest levels of butyrylcholinesterase mRNA in the liver and lungs, tissues known as the principal detoxication sites of the human body. These results indicate that butyrylcholinesterase may be a first line of defense against poisons that are eaten or inhaled.

  4. Infrared absorption of human breast tissues in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liu Chenglin [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Physics Department of Yancheng Teachers' College, Yancheng 224002 (China); Zhang Yuan [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Yan Xiaohui [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Zhang Xinyi [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China) and Shanghai Research Center of Acupuncture and Meridian, Pudong, Shanghai 201203 (China)]. E-mail: xy-zhang@fudan.edu.cn; Li Chengxiang [National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei 230029 (China); Yang Wentao [Cancer Hospital, Medical Center, Fudan University, Shanghai 200032 (China); Shi Daren [Cancer Hospital, Medical Center, Fudan University, Shanghai 200032 (China)

    2006-07-15

    The spectral characteristics of human breast tissues in normal status and during different cancerous stages have been investigated by synchrotron radiation based Fourier transform infrared (SR-FTIR) absorption spectroscopy. Thanks to the excellent synchrotron radiation infrared (IR) source, higher resolving power is achieved in SR-FTIR absorption spectra than in conventional IR absorption measurements. Obvious variations in IR absorption spectrum of breast tissues were found as they change from healthy to diseased, or say in progression to cancer. On the other hand, some specific absorption peaks were found in breast cancer tissues by SR-FTIR spectroscopic methods. These spectral characteristics of breast tissue may help us in early diagnosis of breast cancer.

  5. Analysis of human skin tissue by millimeter-wave reflectometry

    NARCIS (Netherlands)

    Smulders, P.F.M.

    2013-01-01

    Background/pupose: Millimeter-wave reflectometry is a potentially interesting technique to analyze the human skin in vivo in order to determine the water content locally in the skin. Purpose of this work is to investigate the possibility of skin-tissue differentiation. In addition, it addresses the

  6. Human Bites of the Face with Tissue Losses in Cosmopolitan ...

    African Journals Online (AJOL)

    Dr. Milaki Asuku

    A retrospective series of thirty-six cases of human bites to the face with tissue losses requiring reconstruction ..... bite wounds when compared to other forms of trauma in our regional ... References. 1. Liston PN, Tong DC, Firth NA, Kieser JA.

  7. Human meniscal proteoglycan metabolism in long-term tissue culture

    NARCIS (Netherlands)

    Verbruggen, G.; Verdonk, R.; Veys, E. M.; van Daele, P.; de Smet, P.; van den Abbeele, K.; Claus, B.; Baeten, D.

    1996-01-01

    For the purpose of human meniscal allografting, menisci have been maintained viable in in vitro culture. The influence of long-term tissue culture on the extracellular matrix metabolism of the meniscus has been studied. Fetal calf serum (FCS) was used as a supplement for the growth factors necessary

  8. Assessment of permeation of lipoproteins in human carotid tissue

    Science.gov (United States)

    Ghosn, Mohamad G.; Syed, Saba H.; Leba, Michael; Morrisett, Joel D.; Tuchin, Valery V.; Larin, Kirill V.

    2010-02-01

    Cardiovascular disease is among the leading causes of death in the United States. Specifically, atherosclerosis is an increasingly devastating contributor to the tally and has been found to be a byproduct of arterial permeability irregularities in regards to lipoprotein penetration. To further explore arterial physiology and molecular transport, the imaging technique of Optical Coherence Tomography (OCT) was employed. With OCT, the permeation of glucose (MW = 180 Da), low density lipoprotein (LDL; MW = 2.1 × 106 Da), and high density lipoprotein (HDL; MW = 2.5 × 105 Da) in human carotid tissue was studied to determine the effect of different molecular characteristics on permeation in atherosclerotic tissues. The permeability rates calculated from the diffusion of the molecular agents into the abnormal carotid tissue samples is compared to those of normal, healthy tissue. The results show that in the abnormal tissue, the permeation of agents correlate to the size constraints. The larger molecules of LDL diffuse the slowest, while the smallest molecules of glucose diffuse the fastest. However, in normal tissue, LDL permeates at a faster rate than the other two agents, implying the existence of a transport mechanism that facilitates the passage of LDL molecules. These results highlight the capability of OCT as a sensitive and specific imaging technique as well as provide significant information to the understanding of atherosclerosis and its effect on tissue properties.

  9. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  10. [Human herpesvirus-6 pneumonitis following autologous peripheral blood stem cell transplantation].

    Science.gov (United States)

    Saitoh, Yuu; Gotoh, Moritaka; Yoshizawa, Seiichiro; Akahane, Daigo; Fujimoto, Hiroaki; Ito, Yoshikazu; Ohyashiki, Kazuma

    2018-01-01

    A-46-year-old man was diagnosed with peripheral T cell lymphoma, not otherwise specified. He achieved a complete remission after pirarubicin, cyclophosphamide, vincristine, and prednisolone (THP-COP) therapy and successful autologous peripheral blood stem-cell transplantation (AutoSCT). However, 6 months post AutoSCT, he complained of fever. Chest computed tomography of the patient displayed bilateral interstitial pneumonitis. Human herpesvirus-6 (HHV-6) DNA was detected in his bronchoalveolar lavage fluid. Therefore, the patient was confirmed for HHV-6 pneumonitis. The treatment with foscarnet was effective, and no relapse was noticed in the patient. Besides, we have experienced pneumonitis of unknown origin in some patients after autologous or allogeneic stem-cell transplantations. Moreover, most of the above patients were clinically diagnosed using serum or plasma markers. Therefore, examining respiratory symptoms after AutoSCT would enable a more accurate diagnosis as well as treatment of patients with HHV-6 pneumonitis.

  11. Transplantation of colon carcinoma into granulation tissue induces an invasive morphotype

    NARCIS (Netherlands)

    Dingemans, K. P.; Zeeman-Boeschoten, I. M.; Keep, R. F.; Das, P. K.

    1993-01-01

    The stroma surrounding many malignant tumors resembles granulation tissue. To test the hypothesis that such stroma stimulates tumor invasiveness, we compared, by electron microscopy and immunohistochemistry, the growth patterns of CC531 rat colon adenocarcinoma in 2 experimental situations: (i)

  12. Genetically modified human bone marrow derived mesenchymal stem cells for improving the outcome of human islet transplantation.

    Directory of Open Access Journals (Sweden)

    Vaibhav Mundra

    Full Text Available The objective of this study was to determine the potential of human bone marrow derived mesenchymal stem cells (hBMSCs as gene carriers for improving the outcome of human islet transplantation. hBMSCs were characterized for the expression of phenotypic markers and transduced with Adv-hVEGF-hIL-1Ra to overexpress human vascular endothelial growth factor (hVEGF and human interleukin-1 receptor antagonist (hIL-1Ra. Human islets were co-cultured with hBMSCs overexpressing hVEGF and hIL-1Ra. Islet viability was determined by membrane fluorescent method and glucose stimulation test. Transduced hBMSCs and human islets were co-transplanted under the kidney capsule of NOD.Cg-Prkdc(scid Il2rg(tm1Wjl /SzJ (NSG diabetic mice and blood glucose levels were measured over time to demonstrate the efficacy of genetically modified hBMSCs. At the end of study, immunofluorescent staining of kidney section bearing islets was performed for insulin and von Willebrand Factor (vWF. hBMSCs were positive for the expression of CD73, CD90, CD105, CD146 and Stro-1 surface markers as determined by flow cytometry. Transduction of hBMSCs with adenovirus did not affect their stemness and differentiation potential as confirmed by mRNA levels of stem cell markers and adipogenic differentiation of transduced hBMSCs. hBMSCs were efficiently transduced with Adv-hVEGF-hIL-1Ra to overexpress hVEGF and hIL-1Ra. Live dead cell staining and glucose stimulation test have shown that transduced hBMSCs improved the viability of islets against cytokine cocktail. Co-transplantation of human islets with genetically modified hBMSCs improved the glycemic control of diabetic NSG mice as determined by mean blood glucose levels and intraperitoneal glucose tolerance test. Immunofluorescent staining of kidney sections was positive for human insulin and vWF. In conclusion, our results have demonstrated that hBMSCs may be used as gene carriers and nursing cells to improve the outcome of islet

  13. Human and murine very small embryonic-like cells represent multipotent tissue progenitors, in vitro and in vivo.

    Science.gov (United States)

    Havens, Aaron M; Sun, Hongli; Shiozawa, Yusuke; Jung, Younghun; Wang, Jingcheng; Mishra, Anjali; Jiang, Yajuan; O'Neill, David W; Krebsbach, Paul H; Rodgerson, Denis O; Taichman, Russell S

    2014-04-01

    The purpose of this study was to determine the lineage progression of human and murine very small embryonic-like (HuVSEL or MuVSEL) cells in vitro and in vivo. In vitro, HuVSEL and MuVSEL cells differentiated into cells of all three embryonic germ layers. HuVSEL cells produced robust mineralized tissue of human origin compared with controls in calvarial defects. Immunohistochemistry demonstrated that the HuVSEL cells gave rise to neurons, adipocytes, chondrocytes, and osteoblasts within the calvarial defects. MuVSEL cells were also able to differentiate into similar lineages. First round serial transplants of MuVSEL cells into irradiated osseous sites demonstrated that ∼60% of the cells maintained their VSEL cell phenotype while other cells differentiated into multiple tissues at 3 months. Secondary transplants did not identify donor VSEL cells, suggesting limited self renewal but did demonstrate VSEL cell derivatives in situ for up to 1 year. At no point were teratomas identified. These studies show that VSEL cells produce multiple cellular structures in vivo and in vitro and lay the foundation for future cell-based regenerative therapies for osseous, neural, and connective tissue disorders.

  14. Sequence typing of human adenoviruses isolated from Polish patients subjected to allogeneic hematopoietic stem cell transplantation - a single center experience.

    Science.gov (United States)

    Przybylski, Maciej; Rynans, Sylwia; Waszczuk-Gajda, Anna; Bilinski, Jarosław; Basak, Grzegorz W; Jędrzejczak, Wiesław W; Wróblewska, Marta; Młynarczyk, Grażyna; Dzieciątkowski, Tomasz

    2018-03-28

    Human adenoviruses (HAdV) from species A, B and C are commonly recognized as pathogens causing severe morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. The purpose of the present study was to determine HAdV types responsible for viremia in HSCT recipients at a large tertiary hospital in Poland. Analysis of partial nucleotide sequences of HAdV hexon gene was used to type 40 clinical isolates of HAdV obtained from 40 HSCT recipients. We identified six different HAdV serotypes belonging to species B, C and E. We demonstrated high variability in sequences of detected HAdV types, and patients infected with the same HAdV types were not hospitalized at the same time, which suggests the low possibility of cross-infection. In almost all patients, anti-HAdV antibodies in IgG class were detected, which indicates a history of HAdV infection in the past. Clinical symptoms accompanying HAdV viremia were in 89%, and in 61.5% of individuals, HAdV was a sole pathogen detected. There were no cases with high-level HAdV viremia and severe systemic or organ infections. Graft-versus-host disease (GvHD) was present in patients infected with species B and C, but grade II of GvHD was observed only in patients infected with HAdV-B. The predominance of HAdV-C and common presence of anti-HAdV antibodies in IgG class may strongly suggest that most infections in the present study were reactivations of HAdV persisting into the patient's mucosa-associated lymphoid tissues. Variability of HAdV sequences suggests that cross-infections between patients were very rare. GvHD: graft-versus-host disease; HAdV: human adenoviruses; HSCT: hematopoietic stem cell transplantation.

  15. Zicam-induced damage to mouse and human nasal tissue.

    Directory of Open Access Journals (Sweden)

    Jae H Lim

    Full Text Available Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc, a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction.

  16. Human umbilical cord mesenchymal stem cells: osteogenesis in vivo as seed cells for bone tissue engineering.

    Science.gov (United States)

    Diao, Yinze; Ma, Qingjun; Cui, Fuzhai; Zhong, Yanfeng

    2009-10-01

    Mesenchymal stem cells (MSCs) are ideal seed cells for bone tissue engineering. However, intrinsic deficiencies exist for the autologous transplantation strategy of constructing artificial bone with MSCs derived from bone marrow of patients. In this study, MSCs-like cells were isolated from human umbilical cords and were expanded in vitro. Flow cytometric analysis revealed that cells from the fourth passage were positive for CD29, CD44, CD71, CD73, CD90, and CD105 whereas they were negative for CD14, CD34, CD45, and CD117. Furthermore, these cells expressed HLA-A, B, C (MHC-I), but not HLA-DP, DQ, DR (MHC-II), or costimulatory molecules such as CD80 and CD86. Following incubation in specific inductive media for 3 weeks, cultured cells were shown to possess potential to differentiate into adipogenic, osteogenic or chondrogenic lineages in vitro. The umbilical cord-derived MSCs (UC-MSCs) were loaded with a biomimetic artificial bone scaffold material before being implanted subcutaneously in the back of Balb/c nude mice for four to twelve weeks. Our results revealed that UC-MSCs loaded with the scaffold displayed capacity of osteogenic differentiation leading to osteogenesis with human origin in vivo. As a readily available source of seed cells for bone tissue engineering, UC-MSCs should have broad application prospects.

  17. Occurrence of human bocaviruses and parvovirus 4 in solid tissues.

    Science.gov (United States)

    Norja, Päivi; Hedman, Lea; Kantola, Kalle; Kemppainen, Kaisa; Suvilehto, Jari; Pitkäranta, Anne; Aaltonen, Leena-Maija; Seppänen, Mikko; Hedman, Klaus; Söderlund-Venermo, Maria

    2012-08-01

    Human bocaviruses 1-4 (HBoV1-4) and parvovirus 4 (PARV4) are recently discovered human parvoviruses. HBoV1 is associated with respiratory infections of young children, while HBoV2-4 are enteric viruses. The clinical manifestations of PARV4 remain unknown. The objective of this study was to determine whether the DNAs of HBoV1-4 and PARV4 persist in human tissues long after primary infection. Biopsies of tonsillar tissue, skin, and synovia were examined for HBoV1-4 DNA and PARV4 DNA by PCR. Serum samples from the tissue donors were assayed for HBoV1 and PARV4 IgG and IgM antibodies. To obtain species-specific seroprevalences for HBoV1 and for HBoV2/3 combined, the sera were analyzed after virus-like particle (VLP) competition. While HBoV1 DNA was detected exclusively in the tonsillar tissues of 16/438 individuals (3.7%), all of them ≤8 years of age. HBoV2-4 and PARV4 DNAs were absent from all tissue types. HBoV1 IgG seroprevalence was 94.9%. No subject had HBoV1 or PARV4 IgM, nor did they have PARV4 IgG. The results indicate that HBoV1 DNA occurred in a small proportion of tonsils of young children after recent primary HBoV1 infection, but did not persist long in the other tissue types studied, unlike parvovirus B19 DNA. The results obtained by the PARV4 assays are in line with previous results on PARV4 epidemiology. Copyright © 2012 Wiley Periodicals, Inc.

  18. Immunolocalisation of oestrogen receptor beta in human tissues.

    Science.gov (United States)

    Taylor, A H; Al-Azzawi, F

    2000-02-01

    Oestrogens exert their actions via specific nuclear protein receptors that are members of the steroid/thyroid receptor superfamily of transcription factors. Recently, a second oestrogen receptor (ERbeta) has been cloned, and using reverse transcription-PCR and immunohistochemistry it has been shown to have a wide tissue distribution in the rat that is distinct from the classical oestrogen receptor, ERalpha. Using commercial polyclonal antisera against peptides specific to human ERbeta, we have determined the sites of ERbeta expression in archival and formalin-fixed human tissue and compared its expression with that of ERalpha. ERbeta was localised to the cell nuclei of a wide range of normal adult human tissues including ovary, Fallopian tube, uterus, lung, kidney, brain, heart, prostate and testis. In the ovary, ERbeta was present in multiple cell types including granulosa cells in small, medium and large follicles, theca and corpora lutea, whereas ERalpha was weakly expressed in the nuclei of granulosa cells, but not in the theca nor in the copora lutea. In the endometrium, both ERalpha and ERbeta were observed in luminal epithelial cells and in the nuclei of stromal cells but, significantly, ERbeta was weak or absent from endometrial glandular epithelia. Epithelial cells in most male tissues including the prostate, the urothelium and muscle layers of the bladder, and Sertoli cells in the testis, were also immunopositive for ERbeta. Significant ERbeta immunoreactivity was detected in most areas of the brain, with the exception of the hippocampus - a tissue that stained positively for ERalpha. In conclusion, the almost ubiquitous immunohistochemical localisation of ERbeta indicates that ERbeta may play a major role in the mediation of oestrogen action. The differential expression of ERalpha and ERbeta in some of these tissues suggests a more complex control mechanism in oestrogenic potential than originally envisioned.

  19. Usherin expression is highly conserved in mouse and human tissues.

    Science.gov (United States)

    Pearsall, Nicole; Bhattacharya, Gautam; Wisecarver, Jim; Adams, Joe; Cosgrove, Dominic; Kimberling, William

    2002-12-01

    Usher syndrome is an autosomal recessive disease that results in varying degrees of hearing loss and retinitis pigmentosa. Three types of Usher syndrome (I, II, and III) have been identified clinically with Usher type II being the most common of the three types. Usher type II has been localized to three different chromosomes 1q41, 3p, and 5q, corresponding to Usher type 2A, 2B, and 2C respectively. Usherin is a basement membrane protein encoded by the USH2A gene. Expression of usherin has been localized in the basement membrane of several tissues, however it is not ubiquitous. Immunohistochemistry detected usherin in the following human tissues: retina, cochlea, small and large intestine, pancreas, bladder, prostate, esophagus, trachea, thymus, salivary glands, placenta, ovary, fallopian tube, uterus, and testis. Usherin was absent in many other tissues such as heart, lung, liver, kidney, and brain. This distribution is consistent with the usherin distribution seen in the mouse. Conservation of usherin is also seen at the nucleotide and amino acid level when comparing the mouse and human gene sequences. Evolutionary conservation of usherin expression at the molecular level and in tissues unaffected by Usher 2a supports the important structural and functional role this protein plays in the human. In addition, we believe that these results could lead to a diagnostic procedure for the detection of Usher syndrome and those who carry an USH2A mutation.

  20. A draft map of the human ovarian proteome for tissue engineering and clinical applications.

    Science.gov (United States)

    Ouni, Emna; Vertommen, Didier; Chiti, Maria Costanza; Dolmans, Marie-Madeleine; Amorim, Christiani Andrade

    2018-02-23

    Fertility preservation research in women today is increasingly taking advantage of bioengineering techniques to develop new biomimetic materials and solutions to safeguard ovarian cell function and microenvironment in vitro and in vivo. However, available data on the human ovary are limited and fundamental differences between animal models and humans are hampering researchers in their quest for more extensive knowledge of human ovarian physiology and key reproductive proteins that need to be preserved. We therefore turned to multi-dimensional label-free mass spectrometry to analyze human ovarian cortex, as it is a high-throughput and conclusive technique providing information on the proteomic composition of complex tissues like the ovary. In-depth proteomic profiling through two-dimensional liquid chromatography-mass spectrometry, western blot, histological and immunohistochemical analyses, and data mining helped us to confidently identify 1,508 proteins. Moreover, our method allowed us to chart the most complete representation so far of the ovarian matrisome, defined as the ensemble of extracellular matrix proteins and associated factors, including more than 80 proteins. In conclusion, this study will provide a better understanding of ovarian proteomics, with a detailed characterization of the ovarian follicle microenvironment, in order to enable bioengineers to create biomimetic scaffolds for transplantation and three-dimensional in vitro culture. By publishing our proteomic data, we also hope to contribute to accelerating biomedical research into ovarian health and disease in general. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Protein Kinase A Regulatory Subunits in Human Adipose Tissue

    Science.gov (United States)

    Mantovani, Giovanna; Bondioni, Sara; Alberti, Luisella; Gilardini, Luisa; Invitti, Cecilia; Corbetta, Sabrina; Zappa, Marco A.; Ferrero, Stefano; Lania, Andrea G.; Bosari, Silvano; Beck-Peccoz, Paolo; Spada, Anna

    2009-01-01

    OBJECTIVE—In human adipocytes, the cAMP-dependent pathway mediates signals originating from β-adrenergic activation, thus playing a key role in the regulation of important metabolic processes, i.e., lipolysis and thermogenesis. Cyclic AMP effects are mainly mediated by protein kinase A (PKA), whose R2B regulatory isoform is the most expressed in mouse adipose tissue, where it protects against diet-induced obesity and fatty liver development. The aim of the study was to investigate possible differences in R2B expression, PKA activity, and lipolysis in adipose tissues from obese and nonobese subjects. RESEARCH DESIGN AND METHODS—The expression of the different PKA regulatory subunits was evaluated by immunohistochemistry, Western blot, and real-time PCR in subcutaneous and visceral adipose tissue samples from 20 nonobese and 67 obese patients. PKA activity and glycerol release were evaluated in total protein extract and adipocytes isolated from fresh tissue samples, respectively. RESULTS—Expression techniques showed that R2B was the most abundant regulatory protein, both at mRNA and protein level. Interestingly, R2B mRNA levels were significantly lower in both subcutaneous and visceral adipose tissues from obese than nonobese patients and negatively correlated with BMI, waist circumference, insulin levels, and homeostasis model assessment of insulin resistance. Moreover, both basal and stimulated PKA activity and glycerol release were significantly lower in visceral adipose tissue from obese patients then nonobese subjects. CONCLUSIONS—Our results first indicate that, in human adipose tissue, there are important BMI-related differences in R2B expression and PKA activation, which might be included among the multiple determinants involved in the different lipolytic response to β-adrenergic activation in obesity. PMID:19095761

  2. Consent: a Cartesian ideal? Human neural transplantation in Parkinson's disease.

    Science.gov (United States)

    Lopes, Manuel; Meningaud, Jean-Paul; Behin, Anthony; Hervé, Christian

    2003-01-01

    The grafting of human embryonic cells in Parkinson's disease is an innovative and hopefully useful therapeutic approach. However, it still concerns a very small number of patients and is only suggested as a research protocol. We present here a study of the problems of information and consent to research within the framework of this disease in which the efficacy of medical treatment is shortlived. The only French center to use this treatment (Hôpital H. Mondor in Créteil) has received authorization from the Comité Consultatif National d'Ethique (Consultative National Committee on Ethics). Eleven patients were treated between 1991 and 1998. The study of the results of a questionnaire sent to those patients showed the difficulties met in evaluating the perception of information despite intact intellectual capacities in people "prepared to risk everything." In France, the duty to inform patients during research procedures is regulated by the Huriet Act. However, it is not easy to guarantee genuine consent when preliminary information is given to patients psychologically impaired by the slow and ineluctable course of their disease. In these borderline cases, a valid consent seems to be a myth in terms of pure autonomy when considered with the Cartesian aim of elimination of uncertainty. The relevance of this concept of genuine consent probably makes more sense as aiming at a Cartesian ideal which is perhaps more in the spirit rather than in the letter. It is in that same spirit that, from the outset, we propose to define t he practical ways of answering the patients' request for information, even sometimes after consent has been given.

  3. Engineered cartilaginous tubes for tracheal tissue replacement via self-assembly and fusion of human mesenchymal stem cell constructs.

    Science.gov (United States)

    Dikina, Anna D; Strobel, Hannah A; Lai, Bradley P; Rolle, Marsha W; Alsberg, Eben

    2015-06-01

    There is a critical need to engineer a neotrachea because currently there are no long-term treatments for tracheal stenoses affecting large portions of the airway. In this work, a modular tracheal tissue replacement strategy was developed. High-cell density, scaffold-free human mesenchymal stem cell-derived cartilaginous rings and tubes were successfully generated through employment of custom designed culture wells and a ring-to-tube assembly system. Furthermore, incorporation of transforming growth factor-β1-delivering gelatin microspheres into the engineered tissues enhanced chondrogenesis with regard to tissue size and matrix production and distribution in the ring- and tube-shaped constructs, as well as luminal rigidity of the tubes. Importantly, all engineered tissues had similar or improved biomechanical properties compared to rat tracheas, which suggests they could be transplanted into a small animal model for airway defects. The modular, bottom up approach used to grow stem cell-based cartilaginous tubes in this report is a promising platform to engineer complex organs (e.g., trachea), with control over tissue size and geometry, and has the potential to be used to generate autologous tissue implants for human clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation.

    Science.gov (United States)

    Vargas, Hugo E; Laskus, Tomasz; Radkowski, Marek; Wilkinson, Jeff; Balan, Vijay; Douglas, David D; Harrison, M Edwyn; Mulligan, David C; Olden, Kevin; Adair, Debra; Rakela, Jorge

    2002-11-01

    Patients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. The aim of this study is to determine whether hepatitis C virus (HCV) replication could be found in brain tissue in patients with hepatitis C and depression. We report two patients with recurrent hepatitis C after liver transplantation who also developed severe depression. One patient died of multiorgan failure and the other, septicemia caused by Staphylococcus aureussis. Both patients had evidence of severe hepatitis C recurrence with features of cholestatic fibrosing hepatitis. We were able to study samples of their central nervous system obtained at autopsy for evidence of HCV replication. The presence of HCV RNA-negative strand, which is the viral replicative form, was determined by strand-specific Tth-based reverse-transcriptase polymerase chain reaction. Viral sequences were compared by means of single-strand conformation polymorphism and direct sequencing. HCV RNA-negative strands were found in subcortical white matter from one patient and cerebral cortex from the other patient. HCV RNA-negative strands amplified from brain tissue differed by several nucleotide substitutions from serum consensus sequences in the 5' untranslated region. These findings support the concept of HCV neuroinvasion, and we speculate that it may provide a biological substrate to neuropsychiatric disorders observed in patients with chronic hepatitis C. The exact lineage of cells permissive for HCV replication and the possible interaction between viral replication and cerebral function that may lead to depression remain to be elucidated.

  5. Transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into rat spinal cord injuries does not cause harm.

    Science.gov (United States)

    Cloutier, Frank; Siegenthaler, Monica M; Nistor, Gabriel; Keirstead, Hans S

    2006-07-01

    Demyelination contributes to loss of function following spinal cord injury. We have shown previously that transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into adult rat 200 kD contusive spinal cord injury sites enhances remyelination and promotes recovery of motor function. Previous studies using oligodendrocyte lineage cells have noted a correlation between the presence of demyelinating pathology and the survival and migration rate of the transplanted cells. The present study compared the survival and migration of human embryonic stem cell-derived oligodendrocyte progenitors injected 7 days after a 200 or 50 kD contusive spinal cord injury, as well as the locomotor outcome of transplantation. Our findings indicate that a 200 kD spinal cord injury induces extensive demyelination, whereas a 50 kD spinal cord injury induces no detectable demyelination. Cells transplanted into the 200 kD injury group survived, migrated, and resulted in robust remyelination, replicating our previous studies. In contrast, cells transplanted into the 50 kD injury group survived, exhibited limited migration, and failed to induce remyelination as demyelination in this injury group was absent. Animals that received a 50 kD injury displayed only a transient decline in locomotor function as a result of the injury. Importantly, human embryonic stem cell-derived oligodendrocyte progenitor transplants into the 50 kD injury group did not cause a further decline in locomotion. Our studies highlight the importance of a demyelinating pathology as a prerequisite for the function of transplanted myelinogenic cells. In addition, our results indicate that transplantation of human embryonic stem cell-derived oligodendrocyte progenitor cells into the injured spinal cord is not associated with a decline in locomotor function.

  6. Milestones of Hematopoietic Stem Cell Transplantation – From First Human Studies to Current Developments

    Science.gov (United States)

    Juric, Mateja Kralj; Ghimire, Sakhila; Ogonek, Justyna; Weissinger, Eva M.; Holler, Ernst; van Rood, Jon J.; Oudshoorn, Machteld; Dickinson, Anne; Greinix, Hildegard T.

    2016-01-01

    Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation (HSCT) has become an established curative treatment for an increasing number of patients with life-threatening hematological, oncological, hereditary, and immunological diseases. This has become possible due to worldwide efforts of preclinical and clinical research focusing on issues of transplant immunology, reduction of transplant-associated morbidity, and mortality and efficient malignant disease eradication. The latter has been accomplished by potent graft-versus-leukemia (GvL) effector cells contained in the stem cell graft. Exciting insights into the genetics of the human leukocyte antigen (HLA) system allowed improved donor selection, including HLA-identical related and unrelated donors. Besides bone marrow, other stem cell sources like granulocyte-colony stimulating-mobilized peripheral blood stem cells and cord blood stem cells have been established in clinical routine. Use of reduced-intensity or non-myeloablative conditioning regimens has been associated with a marked reduction of non-hematological toxicities and eventually, non-relapse mortality allowing older patients and individuals with comorbidities to undergo allogeneic HSCT and to benefit from GvL or antitumor effects. Whereas in the early years, malignant disease eradication by high-dose chemotherapy or radiotherapy was the ultimate goal; nowadays, allogeneic HSCT has been recognized as cellular immunotherapy relying prominently on immune mechanisms and to a lesser extent on non-specific direct cellular toxicity. This chapter will summarize the key milestones of HSCT and introduce current developments. PMID:27881982

  7. Diagnosis of human metapneumovirus infection in immunosuppressed lung transplant recipients and children evaluated for pertussis.

    Science.gov (United States)

    Dare, Ryan; Sanghavi, Sonali; Bullotta, Arlene; Keightley, Maria-Cristina; George, Kirsten St; Wadowsky, Robert M; Paterson, David L; McCurry, Kenneth R; Reinhart, Todd A; Husain, Shahid; Rinaldo, Charles R

    2007-02-01

    Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is known to cause respiratory tract infections in children and immunocompromised individuals. Given the difficulties of identifying hMPV by conventional culture, molecular techniques could improve the detection of this virus in clinical specimens. In this study, we developed a real-time reverse transcription-PCR (RT-PCR) assay designed to detect the four genetic lineages of hMPV. This assay and a commercial real-time nucleic acid sequence-based amplification (NASBA) assay (bioMérieux, Durham, NC) were used to determine the prevalence of hMPV in 114 immunosuppressed asymptomatic and symptomatic lung transplant recipients and 232 pediatric patients who were being evaluated for pertussis. hMPV was detected in 4.3% of the immunosuppressed lung transplant recipients and in 9.9% of children evaluated for pertussis. Both RT-PCR and NASBA assays were efficient in detection of hMPV infection in respiratory specimens. Even though hMPV was detected in a small number of the lung transplant recipients, it was still the most prevalent etiologic agent detected in patients with respiratory symptoms. In both of these diverse patient populations, hMPV infection was the most frequent viral respiratory tract infection identified. Given our findings, infection with hMPV infection should be determined as part of the differential diagnosis of respiratory illnesses.

  8. Diagnosis of Human Metapneumovirus Infection in Immunosuppressed Lung Transplant Recipients and Children Evaluated for Pertussis▿

    Science.gov (United States)

    Dare, Ryan; Sanghavi, Sonali; Bullotta, Arlene; Keightley, Maria-Cristina; George, Kirsten St.; Wadowsky, Robert M.; Paterson, David L.; McCurry, Kenneth R.; Reinhart, Todd A.; Husain, Shahid; Rinaldo, Charles R.

    2007-01-01

    Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is known to cause respiratory tract infections in children and immunocompromised individuals. Given the difficulties of identifying hMPV by conventional culture, molecular techniques could improve the detection of this virus in clinical specimens. In this study, we developed a real-time reverse transcription-PCR (RT-PCR) assay designed to detect the four genetic lineages of hMPV. This assay and a commercial real-time nucleic acid sequence-based amplification (NASBA) assay (bioMérieux, Durham, NC) were used to determine the prevalence of hMPV in 114 immunosuppressed asymptomatic and symptomatic lung transplant recipients and 232 pediatric patients who were being evaluated for pertussis. hMPV was detected in 4.3% of the immunosuppressed lung transplant recipients and in 9.9% of children evaluated for pertussis. Both RT-PCR and NASBA assays were efficient in detection of hMPV infection in respiratory specimens. Even though hMPV was detected in a small number of the lung transplant recipients, it was still the most prevalent etiologic agent detected in patients with respiratory symptoms. In both of these diverse patient populations, hMPV infection was the most frequent viral respiratory tract infection identified. Given our findings, infection with hMPV infection should be determined as part of the differential diagnosis of respiratory illnesses. PMID:17065270

  9. Transplantation of specific human astrocytes promotes functional recovery after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Stephen J A Davies

    2011-03-01

    Full Text Available Repairing trauma to the central nervous system by replacement of glial support cells is an increasingly attractive therapeutic strategy. We have focused on the less-studied replacement of astrocytes, the major support cell in the central nervous system, by generating astrocytes from embryonic human glial precursor cells using two different astrocyte differentiation inducing factors. The resulting astrocytes differed in expression of multiple proteins thought to either promote or inhibit central nervous system homeostasis and regeneration. When transplanted into acute transection injuries of the adult rat spinal cord, astrocytes generated by exposing human glial precursor cells to bone morphogenetic protein promoted significant recovery of volitional foot placement, axonal growth and notably robust increases in neuronal survival in multiple spinal cord laminae. In marked contrast, human glial precursor cells and astrocytes generated from these cells by exposure to ciliary neurotrophic factor both failed to promote significant behavioral recovery or similarly robust neuronal survival and support of axon growth at sites of injury. Our studies thus demonstrate functional differences between human astrocyte populations and suggest that pre-differentiation of precursor cells into a specific astrocyte subtype is required to optimize astrocyte replacement therapies. To our knowledge, this study is the first to show functional differences in ability to promote repair of the injured adult central nervous system between two distinct subtypes of human astrocytes derived from a common fetal glial precursor population. These findings are consistent with our previous studies of transplanting specific subtypes of rodent glial precursor derived astrocytes into sites of spinal cord injury, and indicate a remarkable conservation from rat to human of functional differences between astrocyte subtypes. In addition, our studies provide a specific population of human

  10. Cryopreservation of porcine fetal ventral mesencephalic tissue for intrastriatal transplantation in Parkinson's disease

    NARCIS (Netherlands)

    Koopmans, J.; Hogenesch, I.; Copray, S.; Middel, B.; van Dijk, H.; Go, K-G.; Staal, M.

    2001-01-01

    In this study we examined the efficacy of cryopreserving porcine fetal mesencephalic tissue. After microscopical dissection of the ventral mesencephalon (VM) from E28 pig fetuses, the collection of explants was randomly divided into two equal parts. One part was directly prepared as cell suspension.

  11. Distribution of Human papilloma virus genotypes in cervical cancer tissues

    Directory of Open Access Journals (Sweden)

    Stamenković M.

    2014-01-01

    Full Text Available Cervical cancer incidence and mortality rates in Serbia are among the highest in Europe and data on Human papilloma virus (HPV type distribution are scarce. The aim of this study was to determine the prevalence of HPV types in archival specimens of cervical cancer tissues of women in the Serbian population. A total of 45 paraffin-embedded tissue samples of cervical carcinoma were used in this study. The procedure included deparaffinization of tissue samples, DNA extraction, PCR, gel electrophoresis and HPV genotyping by direct sequencing. HPV was detected in 32 samples (71%. Genotyping revealed the presence of 6 high-risk HPV types 16, 18, 33, 45, 53 and 58, where HPV type 16 was the most prevalent type (73.7%. The results of this study and further studies will provide more detailed information about HPV genotype distribution and may contribute to the formulation of national guidelines for the prevention of cervical cancer. [175073

  12. High resolution ultrastructure imaging of fractures in human dental tissues

    Directory of Open Access Journals (Sweden)

    Tan Sui

    2014-01-01

    Full Text Available Human dental hard tissues are dentine, cementum, and enamel. These are hydrated mineralised composite tissues with a hierarchical structure and versatile thermo-mechanical properties. The hierarchical structure of dentine and enamel was imaged by transmission electron microscopy (TEM of samples prepared by focused ion beam (FIB milling. High resolution TEM was carried out in the vicinity of a crack tip in dentine. An intricate “random weave” pattern of hydroxyapatile crystallites was observed and this provided a possible explanation for toughening of the mineralized dentine tissue at the nano-scale. The results reported here provide the basis for improved understanding of the relationship between the multi-scale nature and the mechanical properties of hierarchically structured biomaterials, and will also be useful for the development of better prosthetic and dental restorative materials.

  13. JURIDICAL ANALYSIS OF LEGISLATION RELATED TO THE CRIME OF TRADE IN HUMAN ORGANS FOR THE BENEFIT OF THE KIDNEY ORGAN TRANSPLANT (Comparative Studies Between Indonesia with Philippines

    Directory of Open Access Journals (Sweden)

    Benny Situmorang

    2016-06-01

    Full Text Available In accordance with organ transplant’s evolve especially the kidneys it is necessary to rule out specific health legislation  in dealing with transplantation  of human body’s  organs  to prevent  human  trafficking  of human  organs.  The approaches used is the approach of legislation and comparisons to provide an overview of the regulation of transplantation of human body’s organs in Indonesia, and to know the comparison with other countries that have specific rules on transplants. The result is that the regulations in Indonesia does not have rules on organ transplants from living non-related organ donation and found no legal protection againts the donor. Keywords: Organ   transplant,   kidney   transplant,   human   trafficking,   health legislation.

  14. Infections in the tissue material and their impact on the loss of transplants in the Laboratory of in vitro Cell and Tissue Culture with Tissue Bank in the years 2011-2015.

    Science.gov (United States)

    Kitala, D; Klama-Baryła, A; Kawecki, M; Kraut, M; Łabuś, W; Glik, J; Ples, M; Tomanek, E; Nowak, M

    2017-03-01

    Radiation sterilization eliminates microbiological infections but causes the degradation of the cell factor. The negative result of microbiological examination for tissue transplants is one of the conditions for approval for distribution in patients. The study attempts to verify impact of the presence of microbes onto material for transplant loss. In the 2011-2015 period, we analyzed 293 donors of skin and amnion. Microbiological sampling was performed. The total of 21 strains of bacteria, molds and fungi was identified in collected tissue. The widest spectrum of strains was found in skin (17), followed by amnia (8). The total number of positive findings was 147 and was again highest in skin (129), while the number of positive findings in amnia was 18 only. The general percentage of fungal infections was very low. The presence of fungal strains was only observed in allogeneic skin (2%). Large number of microorganisms isolated from the skin before sterilization was observed, so it seems impossible to use allogeneic intravital skin. However, the intravital application of allogeneic amnion obtained from cesarean section remains to be considered.

  15. Overview of marrow transplantation

    International Nuclear Information System (INIS)

    Thomas, E.D.

    1985-01-01

    Bone marrow transplantation is now an accepted form of therapy for many hematologic disorders including aplastic anemia, genetically determined diseases and malignant diseases, particularly leukemia, and for rescue of patients given intensive chemoradiotherapy for malignant disease. The donor may be a healthy identical twin, a family member or even an unrelated person. Selection is made on the basis of human leukocyte antigen tissue typing. Intensive chemoradiotherapy is used to suppress patients' immune systems to facilitate engraftment and destroy diseased marrow. Transfusion of platelets, erythrocytes and granulocytes (or all of these), antibiotic coverage and protection from infection are necessary during the pancytopenic period. Survival rates vary considerably depending on a patient's disease, clinical state and age. Patients with aplastic anemia transplanted early in the course of their disease have a survival rate of approximately 80%. Patients with acute lymphoblastic leukemia are usually transplanted in a second or subsequent remission and have a survival rate of 25% to 40%. Patients with acute nonlymphoblastic leukemia in remission have survivals ranging from 45% to 70%. More than 200 patients in the chronic phase of chronic granulocytic leukemia have been transplanted with survival ranging from 50% to 70%. Complications of marrow transplantation include marrow graft rejection, graft-versus-host disease, immunologic insufficiency and the possibility of recurrence of the leukemia. 14 references

  16. Adipose tissue macrophages impair preadipocyte differentiation in humans.

    Directory of Open Access Journals (Sweden)

    Li Fen Liu

    Full Text Available The physiologic mechanisms underlying the relationship between obesity and insulin resistance are not fully understood. Impaired adipocyte differentiation and localized inflammation characterize adipose tissue from obese, insulin-resistant humans. The directionality of this relationship is not known, however. The aim of the current study was to investigate whether adipose tissue inflammation is causally-related to impaired adipocyte differentiation.Abdominal subcutaneous(SAT and visceral(VAT adipose tissue was obtained from 20 human participants undergoing bariatric surgery. Preadipocytes were isolated, and cultured in the presence or absence of CD14+ macrophages obtained from the same adipose tissue sample. Adipocyte differentiation was quantified after 14 days via immunofluorescence, Oil-Red O, and adipogenic gene expression. Cytokine secretion by mature adipocytes cultured with or without CD14+macrophages was quantified.Adipocyte differentiation was significantly lower in VAT than SAT by all measures (p<0.001. With macrophage removal, SAT preadipocyte differentiation increased significantly as measured by immunofluorescence and gene expression, whereas VAT preadipocyte differentiation was unchanged. Adipocyte-secreted proinflammatory cytokines were higher and adiponectin lower in media from VAT vs SAT: macrophage removal reduced inflammatory cytokine and increased adiponectin secretion from both SAT and VAT adipocytes. Differentiation of preadipocytes from SAT but not VAT correlated inversely with systemic insulin resistance.The current results reveal that proinflammatory immune cells in human SAT are causally-related to impaired preadipocyte differentiation, which in turn is associated with systemic insulin resistance. In VAT, preadipocyte differentiation is poor even in the absence of tissue macrophages, pointing to inherent differences in fat storage potential between the two depots.

  17. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    International Nuclear Information System (INIS)

    Tsuno, Hiroaki; Yoshida, Toshiko; Nogami, Makiko; Koike, Chika; Okabe, Motonori; Noto, Zenko; Arai, Naoya; Noguchi, Makoto; Nikaido, Toshio

    2012-01-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAMα cells and induced to osteogenic status—their in vivo osteogenesis was subsequently investigated in rats. It was found that HAMα cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAMα cells. The expression of osteocalcin mRNA was increased in HAMα cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAMα cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: ► Human amniotic mesenchymal cells include cells (HAMα cells) that have the properties of MSCs. ► HAMα cells have excellent osteogenic differentiation potential. ► Osteogenic differentiation ability of HAMα was amplified by calcium phosphate scaffolds. ► HAMα cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  18. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tsuno, Hiroaki [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Yoshida, Toshiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nogami, Makiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Orthopedic Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Koike, Chika; Okabe, Motonori [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Noto, Zenko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Arai, Naoya; Noguchi, Makoto [Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nikaido, Toshio, E-mail: tnikaido@med.u-toyama.ac.jp [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan)

    2012-12-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAM{alpha} cells and induced to osteogenic status-their in vivo osteogenesis was subsequently investigated in rats. It was found that HAM{alpha} cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAM{alpha} cells. The expression of osteocalcin mRNA was increased in HAM{alpha} cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAM{alpha} cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: Black-Right-Pointing-Pointer Human amniotic mesenchymal cells include cells (HAM{alpha} cells) that have the properties of MSCs. Black-Right-Pointing-Pointer HAM{alpha} cells have excellent osteogenic differentiation potential. Black-Right-Pointing-Pointer Osteogenic differentiation ability of HAM{alpha} was amplified by calcium phosphate scaffolds. Black-Right-Pointing-Pointer HAM{alpha} cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  19. Bioprinted three dimensional human tissues for toxicology and disease modeling.

    Science.gov (United States)

    Nguyen, Deborah G; Pentoney, Stephen L

    2017-03-01

    The high rate of attrition among clinical-stage therapies, due largely to an inability to predict human toxicity and/or efficacy, underscores the need for in vitro models that better recapitulate in vivo human biology. In much the same way that additive manufacturing has revolutionized the production of solid objects, three-dimensional (3D) bioprinting is enabling the automated production of more architecturally and functionally accurate in vitro tissue culture models. Here, we provide an overview of the most commonly used bioprinting approaches and how they are being used to generate complex in vitro tissues for use in toxicology and disease modeling research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Sympathetic reflex control of blood flow in human peripheral tissues

    DEFF Research Database (Denmark)

    Henriksen, O

    1991-01-01

    Sympathetic vasoconstrictor reflexes are essential for the maintenance of arterial blood pressure in upright position. It has been generally believed that supraspinal sympathetic vasoconstrictor reflexes elicited by changes in baroreceptor activity play an important role. Recent studies on human...... sympathetic vasoconstrictor reflexes are blocked. Blood flow has been measure by the local 133Xe-technique. The results indicate the presence of spinal as well as supraspinal sympathetic vasoconstrictor reflexes to human peripheral tissues. Especially is emphasized the presence of a local sympathetic veno...... skeletal muscle, cutaneous and subcutaneous tissues of the limbs indicate that the situation is more complex. Measurements have been carried out during acute as well as chronic sympathetic denervation. Spinal sympathetic reflex mechanisms have been evaluated in tetraplegic patients, where supraspinal...

  1. Engineering bone tissue from human embryonic stem cells

    OpenAIRE

    Marolt, Darja; Campos, Iván Marcos; Bhumiratana, Sarindr; Koren, Ana; Petridis, Petros; Zhang, Geping; Spitalnik, Patrice F.; Grayson, Warren L.; Vunjak-Novakovic, Gordana

    2012-01-01

    In extensive bone defects, tissue damage and hypoxia lead to cell death, resulting in slow and incomplete healing. Human embryonic stem cells (hESC) can give rise to all specialized lineages found in healthy bone and are therefore uniquely suited to aid regeneration of damaged bone. We show that the cultivation of hESC-derived mesenchymal progenitors on 3D osteoconductive scaffolds in bioreactors with medium perfusion leads to the formation of large and compact bone constructs. Notably, the i...

  2. Streamlined bioreactor-based production of human cartilage tissues.

    Science.gov (United States)

    Tonnarelli, B; Santoro, R; Adelaide Asnaghi, M; Wendt, D

    2016-05-27

    Engineered tissue grafts have been manufactured using methods based predominantly on traditional labour-intensive manual benchtop techniques. These methods impart significant regulatory and economic challenges, hindering the successful translation of engineered tissue products to the clinic. Alternatively, bioreactor-based production systems have the potential to overcome such limitations. In this work, we present an innovative manufacturing approach to engineer cartilage tissue within a single bioreactor system, starting from freshly isolated human primary chondrocytes, through the generation of cartilaginous tissue grafts. The limited number of primary chondrocytes that can be isolated from a small clinically-sized cartilage biopsy could be seeded and extensively expanded directly within a 3D scaffold in our perfusion bioreactor (5.4 ± 0.9 doublings in 2 weeks), bypassing conventional 2D expansion in flasks. Chondrocytes expanded in 3D scaffolds better maintained a chondrogenic phenotype than chondrocytes expanded on plastic flasks (collagen type II mRNA, 18-fold; Sox-9, 11-fold). After this "3D expansion" phase, bioreactor culture conditions were changed to subsequently support chondrogenic differentiation for two weeks. Engineered tissues based on 3D-expanded chondrocytes were more cartilaginous than tissues generated from chondrocytes previously expanded in flasks. We then demonstrated that this streamlined bioreactor-based process could be adapted to effectively generate up-scaled cartilage grafts in a size with clinical relevance (50 mm diameter). Streamlined and robust tissue engineering processes, as the one described here, may be key for the future manufacturing of grafts for clinical applications, as they facilitate the establishment of compact and closed bioreactor-based production systems, with minimal automation requirements, lower operating costs, and increased compliance to regulatory guidelines.

  3. Composition of MRI phantom equivalent to human tissues

    International Nuclear Information System (INIS)

    Kato, Hirokazu; Kuroda, Masahiro; Yoshimura, Koichi; Yoshida, Atsushi; Hanamoto, Katsumi; Kawasaki, Shoji; Shibuya, Koichi; Kanazawa, Susumu

    2005-01-01

    We previously developed two new MRI phantoms (called the CAG phantom and the CAGN phantom), with T1 and T2 relaxation times equivalent to those of any human tissue at 1.5 T. The conductivity of the CAGN phantom is equivalent to that of most types of human tissue in the frequency range of 1 to 130 MHz. In this paper, the relaxation times of human tissues are summarized, and the composition of the corresponding phantoms are provided in table form. The ingredients of these phantoms are carrageenan as the gelling agent, GdCl 3 as a T1 modifier, agarose as a T2 modifier, NaCl (CAGN phantom only) as a conductivity modifier, NaN 3 as an antiseptic, and distilled water. The phantoms have T1 values of 202-1904 ms and T2 values of 38-423 ms when the concentrations of GdCl 3 and agarose are varied from 0-140 μmol/kg, and 0%-1.6%, respectively, and the CAGN phantom has a conductivity of 0.27-1.26 S/m when the NaCl concentration is varied from 0%-0.7%. These phantoms have sufficient strength to replicate a torso without the use of reinforcing agents, and can be cut by a knife into any shape. We anticipate the CAGN phantom to be highly useful and practical for MRI and hyperthermia-related research

  4. Amelioration of non-motor dysfunctions after transplantation of human dopamine neurons in a model of Parkinson's disease.

    Science.gov (United States)

    Lelos, M J; Morgan, R J; Kelly, C M; Torres, E M; Rosser, A E; Dunnett, S B

    2016-04-01

    Patients suffering from Parkinson's disease (PD) display cognitive and neuropsychiatric dysfunctions, especially with disease progression. Although these impairments have been reported to impact more heavily upon a patient's quality of life than any motor dysfunctions, there are currently no interventions capable of adequately targeting these non-motor deficits. Utilizing a rodent model of PD, we investigated whether cell replacement therapy, using intrastriatal transplants of human-derived ventral mesencephalic (hVM) grafts, could alleviate cognitive and neuropsychiatric, as well as motor, dysfunctions. Rats with unilateral 6-hydroxydopamine lesions to the medial forebrain bundle were tested on a complex operant task that dissociates motivational, visuospatial and motor impairments sensitive to the loss of dopamine. A subset of lesioned rats received intrastriatal hVM grafts of ~9 weeks gestation. Post-graft, rats underwent repeated drug-induced rotation tests and were tested on two versions of the complex operant task, before post-mortem analysis of the hVM tissue grafts. Post-graft behavioural testing revealed that hVM grafts improved non-motor aspects of task performance, specifically visuospatial function and motivational processing, as well as alleviating motor dysfunctions. We report the first evidence of human VM cell grafts alleviating both non-motor and motor dysfunctions in an animal model of PD. This intervention, therefore, is the first to improve cognitive and neuropsychiatric symptoms long-term in a model of PD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Erythropoietin promotes network formation of transplanted adipose tissue-derived microvascular fragments

    Directory of Open Access Journals (Sweden)

    P Karschnia

    2018-05-01

    Full Text Available The seeding of tissue constructs with adipose tissue-derived microvascular fragments (ad-MVF is an emerging pre-vascularisation strategy. Ad-MVF rapidly reassemble into new microvascular networks after in vivo implantation. Herein it was analysed whether this process was improved by erythropoietin (EPO. Ad-MVF were isolated from green fluorescent protein (GFP+ as well as wild-type C57BL/6 mice and cultivated for 24 h in medium supplemented with EPO (20 IU/mL or vehicle. Freshly isolated, non-cultivated ad-MVF served as controls. Protein expression, cell viability and proliferation of ad-MVF were assessed by proteome profiler array and fluorescence microscopy. GFP+ ad-MVF were seeded on collagen-glycosaminoglycan matrices, which were implanted into dorsal skinfold chambers of C57BL/6 mice, to analyse their vascularisation over 14 d by intravital fluorescence microscopy, histology and immunohistochemistry. Cultivation up-regulated the expression of pro- and anti-angiogenic factors within both vehicle- and EPO-treated ad-MVF when compared with non-cultivated controls. Moreover, EPO treatment suppressed cultivation-associated apoptosis and significantly increased the number of proliferating endothelial cells in ad-MVF when compared with vehicle-treated and non-cultivated ad-MVF. Accordingly, implanted matrices seeded with EPO-treated ad-MVF exhibited an improved vascularisation, as indicated by a significantly higher functional microvessel density. The matrices of the three groups contained a comparably large fraction of GFP+ microvessels originating from the ad-MVF, whereas the tissue surrounding the matrices seeded with EPO-treated ad-MVF exhibited a significantly increased microvessel density when compared with the other two groups. These findings indicated that EPO represents a promising cytokine to further boost the excellent vascularisation properties of ad-MVF in tissue-engineering applications.

  6. Expression cartography of human tissues using self organizing maps

    Directory of Open Access Journals (Sweden)

    Löffler Markus

    2011-07-01

    Full Text Available Abstract Background Parallel high-throughput microarray and sequencing experiments produce vast quantities of multidimensional data which must be arranged and analyzed in a concerted way. One approach to addressing this challenge is the machine learning technique known as self organizing maps (SOMs. SOMs enable a parallel sample- and gene-centered view of genomic data combined with strong visualization and second-level analysis capabilities. The paper aims at bridging the gap between the potency of SOM-machine learning to reduce dimension of high-dimensional data on one hand and practical applications with special emphasis on gene expression analysis on the other hand. Results The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues. SOM mapping reduces the dimension of expression data from ten of thousands of genes to a few thousand metagenes, each representing a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of genes related to specific molecular processes in the respective tissue. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering are better represented and provide better signal-to-noise ratios if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues broadly into three clusters containing nervous, immune system and the remaining tissues

  7. Autologous Cartilage Chip Transplantation Improves Repair Tissue Composition Compared With Marrow Stimulation.

    Science.gov (United States)

    Christensen, Bjørn Borsøe; Olesen, Morten Lykke; Lind, Martin; Foldager, Casper Bindzus

    2017-06-01

    Repair of chondral injuries by use of cartilage chips has recently demonstrated clinical feasibility. To investigate in vivo cartilage repair outcome of autologous cartilage chips compared with marrow stimulation in full-thickness cartilage defects in a minipig model. Controlled laboratory study. Six Göttingen minipigs received two 6-mm chondral defects in the medial and lateral trochlea of each knee. The two treatment groups were (1) autologous cartilage chips embedded in fibrin glue (ACC) (n = 12) and (2) marrow stimulation (MST) (n = 12). The animals were euthanized after 6 months, and the composition of repair tissue was quantitatively determined using histomorphometry. Semiquantitative evaluation was performed by means of the International Cartilage Repair Society (ICRS) II score. Collagen type II staining was used to further evaluate the repair tissue composition. Significantly more hyaline cartilage was found in the ACC (17.1%) compared with MST (2.9%) group ( P cartilage repair tissue compared with MST at 6 months postoperatively. Further studies are needed to investigate ACC as a possible alternative first-line treatment for focal cartilage injuries in the knee.

  8. Ectopic Hard Tissue Formation by Odonto/Osteogenically In Vitro Differentiated Human Deciduous Teeth Pulp Stem Cells.

    Science.gov (United States)

    Kim, Seunghye; Song, Je Seon; Jeon, Mijeong; Shin, Dong Min; Kim, Seong-Oh; Lee, Jae Ho

    2015-07-01

    There have been many attempts to use the pulp tissue from human deciduous teeth for dentin or bone regeneration. The objective of this study was to determine the effects of odonto/osteogenic in vitro differentiation of deciduous teeth pulp stem cells (DTSCs) on their in vivo hard tissue-forming potential. DTSCs were isolated from extracted deciduous teeth using the outgrowth method. These cells were exposed to odonto/osteogenic stimuli for 4 and 8 days (Day 4 and Day 8 groups, respectively), while cells in the control group were cultured in normal medium. The in vitro differentiated DTSCs and the control DTSCs were transplanted subcutaneously into immunocompromised mice with macroporous biphasic calcium phosphate and sacrificed at 8 weeks post-implantation. The effect of odonto/osteogenic in vitro differentiation was evaluated using alkaline phosphatase (ALP) staining and quantitative reverse transcription polymerase chain reaction (RT-PCR). The in vivo effect was evaluated by qualitative RT-PCR, assessment of ALP activity, histologic analysis, and immunohistochemical staining. The amount of hard tissue was greater in Day 4 group than Day 8 group (p = 0.014). However, Day 8 group generated lamellar bone-like structure, which was immunonegative to anti-human dentin sialoprotein with significantly low expression level of DSPP compared with the control group (p = 0.008). This study demonstrates that odonto/osteogenic in vitro differentiation of DTSCs enhances the formation of bone-like tissue, instead of dentin-like tissue, when transplanted subcutaneously using MBCP as a carrier. The odonto/osteogenic in vitro differentiation of DTSCs may be an effective modification that enhances in vivo bone formation by DTSCs.

  9. Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory.

    Science.gov (United States)

    Rheinheimer, Jakeline; Bauer, Andrea C; Silveiro, Sandra P; Estivalet, Aline A F; Bouças, Ana P; Rosa, Annelise R; Souza, Bianca M de; Oliveira, Fernanda S de; Cruz, Lavínia A; Brondani, Letícia A; Azevedo, Mirela J; Lemos, Natália E; Carlessi, Rodrigo; Assmann, Taís S; Gross, Jorge L; Leitão, Cristiane B; Crispim, Daisy

    2015-04-01

    Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with "brittle T1DM", who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de Clínicas de Porto Alegre - Rio Grande do Sul, Brazil.

  10. Human corneal endothelial cell transplantation using nanocomposite gel sheet in bullous keratopathy.

    Science.gov (United States)

    Parikumar, Periasamy; Haraguchi, Kazutoshi; Senthilkumar, Rajappa; Abraham, Samuel Jk

    2018-01-01

    Transplantation of in vitro expanded human corneal endothelial precursors (HCEP) cells using a nanocomposite (D25-NC) gel sheet as supporting material in bovine's cornea has been earlier reported. Herein we report the transplantation of HCEP cells derived from a cadaver donor cornea to three patients using the NC gel sheet. In three patients with bullous keratopathy, one after cataract surgery, one after trauma and another in the corneal graft, earlier performed for congenital corneal dystrophy, not amenable to medical management HCEP cells isolated from a human cadaver donor cornea in vitro expanded using a thermoreversible gelation polymer (TGP) for 26 days were divided into three equal portions and 1.6 × 10 5 HCEP cells were injected on to the endothelium of the affected eye in each patient using the D25-NC gel sheet as a supporting material. The sheets were removed after three days. The bullae in the cornea disappeared by the 3 rd -11 th post-operative day in all the three patients. Visual acuity improved from Perception of light (PL)+/Projection of rays (PR)+ to Hand movements (HM)+ in one of the patients by post-operative day 3 which was maintained at 18 months follow-up. At 18 months follow-up, in another patient the visual acuity had improved from HM+ to 6/60 while in the third patient, visual acuity remained HM+ as it was prior to HCEP transplantation. There were no adverse effects during the follow-up in any of the patients.

  11. Alloreactive lymphoid infiltrates in human heart transplants: Loss of class II-directed cytotoxicity more than 3 months after transplantation

    NARCIS (Netherlands)

    A.J. Ouwehand; L.M.B. Vaessen (Leonard); C.C. Baan (Carla); N.H.P.M. Jutte (Nicolet); A.H.M.M. Balk (Aggie); C.E. Essed; E. Bos (Egbert); F.H.J. Claas (Frans); W. Weimar (Willem)

    1991-01-01

    markdownabstractAbstract From 535 endomyocardial biopsies (87 heart transplant recipients) 283 cell cultures could be generated. All cultures tested contained T lymphocytes and in most cases CD4 was the predominant phenotype at any time posttransplant. A significantly higher proportion of

  12. PVA matches human liver in needle-tissue interaction.

    Science.gov (United States)

    de Jong, Tonke L; Pluymen, Loes H; van Gerwen, Dennis J; Kleinrensink, Gert-Jan; Dankelman, Jenny; van den Dobbelsteen, John J

    2017-05-01

    Medical phantoms can be used to study needle-tissue interaction and to train medical residents. The purpose of this research is to study the suitability of polyvinyl alcohol (PVA) as a liver tissue mimicking material in terms of needle-tissue interaction. Insertions into ex-vivo human livers were used for reference. Six PVA samples were created by varying the mass percentage of PVA to water (4m% and 7m%) and the number of freeze-thaw cycles (1, 2 and 3 cycles, 16hours of freezing at -19°C, 8hours of thawing). The inner needle of an 18 Gauge trocar needle with triangular tip was inserted 13 times into each of the samples, using an insertion velocity of 5 mm/s. In addition, 39 insertions were performed in two ex-vivo human livers. Axial forces on the needle were captured during insertion and retraction and characterized by friction along the needle shaft, peak forces, and number of peak forces per unit length. The concentration of PVA and the number of freeze-thaw cycles both influenced the mechanical interaction between needle and specimen. Insertions into 4m% PVA phantoms with 2 freeze-thaw cycles were comparable to human liver in terms of estimated friction along the needle shaft and the number of peak forces. Therefore, these phantoms are considered to be suitable liver mimicking materials for image-guided needle interventions. The mechanical properties of PVA hydrogels can be influenced in a controlled manner by varying the concentration of PVA and the number of freeze-thaw cycles, to mimic liver tissue characteristics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Formation of Hyaline Cartilage Tissue by Passaged Human Osteoarthritic Chondrocytes.

    Science.gov (United States)

    Bianchi, Vanessa J; Weber, Joanna F; Waldman, Stephen D; Backstein, David; Kandel, Rita A

    2017-02-01

    When serially passaged in standard monolayer culture to expand cell number, articular chondrocytes lose their phenotype. This results in the formation of fibrocartilage when they are used clinically, thus limiting their use for cartilage repair therapies. Identifying a way to redifferentiate these cells in vitro is critical if they are to be used successfully. Transforming growth factor beta (TGFβ) family members are known to be crucial for regulating differentiation of fetal limb mesenchymal cells and mesenchymal stromal cells to chondrocytes. As passaged chondrocytes acquire a progenitor-like phenotype, the hypothesis of this study was that TGFβ supplementation will stimulate chondrocyte redifferentiation in vitro in serum-free three-dimensional (3D) culture. Human articular chondrocytes were serially passaged twice (P2) in monolayer culture. P2 cells were then placed in high-density (3D) culture on top of membranes (Millipore) and cultured for up to 6 weeks in chemically defined serum-free redifferentiation media (SFRM) in the presence or absence of TGFβ. The tissues were evaluated histologically, biochemically, by immunohistochemical staining, and biomechanically. Passaged human chondrocytes cultured in SFRM supplemented with 10 ng/mL TGFβ3 consistently formed a continuous layer of articular-like cartilage tissue rich in collagen type 2 and aggrecan and lacking collagen type 1 and X in the absence of a scaffold. The tissue developed a superficial zone characterized by expression of lubricin and clusterin with horizontally aligned collagen fibers. This study suggests that passaged human chondrocytes can be used to bioengineer a continuous layer of articular cartilage-like tissue in vitro scaffold free. Further study is required to evaluate their ability to repair cartilage defects in vivo.

  14. Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

    Directory of Open Access Journals (Sweden)

    Takayuki Kondo

    2014-08-01

    Full Text Available Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1-mediated amyotrophic lateral sclerosis (ALS. However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

  15. Hematopoietic Stem Cell Transplantation and History

    Directory of Open Access Journals (Sweden)

    Atila Tanyeli

    2014-02-01

    Full Text Available Attemps to employ marrow stem cell for therapeutic purpose began in 1940’s. Marrow transplantation might be of use not only in irradiation protection, but also with therapeutic aim to marrow aplasia, leukemia and other diseases. The use and defining tissue antigens in humans were crucial to the improving of transplantation. The administration of methotrexate for GVHD improved the long term survival. Conditioning regimens for myeloablation designed according to diseases. Cord blood and peripheral blood stem cells were used for transplantion after 1980’s. Cord blood and bone marrow stem cell banks established to find HLA matched donor.

  16. The comparative distribution of thorium and plutonium in human tissues

    International Nuclear Information System (INIS)

    Singh, Narayani P.; Shawki Amin Ibrahim; Cohen, Norman; Wrenn, McDonald E.

    1978-01-01

    Thorium is the most chemically and biologically similar natural element to the manmade element plutonium. Both are actinides, and for both the most stable valency state is +4, and solubility in natural body fluids is low. They are classified together in ICRP Lung Model. The present paper deals with the question of whether or not the analogy between the two actinides in terms of deposition and retention in human tissues is a good one. Preliminary results on the thorium contents ( 228,230 Th and 232 Th) of three sets of human tissues from a western U.S. town containing a uranium tailings pile are compared with the reported values of plutonium content of human tissues from the general populations who are exposed to environmental plutonium from fallout of nuclear detonations. Samples were taken at autopsy where sudden death had occurred. For the three isotopes of thorium, the ratio of the content of each (pCi/organ, normalized by organ weight to ICRP Reference Man) in lung to lymph nodes varies from 2-25 for individuals with a mean of 8; this is similar to that we infer from the literature for 239 , 240 Pu which suggests a ratio of lung to lymph nodes with a mean of approximately 7. However, the relative thorium contents of lung and liver are dissimilar, lung/liver for thorium being 3.5 and for plutonium 0.2 to 0.1. Similarly, the ratios of thorium and plutonium content of liver and bone vary significantly; the ratio for thorium is 0.1 and for plutonium 0.8 to 0.5. The most significant observation at this stage is that the relative accumulation of thorium in human liver is much less than that of plutonium. Some of the plausible reasons will be discussed. (author)

  17. Implications of human tissue studies for radiation protection

    International Nuclear Information System (INIS)

    Kathren, R.L.

    1988-01-01

    Through radiochemical analysis of voluntary tissue donations, the U.S. Transuranium and Uranium Registries (USTR) are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole-body contributions to the USTR revealed an inverse proportionality between actinide concentration and bone ash. The analysis of a whole body with significant 241 Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies with tissues obtained at autopsy suggest that existing biokinetic models for 238 Pu and 241 Am and the currently accepted models and limits on intake, which use these models as their basis, may be inaccurately implying that revisions of existing safety standards may be necessary. Other studies of the registries are designed to evaluate in-vivo estimates of actinide deposition with those derived from postmortem tissue analysis, to compare results of animal experiments with human data, and to review histopathologic slides for tissue changes that might be attributable to exposure to transuranic elements. The implications of these recent findings and other work of the registries is discussed from the standpoint of this potential effect on biokinetic modeling, internal dose assessment, and safety standards and operational health physics practices

  18. Implications of human tissue studies for radiation protection.

    Science.gov (United States)

    Kathren, R L

    1988-08-01

    Through radiochemical analysis of voluntary tissue donations, the U.S. Transuranium and Uranium Registries (USTR) are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole-body contributions to the USTR revealed an inverse proportionality between actinide concentration and bone ash. The analysis of a whole body with significant 241Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies with tissues obtained at autopsy suggest that existing biokinetic models for 238Pu and 241Am and the currently accepted models and limits on intake, which use these models as their basis, may be inaccurately implying that revisions of existing safety standards may be necessary. Other studies of the registries are designed to evaluate in-vivo estimates of actinide deposition with those derived from postmortem tissue analysis, to compare results of animal experiments with human data, and to review histopathologic slides for tissue changes that might be attributable to exposure to transuranic elements. The implications of these recent findings and other work of the registries is discussed from the standpoint of this potential effect on biokinetic modeling, internal dose assessment, and safety standards and operational health physics practices.

  19. Concentration of Po-210 and Pb-210 in human tissues

    International Nuclear Information System (INIS)

    Zhao Lancai; Takizawa, Y.; Yamamoto, M.

    1990-01-01

    The levels of Pb-210 and Po-210 in human tissues of people in Japan were determined. Various tissue samples were obtained at autopsy from the cadavers of 22 oncologic cases, mainly in Niigata Prefecture in northern Japan during the period of 1986 to 1988. Wet ashing, followed by electrochemical deposition and alpha-ray spectrometry were used to separate and determine the Pb-210 and Po-210 presented. Among the tissues analyzed the highest concentrations of Pb-210 and Po-210 were observed in bone, liver and kidneys: 1.29, 1.69 and 1.22 Bq.kg -1 respectively for Po-210, and 1.27, 0.56 and 0.43 Bq/kg for Pb-210 respectively. The Po-210/Pb-210 ratios in liver and kidney are 3.0 and 2.9 respectively. Po-210/Pb-210 ratios in other tissues are close to one. The total body burden of Pb-210 and Po-210 was found to be approximately 15.8 Bq and 19.1 Bq respectively

  20. Arthroscopic treatment of chondral defects in the hip: AMIC, MACI, microfragmented adipose tissue transplantation (MATT and other options

    Directory of Open Access Journals (Sweden)

    Jannelli Eugenio

    2017-01-01

    Full Text Available Chondral lesions are currently considered in the hip as a consequence of trauma, osteonecrosis, dysplasia, labral tears, loose bodies, dislocation, previous slipped capital femoral epiphysis and Femoro-Acetabular-Impingement (FAI. The management of chondral lesions is debated and several techniques are described. The physical examination must be carefully performed, followed by radiographs and magnetic resonance imaging (MRI. Differential diagnosis with other pathologies must be considered. Debridement is indicated in patients younger than 50 years with a chondropathy of 1st or 2nd degree. Microfractures are indicated in patients younger than 50 years with a chondropathy of 3rd or 4th degree less than 2 cm2. Matrix-Induced Autologous Chondrocyte Implantation (MACI and Autologous Matrix-Induced Chondrogenesis (AMIC procedures are indicated in patients with full-thickness symptomatic 3rd–4th degree chondral defects, extended 2 cm2 or more. The AMIC procedure has the advantage of a one-step procedure and much less expense. Microfragmented adipose tissue transplantation (MATT is indicated for the treatment of delamination and 1st and 2nd degree chondral lesions, regardless of the age of the patient. Chondral defects are effective when the joint space is not compromised. When the Tonnis classification is two or greater, treatment of chondral lesions should be considered ineffective.

  1. Graft Product for Autologous Peripheral Blood Stem Cell Transplantation Enhances Thrombin Generation and Expresses Procoagulant Microparticles and Tissue Factor.

    Science.gov (United States)

    Sidibe, Fatoumata; Spanoudaki, Anastasia; Vanneaux, Valerie; Mbemba, Elisabeth; Larghero, Jerome; Van Dreden, Patrick; Lotz, Jean-Pierre; Elalamy, Ismail; Larsen, Annette K; Gerotziafas, Grigoris T

    2018-05-01

    The beneficial effect of autologous peripheral blood stem cell transplantation (APBSCT) may be compromised by acute vascular complications related to hypercoagulability. We studied the impact of graft product on thrombin generation of normal plasma and the expression of tissue factor (TF) and procoagulant platelet-derived procoagulant microparticles (Pd-MPs) in samples of graft products. Graft products from 10 patients eligible for APBSCT were mixed with platelet-poor plasma (PPP) or platelet-rich plasma (PRP) from healthy volunteers and assessed for in vitro thrombin generation. In control experiments, thrombin generation was assessed in (1) PPP and PRP without any exogenous TF and/or procoagulant phospholipids, (2) PPP with the addition of TF (5 pM) and procoagulant phospholipids (4 μM), (3) in PRP with the addition of TF (5 pM). Graft products were assessed with Western blot assay for TF expression, with a specific clotting assay for TF activity and with flow cytometry assay for Pd-MPs. The graft product enhanced thrombin generation and its procoagulant activity was related to the presence of Pd-MPs and TF. The concentration of Pd-MPs in the graft product was characterized by a significant interindividual variability. The present study reveals the need for a thorough quality control of the graft products regarding their procoagulant potential.

  2. Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia

    Science.gov (United States)

    Hering, Bernhard J.; Clarke, William R.; Bridges, Nancy D.; Eggerman, Thomas L.; Alejandro, Rodolfo; Bellin, Melena D.; Chaloner, Kathryn; Czarniecki, Christine W.; Goldstein, Julia S.; Hunsicker, Lawrence G.; Kaufman, Dixon B.; Korsgren, Olle; Larsen, Christian P.; Luo, Xunrong; Markmann, James F.; Naji, Ali; Oberholzer, Jose; Posselt, Andrew M.; Rickels, Michael R.; Ricordi, Camillo; Robien, Mark A.; Senior, Peter A.; Shapiro, A.M. James; Stock, Peter G.; Turgeon, Nicole A.

    2016-01-01

    OBJECTIVE Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50–80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. RESEARCH DESIGN AND METHODS This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA1c transplant. RESULTS The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA1c level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients. CONCLUSIONS Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding

  3. Computational model of soft tissues in the human upper airway.

    Science.gov (United States)

    Pelteret, J-P V; Reddy, B D

    2012-01-01

    This paper presents a three-dimensional finite element model of the tongue and surrounding soft tissues with potential application to the study of sleep apnoea and of linguistics and speech therapy. The anatomical data was obtained from the Visible Human Project, and the underlying histological data was also extracted and incorporated into the model. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus.

  4. Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Katja M. Piltti

    2015-09-01

    Full Text Available The effect of transplantation dose on the spatiotemporal dynamics of human neural stem cell (hNSC engraftment has not been quantitatively evaluated in the central nervous system. We investigated changes over time in engraftment/survival, proliferation, and migration of multipotent human central nervous system-derived neural stem cells (hCNS-SCns transplanted at doses ranging from 10,000 to 500,000 cells in spinal cord injured immunodeficient mice. Transplant dose was inversely correlated with measures of donor cell proliferation at 2 weeks post-transplant (WPT and dose-normalized engraftment at 16 WPT. Critically, mice receiving the highest cell dose exhibited an engraftment plateau, in which the total number of engrafted human cells never exceeded the initial dose. These data suggest that donor cell expansion was inversely regulated by target niche parameters and/or transplantation density. Investigation of the response of donor cells to the host microenvironment should be a key variable in defining target cell dose in pre-clinical models of CNS disease and injury.

  5. Cells in human postmortem brain tissue slices remain alive for several weeks in culture

    NARCIS (Netherlands)

    Verwer, Ronald W. H.; Hermens, Wim T. J. M. C.; Dijkhuizen, PaulaA; ter Brake, Olivier; Baker, Robert E.; Salehi, Ahmad; Sluiter, Arja A.; Kok, Marloes J. M.; Muller, Linda J.; Verhaagen, Joost; Swaab, Dick F.

    2002-01-01

    Animal models for human neurological and psychiatric diseases only partially mimic the underlying pathogenic processes. Therefore, we investigated the potential use of cultured postmortem brain tissue from adult neurological patients and controls. The present study shows that human brain tissue

  6. Pancreatic Islet Cell Transplantation: A new era in transplantation

    OpenAIRE

    Warnock, Garth L.; Rajotte, Ray V.

    1992-01-01

    Transplantation of insulin-producing tissue offers a physiologic approach to restoration of glycemic control. Whereas transplantation of vascularized pancreatic grafts has recently achieved encouraging results, pancreatic islet cell transplantation holds the promise of low morbidity and reduced requirements for agressive immunosuppression for recipients. Islet cell transplantation was recently demonstrated to induce euglycemia with insulin independence.

  7. Mining the human tissue proteome for protein citrullination.

    Science.gov (United States)

    Lee, Chien-Yun; Wang, Dongxue; Wilhelm, Mathias; Zolg, Daniel Paul; Schmidt, Tobias; Schnatbaum, Karsten; Reimer, Ulf; Pontén, Fredrik; Uhlén, Mathias; Hahne, Hannes; Kuster, Bernhard

    2018-04-02

    Citrullination is a post-translational modification of arginine catalyzed by five peptidylarginine deiminases (PADs) in humans. The loss of a positive charge may cause structural or functional alterations and while the modification has been linked to several diseases including rheumatoid arthritis and cancer, its physiological or pathophysiological roles remain largely unclear. In part this is owing to limitations in available methodology able to robustly enrich, detect and localize the modification. As a result, only few citrullination sites have been identified on human proteins with high confidence. In this study, we mined data from mass spectrometry-based deep proteomic profiling of 30 human tissues to identify citrullination sites on endogenous proteins. Database searching of ~70 million tandem mass spectra yielded ~13,000 candidate spectra which were further triaged by spectrum quality metrics and the detection of the specific neutral loss of isocyanic acid from citrullinated peptides to reduce false positives. Because citrullination is easily confused with deamidation, we synthetized ~2,200 citrullinated and 1,300 deamidated peptides to build a library of reference spectra. This led to the validation of 375 citrullination sites on 209 human proteins. Further analysis showed that >80% of the identified modifications sites were new and for 56% of the proteins, citrullination was detected for the first time. Sequence motif analysis revealed a strong preference for Asp and Gly, residues around the citrullination site. Interestingly, while the modification was detected in 26 human tissues with the highest levels found in brain and lung, citrullination levels did not correlate well with protein expression of the PAD enzymes. Even though the current work represents the largest survey of protein citrullination to date, the modification was mostly detected on high abundant proteins arguing that the development of specific enrichment methods would be required in order

  8. Evaluation of the humoral immune response to human leukocyte antigens in Brazilian renal transplant candidates.

    Directory of Open Access Journals (Sweden)

    Patricia Keiko Saito

    Full Text Available Pre-transplant sensitization to human leukocyte antigens (HLA is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA. The percentages of panel-reactive antibodies (PRA and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.. The PRA-positive group consisted of 182 (67.7% patients, and the PRA-negative group of 87 (32.3% patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1% were positive for class I and negative for class II, 39 (21.4% were negative for class I and positive for class II, and 81 (44.5% were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples.

  9. Evaluation of the Humoral Immune Response to Human Leukocyte Antigens in Brazilian Renal Transplant Candidates

    Science.gov (United States)

    Saito, Patricia Keiko; Yamakawa, Roger Haruki; Aparecida, Erica Pereira; da Silva Júnior, Waldir Verissimo; Borelli, Sueli Donizete

    2014-01-01

    Pre-transplant sensitization to human leukocyte antigens (HLA) is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO) combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA). The percentages of panel-reactive antibodies (PRA) and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.). The PRA-positive group consisted of 182 (67.7%) patients, and the PRA-negative group of 87 (32.3%) patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1%) were positive for class I and negative for class II, 39 (21.4%) were negative for class I and positive for class II, and 81 (44.5%) were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples. PMID:24927116

  10. Initial prevalence of anal human papilloma virus infection in liver transplant recipients.

    Science.gov (United States)

    Grąt, Michał; Grąt, Karolina; Hołówko, Wacław; Malejczyk, Magdalena; Walter de Walthoffen, Szymon; Lewandowski, Zbigniew; Kobryń, Konrad; Patkowski, Waldemar; Majewski, Sławomir; Młynarczyk, Grażyna; Krawczyk, Marek

    2014-08-01

    Although liver transplant recipients are at increased risk of human papilloma virus (HPV)-related anal cancer, limited data are available regarding the initial prevalence of anal HPV infection in this population. Anal swabs collected from 50 liver transplant recipients within the first three postoperative weeks were subjected to real-time polymerase chain reaction for detection of the four HPV genotypes: 6, 11, 16, and 18. Predictors of any, low-risk, and high-risk anal HPV infection were evaluated. Overall, the prevalence of any anal HPV infection was 18.0%, with the corresponding rates for high- and low-risk HPV genotypes being 8.0% and 10.0%, respectively. Infection with any type of anal HPV was higher in patients with hepatitis B virus (HBV) infection (P = 0.027), ≥3 sexual partners (P = 0.031), and alcoholic liver disease (P = 0.063). HBV infection was the only factor significantly associated with high-risk HPV infection (P = 0.038). Male sex (P = 0.050), age ≥52 years (P = 0.016), ≥30 sexual partners (P = 0.003), age at first intercourse ≤18 years (P = 0.045), and time since first intercourse ≥38 years (P = 0.012) were identified as predictors of low-risk HPV infection. These results indicate that HPV vaccination of liver transplant candidates and screening for anal HPV infection in high-risk groups should be considered. © 2014 Steunstichting ESOT.

  11. Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells

    NARCIS (Netherlands)

    Forster, Ryan; Chiba, Kunitoshi; Schaeffer, Lorian; Regalado, Samuel G; Lai, Christine S; Gao, Qing; Kiani, Samira; Farin, Henner F; Clevers, Hans; Cost, Gregory J; Chan, Andy; Rebar, Edward J; Urnov, Fyodor D; Gregory, Philip D; Pachter, Lior; Jaenisch, Rudolf; Hockemeyer, Dirk

    2014-01-01

    Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the

  12. Transplantation of human placenta-derived mesenchymal stem cells in a silk fibroin/hydroxyapatite scaffold improves bone repair in rabbits.

    Science.gov (United States)

    Jin, Jun; Wang, Jun; Huang, Jian; Huang, Fang; Fu, Jianhong; Yang, Xinjing; Miao, Zongning

    2014-11-01

    The main requirements for successful tissue engineering of the bone are non-immunogenic cells with osteogenic potential and a porous biodegradable scaffold. The purpose of this study is to evaluate the potential of a silk fibroin/hydroxyapatite (SF/HA) porous material as a delivery vehicle for human placenta-derived mesenchymal stem cells (PMSCs) in a rabbit radius defect model. In this study, we randomly assigned 16 healthy adult New Zealand rabbits into two groups, subjected to transplantation with either SF/HA and PMSCs (experimental group) or SF/HA alone (control group). To evaluate fracture healing, we assessed the extent of graft absorption, the quantity of newly formed bone, and re-canalization of the cavitas medullaris using radiographic and histological tools. We performed flow cytometric analysis to characterize PMSCs, and found that while they express CD90, CD105 and CD73, they stain negative for HLA-DR and the hematopoietic cell surface markers CD34 and CD45. When PMSCs were exposed to osteogenic induction medium, they secreted calcium crystals that were identified by von Kossa staining. Furthermore, when seeded on the surface of SF/HA scaffold, they actively secreted extracellular matrix components. Here, we show, through radiographic and histological analyses, that fracture healing in the experimental group is significantly improved over the control group. This strongly suggests that transplantation of human PMSCs grown in an SF/HA scaffold into injured radius segmental bone in rabbits, can markedly enhance tissue repair. Our finding provides evidence supporting the utility of human placenta as a potential source of stem cells for bone tissue engineering. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  13. Experimental Human Cell and Tissue Models of Pemphigus

    Science.gov (United States)

    van der Wier, Gerda; Pas, Hendri H.; Jonkman, Marcel F.

    2010-01-01

    Pemphigus is a chronic mucocutaneous autoimmune bullous disease that is characterized by loss of cell-cell contact in skin and/or mucous membranes. Past research has successfully identified desmosomes as immunological targets and has demonstrated that acantholysis is initiated through direct binding of IgG. The exact mechanisms of acantholysis, however, are still missing. Experimental model systems have contributed considerably to today's knowledge and are still a favourite tool of research. In this paper we will describe to what extent human cell and tissue models represent the in vivo situation, for example, organ cultures of human skin, keratinocyte cultures, and human skin grafted on mice and, furthermore, how suitable they are to study the pathogenesis of pemphigus. Organ cultures closely mimic the architecture of the epidermis but are less suitable to answer posed biochemical questions. Cultured keratinocyte monolayers are convenient in this respect, but their desmosomal make-up in terms of adhesion molecules does not exactly reflect the in vivo situation. Reconstituted skin is a relatively new model that approaches organ culture. In models of human skin grafted on mice, acantholysis can be studied in actual human skin but now with all the advantages of an animal model. PMID:20585596

  14. Environmental spread of microbes impacts the development of metabolic phenotypes in mice transplanted with microbial communities from humans

    DEFF Research Database (Denmark)

    Zhang, Li; Bahl, Martin Iain; Roager, Henrik Munch

    2017-01-01

    Microbiota transplantation to germ-free animals is a powerful method to study involvement of gut microbes in the aetiology of metabolic syndrome. Owing to large interpersonal variability in gut microbiota, studies with broad coverage of donors are needed to elucidate the establishment of human......, thereby allowing us to explore the extent of microbial spread between cages in a well-controlled environment. Despite high group-wise similarity between obese and control human microbiotas, transplanted mice in the four isolators developed distinct gut bacterial composition and activity, body mass gain......, and insulin resistance. Spread of microbes between cages within isolators interacted with establishment of the transplanted microbiotas in mice, and contributed to the transmission of metabolic phenotypes. Our findings highlight the impact of donor variability and reveal that inter-individual spread...

  15. Peritransplant energy changes and their correlation to outcome after human liver transplantation

    NARCIS (Netherlands)

    Bruinsma, Bote G; Avruch, James H; Sridharan, Gautham V; Weeder, Pepijn D; Jacobs, Marie Louise; Crisalli, Kerry; Amundsen, Beth; Porte, Robert J; Markmann, James F; Uygun, Korkut; Yeh, Heidi

    BACKGROUND: The ongoing shortage of donor livers for transplantation and the increased use of marginal livers necessitate the development of accurate pretransplant tests of viability. Considering the importance energy status during transplantation, we aimed to correlate peritransplant energy

  16. Validation of an LC-MS/MS method to measure tacrolimus in rat kidney and liver tissue and its application to human kidney biopsies.

    Science.gov (United States)

    Noll, Benjamin D; Coller, Janet K; Somogyi, Andrew A; Morris, Raymond G; Russ, Graeme R; Hesselink, Dennis A; Van Gelder, Teun; Sallustio, Benedetta C

    2013-10-01

    Tacrolimus (TAC) has a narrow therapeutic index and high interindividual and intraindividual pharmacokinetic variability, necessitating therapeutic drug monitoring to individualize dosage. Recent evidence suggests that intragraft TAC concentrations may better predict transplant outcomes. This study aimed to develop a method for the quantification of TAC in small biopsy-sized samples of rat kidney and liver tissue, which could be applied to clinical biopsy samples from kidney transplant recipients. Kidneys and livers were harvested from Mrp2-deficient TR- Wistar rats administered TAC (4 mg·kg·d for 14 days, n = 8) or vehicle (n = 10). Tissue samples (0.20-1.00 mg of dry weight) were solubilized enzymatically and underwent liquid-liquid extraction before analysis by liquid chromatography tandem mass spectrometry method. TAC-free tissue was used in the calibrator and quality control samples. Analyte detection was accomplished using positive electrospray ionization (TAC: m/z 821.5 → 768.6; internal standard ascomycin m/z 809.3 → 756.4). Calibration curves (0.04-2.6 μg/L) were linear (R > 0.99, n = 10), with interday and intraday calibrator coefficients of variation and bias <17% at the lower limit of quantification and <15% at all other concentrations (n = 6-10). Extraction efficiencies for TAC and ascomycin were approximately 70%, and matrix effects were minimal. Rat kidney TAC concentrations were higher (range 109-190 pg/mg tissue) than those in the liver (range 22-53 pg/mg of tissue), with median tissue/blood concentrations ratios of 72.0 and 17.6, respectively. In 2 transplant patients, kidney TAC concentrations ranged from 119 to 285 pg/mg of tissue and were approximately 20 times higher than whole blood trough TAC concentrations. The method displayed precision and accuracy suitable for application to TAC measurement in human kidney biopsy tissue.

  17. Chimeric mice transplanted with human hepatocytes as a model for prediction of human drug metabolism and pharmacokinetics.

    Science.gov (United States)

    Sanoh, Seigo; Ohta, Shigeru

    2014-03-01

    Preclinical studies in animal models are used routinely during drug development, but species differences of pharmacokinetics (PK) between animals and humans have to be taken into account in interpreting the results. Human hepatocytes are also widely used to examine metabolic activities mediated by cytochrome P450 (P450) and other enzymes, but such in vitro metabolic studies also have limitations. Recently, chimeric mice with humanized liver (h-chimeric mice), generated by transplantation of human donor hepatocytes, have been developed as a model for the prediction of metabolism and PK in humans, using both in vitro and in vivo approaches. The expression of human-specific metabolic enzymes and metabolic activities was confirmed in humanized liver of h-chimeric mice with high replacement ratios, and several reports indicate that the profiles of P450 and non-P450 metabolism in these mice adequately reflect those in humans. Further, the combined use of h-chimeric mice and r-chimeric mice, in which endogenous hepatocytes are replaced with rat hepatocytes, is a promising approach for evaluation of species differences in drug metabolism. Recent work has shown that data obtained in h-chimeric mice enable the semi-quantitative prediction of not only metabolites, but also PK parameters, such as hepatic clearance, of drug candidates in humans, although some limitations remain because of differences in the metabolic activities, hepatic blood flow and liver structure between humans and mice. In addition, fresh h-hepatocytes can be isolated reproducibly from h-chimeric mice for metabolic studies. Copyright © 2013 John Wiley & Sons, Ltd.

  18. Adaptation of human adipose tissue to hypocaloric diet.

    Science.gov (United States)

    Rossmeislová, L; Mališová, L; Kračmerová, J; Štich, V

    2013-05-01

    Hypocaloric diet is a key component of the weight-reducing treatment of obesity and obesity-related disorders. Hypocaloric diets and the associated weight reduction promote improvement of metabolic profile of obese individuals. Among the mechanisms that underlie this beneficial metabolic outcome, the diet-induced modifications of morphological and functional characteristics of human adipose tissue (AT) are believed to have an important role. Prospective studies of hypocaloric weight-reducing dietary intervention demonstrate effects on adipocyte metabolism, namely lipolysis and lipogenesis, and associated changes of the adipocyte size. The endocrine function of AT, which involves cytokine and adipokine production by adipocytes, as well as by cells of stromavascular fraction, is also regulated by dietary intervention. Related inflammatory status of AT is modulated also as a consequence of the changes in recruitment of immune cells, mainly macrophages, in AT. Here, we give an overview of metabolic and endocrine modifications in human AT induced by a variety of hypocaloric diets.

  19. Preimplantation diagnosis: efficient tool for human leukocyte antigen matched bone marrow transplantation for thalassemia

    Directory of Open Access Journals (Sweden)

    Anver Kuliev

    2011-08-01

    Full Text Available Thalassemia is among the most frequent indications for preimplantation genetic diagnosis (PGD to allow at risk couples reproducing without fear of having an affected child. In addition, those already having the affected child, have also the option to produce an unaffected offspring that may be also a complete human leukocyte antigen (HLA match to affected child to ensure successful bone marrow transplantation. We present here the results of retrospective analysis of 293 PGD cycles for thalassemia, including 144cases of simultaneous HLA typing, resulting in birth of 70 thalassemia-free children and 12 unaffected HLA matched ones, providing their cord blood and/or bone marrow for transplantation treatment of their affected siblings. The present overall experience includes successful cord blood or bone marrow transplantation in more than three dozens of cases with HLA matched stem cells obtained from children born after PGD, demonstrating that PGD is an efficient approach for improving success of bone marrow transplantation treatment for thalassemia.   植入前遗传学诊断(PGD)是地中海贫血(地贫)最常用的疗法,该病患者夫妇无须担心孕儿受到感染。此外,如果已经怀上受到感染的宝宝,他们也可有选择性再生育一个未受感染的后代,提供完全匹配的HLA,来确保骨髓成功移植。本文将提供293个地贫病例的PGD周期诊断结果,包括144例HLA同时配型,有70例宝宝无地贫出生和12例未受感染的HLA配型宝宝出生。将这些健康宝宝的脐带血和/或骨髓取出以完成对他们同胞的移植手术,通过使用经诊断后的,出生宝宝身上取出的HLA配型干细胞,成功完成36例宝宝的脐带或骨髓移植手术。结果表明PGD能有效提高地贫患儿骨髓移植手术的成功率。

  20. Relative impact of human leukocyte antigen mismatching and graft ischemic time after lung transplantation.

    Science.gov (United States)

    Brugière, Olivier; Thabut, Gabriel; Suberbielle, Caroline; Reynaud-Gaubert, Martine; Thomas, Pascal; Pison, Christophe; Saint Raymond, Christel; Mornex, Jean-François; Bertocchi, Michèle; Dromer, Claire; Velly, Jean-François; Stern, Marc; Philippe, Bruno; Dauriat, Gaëlle; Biondi, Giuseppina; Castier, Yves; Fournier, Michel

    2008-06-01

    Recent data strongly suggest that human leukocyte antigen (HLA) mismatching has a negative impact on development of bronchiolitis obliterans syndrome (BOS) and survival after lung transplantation (LTx). Because HLA matching is sometimes achieved by extending ischemic time in other solid-organ transplantation models and ischemic time is a risk factor per se for death after LTx, we sought to compare the theoretical benefit of HLA matching with the negative impact of lengthened ischemic time. In this collaborative study we compared the relative impact of HLA mismatching and ischemic time on BOS and survival in 182 LTx recipients. Using multivariate analyses, we observed a lower incidence of BOS (hazard ratio [HR] = 1.70, 95% confidence interval [CI]: 1.1 to 2.7, p = 0.03) and enhanced survival (HR = 1.91, 95% CI: 1.24 to 2.92, p = 0.01) in patients with zero or one HLA-A mismatch compared with those having two HLA-A mismatches. This beneficial effect on survival was equivalent to a reduction of ischemic time of 168 minutes. We observed a reduced incidence of BOS and a better survival rate in patients well-matched at the HLA-A locus, associated with an opposite effect of an enhanced ischemic time. This suggests that graft ischemic time should be taken into account in future studies of prospective HLA matching in LTx.

  1. Activation and amplification of c-Ki-ras in a chemically induced transplantable human pancreas carcinoma

    International Nuclear Information System (INIS)

    Parsa, I.; Maheshwari, K.K.

    1986-01-01

    Increasing evidence suggests that carcinogenesis is associated with the stepwise activation of oncogenes. The c-Ki-ras oncogene has been demonstrated in several human solid tumors and is shown to be amplified in tumor cell lines. The authors have probed endonuclease cleaved human pancreas (HP) DNAs and DNAs from an in vitro induced transplantable human pancreas carcinoma (HP-T1) for the presence and/or amplification of c-Ki-ras oncogene. The DNAs were cleaved with BamHI, BgIII, EcoRI, HhaI, HinfI, KpnI, PSTI, PvuII, SaII, SstI, TaqI or XbaI and were subjected to Southern blot analysis using 32 P-labelled EcoRI fragments from HiHi3 clone. The hybridization profiles were similar in both DNAs when digested with BamHI, BgIII, HinfI, KpnI, SaII, SstI, or TaqI. The EcoRI cleaved DNAs from HP and HP-T1 revealed two hybridizing fragments of 6.8 and 3.0 kbp. The 3.0 kbp fragments in DNA from HP-T1 showed more than a 100 folds enhancement as compared to that of HP. The 6.8 hybridizing fragments also appeared 10 fold greater in HP-T1 DNA. Similar enhancements were also present in HP-T1 DNA cleaved with PstI and PvuII. Preliminary results from comparison of poly(A) + RNAs, prepared from total HP and HP-T1 RNAs, by Northern blot analysis using the same probe reflect similar enhancement in RNA from transplantable pancreas carcinoma

  2. Recusa de doação de órgãos e tecidos para transplante relatados por familiares de potenciais doadores Negación de donación de órganos y tejidos para transplante relatados por familiares de potenciales donadores Reasons for the family members' refusal to donate organ and tissue for transplant

    Directory of Open Access Journals (Sweden)

    Edvaldo Leal de Moraes

    2009-01-01

    Full Text Available OBJETIVO: Conhecer a percepção de familiares de potenciais doadores sobre os motivos de recusa para doação de órgãos e tecidos para transplante. MÉTODOS: Trata-se de uma pesquisa qualitativa, na vertente fenomenológica, modalidade "estrutura do fenômeno situado". Participaram do estudo oito familiares que recusaram a doação dos órgãos e tecidos. RESULTADOS: Após análise das entrevistas, foram revelados dez motivos de recusa, considerados pelos familiares. CONSIDERAÇÕES FINAIS: As proposições que emergiram revelaram que os motivos de recusa familiar para doação de órgãos e tecidos estão relacionados à crença, valores e inadequações no processo de doação e transplante.OBJETIVO: Conocer la percepción de familiares de potenciales donadores sobre los motivos de su negación para la donación de órganos y tejidos para transplante. MÉTODOS: Se trata de una investigación cualitativa, en la vertiente fenomenológica, modalidad "estructura del fenómeno situado". Participaron del estudio ocho familiares que se negaron a la donación de órganos y tejidos. RESULTADOS: Después del análisis de las entrevistas se revelaron diez motivos de negación expuestos por los familiares. CONSIDERACIONES FINALES: Las proposiciones que emergieron revelaron que los motivos de la negativa familiar para la donación de órganos y tejidos están relacionados a la creencia, valores e inadecuaciones en el proceso de donación y transplante.OBJECTIVE: To understand the perception of family members of potential donors in regard to their reasons for refusal to donate organ and tissue for transplant. METHODS: A qualitative phenomenological approach was used to conduct this study. A sample of eight family members who refused to donate organ and tissue for transplant participated in the study. RESULTS: Participants reported ten reasons for refusal to donate organ and tissue for transplant. FINAL CONSIDERATIONS: Reasons for the family members

  3. Phenolsulphotransferase in human tissue: radiochemical enzymatic assay and biochemical properties

    International Nuclear Information System (INIS)

    Anderson, R.J.; Weinshilboum, R.M.

    1980-01-01

    Phenolsulphotransferase (EC 2.8.2.1) (PST) is an important catecholamine and drug metabolizing enzyme. Optimal conditions have been determined for the accurate measurement of PST activity in the human platelet, human renal cortex, and human jejunum with a radiochemical microassay. 3-Methoxy-4-hydroxyphenylglycol (MHPG) and 35 S-3'-phosphoadenosine-5'-phosphosulfate ( 35 S-PAPS) were the substrates for the reaction. The apparent Michaelis-Menten (Ksub(m)) values for MHPG with platelet, renal cortex, and jejunum were 1.09, 0.46 and 1.16 mmol/l, respectively. Apparent Ksub(m) values for PAPS in the same tissues were 0.14, 0.13 and 0.21 μmol/l. The pH optimum of the reacton in all three tissues was approximately 6.2-6.8 with three different buffer systems. The coefficients of variation for the assay of platelet, renal cortex, and jejunal activities were 6.2%, 3.4% and 4.4%, respectively. Mean platelet PST activity in blood samples from 75 randomly selected adult subjects was 5.0 +- 1.72 mmol of MHPG sulfate formed per hour per mg of platelet protein (8.3 X 10 -5 +- 2.9 X 10 -5 μmol min -1 mg -1 , mean +- S.D.). There was a 5-fold intersubject variation in platelet PST activity within two standard deviations of the mean value. Experiments in which partially purified human erythrocyte PST was added to platelet, kidney and gut homogenates under these assay conditions provided evidence that endogenous PST inhibitors did not affect the observed enzyme activity. (Auth.)

  4. Development of a Cytocompatible Scaffold from Pig Immature Testicular Tissue Allowing Human Sertoli Cell Attachment, Proliferation and Functionality

    Directory of Open Access Journals (Sweden)

    Maxime Vermeulen

    2018-01-01

    Full Text Available Cryopreservation of immature testicular tissue before chemo/radiotherapy is the only option to preserve fertility of cancer-affected prepubertal boys. To avoid reintroduction of malignant cells, development of a transplantable scaffold by decellularization of pig immature testicular tissue (ITT able to support decontaminated testicular cells could be an option for fertility restoration in these patients. We, therefore, compared decellularization protocols to produce a cytocompatible scaffold. Fragments of ITT from 15 piglets were decellularized using three protocols: sodium dodecyl sulfate (SDS-Triton (ST, Triton-SDS-Triton (TST and trypsin 0.05%/ethylenediaminetetraacetic acid (EDTA 0.02%-Triton (TET with varying detergent concentrations. All protocols were able to lower DNA levels. Collagen retention was demonstrated in all groups except ST 1%, and a significant decrease in glycosaminoglycans was observed in the TST 1% and TET 1% groups. When Sertoli cells (SCs were cultured with decellularized tissue, no signs of cytotoxicity were detected. A higher SC proliferation rate and greater stem cell factor secretion were observed than with SCs cultured without scaffold. ST 0.01% and TET 3% conditions offered the best compromise in terms of DNA elimination and extracellular matrix (ECM preservation, while ensuring good attachment, proliferation and functionality of human SCs. This study demonstrates the potential of using decellularized pig ITT for human testicular tissue engineering purposes.

  5. Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.

    Science.gov (United States)

    Tanzi, Elisabetta; Bianchi, Silvia; Frati, Elena R; Amicizia, Daniela; Martinelli, Marianna; Bragazzi, Nicola L; Brisigotti, Maria Pia; Colzani, Daniela; Fasoli, Ester; Zehender, Gianguglielmo; Panatto, Donatella; Gasparini, Roberto

    2015-01-01

    Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified β-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.

  6. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  7. Progranulin serum levels in human kidney transplant recipients: A longitudinal study.

    Science.gov (United States)

    Nicoletto, Bruna Bellincanta; Pedrollo, Elis Forcellini; Carpes, Larissa Salomoni; Coloretti, Natália Gomes; Krolikowski, Thaiana Cirino; Souza, Gabriela Corrêa; Gonçalves, Luiz Felipe Santos; Manfro, Roberto Ceratti; Canani, Luis Henrique

    2018-01-01

    The adipokine progranulin has metabolic proprieties, playing a role in obesity and insulin resistance. Its levels seems to be dependent of renal function, since higher progranulin concentration is observed in patients with end-stage kidney disease. However, the effect of kidney transplantation on progranulin remains unknown. To assess the serum progranulin levels in kidney transplant recipients before and after kidney transplantation. Forty-six prospective kidney transplant recipients were included in this longitudinal study. They were evaluated before transplantation and at three and twelve months after transplantation. Clinical, anthropometric and laboratorial measurements were assessed. Progranulin was determined with enzyme-linked immunosorbent assays. Serum progranulin significantly decreased in the early period after transplantation (from 72.78 ± 2.86 ng/mL before transplantation to 40.65 ± 1.49 ng/mL at three months; pProgranulin was associated with waist circumference and fasting plasma glucose after adjusted for age, gender, study period, glomerular filtration rate, interleukin-6, high sensitivity C reactive protein and adiponectin. Progranulin serum levels are increased before transplantation and a reduction is observed in the early period after transplantation, possibly attributed to an improvement in renal function. At one year after transplantation, an increment in progranulin is observed, seems to be independent of glomerular filtration, and remained significantly lower than before transplantation.

  8. Modeling the behavior of human body tissues on penetration

    Science.gov (United States)

    Conci, A.; Brazil, A. L.; Popovici, D.; Jiga, G.; Lebon, F.

    2018-02-01

    Several procedures in medicine (such as anesthesia, injections, biopsies and percutaneous treatments) involve a needle insertion. Such procedures operate without vision of the internal involved areas. Physicians and anesthetists rely on manual (force and tactile) feedback to guide their movements, so a number of medical practice is strongly based on manual skill. In order to be expert in the execution of such procedures the medical students must practice a number of times, but before practice in a real patient they must be trained in some place and a virtual environment, using Virtual Reality (VR) or Augmented Reality (AR) is the best possible solution for such training. In a virtual environment the success of user practices is improved by the addition of force output using haptic device to improve the manual sensations in the interactions between user and computer. Haptic devices enable simulate the physical restriction of the diverse tissues and force reactions to movements of operator hands. The trainees can effectively "feel" the reactions to theirs movements and receive immediate feedback from the actions executed by them in the implemented environment. However, in order to implement such systems, the tissue reaction to penetration and cutting must be modeled. A proper model must emulate the physical sensations of the needle action in the skin, fat, muscle, and so one, as if it really done in a patient that is as they are holding a real needle and feeling each tissue resistance when inserting it through the body. For example an average force value for human skin puncture is 6.0 N, it is 2.0 N for subcutaneous fat tissue and 4.4 N for muscles: this difference of sensations to penetration of each layers trespassed by the needle makes possible to suppose the correct position inside the body. This work presents a model for tissues before and after the cutting that with proper assumptions of proprieties can model any part of human body. It was based on experiments

  9. The PAXgene(® tissue system preserves phosphoproteins in human tissue specimens and enables comprehensive protein biomarker research.

    Directory of Open Access Journals (Sweden)

    Sibylle Gündisch

    Full Text Available Precise quantitation of protein biomarkers in clinical tissue specimens is a prerequisite for accurate and effective diagnosis, prognosis, and personalized medicine. Although progress is being made, protein analysis from formalin-fixed and paraffin-embedded tissues is still challenging. In previous reports, we showed that the novel formalin-free tissue preservation technology, the PAXgene Tissue System, allows the extraction of intact and immunoreactive proteins from PAXgene-fixed and paraffin-embedded (PFPE tissues. In the current study, we focused on the analysis of phosphoproteins and the applicability of two-dimensional gel electrophoresis (2D-PAGE and enzyme-linked immunosorbent assay (ELISA to the analysis of a variety of malignant and non-malignant human tissues. Using western blot analysis, we found that phosphoproteins are quantitatively preserved in PFPE tissues, and signal intensities are comparable to that in paired, frozen tissues. Furthermore, proteins extracted from PFPE samples are suitable for 2D-PAGE and can be quantified by ELISA specific for denatured proteins. In summary, the PAXgene Tissue System reliably preserves phosphoproteins in human tissue samples, even after prolonged fixation or stabilization times, and is compatible with methods for protein analysis such as 2D-PAGE and ELISA. We conclude that the PAXgene Tissue System has the potential to serve as a versatile tissue fixative for modern pathology.

  10. Distribution of adenosine deaminase complexing protein (ADCP) in human tissues.

    Science.gov (United States)

    Dinjens, W N; ten Kate, J; van der Linden, E P; Wijnen, J T; Khan, P M; Bosman, F T

    1989-12-01

    The normal distribution of adenosine deaminase complexing protein (ADCP) in the human body was investigated quantitatively by ADCP-specific radioimmunoassay (RIA) and qualitatively by immunohistochemistry. In these studies we used a specific rabbit anti-human ADCP antiserum. In all 19 investigated tissues, except erythrocytes, ADCP was found by RIA in the soluble and membrane fractions. From all tissues the membrane fractions contained more ADCP (expressed per mg protein) than the soluble fractions. High membrane ADCP concentrations were found in skin, renal cortex, gastrointestinal tract, and prostate. Immunoperoxidase staining confirmed the predominant membrane-associated localization of the protein. In serous sweat glands, convoluted tubules of renal cortex, bile canaliculi, gastrointestinal tract, lung, pancreas, prostate gland, salivary gland, gallbladder, mammary gland, and uterus, ADCP immunoreactivity was found confined to the luminal membranes of the epithelial cells. These data demonstrate that ADCP is present predominantly in exocrine glands and absorptive epithelia. The localization of ADCP at the secretory or absorptive apex of the cells suggests that the function of ADCP is related to the secretory and/or absorptive process.

  11. Environment as reflected in human tissue and hair: a comparison

    International Nuclear Information System (INIS)

    Dale, I.M.; Lenihan, J.M.A.; Smith, H.

    1974-01-01

    This study looks at variations in trace metal content of a range of human tissues over a period of 10 years, extended comparison of metal concentrations in hair specimens over 200 years, the influence of geographical location on trace element levels in hair and nails and investigates groups of people with particular exposure problems. It is found that there has been little or no change in the concentration of some of the trace elements in human tissue over the past ten years. An extended survey of hair over the past 200 years shows a similar result. Investigation of trace element levels from widely separated localities also indicates little or no change in metal concentrations. It appears from these studies that man's contamination from his environment has remained fairly constant with respect to time and place. However it is shown in further studies that local pockets of significant exposure, e.g., particular professions, industry, agriculture and self-medication, do occur and certainly warrant close attention

  12. Islet-like cell aggregates generated from human adipose tissue derived stem cells ameliorate experimental diabetes in mice.

    Directory of Open Access Journals (Sweden)

    Vikash Chandra

    Full Text Available BACKGROUND: Type 1 Diabetes Mellitus is caused by auto immune destruction of insulin producing beta cells in the pancreas. Currently available treatments include transplantation of isolated islets from donor pancreas to the patient. However, this method is limited by inadequate means of immuno-suppression to prevent islet rejection and importantly, limited supply of islets for transplantation. Autologous adult stem cells are now considered for cell replacement therapy in diabetes as it has the potential to generate neo-islets which are genetically part of the treated individual. Adopting methods of islet encapsulation in immuno-isolatory devices would eliminate the need for immuno-suppressants. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we explore the potential of human adipose tissue derived adult stem cells (h-ASCs to differentiate into functional islet like cell aggregates (ICAs. Our stage specific differentiation protocol permit the conversion of mesodermic h-ASCs to definitive endoderm (Hnf3β, TCF2 and Sox17 and to PDX1, Ngn3, NeuroD, Pax4 positive pancreatic endoderm which further matures in vitro to secrete insulin. These ICAs are shown to produce human C-peptide in a glucose dependent manner exhibiting in-vitro functionality. Transplantation of mature ICAs, packed in immuno-isolatory biocompatible capsules to STZ induced diabetic mice restored near normoglycemia within 3-4 weeks. The detection of human C-peptide, 1155±165 pM in blood serum of experimental mice demonstrate the efficacy of our differentiation approach. CONCLUSIONS: h-ASC is an ideal population of personal stem cells for cell replacement therapy, given that they are abundant, easily available and autologous in origin. Our findings present evidence that h-ASCs could be induced to differentiate into physiologically competent functional islet like cell aggregates, which may provide as a source of alternative islets for cell replacement therapy in type 1 diabetes.

  13. Progranulin serum levels in human kidney transplant recipients: A longitudinal study.

    Directory of Open Access Journals (Sweden)

    Bruna Bellincanta Nicoletto

    Full Text Available The adipokine progranulin has metabolic proprieties, playing a role in obesity and insulin resistance. Its levels seems to be dependent of renal function, since higher progranulin concentration is observed in patients with end-stage kidney disease. However, the effect of kidney transplantation on progranulin remains unknown.To assess the serum progranulin levels in kidney transplant recipients before and after kidney transplantation.Forty-six prospective kidney transplant recipients were included in this longitudinal study. They were evaluated before transplantation and at three and twelve months after transplantation. Clinical, anthropometric and laboratorial measurements were assessed. Progranulin was determined with enzyme-linked immunosorbent assays.Serum progranulin significantly decreased in the early period after transplantation (from 72.78 ± 2.86 ng/mL before transplantation to 40.65 ± 1.49 ng/mL at three months; p<0.01 and increased at one year (53.15 ± 2.55 ng/mL; p<0.01 vs. three months, remaining significantly lower than before transplantation (p<0.01 (pover time<0.01. At one year after transplantation, there was a significant increase in body mass index, trunk fat and waist circumference compared to immediate period after transplantation. Progranulin was associated with waist circumference and fasting plasma glucose after adjusted for age, gender, study period, glomerular filtration rate, interleukin-6, high sensitivity C reactive protein and adiponectin.Progranulin serum levels are increased before transplantation and a reduction is observed in the early period after transplantation, possibly attributed to an improvement in renal function. At one year after transplantation, an increment in progranulin is observed, seems to be independent of glomerular filtration, and remained significantly lower than before transplantation.

  14. The Postischemic Environment Differentially Impacts Teratoma or Tumor Formation After Transplantation of Human Embryonic Stem Cell-Derived Neural Progenitors

    Czech Academy of Sciences Publication Activity Database

    Seminatore, CH.; Polentes, J.; Ellman, D.; Kozubenko, Nataliya; Itier, V.; Tine, S.; Tritschler, L.; Brenot, M.; Guidou, E.; Blondeau, J.; Lhuillier, M.; Bugi, A.; Aubry, L.; Jendelová, Pavla; Syková, Eva; Perrier, A. L.; Finsen, B.; Onteniente, B.

    2010-01-01

    Roč. 41, č. 1 (2010), s. 153-159 ISSN 0039-2499 Institutional research plan: CEZ:AV0Z50390703 Keywords : brain transplantation * human embryonic stem cells * neural differentiation Subject RIV: FH - Neurology Impact factor: 5.756, year: 2010

  15. Improvement of Gynecological Screening of Female Renal Transplant Recipients by Self-Sampling for Human Papillomavirus Detection

    NARCIS (Netherlands)

    Hinten, F.; Hilbrands, L.B.; Meeuwis, K.A.P.; Bergen-Verkuyten, M.C. van; Slangen, B.F.; Rossum, M.M. van; Rahamat-Langendoen, J.C.; Massuger, L.F.A.G.; Hullu, J.A. de; Melchers, W.J.G.

    2017-01-01

    OBJECTIVES: Female renal transplant recipients (RTRs) have increased risk for developing human papillomavirus (HPV)-related (pre)malignancies of the lower genital tract. Annual cervical screening is advised for RTRs, but the participation rate is low. The aim of this study is to investigate whether

  16. The Major Histocompatibility Complex in Transplantation

    Directory of Open Access Journals (Sweden)

    Marco Antonio Ayala García

    2012-01-01

    Full Text Available The transplant of organs is one of the greatest therapeutic achievements of the twentieth century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the principal target of the immune response is the MHC (major histocompatibility complex molecules expressed on the surface of donor cells. However, we should not forget that the innate and adaptive immunities are closely interrelated and should be viewed as complementary and cooperating. When a human transplant is performed, HLA (human leukocyte antigens molecules from a donor are recognized by the recipient's immune system triggering an alloimmune response Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. This paper will present MHC, the innate and adaptive immunities, and clinical HLA testing.

  17. Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant Recipients: Risk Factors and Viral Genome Evolution.

    Science.gov (United States)

    Ogimi, Chikara; Greninger, Alexander L; Waghmare, Alpana A; Kuypers, Jane M; Shean, Ryan C; Xie, Hu; Leisenring, Wendy M; Stevens-Ayers, Terry L; Jerome, Keith R; Englund, Janet A; Boeckh, Michael

    2017-07-15

    Recent data suggest that human coronavirus (HCoV) pneumonia is associated with significant mortality in hematopoietic cell transplant (HCT) recipients. Investigation of risk factors for prolonged shedding and intrahost genome evolution may provide critical information for development of novel therapeutics. We retrospectively reviewed HCT recipients with HCoV detected in nasal samples by polymerase chain reaction (PCR). HCoV strains were identified using strain-specific PCR. Shedding duration was defined as time between first positive and first negative sample. Logistic regression analyses were performed to evaluate factors for prolonged shedding (≥21 days). Metagenomic next-generation sequencing (mNGS) was conducted when ≥4 samples with cycle threshold values of Genome changes were consistent with the expected molecular clock of HCoV. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  18. A novel subcutaneous site of islet transplantation superior to the liver.

    Science.gov (United States)

    Yasunami, Yohichi; Nakafusa, Yuki; Nitta, Naoyoshi; Nakamura, Masafumi; Goto, Masafumi; Ono, Junko; Taniguchi, Masaru

    2018-03-08

    Islet transplantation is an attractive treatment for patients with insulin-dependent diabetes mellitus, and currently the liver is the favored transplantation site. However, an alternative site is desirable because of the low efficiency of hepatic transplantation, requiring 2-3 donors for a single recipient, and because the transplanted islets cannot be accessed or retrieved. We developed a novel procedure of islet transplantation to the inguinal subcutaneous white adipose tissue (ISWAT) of mice and described functional and morphological characteristics of transplanted syngeneic islets. Also, it was determined whether islet allograft rejection in the ISWAT can be prevented by immunosuppressive agents. Furthermore, it was examined whether human islets function when grafted in this particular site of immune-deficient mice. In this site, transplanted islets are engrafted as clusters and function to reverse STZ-induced diabetes in mice. Importantly, transplanted islets can be visualized by CT and are easily retrievable, and allograft rejection is preventable by blockade of co-stimulatory signals. Of much importance, the efficiency of islet transplantation in this site is superior to the liver, in which hyperglycemia of diabetic recipient mice is ameliorated after transplantation of 200 syngeneic islets (the islet number yielded from 1 mouse pancreas) to the ISWAT but not to the liver. Furthermore, human islets transplanted in this particular site function to reverse diabetes in immune-deficient mice. Thus, the ISWAT is superior to the liver as the site of islet transplantation, which may lead to improved outcome of clinical islet transplantation.

  19. [Human umbilical cord blood mononuclear cell transplantation promotes long-term neurobehavioral functional development of newborn SD rats with hypoxic ischemic brain injury].

    Science.gov (United States)

    Huang, Hui-zhi; Wen, Xiao-hong; Liu, Hui; Huang, Jin-hua; Liu, Shang-quan; Ren, Wei-hua; Fang, Wen-xiang; Qian, Yin-feng; Hou, Wei-zhu; Yan, Ming-jie; Yao, You-heng; Li, Wei-Zu; Li, Qian-Jin

    2013-06-01

    To explore the effect of human umbilical cord blood mononuclear cells (UCBMC) promoting nerve behavior function and brain tissue recovery of neonatal SD rat with hypoxic ischemic brain injury (HIBI). A modified newborn rat model that had a combined hypoxic and ischemic brain injury as described by Rice-Vannucci was used, early nervous reflex, the Morris water maze and walking track analysis were used to evaluate nervous behavioral function, and brain MRI, HE staining to evaluate brain damage recovery. Newborn rat Rice-Vannucci model showed significant brain atrophy, obvious hemiplegia of contralateral limbs,e.g right step length [(7.67 ± 0.46) cm vs. (8.22 ± 0.50) cm, F = 1.494] and toe distance [(0.93 ± 0.06) cm vs. (1.12 ± 0.55) cm, F = 0.186] were significantly reduced compared with left side, learning and memory ability was significantly impaired compared with normal control group (P vs.(14.22 ± 5.07) s, t = 4.618] and negative geotaxis reflex time [(7.26 ± 2.00) s vs. (11.76 ± 3.73) s, t = 4.755] on postnatal 14 days of HIBI+ transplantation group were significantly reduced compared with HIBI+NaCl group (P vs. (34.04 ± 12.95) s, t = 3.356] and swimming distance [ (9.12 ± 1.21) cm vs.(12.70 ± 1.53) cm, t = 17.095] of HIBI+transplantation group were significantly reduced compared with those of HIBI+NaCl group (P brain volume on postnatal 10 d [ (75.37 ± 4.53)% vs. (67.17 ± 4.08)%, t = -6.017] and 67 d [ (69.05 ± 3.58)% vs.(60.83 ± 3.69)%, t = -7.148]of HIBI+ transplantation group were significantly larger than those of HIBI+NaCl group (P left cortical edema significantly reduced and nerve cell necrosis of HIBI+ transplantation group is not obvious compared with HIBI+NaCl group. Human UCBMC intraperitoneal transplantation significantly promoted recovery of injured brain cells and neurobehavioral function development.

  20. Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats.

    Directory of Open Access Journals (Sweden)

    Lingying Liu

    Full Text Available BACKGROUND: Severe burns are a common and highly lethal trauma. The key step for severe burn therapy is to promote the wound healing as early as possible, and reports indicate that mesenchymal stem cell (MSC therapy contributes to facilitate wound healing. In this study, we investigated effect of human umbilical cord MSCs (hUC-MSCs could on wound healing in a rat model of severe burn and its potential mechanism. METHODS: Adult male Wistar rats were randomly divided into sham, burn, and burn transplanted hUC-MSCs. GFP labeled hUC-MSCs or PBS was intravenous injected into respective groups. The rate of wound closure was evaluated by Image Pro Plus. GFP-labeled hUC-MSCs were tracked by in vivo bioluminescence imaging (BLI, and human-specific DNA expression in wounds was detected by PCR. Inflammatory cells, neutrophils, macrophages, capillaries and collagen types I/III in wounds were evaluated by histochemical staining. Wound blood flow was evaluated by laser Doppler blood flow meter. The levels of proinflammatory and anti-inflammatory factors, VEGF, collagen types I/III in wounds were analyzed using an ELISA. RESULTS: We found that wound healing was significantly accelerated in the hUC-MSC therapy group. The hUC-MSCs migrated into wound and remarkably decreased the quantity of infiltrated inflammatory cells and levels of IL-1, IL-6, TNF-α and increased levels of IL-10 and TSG-6 in wounds. Additionally, the neovascularization and levels of VEGF in wounds in the hUC-MSC therapy group were markedly higher than those in other control groups. The ratio of collagen types I and III in the hUC-MSC therapy group were markedly higher than that in the burn group at indicated time after transplantation. CONCLUSION: The study suggests that hUC-MSCs transplantation can effectively improve wound healing in severe burned rat model. Moreover, these data might provide the theoretical foundation for the further clinical application of hUC-MSC in burn areas.

  1. Delayed revascularization of islets after transplantation by IL-6 blockade in pig to non-human primate islet xenotransplantation model.

    Science.gov (United States)

    Min, Byoung-Hoon; Shin, Jun-Seop; Kim, Jong-Min; Kang, Seong-Jun; Kim, Hyun-Je; Yoon, Il-Hee; Park, Su-Kyoung; Choi, Ji-Won; Lee, Min-Suk; Park, Chung-Gyu

    2018-01-01

    Pancreatic islet transplantation is currently proven as a promising treatment for type 1 diabetes patients with labile glycemic control and severe hypoglycemia unawareness. Upon islet transplantation, revascularization is essential for proper functioning of the transplanted islets. As IL-6 is important for endothelial cell survival and systemic inflammation related to xenograft, the effect of IL-6 receptor antagonist, tocilizumab, on revascularization of the transplanted islets was examined in pig to non-human primate islet xenotransplantation model. Also, the endothelial cell origin in a new vessel of the transplanted pig islets was determined. Pig islets were isolated from designated pathogen-free (DPF) SNU miniature pigs and transplanted via portal vein into five streptozotocin-induced diabetic monkeys. One group (n = 2, basal group) was treated with anti-thymoglobulin (ATG), anti-CD40 antibody (2C10R4), sirolimus, and tacrolimus, and the other group was additionally given tocilizumab on top of basal immunosuppression (n = 3, Tocilizumab group). To confirm IL-6 blocking effect, C-reactive protein (CRP) levels and serum IL-6 concentration were measured. Scheduled biopsy of the margin of the posterior segment right lobe inferior of the liver was performed at 3 weeks after transplantation to assess the degree of revascularization of the transplanted islets. Immunohistochemical staining using anti-insulin, anti-CD31 antibodies, and lectin IB4 was conducted to find the origin of endothelial cells in the islet graft. CRP significantly increased at 1~2 days after transplantation in Basal group, but not in Tocilizumab group, and higher serum IL-6 concentration was measured in latter group, showing the biological potency of tocilizumab. In Basal group, well-developed endothelial cells were observed on the peri- and intraislet area, whereas the number of CD31 + cells in the intraislet space was significantly reduced in Tocilizumab group. Finally, new endothelial

  2. Acquired Epidermodysplasia Verruciformis Associated with Human Papilloma Virus Type 14 in a Small Bowel Transplanted Child--A Case Report.

    Science.gov (United States)

    Hirschman, Derek; Tacastacas, Joselin; Rady, Peter L; Tyring, Stephen K; Cooper, Kevin; Honda, Kord

    2016-01-01

    A 3-year-old African American girl taking sirolimus and tacrolimus for a small bowel transplantation presented with hypopigmented macules and papules throughout her trunk. A biopsy diagnosed epidermodysplasia verruciformis (EV) that was found to be associated with human papillomavirus (HPV) type 14 according to polymerase chain reaction analysis. There are few cases of acquired EV in the setting of organ transplantation. Although there is no standardized treatment for acquired EV, prevention and surveillance for transformation to squamous cell carcinoma are primary concerns. © 2015 Wiley Periodicals, Inc.

  3. EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

    Science.gov (United States)

    Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

    2011-03-01

    Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

  4. [Hepatic cell transplantation. Technical and methodological aspects].

    Science.gov (United States)

    Pareja, Eugenia; Martínez, Amparo; Cortés, Miriam; Bonora, Ana; Moya, Angel; Sanjuán, Fernando; Gómez-Lechón, M José; Mir, José

    2010-03-01

    Hepatic cell transplantation consists of grafting already differentiated cells such as hepatocytes. Human hepatocytes are viable and functionally active. Liver cell transplantation is carried out by means of a 3-step method: isolation of hepatocytes from donor liver rejected for orthotopic transplantation, preparing a cell suspension for infusion and, finally, hepatocytes are implanted into the recipient. There are established protocols for the isolation of human hepatocytes from unused segments of donor livers, based on collagenase digestion of cannulated liver tissue at 37 degrees C. The hepatocytes can be used fresh or cryopreserved. Cryopreservation of isolated human hepatocytes would then be available for planned use. In cell transplant, the important aspects are: infusion route, number of cells, number of infusions and viability of the cells. The cells are infused into the patient through a catheter inserted via portal vein or splenic artery. Liver cell transplantation allows liver tissue to be used that would, otherwise, be discarded, enabling multiple patients to be treated with hepatocytes from a single tissue donor. Copyright 2009 AEC. Published by Elsevier Espana. All rights reserved.

  5. Transplantation tolerance after total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Strober, S.; Slavin, S.; Fuks, Z.; Kaplan, H.S.; Gottlieb, M.; Bieber, C.; Hoppe, R.T.; Grumet, F.C.

    1979-03-01

    We have presented an animal model of tissue transplantation tolerance using the unusual effects of TLI on the immune system. The application of TLI to bone marrow and whole-organ transplantation in humans merits further study, since TLI offers several advantages over presently used therapeutic modalities. Current regimens used to prepare patients for marrow transplantation are lethal in the absence of allogeneic marrow engraftment, and marrow donors are restricted to HLA-matched siblings due to the danger of GHVD. On the other hand, TLI is a nonlethal procedure that has been used successfully in animals to transplant allogeneic marrow from unmatched donors without the development of GHVD. Thus, TLI might allow for marrow transplantation in all patients with a single sibling, whereas conventional procedures are feasible in only one of four such cases (probability of finding a single HLA-matched sibling). In addition, the induction of transplantation tolerance with TLI would obviate the requirement for the use of maintenance immunosuppressive drugs after whole-organ transplantation. Systemic infections associated with the use of these drugs currently account for the majority of deaths in heart transplant patients. Serious infectious complications associated with TLI are rare; thus this therapeutic regimen may offer considerable improvement in the long-term survival of organ graft recipients as compared to that presently obtained with immunosuppressive drugs.

  6. Single dose total lymphoid irradiation combined with cyclophosphamide as immunosuppression for human marrow transplantation in aplastic anemia

    International Nuclear Information System (INIS)

    Kim, T.H.; Kersey, J.H.; Khan, F.M.; Sewchand, W.; Ramsey, N.; Krivit, W.; Coccia, P.; Nesbit, M.E.; Levitt, S.H.

    1979-01-01

    Six patients with aplastic anemia underwent bone marrow transplantation following conditioning with high dose cyclophosphamide and single dose total lymphoid irradiation with 750 rad, 26 rad/min at the midplane of the patient. They all received bone marrow from human leukocyte antigens/mixed lymphocyte culture (HLA/MLC) matched siblings. Five of 6 patients were alive without complications at 12, 11, 7, 4 and 4 months respectively. The remaining patient died from sepis which he had prior to transplantation. There were no graft rejection, graft-vs-Host Disease (GVHD) or interstitial pneumonitis among these patients. The procedure was well tolerated with minimal side effects. The results will be compared with those of groups whose bone marrow was previously transplanted with different immunosuppressive methods

  7. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.

    Science.gov (United States)

    Keirstead, Hans S; Nistor, Gabriel; Bernal, Giovanna; Totoiu, Minodora; Cloutier, Frank; Sharp, Kelly; Steward, Oswald

    2005-05-11

    Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.

  8. A comparative study on the transplantation of different concentrations of human umbilical mesenchymal cells into diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Jia-Hui; Kong; Dan; Zheng; Song; Chen; Hong-Tao; Duan; Yue-Xin; Wang; Meng; Dong; Jian; Song

    2015-01-01

    AIM: To observe the effects of intravitreal injections of different concentrations of human umbilical mesenchymal stem cells on retinopathy in rats with diabetes mellitus.METHODS: Healthy and adult male Sprague-Dawley(SD) rats were randomly assigned to a normal control group(group A), a diabetic retinopathy(DR) blank control group(group B), a high-concentration transplantation group(group C), a low-concentration transplantation group(group D) and a placebo transplantation group(group E). The expression of nerve growth factor(NGF)protein in the retinal layers was detected by immunohistochemical staining at 2, 4, 6 and 8wk.RESULTS: The expression of NGF was positive in group A and most positive in the retinal ganglion cell layer. In groups B and E, the expression of NGF was positive 2wk after transplantation and showed an increase in all layers. However, the level of expression had decreased in all layers at 4wk and was significantly reduced at 8wk. In groups C and D, the expression of NGF had increased at 2wk and continued to increase up to 8wk. The level of expression in group C was much higher than that in group D.CONCLUSION: DR can be improved by intravitreal injection of human umbilical mesenchymal stem cells.High concentrations of human umbilical mesenchymal stem cells confer a better protective effect on DR than low concentrations.

  9. Multiplexed color-coded probe-based gene expression assessment for clinical molecular diagnostics in formalin-fixed paraffin-embedded human renal allograft tissue.

    Science.gov (United States)

    Adam, Benjamin; Afzali, Bahman; Dominy, Katherine M; Chapman, Erin; Gill, Reeda; Hidalgo, Luis G; Roufosse, Candice; Sis, Banu; Mengel, Michael

    2016-03-01

    Histopathologic diagnoses in transplantation can be improved with molecular testing. Preferably, molecular diagnostics should fit into standard-of-care workflows for transplant biopsies, that is, formalin-fixed paraffin-embedded (FFPE) processing. The NanoString(®) gene expression platform has recently been shown to work with FFPE samples. We aimed to evaluate its methodological robustness and feasibility for gene expression studies in human FFPE renal allograft samples. A literature-derived antibody-mediated rejection (ABMR) 34-gene set, comprised of endothelial, NK cell, and inflammation transcripts, was analyzed in different retrospective biopsy cohorts and showed potential to molecularly discriminate ABMR cases, including FFPE samples. NanoString(®) results were reproducible across a range of RNA input quantities (r = 0.998), with different operators (r = 0.998), and between different reagent lots (r = 0.983). There was moderate correlation between NanoString(®) with FFPE tissue and quantitative reverse transcription polymerase chain reaction (qRT-PCR) with corresponding dedicated fresh-stabilized tissue (r = 0.487). Better overall correlation with histology was observed with NanoString(®) (r = 0.354) than with qRT-PCR (r = 0.146). Our results demonstrate the feasibility of multiplexed gene expression quantification from FFPE renal allograft tissue. This represents a method for prospective and retrospective validation of molecular diagnostics and its adoption in clinical transplantation pathology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. MicroRNA expression variability in human cervical tissues.

    Directory of Open Access Journals (Sweden)

    Patrícia M Pereira

    Full Text Available MicroRNAs (miRNAs are short (approximately 22 nt non-coding regulatory RNAs that control gene expression at the post-transcriptional level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. Cervical cancer is one of the most common cancers in women worldwide and there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform containing probes for mature miRNAs. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL and 9 low-grade squamous intraepithelial lesion (LSIL samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, deregulated miRNAs were identified in malignant and pre-malignant cervical tissues after tackling the high expression variability observed. We were also able to identify putative target genes of relevant candidate miRNAs. Our results show that miRNA expression shows natural variability among human samples, which complicates miRNA data profiling analysis. However, such expression noise can be filtered and does not prevent the identification of deregulated miRNAs that play a role in the malignant transformation of cervical squamous cells. Deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of this tumour type.

  11. Photobiomodulation in human muscle tissue: an advantage in sports performance?

    Science.gov (United States)

    Ferraresi, Cleber; Huang, Ying-Ying; Hamblin, Michael R

    2016-12-01

    Photobiomodulation (PBM) describes the use of red or near-infrared (NIR) light to stimulate, heal, and regenerate damaged tissue. Both preconditioning (light delivered to muscles before exercise) and PBM applied after exercise can increase sports performance in athletes. This review covers the effects of PBM on human muscle tissue in clinical trials in volunteers related to sports performance and in athletes. The parameters used were categorized into those with positive effects or no effects on muscle performance and recovery. Randomized controlled trials and case-control studies in both healthy trained and untrained participants, and elite athletes were retrieved from MEDLINE up to 2016. Performance metrics included fatigue, number of repetitions, torque, hypertrophy; measures of muscle damage and recovery such as creatine kinase and delayed onset muscle soreness. Searches retrieved 533 studies, of which 46 were included in the review (n = 1045 participants). Studies used single laser probes, cluster of laser diodes, LED clusters, mixed clusters (lasers and LEDs), and flexible LED arrays. Both red, NIR, and red/NIR mixtures were used. PBM can increase muscle mass gained after training, and decrease inflammation and oxidative stress in muscle biopsies. We raise the question of whether PBM should be permitted in athletic competition by international regulatory authorities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Deepak A Lamba

    2010-01-01

    Full Text Available Inherited and acquired retinal degenerations are frequent causes of visual impairment and photoreceptor cell replacement therapy may restore visual function to these individuals. To provide a source of new retinal neurons for cell based therapies, we developed methods to derive retinal progenitors from human ES cells.In this report we have used a similar method to direct induced pluripotent stem cells (iPS from human fibroblasts to a retinal progenitor fate, competent to generate photoreceptors. We also found we could purify the photoreceptors derived from the iPS cells using fluorescence activated cell sorting (FACS after labeling photoreceptors with a lentivirus driving GFP from the IRBP cis-regulatory sequences. Moreover, we found that when we transplanted the FACS purified iPSC derived photoreceptors, they were able to integrate into a normal mouse retina and express photoreceptor markers.This report provides evidence that enriched populations of human photoreceptors can be derived from iPS cells.

  13. Variation in tissue outcome of ovine and human engineered heart valve constructs : relevance for tissue engineering

    NARCIS (Netherlands)

    Geemen, van D.; Driessen - Mol, A.; Grootzwagers, L.G.M.; Soekhradj - Soechit, R.S.; Riem Vis, P.W.; Baaijens, F.P.T.; Bouten, C.V.C.

    AIM: Clinical application of tissue engineered heart valves requires precise control of the tissue culture process to predict tissue composition and mechanical properties prior to implantation, and to understand the variation in tissue outcome. To this end we investigated cellular phenotype and

  14. Complete human serum maintains viability and chondrogenic potential of human synovial stem cells: suitable conditions for transplantation.

    Science.gov (United States)

    Mizuno, Mitsuru; Katano, Hisako; Otabe, Koji; Komori, Keiichiro; Kohno, Yuji; Fujii, Shizuka; Ozeki, Nobutake; Horie, Masafumi; Tsuji, Kunikazu; Koga, Hideyuki; Muneta, Takeshi; Sekiya, Ichiro

    2017-06-13

    In our clinical practice, we perform transplantations of autologous synovial mesenchymal stem cells (MSCs) for cartilage and meniscus regenerative medicine. One of the most important issues to ensuring clinical efficacy involves the transport of synovial MSCs from the processing facility to the clinic. Complete human serum (100% human serum) is an attractive candidate material in which to suspend synovial MSCs for their preservation during transport. The purpose of this study was to investigate whether complete human serum maintained MSC viability and chondrogenic potential and to examine the optimal temperature conditions for the preservation of human synovial MSCs. Human synovium was harvested from the knees of 14 donors with osteoarthritis during total knee arthroplasty. Passage 2 synovial MSCs were suspended at 2 million cells/100 μL in Ringer's solution or complete human serum at 4, 13, and 37 °C for 48 h. These cells were analyzed for live cell rates, cell surface marker expression, metabolic activity, proliferation, and adipogenic, calcification, and chondrogenic differentiation potentials before and after preservation. After preservation, synovial MSCs maintained higher live cell rates in human serum than in Ringer's solution at 4 and 13 °C. Synovial MSCs preserved in human serum at 4 and 13 °C also maintained high ratios of propidium iodide - and annexin V - cells. MSC surface marker expression was not altered in cells preserved at 4 and 13 °C. The metabolic activities of cells preserved in human serum at 4 and 13 °C was maintained, while significantly reduced in other conditions. Replated MSCs retained their proliferation ability when preserved in human serum at 4 and 13 °C. Adipogenesis and calcification potential could be observed in cells preserved in each condition, whereas chondrogenic potential was retained only in cells preserved in human serum at 4 and 13 °C. The viability and chondrogenic potential of synovial MSCs were

  15. Expression of a Chimeric Antigen Receptor Specific for Donor HLA Class I Enhances the Potency of Human Regulatory T Cells in Preventing Human Skin Transplant Rejection.

    Science.gov (United States)

    Boardman, D A; Philippeos, C; Fruhwirth, G O; Ibrahim, M A A; Hannen, R F; Cooper, D; Marelli-Berg, F M; Watt, F M; Lechler, R I; Maher, J; Smyth, L A; Lombardi, G

    2017-04-01

    Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically translatable synthetic fusion proteins that can redirect the specificity of T cells toward designated antigens. We used CAR technology to redirect human polyclonal Tregs toward donor-MHC class I molecules, which are ubiquitously expressed in allografts. Two novel HLA-A2-specific CARs were engineered: one comprising a CD28-CD3ζ signaling domain (CAR) and one lacking an intracellular signaling domain (ΔCAR). CAR Tregs were specifically activated and significantly more suppressive than polyclonal or ΔCAR Tregs in the presence of HLA-A2, without eliciting cytotoxic activity. Furthermore, CAR and ΔCAR Tregs preferentially transmigrated across HLA-A2-expressing endothelial cell monolayers. In a human skin xenograft transplant model, adoptive transfer of CAR Tregs alleviated the alloimmune-mediated skin injury caused by transferring allogeneic peripheral blood mononuclear cells more effectively than polyclonal Tregs. Our results demonstrated that the use of CAR technology is a clinically applicable refinement of Treg therapy for organ transplantation. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  16. Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient uPA mice.

    Directory of Open Access Journals (Sweden)

    Marina E Fomin

    Full Text Available Liver sinusoidal endothelial cells (LSECs form a semi-permeable barrier between parenchymal hepatocytes and the blood. LSECs participate in liver metabolism, clearance of pathological agents, immunological responses, architectural maintenance of the liver and synthesis of growth factors and cytokines. LSECs also play an important role in coagulation through the synthesis of Factor VIII (FVIII. Herein, we phenotypically define human LSECs isolated from fetal liver using flow cytometry and immunofluorescence microscopy. Isolated LSECs were cultured and shown to express endothelial markers and markers specific for the LSEC lineage. LSECs were also shown to engraft the liver when human fetal liver cells were transplanted into immunodeficient mice with liver specific expression of the urokinase-type plasminogen activator (uPA transgene (uPA-NOG mice. Engrafted cells expressed human Factor VIII at levels approaching those found in human plasma. We also demonstrate engraftment of adult LSECs, as well as hepatocytes, transplanted into uPA-NOG mice. We propose that overexpression of uPA provides beneficial conditions for LSEC engraftment due to elevated expression of the angiogenic cytokine, vascular endothelial growth factor. This work provides a detailed characterization of human midgestation LSECs, thereby providing the means for their purification and culture based on their expression of CD14 and CD32 as well as a lack of CD45 expression. The uPA-NOG mouse is shown to be a permissive host for human LSECs and adult hepatocytes, but not fetal hepatoblasts. Thus, these mice provide a useful model system to study these cell types in vivo. Demonstration of human FVIII production by transplanted LSECs encourages further pursuit of LSEC transplantation as a cellular therapy for the treatment of hemophilia A.

  17. Liver transplant

    Science.gov (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  18. Hair Transplants

    Science.gov (United States)

    ... Search Skin Experts Skin Treatments Hair Transplants Share » HAIR TRANSPLANTS Before (left) and after (right) - front of ... transplant. Photo courtesy of N. Sadick What are hair transplants? In punch transplanting, a plug containing hair ...

  19. Animal study on transplantation of human umbilical vein endothelial cells for corneal endothelial decompensation

    Directory of Open Access Journals (Sweden)

    Li Cui

    2014-06-01

    Full Text Available AIM: To explore the feasibility of culturing human umbilical vein endothelial cells(HUVECon acellular corneal stroma and performing the posterior lamellar endothelial keratoplasty(PLEKtreating corneal endothelial decompensation.METHODS: Thirty New-Zealand rabbits were divided into three groups randomly, 10 rabbits for experimental group, 10 for stroma group and 10 for control group. Corneal endothelial cells were removed to establish animal model of corneal endothelial failure. PLEK was performed on the rabbits of experimental group and stroma group, and nothing was transplantated onto the rabbits of control group with the deep layer excised only. Postoperative observation was taken for 3mo. The degree of corneal edema and central corneal thickness were recorded for statistical analysis.RESULTS: Corneas in experimental group were relieved in edema obviously compared with that in stroma group and the control group, and showed increased transparency 7d after the operation. The average density of endothelial cells was 2 026.4±129.3cells/mm2, and average central corneal thickness was 505.2±25.4μm in experimental group, while 1 535.6±114.5μm in stroma group and 1 493.5±70.2μm in control group 3mo after operation.CONCLUSION:We achieved preliminary success in our study that culturing HUVEC on acellular corneal stroma and performing PLEK for corneal endothelial decompensation. HUVEC transplanted could survive in vivo, and have normal biological function of keeping cornea transparent. This study provides a new idea and a new way clinically for the treatment of corneal endothelial diseases.

  20. Successful transplantation of in vitro expanded human corneal endothelial precursors to corneal endothelial surface using a nanocomposite sheet

    Directory of Open Access Journals (Sweden)

    Parikumar P

    2011-01-01

    Full Text Available Background: Though the transplantation of in vitro expanded human corneal endothelial precursors in animal models of endothelial damage by injecting into the anterior chamber has been reported, the practical difficulties of accomplishing such procedure in human patients have been a hurdle to clinical translation. Here we report the successful transplantation of in vitro expanded human corneal precursor cells to an animal eye using a transparent Nano-composite sheet and their engraftment.Materials and Methods: Human Corneal endothelial cells (HCEC were isolated from human cadaver eyes with informed consent and expanded in the lab using a sphere forming assay in a novel Thermoreversible Gelation Polymer (TGP for 26 days. HCEC obtained by sphere forming assay were seeded in a novel Nano-composite sheet, which was made of PNIPA-NC gels by in-situ, free-radical polymerization of NIPA monomer in the presence of exfoliated clay (synthetic hectorite “Laponite XLG” uniformly dispersed in aqueous media. After a further seven days in vitro culture of HCEC in the Nano-composite sheet, cells were harvested and transplanted on cadaver-bovine eyes (n=3. The cells were injected between the corneal endothelial layer and the Nano-composite sheet that had been placed prior to the injection in close proximity to the endothelial layer. After three hours, the transplanted Nano-composite sheets were removed from the bovine eyes and subjected to microscopic examination. The corneas were subjected to Histo-pathological studies along with controls. Results: HCEC formed sphere like colonies in TGP which expressed relevant markers as confirmed by RT-PCR. Microscopic studies of the Nanosheets and histopathological studies of the cornea of the Bull’s eye revealed that the HCEC got engrafted to the corneal endothelial layer of the bovine eyes with no remnant cells in the Nanosheet. Conclusion: Transplantation of in vitro expanded donor human corneal endothelial cells

  1. Endothelial cell chimerism associated with graft rejection after human lung transplantation.

    OpenAIRE

    Ratajczak , Philippe; Murata , Hideyuki; Meignin , Véronique; Groussard , Odile; Fournier , Michel; Socié , Gérard; Mal , Hervé; Janin , Anne

    2008-01-01

    International audience; Endotheliitis is a major sign of graft rejection. Recipient-derived endothelial cells found in two series of liver and kidney transplants were related to graft rejection. Here, we assessed the presence and the number of chimeric endothelial cells in lung transplants, and their relation with graft rejection. In six males grafted with female lungs out of 193 lung transplantations, endothelial chimerism was studied by combined XY-fluorescent in situ hybridization with CD3...

  2. Human Papilloma Virus in Retinoblastoma Tissues from Korean Patients

    Science.gov (United States)

    Ryoo, Na-Kyung; Kim, Ji-Eun; Kim, Namju; Lee, Min-Jeong; Khwarg, Sang-In

    2013-01-01

    Purpose Recent reports suggest the association of human papilloma virus (HPV) with retinoblastoma. This study was performed to elucidate whether HPV infection is related to retinoblastoma among Koreans. Methods A total of 54 cases diagnosed with retinoblastoma were enrolled from Seoul National University Children's Hospital and Seoul Metropolitan Government-Seoul National University Boramae Medical Center. Presence of human papilloma viral DNA was detected by in situ hybridization in formalin-fixed paraffin-embedded retinoblastoma tissues using both probes against high- and low risk HPV types. Results The mean age at diagnosis was 22.0 months (range, 1.1 to 98.0 months), and the mean age at enucleation was 27.8 months (range, 1.5 to 112.7 months) among the 54 patients with retinoblastoma. HPV was not detected in any of the retinoblastoma samples using either high risk or low risk HPV probes. Conclusions Our study, being the first study in the Korean population, proposes that HPV infection may have no causal relationship with retinoblastoma in Koreans. PMID:24082775

  3. Early humoral-mediated graft injuries in ABO-incompatible kidney transplantation in human beings.

    Science.gov (United States)

    Sekijima, M; Shimizu, A; Ishii, Y; Kudo, S; Horita, S; Nakajima, I; Fuchinoue, S; Teraoka, S

    2010-04-01

    Acute humoral rejection is the most important risk factor for early graft loss in ABO-incompatible (ABO-i) renal transplantation (RTx) and is present from the early period after RTx. However, the characteristics of early humoral-mediated graft injury are pathologically uncertain. To analyze tissue from 10 protocol graft biopsies performed in 10 patients within 30 days post-RTx to clarify the pathologic features of early humoral-mediated graft injuries in ABO-i RTx. Pathologic findings were examined using light and electron microscopy and immunofluorescence studies for C4d. Protocol biopsies were performed within 30 days after RTx in the absence of an episode of dysfunction (creatinine concentration 1.21-1.81 mg/dL). The immunofluorescence study demonstrated C4d deposition in peritubular and glomerular capillaries. Acute glomerulitis with infiltration of mononuclear cells and neutrophils was observed in 3 patients. Furthermore, glomerulitis was accompanied by endothelial cell injuries, widening of subendothelial spaces with a double-contoured glomerular basement membrane, and mesangiolysis. In ABO-i RTx, early humoral-mediated graft injuries were observed in approximately 30% of patients despite normal graft function. They were characterized by C4d deposition and glomerular capillary injury. These findings suggest that renal glomeruli are the first site of graft injury by anti-A or anti-B blood type antibody with complement activation in ABO-i RTx.

  4. The effects of compound danshen dripping pills and human umbilical cord blood mononuclear cell transplant after acute myocardial infarction.

    Science.gov (United States)

    Jun, Yi; Chunju, Yuan; Qi, Ai; Liuxia, Deng; Guolong, Yu

    2014-04-01

    The low frequency of survival of stem cells implanted in the myocardium after acute myocardial infarction may be caused by inflammation and oxidative stress in the myocardial microenvironment. We evaluated the effects of a traditional Chinese medicine, Compound Danshen Dripping Pills, on the cardiac microenvironment and cardiac function when used alone or in combination with human umbilical cord blood mononuclear cell transplant after acute myocardial infarction. After surgically induced acute myocardial infarction, rabbits were treated with Compound Danshen Dripping Pills alone or in combination with human umbilical cord blood mononuclear cell transplant. Evaluation included histology, measurement of left ventricular ejection fraction and fractional shortening, leukocyte count, count of green fluorescent protein positive cells, superoxide dismutase activity, and malondialdehyde content. Combination treatment with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cell transplant significantly increased the survival of implanted cells, inhibited cardiac cell apoptosis, decreased oxidative stress, decreased the inflammatory response, and improved cardiac function. Rabbits treated with either Compound Danshen Dripping Pills or human umbilical cord blood mononuclear cells alone had improvement in these effects compared with untreated control rabbits. Combination therapy with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cells may improve cardiac function and morphology after acute myocardial infarction.

  5. Non-invasive determination of metabolite concentrations in human transplanted kidney in vivo by 31P MR spectroscopy

    International Nuclear Information System (INIS)

    Kugel, H.; Wittsack, H.J.; Wenzel, F.; Heindel, W.; Lackner, K.; Stippel, D.

    2000-01-01

    To investigate concentrations of phosphorus-containing metabolites in human transplanted kidney in vivo by quantitative 31 P MR spectroscopy (MRS) using surface coils and to compare the obtained values with previous data. Material and Methods: In 5 patients with well-functioning transplanted kidneys, 31 P spectra were obtained with the three-dimensional localization image-selected in vivo spectroscopy technique applying a protocol for quantitative spectroscopy using surface coils. Relaxation corrected signal intensities determined by time domain fitting were used to derive absolute molar concentrations for phosphate-containing metabolites. Results: Little or no phosphocreatine in all spectra verified the absence of muscle contamination, confirming proper volume localization. The mean concentrations in the transplanted kidneys were as follows: ATP 1.60±0.26 mmol/l, PDE 2.14±0.91 mmol/l, Pi 0.66±0.25 mmol/l, PME 2.32±0.50 mmol/l. These values are consistent with previously reported values determined by other techniques. Conclusion: The non-invasive determination of absolute metabolite concentrations in human kidney using MRS supplements the use of signal intensity ratios to detect pathologic changes in the energy metabolism of transplanted kidneys

  6. Human amniotic epithelial cell transplantation for the repair of injured brachial plexus nerve: evaluation of nerve viscoelastic properties

    Directory of Open Access Journals (Sweden)

    Hua Jin

    2015-01-01

    Full Text Available The transplantation of embryonic stem cells can effectively improve the creeping strength of nerves near an injury site in animals. Amniotic epithelial cells have similar biological properties as embryonic stem cells; therefore, we hypothesized that transplantation of amniotic epithelial cells can repair peripheral nerve injury and recover the creeping strength of the brachial plexus nerve. In the present study, a brachial plexus injury model was established in rabbits using the C 6 root avulsion method. A suspension of human amniotic epithelial cells was repeatedly injected over an area 4.0 mm lateral to the cephal and caudal ends of the C 6 brachial plexus injury site (1 × 10 6 cells/mL, 3 μL/injection, 25 injections immediately after the injury. The results showed that the decrease in stress and increase in strain at 7,200 seconds in the injured rabbit C 6 brachial plexus nerve were mitigated by the cell transplantation, restoring the viscoelastic stress relaxation and creep properties of the brachial plexus nerve. The forepaw functions were also significantly improved at 26 weeks after injury. These data indicate that transplantation of human amniotic epithelial cells can effectively restore the mechanical properties of the brachial plexus nerve after injury in rabbits and that viscoelasticity may be an important index for the evaluation of brachial plexus injury in animals.

  7. Interspecies chimeric complementation for the generation of functional human tissues and organs in large animal hosts.

    Science.gov (United States)

    Wu, Jun; Izpisua Belmonte, Juan Carlos

    2016-06-01

    The past decade's rapid progress in human pluripotent stem cell (hPSC) research has generated hope for meeting the rising demand of organ donation, which remains the only effective cure for end-stage organ failure, a major cause of death worldwide. Despite the potential, generation of transplantable organs from hPSCs using in vitro differentiation is far-fetched. An in vivo interspecies chimeric complementation strategy relying on chimeric-competent hPSCs and zygote genome editing provides an auspicious alternative for providing unlimited organ source for transplantation.

  8. Radioimmunoassay of cholecystokinin in human tissue and plasma

    International Nuclear Information System (INIS)

    Jansen, J.B.M.J.; Lamers, C.B.H.W.

    1983-01-01

    A highly sensitive radioimmunoassay for cholecystokinin (CCK) without any cross-reactivity with gastrin is described. The antibody was raised in a rabbit by immunisation with 30% CCK and bound to all COOH-terminal CCK-peptides containing at least 14 amino acid residues. The affinity constant of the antibody was 59.4 x 10 10 l/mol. CCK 33 conjugated to [ 125 I]hydroxyphenylpropionic acid-succinimide ester was used as label. The binding between label and antibody was inhibited by 50% (ID 50 ) at a concentration of 2.8 pmol/l cholecystokinin 33. The detection limit of the assay was between 0.5 and 1.0 pmol/l plasma. Concentrations of CCK in aqueous acid extracts of human upper small intestine were 36.5 +- 9.8 pmol/g and of human cerebral cortex 28.2 +- 2.5 pmol/g tissue. Plasma samples were extracted in 96% ethanol prior to assay. No advantage was obtained by adding aprotinin to the tubes. When frozen at -20 0 C plasma CCK was stable for at least 6 months. Basal plasma CCK concentrations in 30 normal subjects were very low, 0.9 +- 0.1 pmol/l, range 0.5 to 3.1 pmol/l. Intraduodenal administration of fat induced significant increases in plasma CCK from 1.1 +- 0.1 to 8.2 +- 1.3 pmol/l (p = 0.01). Infusion of exogenous CCK, resulting in plasma CCK levels slightly lower than those measured during administration of fat, induced pancreatic enzyme secretion and gallbladder contraction. The reliability of this radioimmunoassay for measurements of CCK in human plasma was extensively evaluated. (Auth.)

  9. Cryopreservation of ovarian tissue for a decade in Denmark: a view of the technique

    DEFF Research Database (Denmark)

    Rosendahl, Mikkel; Schmidt, Kirsten Louise Tryde; Ernst, Erik

    2011-01-01

    evaluation of mouse and human ovarian tissue after freezing with four different combinations of cryoprotectants. Viability was confirmed by transplantation of frozen-thawed human ovarian tissue (n = 49) to oophorectomized Nude mice. Viability after transport of fresh tissue 4-5 h prior to freezing had...... previously been validated. Overnight transport of fresh ovarian tissue prior to cryopreservation was evaluated when human ovarian tissue was kept on ice for 20 h and then cryopreserved. The thawed ovarian tissue was transplanted to an oophorectomized Nude mouse and histology confirmed viability. In Denmark...

  10. Assessment of heavy metal residues in water, fish tissue and human ...

    African Journals Online (AJOL)

    MICHAEL HORSFALL

    ABSTRACT: Residual levels of lead, chromium, cadmium and zinc in water and fish tissue from. Ubeji River ... Key Words : Heavy metal residues , Fish tissue, Human blood, Ubeji River. ... is of critical concern because of their toxicity and.

  11. Radiosensitivity and cell kinetics of the human solid cancer transplanted to nude mouse

    International Nuclear Information System (INIS)

    Ikeuchi, Shunji

    1983-01-01

    This study was undertaken to analyse the relationship between radiosensitivity and cell kinetics of human solid cancer in experimental nude mouse system. Four strains of tumors used for the experiment were poorly differentiated squamous cell carcinoma of the lung (Lu-9), oat cell carcinoma of the lung (Lu-24), well differentiated squamous cell carcinoma of the tongue (To-1) and moderately differentiated squamous cell carcinoma of the esophagus (Es-4) which were serially transplantable to BALB/c nude mice. Radiosensitivity was evaluated by tumor growth in terms of inhibition rate, histological change and host reaction after irradiation. Cell kinetics were studied by autoradiography with pulse administration of 3 H-thymidine to mice. Although Lu-24 was most radiosensitive, followed by To-1, Es-4 and Lu-9 in the order of sensitivity, it was suggested that they might be more radioresistant in nude mice without T-cell function than in human. Regarding squamous cell carcinomas, well differentiated type was more radiosensitive than poorly differentiated one. All of these tumors in nude mouse revealed distinct percent labeled mitosis curves with two clear peaks which were quite different from those in human body. Lu-24 showed a characteristic pattern with a long time lag before visible growth, short G 1 , and low growth fraction, compared to other three tumors. Three strains of squamous cell carcinoma demonstrated similar cell kinetic factors which were almost the same as those in human body reported previously. The differences in volume doubling time of tumor, growth fraction and cell loss factor were partially related to those of radiosensitivities among tumors except for Lu-24. The theoretical volume doubling time was proved to be most reliable for estimation of effectiveness of irradiation, but the labeling index was not a valuable indicator for it. (author)

  12. In search of better spermatogonial preservation by supplementation of cryopreserved human immature testicular tissue xenografts with N-acetylcysteine and testosterone

    Directory of Open Access Journals (Sweden)

    Jonathan ePoels

    2014-12-01

    Full Text Available Controlled slow-freezing is the procedure currently applied for immature testicular tissue cryobanking in clinical practice. Vitrification has been proposed as a promising alternative, with a view to better preserving spermatogonial stem cells for future fertility restoration by autografting in young boys suffering from cancer. It appears that besides the potential influence of the cryopreservation technique used, the transplantation procedure itself has a significant impact on spermatogonial loss observed in ITT xenografts. Eighteen immature testicular tissue pieces issuing from 6 patients aged 2-15 years were used. Fragments of fresh tissue (serving as ungrafted controls, frozen-thawed tissue, frozen-thawed tissue supplemented with N-acetylcysteine and frozen-thawed tissue supplemented with testosterone xenografted to nude mice for 5 days were compared. Upon graft removal, histological and immunohistochemical analyses were performed to evaluate spermatogonia, intratubular proliferation and intrinsic and extrinsic apoptosis. A significant decrease in the integrity of intact seminiferous tubules was found in all three grafted groups. Spermatogonia were observed by immunohistochemistry in all grafted groups, with recovery rates of 67%, 63% and 53% respectively for slow-frozen tissue, slow-frozen tissue supplemented with N-acetylcysteine and slow-frozen tissue supplemented with testosterone. Apoptosis evidenced by active caspase-3 and TUNEL was similar in all grafts. The study is limited by the low availability of immature testicular tissue samples of human origin, and no clear impact of graft supplementation was found. The mouse xenotransplantation model needs to be refined to investigate human spermatogenesis in human immature testicular tissue grafts.

  13. Fascia tissue engineering with human adipose-derived stem cells in a murine model: Implications for pelvic floor reconstruction

    Directory of Open Access Journals (Sweden)

    Man-Jung Hung

    2014-10-01

    Conclusion: Our results suggest the ADSC-seeded implant is better than the implant alone in enhancing tissue regeneration after transplantation. ADSCs with or without fibroblastic differentiation might have a potential but different role in fascia tissue engineering to repair POP in the future.

  14. 78 FR 44134 - Submission for OMB Review; 30-day Comment Request: Financial Sustainability of Human Tissue...

    Science.gov (United States)

    2013-07-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Submission for OMB Review; 30-day Comment Request: Financial Sustainability of Human Tissue Biobanking (NCI) SUMMARY: Under the... Collection: Financial Sustainability of Human Tissue Biobanking, 0925-NEW, National Cancer Institute (NCI...

  15. Distribution of transplanted human mesenchymal stem cells from Wharton’s Jelly in the central nervous systems of the EAE rats

    Directory of Open Access Journals (Sweden)

    Kovalchuk M. V.

    2015-10-01

    Full Text Available Human Wharton’s Jelly MSCs (hWJ-MSCs have a considerable advantage and potential in treating the central nervous system diseases and can be a new alternative treatment of Multiple Sclerosis (MS. Aim. To study the persistence and distribution of hWJ-MSCs along the neuraxis following transplantation in central nervous system of rats with experimental autoimmune encephalomyelitis (EAE, the animal model of MS. Methods. Isolation and cultivation of hWJ-MSCs in vitro. Immunological phenotyping by flow cytometry. EAE induction. Intrathecal (suboccipital injection of MSCs into CNS of SCH-induced EAE rats. Persistence of hWJ-MSCs in the CNS of hWJ-MSCs -treated rats was detected through detection of the human alpha-satellite DNA in the tissue sections and the cerebrospinal fluid (CSF by PCR at days 2, 3, 4 and 5 Results. PCR-assays for alpha-satellite sequences revealed that Human DNA was detected during 5 days following intrathecal injection at the peak of disease in the treated rats. It has been demonstrated that the human DNA was traced in CSF and various segments of a spinal cord. Conclusions. The data obtained suggest that intrathecally delivered hWJ-MSCs, with time, can migrate through the CSF from the injection site to various segments of CNS and persist therein during the first week of post transplantation, which was performed at the EAE disease peak in the xenogeneic setting without immunosuppression. hWJ-MSCs may be considered as a delivery cell source of therapeutic molecules for CNS inflammatory diseases.

  16. Regenerative therapy for vestibular disorders using human induced pluripotent stem cells (iPSCs): neural differentiation of human iPSC-derived neural stem cells after in vitro transplantation into mouse vestibular epithelia.

    Science.gov (United States)

    Taura, Akiko; Nakashima, Noriyuki; Ohnishi, Hiroe; Nakagawa, Takayuki; Funabiki, Kazuo; Ito, Juichi; Omori, Koichi

    2016-10-01

    Vestibular ganglion cells, which convey sense of motion from vestibular hair cells to the brainstem, are known to degenerate with aging and after vestibular neuritis. Thus, regeneration of vestibular ganglion cells is important to aid in the recovery of balance for associated disorders. The present study derived hNSCs from induced pluripotent stem cells (iPSCs) and transplanted these cells into mouse utricle tissues. After a 7-day co-culture period, histological and electrophysiological examinations of transplanted hNSCs were performed. Injected hNSC-derived cells produced elongated axon-like structures within the utricle tissue that made contact with vestibular hair cells. A proportion of hNSC-derived cells showed spontaneous firing activities, similar to those observed in cultured mouse vestibular ganglion cells. However, hNSC-derived cells around the mouse utricle persisted as immature neurons or occasionally differentiated into putative astrocytes. Moreover, electrophysiological examination showed hNSC-derived cells around utricles did not exhibit any obvious spontaneous firing activities. Injected human neural stem cells (hNSCs) showed signs of morphological maturation including reconnection to denervated hair cells and partial physiological maturation, suggesting hNSC-derived cells possibly differentiated into neurons.

  17. Human cardiomyocyte progenitor cell transplantation preserves long-term function of the infarcted mouse myocardium

    NARCIS (Netherlands)

    Smits, Anke M.; van Laake, Linda W.; den Ouden, Krista; Schreurs, Chantal; Szuhai, Karoly; van Echteld, Cees J.; Mummery, Christine L.; Doevendans, Pieter A.; Goumans, Marie-Jose

    2009-01-01

    Recent clinical studies revealed that positive results of cell transplantation on cardiac function are limited to the short- and mid-term restoration phase following myocardial infarction (MI), emphasizing the need for long-term follow-up. These transient effects may depend on the transplanted

  18. Polybrominated diphenyl ethers: human tissue levels and toxicology.

    Science.gov (United States)

    Gill, Udai; Chu, Ih; Ryan, John J; Feeley, Mark

    2004-01-01

    with behavioral alterations in neonatal mice. When considering the outlier value for PBDE-99 at 229 ng/g, this would result in an estimated PBDE-99 body burden of 46 microg/kg, or a MOS of only 9. However, no toxicokinetics data are available for humans, and the actual margin of safety may be much smaller if based on levels in critical target organs or tissues.

  19. Construction of engineering adipose-like tissue in vivo utilizing human insulin gene-modified umbilical cord mesenchymal stromal cells with silk fibroin 3D scaffolds.

    Science.gov (United States)

    Li, Shi-Long; Liu, Yi; Hui, Ling

    2015-12-01

    We evaluated the use of a combination of human insulin gene-modified umbilical cord mesenchymal stromal cells (hUMSCs) with silk fibroin 3D scaffolds for adipose tissue engineering. In this study hUMSCs were isolated and cultured. HUMSCs infected with Ade-insulin-EGFP were seeded in fibroin 3D scaffolds with uniform 50-60 µm pore size. Silk fibroin scaffolds with untransfected hUMSCs were used as control. They were cultured for 4 days in adipogenic medium and transplanted under the dorsal skins of female Wistar rats after the hUMSCs had been labelled with chloromethylbenzamido-1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (CM-Dil). Macroscopical impression, fluorescence observation, histology and SEM were used for assessment after transplantation at 8 and 12 weeks. Macroscopically, newly formed adipose tissue was observed in the experimental group and control group after 8 and 12 weeks. Fluorescence observation supported that the formed adipose tissue originated from seeded hUMSCs rather than from possible infiltrating perivascular tissue. Oil red O staining of newly formed tissue showed that there was substantially more tissue regeneration in the experimental group than in the control group. SEM showed that experimental group cells had more fat-like cells, whose volume was larger than that of the control group, and degradation of the silk fibroin scaffold was greater under SEM observation. This study provides significant evidence that hUMSCs transfected by adenovirus vector have good compatibility with silk fibroin scaffold, and adenoviral transfection of the human insulin gene can be used for the construction of tissue-engineered adipose. Copyright © 2013 John Wiley & Sons, Ltd.

  20. Business oriented EU human cell and tissue product legislation will adversely impact Member States' health care systems.

    Science.gov (United States)

    Pirnay, Jean-Paul; Vanderkelen, Alain; De Vos, Daniel; Draye, Jean-Pierre; Rose, Thomas; Ceulemans, Carl; Ectors, Nadine; Huys, Isabelle; Jennes, Serge; Verbeken, Gilbert

    2013-12-01

    The transplantation of conventional human cell and tissue grafts, such as heart valve replacements and skin for severely burnt patients, has saved many lives over the last decades. The late eighties saw the emergence of tissue engineering with the focus on the development of biological substitutes that restore or improve tissue function. In the nineties, at the height of the tissue engineering hype, industry incited policymakers to create a European regulatory environment, which would facilitate the emergence of a strong single market for tissue engineered products and their starting materials (human cells and tissues). In this paper we analyze the elaboration process of this new European Union (EU) human cell and tissue product regulatory regime-i.e. the EU Cell and Tissue Directives (EUCTDs) and the Advanced Therapy Medicinal Product (ATMP) Regulation and evaluate its impact on Member States' health care systems. We demonstrate that the successful lobbying on key areas of regulatory and policy processes by industry, in congruence with Europe's risk aversion and urge to promote growth and jobs, led to excessively business oriented legislation. Expensive industry oriented requirements were introduced and contentious social and ethical issues were excluded. We found indications that this new EU safety and health legislation will adversely impact Member States' health care systems; since 30 December 2012 (the end of the ATMP transitional period) there is a clear threat to the sustainability of some lifesaving and established ATMPs that were provided by public health institutions and small and medium-sized enterprises under the frame of the EUCTDs. In the light of the current economic crisis it is not clear how social security systems will cope with the inflation of costs associated with this new regulatory regime and how priorities will be set with regard to reimbursement decisions. We argue that the ATMP Regulation should urgently be revised to focus on delivering

  1. Secretion of autoimmune antibodies in the human subcutaneous adipose tissue.

    Science.gov (United States)

    Frasca, Daniela; Diaz, Alain; Romero, Maria; Thaller, Seth; Blomberg, Bonnie B

    2018-01-01

    The adipose tissue (AT) contributes to systemic and B cell intrinsic inflammation, reduced B cell responses and sec