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.

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...

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

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

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.

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

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

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

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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...

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

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.

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

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.

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

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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

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

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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.

Bioprinting scale-up tissue and organ constructs for transplantation.

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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.

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

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

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.

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.

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.

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.

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

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.

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

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

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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.

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

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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.

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

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

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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

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

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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.

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

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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.

A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

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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

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....

[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.

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

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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.

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

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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.

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

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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.

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...

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

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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.

Stem Cell Transplants (For Parents)

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... 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 ...

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.

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

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.

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.

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

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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.

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

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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.

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

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

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.

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

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...

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.

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

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

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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

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.

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

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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

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

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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

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

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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.

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.

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...

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.

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.

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

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.

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.

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

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

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.

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

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.

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 %).

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.

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.

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....

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

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

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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

The International Registry on Hand and Composite Tissue Transplantation.

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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).

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

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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

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

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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.

PHENOMENON OF DEMIKHOV. "Transplantation of vital organs In experiment" (1960. Transplantation immunity, artifi cial circulation in organ transplantation

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S. P. Glyantsev

2017-01-01

Full Text Available The article (the fourth of five presents the analysis of the 4th and 5th chapters from V.P.Demikhov's monograph "Transplantation of vital organs in experiment" (MedGIz Publisher, Moscow, 1960, where he described his studies of transplantation immunity in originally created models and his use of artificial blood-circulation systems in experimental organ transplantation. It has been shown that V.P.Demikhov changed his views on the tissue biological incompatibility in homoplastic transplants and turned from the Michurin-Pavlov's concepts (1946–1953 to natural-scientific views (1959. Meanwhile, his multiple attempts to study both the morphological and humoral immunological response to transplanted organs did not give conclusive results because of lacking the experience of such studies even in the country's leading scientists and due the imperfection of their techniques. Realizing that the retrieval of a beating heart from a human would have created further problems for its subsequent transplantation, V.P. Demikhov attempted to reanimate human hearts in corpses by means of extracorporeal devices to provide artificial circulation. Methodologically, those devices were based on S.S.Bryukhonenko's research and his "auto-injector" pump modified by V.P.Demikhov. However, by 1960, those studies had not come beyond the experiments.

Organ transplantation: legal, ethical and islamic perspective in Nigeria.

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Bakari, Abubakar A; Abbo Jimeta, Umar S; Abubakar, Mohammed A; Alhassan, Sani U; Nwankwo, Emeka A

2012-07-01

Organ transplantation dates back to the ancient times and since then it has become one of the important developments in modern medicine; saving the lives, as well as improving the quality of life of many patients. As the demand for organ transplantation far exceeds the organ availability, the transplant program is often saddled with complex legal and ethical issues. This review article highlights the legal and ethical issues that might arise regarding organ transplantation and appraises the existing legal frame work governing organ transplantation in Nigeria. Information on legal, cultural, religious and medical ethical issues regarding organ transplantation in Nigeria was obtained by searching the PubMed and Google Scholar, conference proceedings, seminar paper presentations, law library and other related publications were collated and analyzed. In decision making for organ transplantation, the bioethical principles like autonomy, beneficence and justice must be employed. It was believed by Catholic theologians that to mutilate one living person to benefit another violates the principle of Totality. Among Muslim scholars and researchers, there are those who throw legal support as to its permissibility while the other group sees it as illegal. Organ/tissues transplantation is considered a medical intervention that touches on the fundamental rights of the donor or the recipient. Where there is an unlawful infringement of the right of such persons in any way may be regarded as against Section 34 of the 1999 Nigerian Constitution dealing with right to dignity of the human person. Worldwide, the researchers and government bodies have agreed on informed consent for organ/tissue donation and for recipient should be obtained without coercion before embarking on such medical treatment Worldwide organ transplantation has become the best medical treatment for patients with end stage organ failure. However, there is no law/legislation backing organ/tissues transplantation in

Organ Transplantation: Legal, Ethical and Islamic Perspective in Nigeria

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Bakari, Abubakar A; Abbo Jimeta, Umar S; Abubakar, Mohammed A; Alhassan, Sani U; Nwankwo, Emeka A

2012-01-01

Organ transplantation dates back to the ancient times and since then it has become one of the important developments in modern medicine; saving the lives, as well as improving the quality of life of many patients. As the demand for organ transplantation far exceeds the organ availability, the transplant program is often saddled with complex legal and ethical issues. This review article highlights the legal and ethical issues that might arise regarding organ transplantation and appraises the existing legal frame work governing organ transplantation in Nigeria. Information on legal, cultural, religious and medical ethical issues regarding organ transplantation in Nigeria was obtained by searching the PubMed and Google Scholar, conference proceedings, seminar paper presentations, law library and other related publications were collated and analyzed. In decision making for organ transplantation, the bioethical principles like autonomy, beneficence and justice must be employed. It was believed by Catholic theologians that to mutilate one living person to benefit another violates the principle of Totality. Among Muslim scholars and researchers, there are those who throw legal support as to its permissibility while the other group sees it as illegal. Organ/tissues transplantation is considered a medical intervention that touches on the fundamental rights of the donor or the recipient. Where there is an unlawful infringement of the right of such persons in any way may be regarded as against Section 34 of the 1999 Nigerian Constitution dealing with right to dignity of the human person. Worldwide, the researchers and government bodies have agreed on informed consent for organ/tissue donation and for recipient should be obtained without coercion before embarking on such medical treatment Worldwide organ transplantation has become the best medical treatment for patients with end stage organ failure. However, there is no law/legislation backing organ/tissues transplantation in

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

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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.

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

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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

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

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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

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

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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.

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

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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.

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

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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.

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

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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

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

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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.

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

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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.

Uterus transplantation: Experimental animal models and recent experience in humans

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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.

Cryopreservation of ovarian tissue for a decade in Denmark: a view of the technique

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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...

Microsurgical Composite Tissue Transplantation

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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

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

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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.

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

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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.

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

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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.

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

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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....

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

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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.

The Major Histocompatibility Complex in Transplantation

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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.

Organ transplantation: Legal, ethical and Islamic perspective in Nigeria

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Abubakar A Bakari

2012-01-01

Full Text Available Organ transplantation dates back to the ancient times and since then it has become one of the important developments in modern medicine; saving the lives, as well as improving the quality of life of many patients. As the demand for organ transplantation far exceeds the organ availability, the transplant program is often saddled with complex legal and ethical issues. This review article highlights the legal and ethical issues that might arise regarding organ transplantation and appraises the existing legal frame work governing organ transplantation in Nigeria. Information on legal, cultural, religious and medical ethical issues regarding organ transplantation in Nigeria was obtained by searching the PubMed and Google Scholar, conference proceedings, seminar paper presentations, law library and other related publications were collated and analyzed. In decision making for organ transplantation, the bioethical principles like autonomy, beneficence and justice must be employed. It was believed by Catholic theologians that to mutilate one living person to benefit another violates the principle of Totality. Among Muslim scholars and researchers, there are those who throw legal support as to its permissibility while the other group sees it as illegal. Organ/tissues transplantation is considered a medical intervention that touches on the fundamental rights of the donor or the recipient. Where there is an unlawful infringement of the right of such persons in any way may be regarded as against Section 34 of the 1999 Nigerian Constitution dealing with right to dignity of the human person. Worldwide, the researchers and government bodies have agreed on informed consent for organ/tissue donation and for recipient should be obtained without coercion before embarking on such medical treatment Worldwide organ transplantation has become the best medical treatment for patients with end stage organ failure. However, there is no law/legislation backing organ/tissues

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

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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

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

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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.

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

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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.

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

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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.

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

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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.

Colonic complications following human bone marrow transplantation

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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

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

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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.

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

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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.

A glow of HLA typing in organ transplantation

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2013-01-01

The transplant of organs and tissues is one of the greatest curative achievements of this century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the main goal of the immune response is the MHC (major histocompatibility complex) molecules expressed on the surface of donor cells. Cell surface molecules that induce an antigenic stimulus cause the rejection immune response to grafted tissue or organ. A wide variety of transplantation antigens have been described, including the major histocompatibility molecules, minor histocompatibility antigens, ABO blood group antigens and endothelial cell antigens. The sensitization to MHC antigens may be caused by transfusions, pregnancy, or failed previous grafts leading to development of anti-human leukocyte antigen (HLA) antibodies that are important factor responsible for graft rejection in solid organ transplantation and play a role in post-transfusion complication Anti-HLA Abs may be present in healthy individuals. Methods for HLA typing are described, including serological methods, molecular techniques of sequence-specific priming (SSP), sequence-specific oligonucleotide probing (SSOP), Sequence based typing (SBT) and reference strand-based conformation analysis (RSCA) method. Problems with organ transplantation are reservoir of organs and immune suppressive treatments that used to decrease rate of rejection with less side effect and complications. PMID:23432791

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

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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.

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

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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

Hematopoietic Stem Cell Transplantation and History

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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.

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 ...

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.

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...

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....

TISSUE BANKING – A NEW HOPE FOR RENERATIVE MEDICINE

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Mihail George Man

2013-12-01

Full Text Available Cells, tissues and organs banks are specialised facilities in hospitals or medical institutions performing processing, preservation, banking and distribution activities of human morphological components. The authorisation criterias of such facilities are established according to the legislation regarding the human cells, tissues and organs transplantation (the law no. 48/2008 of the Romanian Parliament. Those „cells and tissues banks” are obliged to respect the instructions reguardind the donation, testing, processing, storage, distribution, encoding and trasability of the tissues and cells of human origin, used for therapeutical purposes, as well as the notification of the severe accidents and side effects during the transplantation process. The prelevation, embeding, labeling and transportation of human cells and tissues are performed according to the technical specifications in order to minimise the risk of biological contamination and only after obtaining the informed consent of the living donor and strictely respecting the legal aspects on the decesed donor.

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

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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.

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: �

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

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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.

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

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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

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.

Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues.

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Eduardo K Moioli

Full Text Available Poor angiogenesis is a major road block for tissue repair. The regeneration of virtually all tissues is limited by angiogenesis, given the diffusion of nutrients, oxygen, and waste products is limited to a few hundred micrometers. We postulated that co-transplantation of hematopoietic and mesenchymal stem/progenitor cells improves angiogenesis of tissue repair and hence the outcome of regeneration. In this study, we tested this hypothesis by using bone as a model whose regeneration is impaired unless it is vascularized. Hematopoietic stem/progenitor cells (HSCs and mesenchymal stem/progenitor cells (MSCs were isolated from each of three healthy human bone marrow samples and reconstituted in a porous scaffold. MSCs were seeded in micropores of 3D calcium phosphate (CP scaffolds, followed by infusion of gel-suspended CD34(+ hematopoietic cells. Co-transplantation of CD34(+ HSCs and CD34(- MSCs in microporous CP scaffolds subcutaneously in the dorsum of immunocompromised mice yielded vascularized tissue. The average vascular number of co-transplanted CD34(+ and MSC scaffolds was substantially greater than MSC transplantation alone. Human osteocalcin was expressed in the micropores of CP scaffolds and was significantly increased upon co-transplantation of MSCs and CD34(+ cells. Human nuclear staining revealed the engraftment of transplanted human cells in vascular endothelium upon co-transplantation of MSCs and CD34(+ cells. Based on additional in vitro results of endothelial differentiation of CD34(+ cells by vascular endothelial growth factor (VEGF, we adsorbed VEGF with co-transplanted CD34(+ and MSCs in the microporous CP scaffolds in vivo, and discovered that vascular number and diameter further increased, likely owing to the promotion of endothelial differentiation of CD34(+ cells by VEGF. Together, co-transplantation of hematopoietic and mesenchymal stem/progenitor cells may improve the regeneration of vascular dependent tissues such as bone

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 ...

Global initiatives to tackle organ trafficking and transplant tourism.

Science.gov (United States)

Bagheri, Alireza; Delmonico, Francis L

2013-11-01

The increasing gap between organ supply and demand has opened the door for illegal organ sale, trafficking of human organs, tissues and cells, as well as transplant tourism. Currently, underprivileged and vulnerable populations in resource-poor countries are a major source of organs for rich patient-tourists who can afford to purchase organs at home or abroad. This paper presents a summary of international initiatives, such as World Health Organization's Principle Guidelines, The Declaration of Istanbul, Asian Task Force Recommendations, as well as UNESCO's and the United Nation's initiatives against trafficking of human organs, tissues, cells, and transplant tourism. Beyond the summary, it calls for more practical measures to be taken to implement the existing guidelines and recommendations, in order to prevent exploitation of the poor as organ providers. The paper suggests that an international legally binding agreement in criminalizing organ trafficking would be a step forward to bring a change in the global picture of organ trafficking and transplant tourism.

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

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.

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.

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

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

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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.

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

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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.

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

Hyaline cartilage degenerates after autologous osteochondral transplantation.

Science.gov (United States)

Tibesku, C O; Szuwart, T; Kleffner, T O; Schlegel, P M; Jahn, U R; Van Aken, H; Fuchs, S

2004-11-01

Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

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

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.

Ethics, transplantation, and the changing role of anatomists.

Science.gov (United States)

Satyapal, K S

2005-03-01

Anatomists are regarded as custodians of cadaveric material donated to science. Almost every facet of medical science has experienced explosive advances. This has impacted directly on anatomists and their role. Increasingly, anatomists are raising concerns with regard to the treatment of human tissue (Jones,2002, Clin. Anat. 15:436-440). The Korperwelten (Bodyworlds) of Gunther von Hagens et al. (1987, Anat. Embryol. 175:411-421) has evoked considerable debate about the treatment of human cadavers. Thus far clinical anatomists have had little role to play in policy formulation, legislation, and ethical imperatives as applied to cadaveric donation for organ transplantation. Anatomists play an even more negligible role in the raging ethical controversy around live related/unrelated organ transplantation. Due to the critical international shortage of cadaveric donors, boundaries are being pushed to meet the needs of potential recipients (Ohler,2001, Prog. Transplant. 11:160-161). Constant reappraisal of these ethical and moral issues is therefore appropriate. Issues that relate to cultural and economic imperialism and pronouncements of international transplant societies may also require re-evaluation. The legislature governing the donation of human tissue in various countries is usually governed by a Human Tissue Act or its equivalent. In general, such acts are congruent with the Human Tissue Act (South Africa: Government Gazette 9, November 2001; No. 22824) that states "It is an offense to charge a fee in relation to the donation of human organs." In many countries, however, various lay press report that "the sale of body parts is now coming of age." Terms such as "rewarded gifting" and "donors" being transformed into "vendors" are opening a Pandora's Box (Nelson et al.,1993, "Financial incentives for organ donation: a report on the UNOS ethics committee payment subcommittee"). Cameron and Hoffenberg (1999, Kidney Int. 55:724-732) feel strongly that arguments in

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

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)

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.

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)

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.

Generation of Scaffoldless Hyaline Cartilaginous Tissue from Human iPSCs

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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.

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.

Role of pancreatic polypeptide as a market of transplanted insulin-producing fetal pig cells.

Science.gov (United States)

Tuch, B E; Tabiin, M T; Casamento, F M; Yao, M; Georges, P; Amaratunga, A; Pinto, A N

2001-01-01

it is transplanted into mice. These findings may have relevance to fetal pancreatic tissue transplanted into humans if suitable techniques can be developed to separate pig from human PP.

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)

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

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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.

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.

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.

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.

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...

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

The ethics of uterus transplantation.

Science.gov (United States)

Catsanos, Ruby; Rogers, Wendy; Lotz, Mianna

2013-02-01

Human uterus transplantation (UTx) is currently under investigation as a treatment for uterine infertility. Without a uterus transplant, the options available to women with uterine infertility are adoption or surrogacy; only the latter has the potential for a genetically related child. UTx will offer recipients the chance of having their own pregnancy. This procedure occurs at the intersection of two ethically contentious areas: assisted reproductive technologies (ART) and organ transplantation. In relation to organ transplantation, UTx lies with composite tissue transplants such as face and limb grafts, and shares some of the ethical concerns raised by these non-life saving procedures. In relation to ART, UTx represents one more avenue by which a woman may seek to meet her reproductive goals, and as with other ART procedures, raises questions about the limits of reproductive autonomy. This paper explores the ethical issues raised by UTx with a focus on the potential gap between women's desires and aspirations about pregnancy and the likely functional outcomes of successful UTx. © 2011 Blackwell Publishing Ltd.

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

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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.

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.

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.

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.

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...

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.

Trends in Tissue Engineering for Blood Vessels

Directory of Open Access Journals (Sweden)

Judee Grace Nemeno-Guanzon

2012-01-01

Full Text Available Over the years, cardiovascular diseases continue to increase and affect not only human health but also the economic stability worldwide. The advancement in tissue engineering is contributing a lot in dealing with this immediate need of alleviating human health. Blood vessel diseases are considered as major cardiovascular health problems. Although blood vessel transplantation is the most convenient treatment, it has been delimited due to scarcity of donors and the patient’s conditions. However, tissue-engineered blood vessels are promising alternatives as mode of treatment for blood vessel defects. The purpose of this paper is to show the importance of the advancement on biofabrication technology for treatment of soft tissue defects particularly for vascular tissues. This will also provide an overview and update on the current status of tissue reconstruction especially from autologous stem cells, scaffolds, and scaffold-free cellular transplantable constructs. The discussion of this paper will be focused on the historical view of cardiovascular tissue engineering and stem cell biology. The representative studies featured in this paper are limited within the last decade in order to trace the trend and evolution of techniques for blood vessel tissue engineering.

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

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Dominique E. Martin

2011-09-01

Full Text Available 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 and societal groups led by the Sindh Institute of Urology and Transplantation, show that organ trading can be effectively discouraged and equitable programs of organ procurement and transplantation pursued despite multiple challenges. In this paper, the factors that have contributed to Pakistan’s progress towards self-sufficiency in organ transplantation are identified and discussed. The case of Pakistan highlights the need for countries to protect their own organ and tissue providers who may be vulnerable in the global healthcare market. Pakistan provides an excellent example for other countries in the region and throughout the world to consider when regulating their own transplantation programs and considering the pursuit of national self-sufficiency.

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.

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.

Proteomic analysis of tyrosine phosphorylation during human liver transplantation

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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.

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.

Organ Transplantation: Legal, Ethical and Islamic Perspective in ...

African Journals Online (AJOL)

As the demand for organ transplantation far exceeds the organ availability, the ... conference proceedings, seminar paper presentations, law library and other ... may be regarded as against Section 34 of the 1999 Nigerian Constitution dealing ... problem of national and international trafficking in human tissues and organs, ...

Pancreatic islet transplantation

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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

Preliminary study of coconut water for graft tissues preservation in transplantation

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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.

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

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

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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.

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...

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...

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

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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.

Human endothelial colony-forming cells expanded with an improved protocol are a useful endothelial cell source for scaffold-based tissue engineering.

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Denecke, Bernd; Horsch, Liska D; Radtke, Stefan; Fischer, Johannes C; Horn, Peter A; Giebel, Bernd

2015-11-01

One of the major challenges in tissue engineering is to supply larger three-dimensional (3D) bioengineered tissue transplants with sufficient amounts of nutrients and oxygen and to allow metabolite removal. Consequently, artificial vascularization strategies of such transplants are desired. One strategy focuses on endothelial cells capable of initiating new vessel formation, which are settled on scaffolds commonly used in tissue engineering. A bottleneck in this strategy is to obtain sufficient amounts of endothelial cells, as they can be harvested only in small quantities directly from human tissues. Thus, protocols are required to expand appropriate cells in sufficient amounts without interfering with their capability to settle on scaffold materials and to initiate vessel formation. Here, we analysed whether umbilical cord blood (CB)-derived endothelial colony-forming cells (ECFCs) fulfil these requirements. In a first set of experiments, we showed that marginally expanded ECFCs settle and survive on different scaffold biomaterials. Next, we improved ECFC culture conditions and developed a protocol for ECFC expansion compatible with 'Good Manufacturing Practice' (GMP) standards. We replaced animal sera with human platelet lysates and used a novel type of tissue-culture ware. ECFCs cultured under the new conditions revealed significantly lower apoptosis and increased proliferation rates. Simultaneously, their viability was increased. Since extensively expanded ECFCs could still settle on scaffold biomaterials and were able to form tubular structures in Matrigel assays, we conclude that these ex vivo-expanded ECFCs are a novel, very potent cell source for scaffold-based tissue engineering. Copyright © 2013 John Wiley & Sons, Ltd.

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...

A novel subcutaneous site of islet transplantation superior to the liver.

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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.

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

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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.

Neocortical Transplants in the Mammalian Brain Lack a Blood-Brain Barrier to Macromolecules

Science.gov (United States)

Rosenstein, Jeffrey M.

1987-02-01

In order to determine whether the blood-brain barrier was present in transplants of central nervous tissue, fetal neocortex, which already possesses blood-brain and blood-cerebrospinal fluid barriers to protein, was grafted into the undamaged fourth ventricle or directly into the neocortex of recipient rats. Horseradish peroxidase or a conjugated human immunoglobulin G-peroxidase molecule was systemically administered into the host. These proteins were detected within the cortical transplants within 2 minutes regardless of the age of the donor or postoperative time. At later times these compounds, which normally do not cross the blood-brain barrier, inundated the grafts and adjacent host brain and also entered the cerebrospinal fluid. Endogenous serum albumin detected immunocytochemically in untreated hosts had a comparable although less extensive distribution. Thus, transplants of fetal central nervous tissue have permanent barrier dysfunction, probably due to microvascular changes, and are not integrated physiologically within the host. Blood-borne compounds, either systemically administered or naturally occurring, which should never contact normal brain tissue, have direct access to these transplants and might affect neuronal function.

Comprehensive evaluation of leukocyte lineage derived from human hematopoietic cells in humanized mice.

Science.gov (United States)

Takahashi, Masayuki; Tsujimura, Noriyuki; Otsuka, Kensuke; Yoshino, Tomoko; Mori, Tetsushi; Matsunaga, Tadashi; Nakasono, Satoshi

2012-04-01

Recently, humanized animals whereby a part of the animal is biologically engineered using human genes or cells have been utilized to overcome interspecific differences. Herein, we analyzed the detail of the differentiation states of various human leukocyte subpopulations in humanized mouse and evaluated comprehensively the similarity of the leukocyte lineage between humanized mice and humans. Humanized mice were established by transplanting human CD34(+) cord blood cells into irradiated severely immunodeficient NOD/Shi-scid/IL2Rγ(null) (NOG) mice, and the phenotypes of human cells contained in bone marrow, thymus, spleen and peripheral blood from the mice were analyzed at monthly intervals until 4 months after cell transplantation. The analysis revealed that transplanted human hematopoietic stem cells via the caudal vein homed and engrafted themselves successfully at the mouse bone marrow. Subsequently, the differentiated leukocytes migrated to the various tissues. Almost all of the leukocytes within the thymus were human cells. Furthermore, analysis of the differentiation states of human leukocytes in various tissues and organs indicated that it is highly likely that the human-like leukocyte lineage can be developed in mice. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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

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.

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.

MAPC transplantation confers a more durable benefit than AC133+ cell transplantation in severe hind limb ischemia.

Science.gov (United States)

Aranguren, Xabier L; Pelacho, Beatriz; Peñuelas, Ivan; Abizanda, Gloria; Uriz, Maialen; Ecay, Margarita; Collantaes, María; Araña, Miriam; Beerens, Manu; Coppiello, Giulia; Prieto, Inés; Perez-Ilzarbe, Maitane; Andreu, Enrique J; Luttun, Aernout; Prósper, Felipe

2011-01-01

There is a need for comparative studies to determine which cell types are better candidates to remedy ischemia. Here, we compared human AC133(+) cells and multipotent adult progenitor cells (hMAPC) in a mouse model reminiscent of critical limb ischemia. hMAPC or hAC133(+) cell transplantation induced a significant improvement in tissue perfusion (measured by microPET) 15 days posttransplantation compared to controls. This improvement persisted for 30 days in hMAPC-treated but not in hAC133(+)-injected animals. While transplantation of hAC133(+) cells promoted capillary growth, hMAPC transplantation also induced collateral expansion, decreased muscle necrosis/fibrosis, and improved muscle regeneration. Incorporation of differentiated hAC133(+) or hMAPC progeny into new vessels was limited; however, a paracrine angio/arteriogenic effect was demonstrated in animals treated with hMAPC. Accordingly, hMAPC-conditioned, but not hAC133(+)-conditioned, media stimulated vascular cell proliferation and prevented myoblast, endothelial, and smooth muscle cell apoptosis in vitro. Our study suggests that although hAC133(+) cell and hMAPC transplantation both contribute to vascular regeneration in ischemic limbs, hMAPC exert a more robust effect through trophic mechanisms, which translated into collateral and muscle fiber regeneration. This, in turn, conferred tissue protection and regeneration with longer term functional improvement. © 2011 Cognizant Comm. Corp.

Long-term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation.

Science.gov (United States)

Weiner, Joshua; Zuber, Julien; Shonts, Brittany; Yang, Suxiao; Fu, Jianing; Martinez, Mercedes; Farber, Donna L; Kato, Tomoaki; Sykes, Megan

2017-10-01

Little is known about innate lymphoid cell (ILC) populations in the human gut, and the turnover of these cells and their subsets after transplantation has not been described. Intestinal samples were taken from 4 isolated intestine and 3 multivisceral transplant recipients at the time of any operative resection, such as stoma closure or revision. ILCs were isolated and analyzed by flow cytometry. The target population was defined as being negative for lineage markers and double-positive for CD45/CD127. Cells were further stained to define ILC subsets and a donor-specific or recipient-specific HLA marker to analyze chimerism. Donor-derived ILCs were found to persist greater than 8 years after transplantation. Additionally, the percentage of cells thought to be lymphoid tissue inducer cells among donor ILCs was far higher than that among recipient ILCs. Our findings demonstrate that donor-derived ILCs persist long-term after transplantation and support the notion that human lymphoid tissue inducer cells may form in the fetus and persist throughout life, as hypothesized in rodents. Correlation between chimerism and rejection, graft failure, and patient survival requires further study.

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

Engineered cartilaginous tubes for tracheal tissue replacement via self-assembly and fusion of human mesenchymal stem cell constructs.

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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.

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.

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

Selection, processing and clinical application of muscle-skeletal tissue

International Nuclear Information System (INIS)

Luna Z, D.; Reyes F, M.L.; Lavalley E, C.; Castaneda J, G.

2007-01-01

Due to the increase in the average of the world population's life, people die each time to more age, this makes that the tissues of support of the human body, as those muscle-skeletal tissues, when increasing the individual's age go weakening, this in turn leads to the increment of the illnesses like the osteoporosis and the arthritis, that undoubtedly gives as a result more injure of the muscle-skeletal tissues joined a greater number of traffic accidents where particularly these tissues are affected, for that the demand of tissues muscle-skeletal for transplant every day will be bigger. The production of these tissues in the Bank of Radio sterilized Tissues, besides helping people to improve its quality of life saved foreign currencies because most of the muscle-skeletal tissues transplanted in Mexico are of import. The use of the irradiation to sterilize tissues for transplant has shown to be one of the best techniques with that purpose for what the International Atomic Energy Agency believes a Technical cooperation program to establish banks of tissues using the nuclear energy, helping mainly to countries in development. In this work the stages that follows the bank of radio sterilized tissues of the National Institute of Nuclear Research for the cadaverous donor's of muscle-skeletal tissue selection are described, as well as the processing and the clinical application of these tissues. (Author)

The survival condition and immunoregulatory function of adipose stromal vascular fraction (SVF in the early stage of nonvascularized adipose transplantation.

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Ziqing Dong

Full Text Available INTRODUCTION: Adipose tissue transplantation is one of the standard procedures for soft-tissue augmentation, reconstruction, and rejuvenation. However, it is unknown as to how the graft survives after transplantation. We thus seek out to investigate the roles of different cellular components in the survival of graft. MATERIALS & METHODS: The ratios of stromal vascular fraction (SVF cellular components from human adipose tissue were evaluated using flow cytometry. Human liposuction aspirates that were either mixed with marked SVF cells or PBS were transplanted into nude mice. The graft was harvested and stained on days 1,4,7 and 14. The inflammation level of both SVF group and Fat-only group were also evaluated. RESULTS: Flow cytometric analysis showed SVF cells mainly contained blood-derived cells, adipose-derived stromal cells (ASCs, and endothelial cells. Our study revealed that most cells are susceptible to death after transplantation, although CD34+ ASCs can remain viable for 14 days. Notably, we found that ASCs migrated to the peripheral edge of the graft. Moreover, the RT-PCR and the immuno-fluorescence examination revealed that although the SVF did not reduce the number of infiltrating immune cells (macrophages in the transplant, it does have an immunoregulatory function of up-regulating the expression of CD163 and CD206 and down-regulating that of IL-1β, IL-6. CONCLUSIONS: Our study suggests that the survival of adipose tissue after nonvascularized adipose transplantation may be due to the ASCs in SVF cells. Additionally, the immunoregulatory function of SVF cells may be indirectly contributing to the remolding of adipose transplant, which may lead to SVF-enriched adipose transplantation.

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

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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.

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

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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.

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

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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,

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

Soft tissue engineering with micronized-gingival connective tissues.

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Noda, Sawako; Sumita, Yoshinori; Ohba, Seigo; Yamamoto, Hideyuki; Asahina, Izumi

2018-01-01

The free gingival graft (FGG) and connective tissue graft (CTG) are currently considered to be the gold standards for keratinized gingival tissue reconstruction and augmentation. However, these procedures have some disadvantages in harvesting large grafts, such as donor-site morbidity as well as insufficient gingival width and thickness at the recipient site post-treatment. To solve these problems, we focused on an alternative strategy using micronized tissue transplantation (micro-graft). In this study, we first investigated whether transplantation of micronized gingival connective tissues (MGCTs) promotes skin wound healing. MGCTs (≤100 µm) were obtained by mincing a small piece (8 mm 3 ) of porcine keratinized gingiva using the RIGENERA system. The MGCTs were then transplanted to a full skin defect (5 mm in diameter) on the dorsal surface of immunodeficient mice after seeding to an atelocollagen matrix. Transplantations of atelocollagen matrixes with and without micronized dermis were employed as experimental controls. The results indicated that MGCTs markedly promote the vascularization and epithelialization of the defect area 14 days after transplantation compared to the experimental controls. After 21 days, complete wound closure with low contraction was obtained only in the MGCT grafts. Tracking analysis of transplanted MGCTs revealed that some mesenchymal cells derived from MGCTs can survive during healing and may function to assist in wound healing. We propose here that micro-grafting with MGCTs represents an alternative strategy for keratinized tissue reconstruction that is characterized by low morbidity and ready availability. © 2017 Wiley Periodicals, Inc.

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

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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.

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

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

Multiplexed color-coded probe-based gene expression assessment for clinical molecular diagnostics in formalin-fixed paraffin-embedded human renal allograft tissue.

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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.

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

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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

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

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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.

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

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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.

The immunologic considerations in human head transplantation.

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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.

Radiation sterilization of tissue allografts: Requirements for validation and routine control. A code of practice

International Nuclear Information System (INIS)

2007-12-01

These recommendations for the radiation sterilization of tissue allografts adopt the principles that the International Organization for Standardization (ISO) applies to the radiation sterilization of health care products. The approach has been adapted to take into account the special features associated with human tissues and the features that distinguish them from industrially produced sterile health care products. The approach as described here is not applicable if viral contamination is identified. Thus it is emphasized that the human donors of the tissues must be medically and serologically screened. To further support this screening it is recommended that autopsy reports be reviewed if available. This adaptation of established ISO methods can thus only be applied to sterilization of tissue allografts if the radiation sterilization described here is the terminal stage of a careful, detailed, documented sequence of procedures involving: donor selection; tissue retrieval; tissue banking general procedures; specific processing procedures; labelling; and distribution. The methods proposed here for the establishment of a sterilization dose are based on statistical approaches used for the sterilization of health care products and modified appropriately for the low numbers of tissue allograft samples typically available. This code of practice will be useful to tissue banking staff, surgeons using tissues for transplantation, regulators who oversee the safety of transplantation and radiation sterilization procedures, members of tissue banking associations, health service personnel in hospitals in which tissue transplantations are performed and inter-governmental organizations involved in transplantation issues, for example the World Health Organization. This publication was discussed extensively at an international meeting in Wrexham in the United Kingdom and was approved by the Technical Advisory Committee of the relevant IAEA project, which included the Chairpersons

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

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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.

Validation of an LC-MS/MS method to measure tacrolimus in rat kidney and liver tissue and its application to human kidney biopsies.

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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.

Transplantation: a religio-ethical imperative

International Nuclear Information System (INIS)

Abu Bakar Abdul Majeed; Abu Bakar Yang; Wan Roslili Abdul Majid

1999-01-01

Transplantation as a mode of treatment for serious and life-dementing diseases is expected to progress, and in all probability, will show better prospects for success in the future. Though medical considerations are paramount subjective judgments often come into play. Even now, complex moral and ethical questions on transplantation are being raised. Therefore, religious authorities and ethicists, must provide the practitioners and society with balanced and well-founded views on these matters. Some of the issues of transplantation discussed in this paper are the rights of per-sons to donate their own organs and tissues, the determination of death and the sourcing of cadaveric organs and tissues, and the selection of recipients for scarce organs and tissues. These are first viewed from the prevalent general theories of ethics, such as utilitarianism.Then, the religious perspectives of these issues are looked at. The Islamic usul-fikh or the fundamentals of Islamic jurisprudence, through which Muslim jurists reach their fatwas or nilings, are discussed briefly. The historical background of the Islamic jurists views on organ and tissue donation and transplantation is reviewed, while the recent fatwas are highlighted.The Islamic teachings and fatwas allow all types of organ and tissue transplantation, if certain required conditions are met. The permission is granted based on three principles of the Islamic law, namely, o f choosing the lesser of the two evils if neither is avoidable , o f necessities overruling prohibitions', and o f seeking remedy for every illness . The preconditions attached to the fatwas are; that the life of the potential recipient is in grave danger and the transplantation has a high probability of success, death of cadaveric donors is ascertained by the required medical criteria, the life of donor is not jeopardised m any way, there is no commercialisation of organs and tissues, and permission for the removal of organs and tissues granted by the

Practical experience in post-mortem tissue donation in consideration of the European tissue law.

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Karbe, Thomas; Braun, Christian; Wulff, Birgit; Schröder, Ann Sophie; Püschel, Klaus; Bratzke, Hansjürgen; Parzeller, Markus

2010-03-01

In consequence of the European guidelines of safety and quality standards for the donation, retrieval, storing and distribution of human tissues and cells the purpose of tissue transplantation was implemented into German legislation in May 2007. The law came into effect on August 1st 2007 considering of the European rules. The Institutes for Legal Medicine of the University of Frankfurt/Main and the University Medical Center Hamburg-Eppendorf developed a model for tissue retrieval. The Institute of Legal Medicine (I.f.R.) at the University Medical Center Hamburg cooperates with the German Institute of Cell and Tissue Replacement (Deutsches Institut für Zell--und Gewebeersatz DIZG). Potential post-mortem tissue donors (PMTD) among the deceased are selected by standardized sets of defined criteria. The procedure is guided by the intended exclusion criteria of the tissue regulation draft (German Transplant Law TPG GewV) in accordance with the European Guideline (2006/17/EC). Following the identification of the donor and subsequent removal of tissue, the retrieved samples were sent to the DIZG, a non-profit tissue bank according to the tissue regulation. Here the final processing into transplantable tissue grafts takes place, which then results in the allocation of tissue to hospitals in Germany and other European countries. The Center of Legal Medicine at the Johann Wolfgang Goethe-University Medical Center Frankfurt/Main cooperates since 2000 with Tutogen, a pharmaceutical company. Harvesting of musculoskeletal tissues follows corresponding regulations. To verify the outcome of PMTD at the I.f.R. Hamburg, two-statistic analysis over 12 and 4 months have been implemented. Our results have shown an increasing number of potential appropriate PMTD within the second inquiry interval but a relatively small and unvaryingly rate of successful post-mortem tissue retrievals similar to the first examination period. Thus, the aim of the model developed by the I.f.R. is to

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

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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

Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

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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.

Fate of bone marrow mesenchymal stromal cells following autologous transplantation in a rabbit model of osteonecrosis.

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Sugaya, Hisashi; Mishima, Hajime; Gao, Ran; Kaul, Sunil C; Wadhwa, Renu; Aoto, Katsuya; Li, Meihua; Yoshioka, Tomokazu; Ogawa, Takeshi; Ochiai, Naoyuki; Yamazaki, Masashi

2016-02-01

Internalizing quantum dots (i-QDs) are a useful tool for tracking cells in vivo in models of tissue regeneration. We previously synthesized i-QDs by conjugating QDs with a unique internalizing antibody against a heat shock protein 70 family stress chaperone. In the present study, i-QDs were used to label rabbit mesenchymal stromal cells (MSCs) that were then transplanted into rabbits to assess differentiation potential in an osteonecrosis model. The i-QDs were taken up by bone marrow-derived MSCs collected from the iliac of 12-week-old Japanese white rabbits that were positive for cluster of differentiation (CD)81 and negative for CD34 and human leukocyte antigen DR. The average rate of i-QD internalization was 93.3%. At 4, 8, 12, and 24 weeks after transplantation, tissue repair was evaluated histologically and by epifluorescence and electron microscopy. The i-QDs were detected at the margins of the drill holes and in the necrotized bone trabecular. There was significant colocalization of the i-QD signal in transplanted cells and markers of osteoblast and mineralization at 4, 8, and 12 weeks post-transplantation, while i-QDs were detected in areas of mineralization at 12 and 24 weeks post-transplantation. Moreover, i-QDs were observed in osteoblasts in regenerated tissue by electron microscopy, demonstrating that the tissue was derived from transplanted cells. These results indicate that transplanted MSCs can differentiate into osteoblasts and induce tissue repair in an osteonecrosis model and can be tracked over the long term by i-QD labeling. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Human papilloma virus infection in female kidney transplant recipients

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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.

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.

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

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...

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

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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.

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

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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

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....

ASSOCIATION OF EPSTEIN-BARR VIRUS (EBV) BUT NOT HUMAN PAPILLOMAVIRUS (HPV) WITH GINGIVITIS AND/OR PERIODONTITIS IN TRANSPLANTED INDIVIDUALS.

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Baez, Camila Freze; Savassi-Ribas, Flavia; Rocha, Wilker Menezes da; Almeida, Stéphanie G S; Gonçalves, Marianna T V; Guimarães, Maria Angelica A M; Cavalcanti, Silvia Maria B; Varella, Rafael B

2016-07-11

The aim of this study was to investigate the association of EBV and HPV with gingivitis and/or periodontitis according to the immunologic status. To this end, 74 oral biopsies from transplanted and non-transplanted individuals with the abovementioned oral manifestations were submitted to a screening by PCR for both viruses. According to the results, EBV was strongly associated with gingivitis and/or periodontitis in transplanted individuals (p = 0.011) but not HPV (p = 0.766). EBV-HPV co-detections did not enhance the presence of tissue injury as well. Although a causal relationship was not investigated in this study, the higher frequency of these two oncoviruses in lesion tissues must be investigated in follow-up studies, especially among immunocompromised individuals.

Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells

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Dreyer-Andersen, Nanna; Almeida, Ana Sofia; Jensen, Pia

2018-01-01

Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson's disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem...... cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting...... in Parkinson's disease....

Cryopreserved Dental Pulp Tissues of Exfoliated Deciduous Teeth Is a Feasible Stem Cell Resource for Regenerative Medicine

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Yamaza, Haruyoshi; Akiyama, Kentaro; Hoshino, Yoshihiro; Song, Guangtai; Kukita, Toshio; Nonaka, Kazuaki; Shi, Songtao; Yamaza, Takayoshi

2012-01-01

Human exfoliated deciduous teeth have been considered to be a promising source for regenerative therapy because they contain unique postnatal stem cells from human exfoliated deciduous teeth (SHED) with self-renewal capacity, multipotency and immunomodulatory function. However preservation technique of deciduous teeth has not been developed. This study aimed to evaluate that cryopreserved dental pulp tissues of human exfoliated deciduous teeth is a retrievable and practical SHED source for cell-based therapy. SHED isolated from the cryopreserved deciduous pulp tissues for over 2 years (25–30 months) (SHED-Cryo) owned similar stem cell properties including clonogenicity, self-renew, stem cell marker expression, multipotency, in vivo tissue regenerative capacity and in vitro immunomodulatory function to SHED isolated from the fresh tissues (SHED-Fresh). To examine the therapeutic efficacy of SHED-Cryo on immune diseases, SHED-Cryo were intravenously transplanted into systemic lupus erythematosus (SLE) model MRL/lpr mice. Systemic SHED-Cryo-transplantation improved SLE-like disorders including short lifespan, elevated autoantibody levels and nephritis-like renal dysfunction. SHED-Cryo amended increased interleukin 17-secreting helper T cells in MRL/lpr mice systemically and locally. SHED-Cryo-transplantation was also able to recover osteoporosis bone reduction in long bones of MRL/lpr mice. Furthermore, SHED-Cryo-mediated tissue engineering induced bone regeneration in critical calvarial bone-defect sites of immunocompromised mice. The therapeutic efficacy of SHED-Cryo transplantation on immune and skeletal disorders was similar to that of SHED-Fresh. These data suggest that cryopreservation of dental pulp tissues of deciduous teeth provide a suitable and desirable approach for stem cell-based immune therapy and tissue engineering in regenerative medicine. PMID:23251621

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.

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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.

In search of better spermatogonial preservation by supplementation of cryopreserved human immature testicular tissue xenografts with N-acetylcysteine and testosterone

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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.

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.

Construction of engineering adipose-like tissue in vivo utilizing human insulin gene-modified umbilical cord mesenchymal stromal cells with silk fibroin 3D scaffolds.

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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.

Adipose tissue engineering: state of the art, recent advances and innovative approaches.

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Tanzi, Maria Cristina; Farè, Silvia

2009-09-01

Adipose tissue is a highly specialized connective tissue found either in white or brown forms, the white form being the most abundant in adult humans. Loss or damage of white adipose tissue due to aging or pathological conditions needs reconstructive approaches. To date, two main strategies are being investigated for generating functional adipose tissue: autologous tissue/cell transplantation and adipose tissue engineering. Free-fat transplantation rarely achieves sufficient tissue augmentation owing to delayed neovascularization, with subsequent cell necrosis and graft volume shrinkage. Tissue engineering approaches represent, instead, a more suitable alternative for adipose tissue regeneration; they can be performed either with in situ or de novo adipogenesis. In situ adipogenesis or transplantation of encapsulated cells can be useful in healing small-volume defects, whereas restoration of large defects, where vascularization and a rapid volumetric gain are strict requirements, needs de novo strategies with 3D scaffold/filling matrix combinations. For adipose tissue engineering, the use of adult mesenchymal stem cells (both adipose- and bone marrow-derived stem cells) or of preadipocytes is preferred to the use of mature adipocytes, which have low expandability and poor ability for volume retention. This review intends to assemble and describe recent work on this topic, critically presenting successes obtained and drawbacks faced to date.

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

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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.

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

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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

Transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into rat spinal cord injuries does not cause harm.

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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.

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

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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).

Overview of Twenty Years of Radiation and Tissue Banking Activity in Argentina

International Nuclear Information System (INIS)

Kairiyama, E.

2015-01-01

Radiation sterilization of human tissues in Argentina was a consequence of health care products sterilization by gamma radiation. Radiation technology was implemented in 1970 when the first multipurpose gamma facility was built at the Ezeiza Atomic Centre of CNEA. Organ and tissue transplantation is a well established effective therapy that saves lives and significantly improves the quality of life. Ionizing radiation is used for sterilization in order to provide clinically safe tissue for therapeutic purposes of implantation in every patient in need. Argentina radiation and tissue banking activity started in 1993 with the establishment of two tissue banks using radiation under the IAEA programme of technical cooperation, a skin bank and a bone one. Additionally to this start, other tissue banks have adopted tissue sterilization by irradiation. The compatible tissues sterilized with this methodology are mainly skin (frozen, glycerolized), bone (lyophilized, frozen), and amniotic membrane (glycerolized, frozen, dehydrated). The donation and transplant of human organ, tissue and cells is regulated and coordinated by the National Institute Unique Central Coordinator of Ablation and Implant (INCUCAI). In regards to radiation and nuclear safety, physical protection and nuclear non-proliferation issues are regulated and contorted by the Nuclear Regulatory Authority (ARN). Eight tissue banks use gamma radiation for sterilization of human tissues (6 musculoskeletal, 1 skin and 1 amniotic membrane). Argentina has participated actively in several IAEA projects regarding radiation and tissue banking program, and it has been selected by the IAEA to host the Regional Training Centre for the Latin American region. The following activities were implemented: regional training courses in Buenos Aires, face to face (five) and virtual (four) modalities; collaboration on several materials related to tissue banking and radiation sterilization of tissue allograft, codes of practice for

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

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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.

Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury

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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.

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.

Three-year post-transplant medicare payments in kidney transplant recipients: Associations with pre-transplant comorbidities

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Gerardo Machnicki

2011-01-01

Full Text Available Little is known about the influence of pre-transplant comorbidities on post-transplant expenditures. We estimated the associations between pre-transplant comorbidities and post-transplant Medicare costs, using several comorbidity classification systems. We included recipients of first-kidney deceased donor transplants from 1995 through 2002 for whom Medicare was the primary payer for at least one year pre-transplant (N = 25,175. We examined pre-transplant comorbidities as classified by International Classification of Diseases (ICD-9-CM codes from Medicare claims with the Clinical Cla-ssifications Software (CCS and Charlson and Elixhauser algorithms. Post-transplant costs were calcu-lated from payments on Medicare claims. We developed models considering Organ Procurement and Transplantation Network (OPTN variables plus: 1 CCS categories, 2 Charlson, 3 Elixhauser, 4 num-ber of Charlson and 5 number of Elixhauser comorbidities, independently. We applied a novel regression methodology to account for censoring. Costs were estimated at individual and population levels. The comorbidities with the largest impact on mean Medicare payments included cardiovascular disease, ma-lignancies, cerebrovascular disease, mental conditions and functional limitations. Skin ulcers and infec-tions, rheumatic and other connective tissue disease and liver disease also contributed to payments and have not been considered or described previously. A positive graded relationship was found between costs and the number of pre-transplant comorbidities. In conclusion, we showed that expansion beyond the usually considered pre-transplant comorbidities with inclusion of CCS and Charlson or Elixhauser comorbidities increased the knowledge about comorbidities related to augmented Medicare payments. Our expanded methodology can be used by others to assess more accurately the financial implications of renal transplantation to Medicare and individual transplant centers.

Hematopoietic chimerism and transplantation tolerance: a role for regulatory T cells

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Lise ePasquet

2011-12-01

Full Text Available The major obstacle in transplantation medicine is rejection of donor tissues by the host’s immune system. Immunosuppressive drugs can delay but not prevent loss of transplants, and their efficiency is strongly impacted by inter-individual pharmacokinetic differences. Moreover, due to the global immunosuppression induced and to the broad distribution of their targets amongst human tissues, these drugs have severe side effects. Induction of donor-specific non-responsiveness (i.e. immunological tolerance to transplants would solve these problems and would substantially ameliorate patients’ quality of life. It is widely believed that bone marrow or hematopoietic stem cell transplantation, and resulting (mixed hematopoietic chimerism, invariably leads to immunological tolerance to organs of the same donor. A careful analysis of the literature, reviewed here, indeed shows that chimerism consistently prolongs allograft survival. However, in absence of additional conditioning leading to the development of active regulatory mechanisms, it does not prevent chronic rejection. A central role for active tolerance in transplantation-tolerance is also supported by recent data showing that genuine immunological tolerance to organ allografts can be achieved by combining induction of hematopoietic chimerism with infusion of regulatory T lymphocytes. Therefore, conditioning regimens that lead to the establishment of hematopoietic chimerism plus active regulatory mechanisms appear required for induction of genuine tolerance to allogeneic grafts.

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

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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.

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...

Human Bone Derived Collagen for the Development of an Artificial Corneal Endothelial Graft. In Vivo Results in a Rabbit Model.

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Natalia Vázquez

Full Text Available Corneal keratoplasty (penetrating or lamellar using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world's population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane. Human corneal endothelial cells were cultured from corneal rims after corneal penetrating keratoplasty and type I collagen was isolated from remnant cancellous bone chips. Isolated type I collagen was analyzed by western blot, liquid chromatography -mass spectrometry and quantified using the exponentially modified protein abundance index. Later on, collagen solution was casted at room temperature obtaining an optically transparent and mechanically manageable membrane that supports the growth of human and rabbit corneal endothelial cells which expressed characteristic markers of corneal endothelium: zonula ocluddens-1 and Na+/K+ ATPase. To evaluate the therapeutic efficiency of our artificial endothelial grafts, human purified type I collagen membranes cultured with rabbit corneal endothelial cells were transplanted in New Zealand white rabbits that were kept under a minimal immunosuppression regimen. Transplanted corneas maintained transparency for as long as 6 weeks without obvious edema or immune rejection and maintaining the same endothelial markers that in a healthy cornea. In conclusion, it is possible to develop an artificial human corneal endothelial graft using remnant tissues that are not employed in transplant procedures. This artificial endothelial graft can restore the integrality of corneal endothelium in an experimental model of

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...

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

Determining the origin of cells in tissue engineered skin substitutes: a pilot study employing in situ hybridization.

Science.gov (United States)

Weber, Andreas Daniel; Pontiggia, Luca; Biedermann, Thomas; Schiestl, Clemens; Meuli, Martin; Reichmann, Ernst

2011-03-01

Definitive and high-quality coverage of large and, in particular, massive skin defects remains a significant challenge in burn as well as plastic and reconstructive surgery because of donor site shortage. A novel and promising approach to overcome these problems is tissue engineering of skin. Clearly, before eventual clinical application, engineered skin substitutes of human origin must be grafted and then evaluated in animal models. For the various tests to be conducted it is indispensable to be able to identify human cells as such in culture and also to distinguish between graft and recipient tissue after transplantation. Here we describe a tool to identify human cells in vitro and in vivo. In situ hybridization allows for the detection and localization of specific DNA or RNA sequences in morphologically preserved cells in culture or tissue sections, respectively. We used digoxigenin-labeled DNA probes corresponding to human-specific Alu repeats in order to identify human keratinocytes grown in culture together with rat cells, and also to label split and full thickness skin grafts of human origin after transplantation on immuno-incompetent rats. Digoxigenin-labeled DNA probing resulted in an intensive nuclear staining of human cells, both in culture and after transplantation onto recipient animals, while recipient animal cells (rat cells) did not stain. In situ hybridization using primate-specific Alu probes reliably allows distinguishing between cells of human and non-human origin both in culture as well as in histological sections. This method is an essential tool for those preclinical experiments (performed on non-primate animals) that must be conducted before novel tissue engineered skin substitutes might be introduced into clinical practice.

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

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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.

Human Breast Adipose-Derived Stem Cells Transfected with the Stromal Cell-Derived Factor-1 Receptor CXCR4 Exhibit Enhanced Viability in Human Autologous Free Fat Grafts

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Fang-tian Xu

2014-11-01

Full Text Available Background: The main complication of autologous free fat tissue transplantation is fat resorption and calcification due to the ischemic necrosis of fat. The promotion of transplant neovascularization soon after autologous free fat grafts may reduce these outcomes. In adulthood, stromal cell-derived factor-1 (SDF-1 and its membrane receptor C-X-C chemokine receptor type 4 (CXCR4 are involved in the homing and migration of multiple stem cell types, neovascularization, and cell proliferation. We hypothesized that CXCR4 may improve the long-term survival of free fat tissue transplants by recruiting endothelial progenitor cells (EPCs and may therefore improve graft revascularization. In this study, we aimed to determine the effect of human breast adipose-derived stem cells (HBASCs transfected with the CXCR4 gene on the survival rate of human autologous free fat transplants in nude mice. Methods: Human breast adipose-derived stem cells (HBASCs were expanded ex vivo for 3 passages, labeled with green fluorescent protein (GFP and transfected with CXCR4 or left untransfected. Autologous fat tissues were mixed with the GFP-labeled, CXCR4-transfected HBASCs (group A, GFP-labeled HBASCs (group B, the known vascularization-promoting agent VEGF (group C, or medium (group D and then injected subcutaneously into 32 nude mice at 4 spots in a random fashion. Six months later, the transplanted tissue volume and histology were evaluated, and neo-vascularization was quantified by counting the capillaries. CXCR4 and SDF-1α mRNA expression in the transplants was determined using real-time quantitative PCR analysis (qPCR. Results: The data revealed that the control (group D transplant volume survival was 28.3 ± 4.5%. Mixing CXCR4-transfected (group A and untransfected (group B HBASCs significantly increased transplant volume survival (79.5 ± 8.3% and 67.2 ± 5.9%, respectively, whereas VEGF-transfected HBASCs (group C were less effective (41.2 ± 5.1%. Histological

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

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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.

Predicting acute cardiac rejection from donor heart and pre-transplant recipient blood gene expression.

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Hollander, Zsuzsanna; Chen, Virginia; Sidhu, Keerat; Lin, David; Ng, Raymond T; Balshaw, Robert; Cohen-Freue, Gabriela V; Ignaszewski, Andrew; Imai, Carol; Kaan, Annemarie; Tebbutt, Scott J; Wilson-McManus, Janet E; McMaster, Robert W; Keown, Paul A; McManus, Bruce M

2013-02-01

Acute rejection in cardiac transplant patients remains a contributory factor to limited survival of implanted hearts. Currently, there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplant acute cellular rejection. Such a development would be of great value in personalizing immunosuppressive treatment. Recipient age, donor age, cold ischemic time, warm ischemic time, panel-reactive antibody, gender mismatch, blood type mismatch and human leukocyte antigens (HLA-A, -B and -DR) mismatch between recipients and donors were tested in 53 heart transplant patients for their power to predict post-transplant acute cellular rejection. Donor transplant biopsy and recipient pre-transplant blood were also examined for the presence of genomic biomarkers in 7 rejection and 11 non-rejection patients, using non-targeted data mining techniques. The biomarker based on the 8 clinical variables had an area under the receiver operating characteristic curve (AUC) of 0.53. The pre-transplant recipient blood gene-based panel did not yield better performance, but the donor heart tissue gene-based panel had an AUC = 0.78. A combination of 25 probe sets from the transplant donor biopsy and 18 probe sets from the pre-transplant recipient whole blood had an AUC = 0.90. Biologic pathways implicated include VEGF- and EGFR-signaling, and MAPK. Based on this study, the best predictive biomarker panel contains genes from recipient whole blood and donor myocardial tissue. This panel provides clinically relevant prediction power and, if validated, may personalize immunosuppressive treatment and rejection monitoring. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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...

Islet alloautotransplantation: Allogeneic pancreas transplantation followed by transplant pancreatectomy and islet transplantation.

Science.gov (United States)

Nijhoff, M F; Dubbeld, J; van Erkel, A R; van der Boog, P J M; Rabelink, T J; Engelse, M A; de Koning, E J P

2018-04-01

Simultaneous pancreas-kidney (SPK) transplantation is an important treatment option for patients with type 1 diabetes (T1D) and end-stage renal disease (ESRD). Due to complications, in up to 10% of patients, allograft pancreatectomy is necessary shortly after transplantation. Usually the donor pancreas is discarded. Here, we report on a novel procedure to rescue endocrine tissue after allograft pancreatectomy. A 39-year-old woman with T1D and ESRD who had undergone SPK transplantation required emergency allograft pancreatectomy due to bleeding at the vascular anastomosis. Islets were isolated from the removed pancreas allograft, and almost 480 000 islet equivalents were infused into the portal vein. The patient recovered fully. After 3 months, near-normal mixed meal test (fasting glucose 7.0 mmol/L, 2-hour glucose 7.5 mmol/L, maximal stimulated C-peptide 3.25 nmol/L, without insulin use in the preceding 36 hours) was achieved. Glycated hemoglobin while taking a low dose of long-acting insulin was 32.7 mmol/mol hemoglobin (5.3%). When a donor pancreas is lost after transplantation, rescue β cell therapy by islet alloautotransplantation enables optimal use of scarce donor pancreata to optimize glycemic control without additional HLA alloantigen exposure. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Establishment of a humanized APL model via the transplantation of PML-RARA-transduced human common myeloid progenitors into immunodeficient mice.

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Hiromichi Matsushita

Full Text Available Recent advances in cancer biology have revealed that many malignancies possess a hierarchal system, and leukemic stem cells (LSC or leukemia-initiating cells (LIC appear to be obligatory for disease progression. Acute promyelocytic leukemia (APL, a subtype of acute myeloid leukemia characterized by the formation of a PML-RARα fusion protein, leads to the accumulation of abnormal promyelocytes. In order to understand the precise mechanisms involved in human APL leukemogenesis, we established a humanized in vivo APL model involving retroviral transduction of PML-RARA into CD34(+ hematopoietic cells from human cord blood and transplantation of these cells into immunodeficient mice. The leukemia well recapitulated human APL, consisting of leukemic cells with abundant azurophilic abnormal granules in the cytoplasm, which expressed CD13, CD33 and CD117, but not HLA-DR and CD34, were clustered in the same category as human APL samples in the gene expression analysis, and demonstrated sensitivity to ATRA. As seen in human APL, the induced APL cells showed a low transplantation efficiency in the secondary recipients, which was also exhibited in the transplantations that were carried out using the sorted CD34- fraction. In order to analyze the mechanisms underlying APL initiation and development, fractionated human cord blood was transduced with PML-RARA. Common myeloid progenitors (CMP from CD34(+/CD38(+ cells developed APL. These findings demonstrate that CMP are a target fraction for PML-RARA in APL, whereas the resultant CD34(- APL cells may share the ability to maintain the tumor.

The Economics of Organ Transplantation.

Science.gov (United States)

Altınörs, Nur; Haberal, Mehmet

2018-03-01

To determine the cost effectiveness of transplantation, we analyzed the financial economics of the organ and tissue transplant process. We compared the cost of this process with traditional modalities for treating endstage liver and kidney disease. Medical, surgical, legal, social, ethical, and religious issues are important in organ transplant procedures. Government, health insurance companies, and uninsured individuals are affected by the financial economics of organ transplantation. The distribution of financial burden differs among countries and is dependent on the unique circumstances of each country.

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

Transplantation: fantasy, fiction and fact.

Science.gov (United States)

Magee, Reginald

2004-03-01

Today organ transplantation is considered a routine surgical procedure. The idea of transferring tissues from one person to another has been inspiring to the minds of artists depicting the Saints Cosmos and Damian and also writers such as Mary Shelley. Early attempts at tissue transplantation were unsuccessful but in the last 50 years medical research has brought it into reality. The present paper looks at the subject from the realms of fantasy through the works of fiction and finally into everyday fact.

Transplant Biology at a Crossroads

OpenAIRE

Sedwick, Caitlin

2008-01-01

Despite major advances in transplantation biology, allowing transplants not just of critical organs like heart and kidney but also of limbs and faces, researchers are still struggling to minimize the risks from achieving the level of immunosuppression needed to make the body accept foreign tissues.

Successful transplantation of in vitro expanded human corneal endothelial precursors to corneal endothelial surface using a nanocomposite sheet

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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

Ethical issues in organ transplantation.

Science.gov (United States)

Abouna, George M

2003-01-01

Clinical organ transplantation has been recognized as one of the most gripping medical advances of the century as it 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

Modeling Human Leukemia Immunotherapy in Humanized Mice

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Jinxing Xia

2016-08-01

Full Text Available The currently available human tumor xenograft models permit modeling of human cancers in vivo, but in immunocompromised hosts. Here we report a humanized mouse (hu-mouse model made by transplantation of human fetal thymic tissue plus hematopoietic stem cells transduced with a leukemia-associated fusion gene MLL-AF9. In addition to normal human lymphohematopoietic reconstitution as seen in non-leukemic hu-mice, these hu-mice showed spontaneous development of B-cell acute lymphoblastic leukemia (B-ALL, which was transplantable to secondary recipients with an autologous human immune system. Using this model, we show that lymphopenia markedly improves the antitumor efficacy of recipient leukocyte infusion (RLI, a GVHD-free immunotherapy that induces antitumor responses in association with rejection of donor chimerism in mixed allogeneic chimeras. Our data demonstrate the potential of this leukemic hu-mouse model in modeling leukemia immunotherapy, and suggest that RLI may offer a safe treatment option for leukemia patients with severe lymphopenia.

Differentiation of insulin-producing cells from human neural progenitor cells.

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Yuichi Hori

2005-04-01

Full Text Available BACKGROUND: Success in islet-transplantation-based therapies for type 1 diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Islets and neurons share features, including common developmental programs, and in some species brain neurons are the principal source of systemic insulin. METHODS AND FINDINGS: Here we show that brain-derived human neural progenitor cells, exposed to a series of signals that regulate in vivo pancreatic islet development, form clusters of glucose-responsive insulin-producing cells (IPCs. During in vitro differentiation of neural progenitor cells with this novel method, genes encoding essential known in vivo regulators of pancreatic islet development were expressed. Following transplantation into immunocompromised mice, IPCs released insulin C-peptide upon glucose challenge, remained differentiated, and did not form detectable tumors. CONCLUSION: Production of IPCs solely through extracellular factor modulation in the absence of genetic manipulations may promote strategies to derive transplantable islet-replacement tissues from human neural progenitor cells and other types of multipotent human stem cells.

Islet-like cell aggregates generated from human adipose tissue derived stem cells ameliorate experimental diabetes in mice.

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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.

Perception Of The Nurse In The Process Of Donation Of Organs And Fabrics For Transplantation

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Vanessa Vargas

2017-06-01

Full Text Available Objective: to know the nurses' perception in the process of organ and tissue donation for transplants. Methods: qualitative research with data collection performed through a semistructured interview with 16 nurses from a hospital. The data were submitted to Bardin content analysis. Results: categories emerged after content analysis were as follows: Organ donation process: nurses' experience; Nursing care for potential donors; Family approach; Main difficulties in the donation process. Conclusion: the research demonstrated the real difficulties of the professionals during the donation process, such as lack of human resources, extensive protocols, and lack of awareness of the society to understand the donation process and the family approach. Keywords: Transplantation of Organs; Obtaining Tissues and Organs; Nursing care.

Ginsenoside Rg1 and platelet-rich fibrin enhance human breast adipose-derived stem cells function for soft tissue regeneration

Science.gov (United States)

Li, Hong-Mian; Peng, Qi-Liu; Huang, Min-Hong; Li, De-Quan; Liang, Yi-Dan; Chi, Gang-Yi; Li, De-Hui; Yu, Bing-Chao; Huang, Ji-Rong

2016-01-01

Adipose-derived stem cells (ASCs) can be used to repair soft tissue defects, wounds, burns, and scars and to regenerate various damaged tissues. The cell differentiation capacity of ASCs is crucial for engineered adipose tissue regeneration in reconstructive and plastic surgery. We previously reported that ginsenoside Rg1 (G-Rg1 or Rg1) promotes proliferation and differentiation of ASCs in vitro and in vivio. Here we show that both G-Rg1 and platelet-rich fibrin (PRF) improve the proliferation, differentiation, and soft tissue regeneration capacity of human breast adipose-derived stem cells (HBASCs) on collagen type I sponge scaffolds in vitro and in vivo. Three months after transplantation, tissue wet weight, adipocyte number, intracellular lipid, microvessel density, and gene and protein expression of VEGF, HIF-1α, and PPARγ were higher in both G-Rg1- and PRF-treated HBASCs than in control grafts. More extensive new adipose tissue formation was evident after treatment with G-Rg1 or PRF. In summary, G-Rg1 and/or PRF co-administration improves the function of HBASCs for soft tissue regeneration engineering. PMID:27191987

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

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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.

Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient uPA mice.

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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.

Setting up a Tissue Bank in India: The Tata Memorial Hospital Experience.

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Gajiwala, A L

2003-01-01

In India, the procurement of tissues for transplantation is governed by the Transplantation of Human Organs Act, 1994. However, although this law exists, it is primarily applied to organ transplantation and rules and regulations that are specific to tissue banking have yet to be developed.The Tata Memorial Hospital (TMH) Tissue Bank was started in 1988 as part of an International Atomic Energy Agency (IAEA) programme to promote the use of ionising radiation for the sterilisation of biological tissues. It represents the Government of India within this project and was the first such facility in the country. It is registered with the Health Services Maharashtra State and provides lyophilised amnion, dura mater, skin and bone that have been terminally sterilised with exposure to 25 kGy of gamma radiation from a Cobalt 60 source. These are obtained either from cadavers or live donors.To date the TMH Tissue Bank has provided 6328 allografts for use as biological dressings or in various reconstructive procedures.The TMH Tissue Bank has helped initiate a Tissue Bank at the Defence Laboratory (DL), Jodhpur. At present these are the only two Banks in the country using radiation for terminal sterilisation of banked tissues.The availability of safe, clinically useful and cost effective grafts have resulted in changes in surgical treatment with a concomitant increase in demand for grafts and an interest in developing more tissue banks. The availability of donor tissue however, continues to be a major limitation.

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

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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.

Fluorescence spectroscopy for assessment of liver transplantation grafts concerning graft viability and patient survival

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Vollet Filho, José D.; da Silveira, Marina R.; Castro-e-Silva, Orlando; Bagnato, Vanderlei S.; Kurachi, Cristina

2015-06-01

Evaluating transplantation grafts at harvest is essential for its success. Laser-induced fluorescence spectroscopy (LIFS) can help monitoring changes in metabolic/structural conditions of tissue during transplantation. The aim of the present study is to correlate LIFSobtained spectra of human hepatic grafts during liver transplantation with post-operative patients' mortality rate and biochemical parameters, establishing a method to exclude nonviable grafts before implantation. Orthotopic liver transplantation, piggyback technique was performed in 15 patients. LIFS was performed under 408nm excitation. Collection was performed immediately after opening donor's abdominal cavity, after cold perfusion, end of back-table period, and 5 min and 1 h after warm perfusion at recipient. Fluorescence information was compared to lactate, creatinine, bilirubin and INR levels and to survival status. LIFS was sensitive to liver changes during transplantation stages. Study-in-progress; initial results indicate correlation between fluorescence and life/death status of patients.

Distribution of transplanted human mesenchymal stem cells from Wharton’s Jelly in the central nervous systems of the EAE rats

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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.

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

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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.

Human-to-human transmission of Brucella - a systematic review.

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Tuon, Felipe F; Gondolfo, Regina B; Cerchiari, Natacha

2017-05-01

The most common form of transmitting human brucellosis is through contaminated food or direct contact with infected animals. Human-to-human transmission (HHT) has been described as isolated case reports. The aim of this systematic review was to describe all cases of HHT of human brucellosis reported in the medical literature. A literature search was conducted using PubMed, Scopus and Scielo databases using specific search terms published until March 2016. Two investigators independently determined study eligibility. All clinical data were evaluated to construct a table comprising the most important clinical aspects, age, gender, confirmed infection and detection method, transmission method and HHT confirmation and potential source of infection for human transmission. No statistical method was employed in this study. The initial search resulted in 615 publications, but only 35 were included. 45 brucellosis HHT cases were identified. 61% of patients who acquired brucellosis from another human were <1 year old (newborn and breastfeeding). Other cases include sexual transmission, blood transfusion, bone marrow transplantation and aerosol from an infected patient. Most patients (40/45) presented symptoms upon diagnosis. Diagnostic tests included culture, molecular methods and serum testing. Human brucellosis is a disease liable to transmission between humans by placental barrier, lactation, sexual and tissues such as blood and bone marrow. The indication for screening in tissue banks, transplants, blood and pregnancy is not yet established. © 2017 John Wiley & Sons Ltd.

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

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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.

Risk factors for chronic transplant dysfunction and cardiovascular disease are related to accumulation of advanced glycation end-products in renal transplant recipients

NARCIS (Netherlands)

Hartog, Jasper W. L.; de Vries, Aiko P. J.; Bakker, Stephan J. L.; Graaff, Reindert; van Son, Willem J.; Homan van der Heide, Jaap J.; Gans, Reinold O. B.; Wolffenbuttel, Bruce H. R.; de Jong, Paul E.; Smit, Andries J.

2006-01-01

Accumulation of advanced glycation end-products (AGEs) has been implicated in the pathogenesis of chronic transplant dysfunction and cardiovascular disease in renal transplant recipients. We aimed to investigate which factors are associated with tissue AGE accumulation in renal transplant

[Human umbilical cord blood mononuclear cell transplantation promotes long-term neurobehavioral functional development of newborn SD rats with hypoxic ischemic brain injury].

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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.

Intestinal transplantation: The anesthesia perspective.

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Dalal, Aparna

2016-04-01

Intestinal transplantation is a complex and challenging surgery. It is very effective for treating intestinal failure, especially for those patients who cannot tolerate parenteral nutrition nor have extensive abdominal disease. Chronic parental nutrition can induce intestinal failure associated liver disease (IFALD). According to United Network for Organ Sharing (UNOS) data, children with intestinal failure affected by liver disease secondary to parenteral nutrition have the highest mortality on a waiting list when compared with all candidates for solid organ transplantation. Intestinal transplant grafts can be isolated or combined with the liver/duodenum/pancreas. Organ Procurement and Transplantation Network (OPTN) has defined intestinal donor criteria. Living donor intestinal transplant (LDIT) has the advantages of optimal timing, short ischemia time and good human leukocyte antigen matching contributing to lower postoperative complications in the recipient. Thoracic epidurals provide excellent analgesia for the donors, as well as recipients. Recipient management can be challenging. Thrombosis and obstruction of venous access maybe common due to prolonged parenteral nutrition and/or hypercoaguability. Thromboelastography (TEG) is helpful for managing intraoperative product therapy or thrombosis. Large fluid shifts and electrolyte disturbances may occur due to massive blood loss, dehydration, third spacing etc. Intestinal grafts are susceptible to warm and cold ischemia and ischemia-reperfusion injury (IRI). Post-reperfusion syndrome is common. Cardiac or pulmonary clots can be monitored with transesophageal echocardiography (TEE) and treated with recombinant tissue plasminogen activator. Vasopressors maybe used to ensure stable hemodynamics. Post-intestinal transplant patients may need anesthesia for procedures such as biopsies for surveillance of rejection, bronchoscopy, endoscopy, postoperative hemorrhage, anastomotic leaks, thrombosis of grafts etc. Asepsis

Development of a Cytocompatible Scaffold from Pig Immature Testicular Tissue Allowing Human Sertoli Cell Attachment, Proliferation and Functionality

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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.

High-level transfer and long-term expression of the human beta-globin gene in a mouse transplant model.

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Raftopoulos, H; Ward, M; Bank, A

1998-06-30

Insertion of a normally functioning human beta-globin gene into the hematopoietic stem cells (HSC) of patients with beta-thalassemia may be an effective approach to the therapy of this disorder. Safe, efficient gene transfer and long-term, high-level expression of the transferred human beta-globin gene in animal models are prerequisites for HSC somatic gene therapy. We have recently shown for the first time that, using a modified beta-globin retroviral vector in a mouse transplant model, long-term, high-level expression of a transferred human beta-globin gene is possible. The human beta-globin gene continues to be detected up to eight months post-transplantation of beta-globin-transduced hematopoietic cells into lethally irradiated mice. The transferred human beta-globin gene is detected in three of five mice surviving long-term (> 4 months) transplanted with bone marrow cells transduced with high-titer virus. The unrearranged 5.1 kb human beta-globin gene-containing provirus is seen by Southern blotting in two of these mice. More importantly, long-term expression of the transferred gene is seen in two mice at levels of 5% and 20% that of endogenous murine beta-globin. We document stem cell transduction by showing continued high-level expression of the human beta-globin gene in secondarily transplanted recipient mice. These results provide evidence of HSC transduction with a human beta-globin gene in animals and demonstrate that retroviral-mediated unrearranged human beta-globin gene transfer leads to a high level of human beta-globin gene expression in the long term for the first time. A gene therapy strategy may be a feasible therapeutic approach to the beta-thalassemias if consistent human beta-globin gene transfer and expression into HSC can be achieved.

Radiosterilization of Tissues Preserved for Clinical Purposes: Effect on Tissue Antigenicity

International Nuclear Information System (INIS)

Ostrowski, K.; Kossowska, B.; Moskalewski, S.; Komender, A.; Kurnatowski, W.

1967-01-01

The first part of the paper contains practical considerations on the radiosterilization of preserved human bone, human and calf cartilage, cow’s fascia and aponeurosis, based on material from the Tissue Bank which produces about 2500 transplants yearly. The method of preservation and packing of each type of tissue is mentioned briefly. The preserved tissues are irradiated in a cobalt bomb or in a nuclear reactor. The conditions of irradiation and the control of sterility are described. The advantages and disadvantages of radiosterilization are discussed on the basis of the authors’ own experience and clinical reports of surgeons using radiosterilized tissues in practice. In the second part of the paper, experimental studies on the influence of freezing, lyophilization and radiosterilization on tissue antigenicity are reported. The regional lymph node reacts to an antigenic stimulus by an increased production of large, pyroninophylic cells, so-called ''blast'' cells. The rabbits used as recipients received grafts of allogeneic cancellous bone, fresh or subjected to different experimental procedures. Smears from lymph node cell suspension were prepared and the percentage of blast cells was estimated. On the basis of the lymph node response, it appears that freezing and lyophilization, as well as radiosterilization, may abolish the antigenicity of cancellous bone. The practical implication of these results for methods of preservation of tissues for clinical purposes is discussed. (author)

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

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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.

Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation: Review of Preclinical and Clinical Studies.

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Yamasaki, Shinya; Mera, Hisashi; Itokazu, Maki; Hashimoto, Yusuke; Wakitani, Shigeyuki

2014-10-01

Clinical trials of various procedures, including bone marrow stimulation, mosaicplasty, and autologous chondrocyte implantation, have been explored to treat articular cartilage defects. However, all of them have some demerits. We focused on autologous culture-expanded bone marrow mesenchymal stem cells (BMSC), which can proliferate without losing their capacity for differentiation. First, we transplanted BMSC into the defective articular cartilage of rabbit and succeeded in regenerating osteochondral tissue. We then applied this transplantation in humans. Our previous reports showed that treatment with BMSC relieves the clinical symptoms of chondral defects in the knee and elbow joint. We investigated the efficacy of BMSC for osteoarthritic knee treated with high tibial osteotomy, by comparing 12 BMSC-transplanted patients with 12 cell-free patients. At 16-month follow-up, although the difference in clinical improvement between both groups was not significant, the arthroscopic and histological grading score was better in the cell-transplanted group. At the over 10-year follow-up, Hospital for Special Surgery knee scores improved to 76 and 73 in the BMSC-transplanted and cell-free groups, respectively, which were better than preoperative scores. Additionally, neither tumors nor infections were observed in all patients, and in the clinical study, we have never observed hypertrophy of repaired tissue, thereby guaranteeing the clinical safety of this therapy. Although we have never observed calcification above the tidemark in rabbit model and human histologically, the repair cartilage was not completely hyaline cartilage. To elucidate the optimum conditions for cell therapy, other stem cells, culture conditions, growth factors, and gene transfection methods should be explored.

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

Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease

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Kim, Manbok, E-mail: manbok66@dankook.ac.kr [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Rahman, Masmudur M. [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Cogle, Christopher R. [Department of Hematology/Oncology, University of Florida, Gainesville, FL 32610 (United States); McFadden, Grant [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States)

2015-07-10

Epstein–Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases.

Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease

International Nuclear Information System (INIS)

Kim, Manbok; Rahman, Masmudur M.; Cogle, Christopher R.; McFadden, Grant

2015-01-01

Epstein–Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases

Nanotopography-guided tissue engineering and regenerative medicine☆

Science.gov (United States)

Kim, Hong Nam; Jiao, Alex; Hwang, Nathaniel S.; Kim, Min Sung; Kang, Do Hyun; Kim, Deok-Ho; Suh, Kahp-Yang

2017-01-01

Human tissues are intricate ensembles of multiple cell types embedded in complex and well-defined structures of the extracellular matrix (ECM). The organization of ECM is frequently hierarchical from nano to macro, with many proteins forming large scale structures with feature sizes up to several hundred microns. Inspired from these natural designs of ECM, nanotopography-guided approaches have been increasingly investigated for the last several decades. Results demonstrate that the nanotopography itself can activate tissue-specific function in vitro as well as promote tissue regeneration in vivo upon transplantation. In this review, we provide an extensive analysis of recent efforts to mimic functional nanostructures in vitro for improved tissue engineering and regeneration of injured and damaged tissues. We first characterize the role of various nanostructures in human tissues with respect to each tissue-specific function. Then, we describe various fabrication methods in terms of patterning principles and material characteristics. Finally, we summarize the applications of nanotopography to various tissues, which are classified into four types depending on their functions: protective, mechano-sensitive, electro-active, and shear stress-sensitive tissues. Some limitations and future challenges are briefly discussed at the end. PMID:22921841

SUITABILITY OF CORNEAL TISSUE FOR TRANSPLANTATION PROCURED FROM HANGING CASES

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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

Fascia tissue engineering with human adipose-derived stem cells in a murine model: Implications for pelvic floor reconstruction

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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.

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.

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

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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.

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.

Organ culture studies for pancreatic islet transplantation

International Nuclear Information System (INIS)

Reemtsma, K.; Weber, C.J.; Pi-Sunyer, F.X.; Lerner, R.; Zimmerman, E.; Hardy, M.A.

1979-01-01

Data support the usefulness of tissue culture in isolation and preservation of islets prior to transplantation. Rodent islet viability in culture was demonstrated histologically and by functional analyses of hormone production. For reasons that remain to be defined, acinar cells disappeared rapidly in tissue culture, yielding an implant preparation relatively rich in islets and devoid of pancreatic exocrine elements. Isografts of cultured and noncultured islets were well tolerated intraperitoneally and intramuscularly; and prompt and lasting reversal of short- and long-standing experimental diabetes was observed regularly. In vitro studies of rodent islet viability after immunosuppressive treatment of donors or islet cultures showed insulin production comparable to that of control experiments, suggesting that immunologic modification of donors or islets might be feasible in eventual human islet allotransplantation

Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

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Xiaolin He

Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

LeFort I osteotomy and secondary procedures in full-face transplant patients.

Science.gov (United States)

Barret, Juan P; Serracanta, Jordi

2013-05-01

Composite tissue allotransplantion has been the latest addition to reconstructive plastic surgery of limbs and faces. These techniques have opened up a new paradigm in reconstruction. However, plastic surgeons will have to face a new patient population that receives the application of vascularised tissue allografts and immunosuppression. Secondary surgery may be necessary in this population, especially in the transplanted tissues, to improve aesthetics and function following the transplant, although little is known regarding the exact clinical protocol to be followed and the feasibility of standard plastic surgery techniques on transplanted tissues. We present our experience of a LeFort I osteotomy, limited ritidectomy and blepharoplasty in a full-face transplant recipient. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Bacteriology laboratories and musculoskeletal tissue banks in Australia.

Science.gov (United States)

Varettas, Kerry

2012-11-01

In Australia, there are six Therapeutic Goods Administration-licensed clinical bacteriology laboratories providing bacterial and fungal bioburden testing of allograft musculoskeletal samples sent from 10 tissue banks. Musculoskeletal swab and/or tissue biopsy samples are collected at the time of allograft retrieval and sent to bacteriology laboratories for bioburden testing, in some cases requiring interstate transport. Bacteria and fungi may be present within the allograft at the time of retrieval or contaminated from an external source. The type of organism recovered will determine if the allograft is rejected for transplant, which may include all allografts from the same donor. Bacteriology staff also provides unpaid support of tissue banks through meeting involvement, consultations, licence-related activities, validations and research funded by their organisation and not part of any contractual agreement. Bacteriology laboratories and tissue banks must be compliant to the Code of Good Manufacturing Practice - Human Blood and Tissues and regulated by the Therapeutic Goods Administration. Clinical bacteriology laboratories also require mandatory accreditation to Standards Australia International Organisation for Standardisation (ISO) 15189:2009 medical laboratories - particular requirements for quality and competence, and may also attain Standards Australia/New Zealand Standard ISO 9001:2000 quality management systems certification. Bacteriology laboratories and musculoskeletal tissue banks are integral partners in providing safe allograft musculoskeletal tissue for transplant. © 2012 The Author. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.

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.

Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

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Madsen, O.D.; Andersen, L.C.; Michelsen, B.; Owerbach, D.; Larsson, L.I.; Lernmark, A.; Steiner, D.F. (Hagedorn Research Laboratory, Gentofte (Denmark))

1988-09-01

The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. The authors propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression.

Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

International Nuclear Information System (INIS)

Madsen, O.D.; Andersen, L.C.; Michelsen, B.; Owerbach, D.; Larsson, L.I.; Lernmark, A.; Steiner, D.F.

1988-01-01

The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. The authors propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression

Bone transplantation and tissue engineering, part I. Mythology, miracles and fantasy: from Chimera to the Miracle of the Black Leg of Saints Cosmas and Damian and the cock of John Hunter.

Science.gov (United States)

Hernigou, Philippe

2014-12-01

The replacement of diseased organs and tissues by the healthy ones of others has been a unique milestone in modern medicine. However, even though cloning, member transplantation and regenerative therapies with stem cells are available in the twentieth and twenty-first centuries, one should remember that all these techniques were in the imagination more than 2,000 years ago. For centuries, transplantation remained a theme of mythology, miracle or fantasy and was found only in literature and arts. This first paper explains the concept of tissue transplantation from the period when it was relegated to the imagination to the work of the Scottish surgeon and anatomist, John Hunter, who demonstrated the viability of bone allograft.

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

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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.

The Reconfigured Body. Human-animal relations in xenotransplantation

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Kristofer Hansson

2011-12-01

Full Text Available The article explores issues concerning the reconfiguration of human and animal bodies in modern biotechnology. The examples are based on xenotransplantation: Transplantation of cells, tissue and organs from animals to humans. Three thematic issues that emerged from xenotransplantation research in Sweden in the 1990s and early 2000s are examined in the article. The first issue concerns how the pig was introduced as a donor animal in xenotransplantation and, at the same time, dehumanized in relation to what is human. Baboons and chimpanzees that had previously been used in xenotransplantation now became an ethically problematic choice, and were in stead humanized. The second issue concerns the introduction of transgenic and cloned pigs as commoditized objects. The biotechnological development reconfigured the pig’s cells, tissue and organs to become more human-like. The third issue concerns the risk that pigs contain retrovirus that could infect the transplanted patients. The human body became part of a network of both animal and retrovirus. Boundlessness between human and animal bodies appears in these three thematic phases and is analysed from a cultural perspective.

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...

Islet transplantation: the quest for an ideal source

International Nuclear Information System (INIS)

Younes, Nidal A.; Nothias, J.; Garfinkel, Marc R.

2008-01-01

The progress of islet transplantation as a new therapy for patients with diabetes mellitus depends directly upon the development of efficient and practical immunoisolation methods for the supply of sufficient quantities of islet cells. Without these methods, large scale clinical application of this therapy would be impossible. Two eras of advances can be identified in the development of islet transplantation. The first was an era of experimental animal and human research that centered on islet isolation procedures and transplantation in different species as evidence that transplanted islets have the capability to reverse diabetes. The second was the era of Edmonton protocol, when the focus became the standardization of isolation procedures and introduction of new immunosuppressive drugs to maintain human allograft transplantation. The quest for an alternative source for islets (xenographs, stem cells and cell cultures) to overcome the shortage of human islets was an important issue during these eras. This paper reviews the history of islet transplantation and the current procedures in human allotransplantation, as well as different types of immunoisolation methods. It explores novel approaches to enhancing transplantation site vascularity and islet cell function, whereby future immunoisolation technology could offer additional therapeutic advantages to human islet allotransplantation. (author)

Polyomavirus – an emergent pathogen in transplant recipients

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Juliana de Moura Montagner

2007-06-01

Full Text Available Medical centers that work with transplants often face opportunisticinfections that demand specific tools to make diagnosis. Theprevalence of latent polyomavirus infections is high, and the mostcommon site of latency of the most prevalent polyomavirus in humans,BK virus (BKV, is the renal tissue. Hence, renal transplanted patientsare particularly vulnerable to the damage caused by viral reactivationduring immunosupression. In such patients BKV is associated toureteral stenosis and/or BKV nephropathy, leading to progressivedysfunction and graft loss, often diagnosed as rejection. In other organsrecipients (namely lung, liver, heart and pancreas, BKN is also the mostimportant clinical manifestation, whereas in bone marrow recipients themost common is hemorrhagic cystitis. This review presents the viralbiology and discusses the pathophysiology of polyomavirus diseasesand the diagnostic efficacy of the laboratory tests available, guidingto the best strategy for assessment and monitoring of patients at riskor under specific treatment.

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.

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.

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

In vitro generation of functional insulin-producing cells from lipoaspirated human adipose tissue-derived stem cells.

Science.gov (United States)

Mohamad Buang, Mohamad Lizan; Seng, Heng Kien; Chung, Lee Han; Saim, Aminuddin Bin; Idrus, Ruszymah Bt Hj

2012-01-01

Tissue engineering strategy has been considered as an alternative treatment for diabetes mellitus due to lack of permanent pharmaceutical treatment and islet donors for transplantation. Various cell lines have been used to generate functional insulin-producing cells (IPCs) including progenitor pancreatic cell lines, embryonic stem cells (ESCs), umbilical cord blood stem cells (UCB-SCs), adult bone marrow stem cells (BMSCs), and adipose tissue-derived stem cells (ADSCs). Human ADSCs from lipoaspirated abdominal fat tissue was differentiated into IPCs following a two-step induction protocol based on a combination of alternating high and low glucose, nicotinamide, activin A and glucagon-like peptide 1 (GLP-1) for a duration of 3 weeks. During differentiation, histomorphological changes of the stem cells towards pancreatic β-islet characteristics were observed via light microscope and transmission electron microscope (TEM). Dithizone (DTZ) staining, which is selective towards IPCs, was used to stain the new islet-like cells. Production of insulin hormone by the cells was analyzed via enzyme-linked immunosorbent assay (ELISA), whereas its hormonal regulation was tested via a glucose challenge test. Histomorphological changes of the differentiated cells were noted to resemble pancreatic β-cells, whereas DTZ staining positively stained the cells. The differentiated cells significantly produced human insulin as compared to the undifferentiated ADSCs, and its production was increased with an increase of glucose concentration in the culture medium. These initial data indicate that human lipoaspirated ADSCs have the potential to differentiate into functional IPCs, and could be used as a therapy to treat diabetes mellitus in the future. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

Human amnion epithelial cells expressing HLA-G as novel cell-based treatment for liver disease.

Science.gov (United States)

Strom, Stephen C; Gramignoli, Roberto

2016-09-01

Despite routine liver transplantation and supporting medical therapies, thousands of patients currently wait for an organ and there is an unmet need for more refined and widely available regenerative strategies to treat liver diseases. Cell transplants attempt to maximize the potential for repair and/or regeneration in liver and other organs. Over 40years of laboratory pre-clinical research and 25years of clinical procedures have shown that certain liver diseases can be treated by the infusion of isolated cells (hepatocyte transplant). However, like organ transplants, hepatocyte transplant suffers from a paucity of tissues useful for cell production. Alternative sources have been investigated, yet with limited success. The tumorigenic potential of pluripotent stem cells together with their primitive level of hepatic differentiation, have limited the use of stem cell populations. Stem cell sources from human placenta, and the amnion tissue in particular are receiving renewed interest in the field of regenerative medicine. Unlike pluripotent stem cells, human amnion epithelial (AE) cells are easily available without ethical or religious concerns; they do not express telomerase and are not immortal or tumorigenic when transplanted. In addition, AE cells have been reported to express genes normally expressed in mature liver, when transplanted into the liver. Moreover, because of the possibility of an immune-privileged status related to their expression of HLA-G, it might be possible to transplant human AE cells without immunosuppression of the recipient. Copyright © 2016. Published by Elsevier Inc.

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

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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.

Long-term transfer and expression of the human beta-globin gene in a mouse transplant model.

Science.gov (United States)

Raftopoulos, H; Ward, M; Leboulch, P; Bank, A

1997-11-01

Somatic gene therapy of hemoglobinopathies depends initially on the demonstration of safe, efficient gene transfer and long-term, high-level expression of the transferred human beta-globin gene in animal models. We have used a beta-globin gene/beta-locus control region retroviral vector containing several modifications to optimize gene transfer and expression in a mouse transplant model. In this report we show that transplantation of beta-globin-transduced hematopoietic cells into lethally irradiated mice leads to the continued presence of the gene up to 8 months posttransplantation. The transferred human beta-globin gene is detected in 3 of 5 mice surviving long term (>4 months) transplanted with bone marrow cells transduced with high-titer virus. Southern blotting confirms the presence of the unrearranged 5.1-kb human beta-globin gene-containing provirus in 2 of these mice. In addition, long-term expression of the transferred gene is seen in 2 mice at levels of 5% and 20% that of endogenous murine beta-globin at 6 and 8 months posttransplantation. We further document stem cell transduction by the successful transfer and high-level expression of the human beta-globin gene from mice transduced 9 months earlier into irradiated secondary recipient mice. These results demonstrate high-level, long-term somatic human beta-globin gene transfer into the hematopoietic stem cells of an animal for the first time, and suggest the potential feasibility of a retroviral gene therapy approach to sickle cell disease and the beta thalassemias.

Development of tissue bank

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R P Narayan

2012-01-01

Full Text Available The history of tissue banking is as old as the use of skin grafting for resurfacing of burn wounds. Beneficial effects of tissue grafts led to wide spread use of auto and allograft for management of varied clinical conditions like skin wounds, bone defects following trauma or tumor ablation. Availability of adequate amount of tissues at the time of requirement was the biggest challenge that forced clinicians to find out techniques to preserve the living tissue for prolonged period of time for later use and thus the foundation of tissue banking was started in early twentieth century. Harvesting, processing, storage and transportation of human tissues for clinical use is the major activity of tissue banks. Low temperature storage of processed tissue is the best preservation technique at present. Tissue banking organization is a very complex system and needs high technical expertise and skilled personnel for proper functioning in a dedicated facility. A small lapse/deviation from the established protocol leads to loss of precious tissues and or harm to recipients as well as the risk of transmission of deadly diseases and tumors. Strict tissue transplant acts and stringent regulations help to streamline the whole process of tissue banking safe for recipients and to community as whole.

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...

Long-term high-level expression of human beta-globin occurs following transplantation of transgenic marrow into irradiated mice.

Science.gov (United States)

Himelstein, A; Ward, M; Podda, S; de la Flor Weiss, E; Costantini, F; Bank, A

1993-03-01

When the human beta-globin gene is transferred into the bone marrow cells of live mice, its expression is very low. To investigate the reason for this, we transferred the bone marrow of transgenic mice containing and expressing the human beta-globin into irradiated recipients. We demonstrate that long-term high level expression of the human beta-globin gene can be maintained in the marrow and blood of irradiated recipients following transplantation. Although expression decreased over time in most animals because of host marrow reconstitution, the ratio of human beta-globin transgene expression to endogenous mouse beta-globin gene expression in donor-derived erythroid cells remained constant over time. We conclude that there is no inherent limitation to efficient expression of an exogenous human beta-globin gene in mouse bone marrow cells following marrow transplantation.

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.

Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats.

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So Yoon Ahn

Full Text Available Recently, we showed that intracerebroventricular (IC transplantation of human umbilical cord blood (UCB-derived mesenchymal stem cells (MSCs significantly attenuates posthemorrhagic hydrocephalus (PHH and brain damage after severe IVH in newborn rats. This study was performed to determine the optimal route for transplanting MSCs for severe IVH by comparing IC transplantation, intravenous (IV transplantation, and IV transplantation plus mannitol infusion. Severe IVH was induced by injecting 100 uL of blood into each ventricle of Sprague-Dawley rats on postnatal day 4 (P4. After confirming severe IVH with brain magnetic resonance imaging (MRI at P5, human UCB-derived MSCs were transplanted at P6 by an IC route (1×105, an IV route (5×105, or an IV route with mannitol infused. Follow-up brain MRIs and rotarod tests were performed. At P32, brain tissue samples were obtained for biochemical and histological analyses. Although more MSCs localized to the brain after IC than after IV delivery, both methods were equally effective in preventing PHH; attenuating impaired rotarod test; increasing the number of TUNEL-positive cells, inflammatory cytokines, and astrogliosis; and reducing corpus callosal thickness and myelin basic protein expression after severe IVH regardless of mannitol co-infusion. Despite the superior delivery efficacy with IC than with the IV route, both IC and IV transplantation of MSCs had equal therapeutic efficacy in protecting against severe IVH. These findings suggest that the less invasive IV route might be a good alternative for clinically unstable, very preterm infants that cannot tolerate a more invasive IC delivery of MSCs.

Tissue engineering applications: cartilage lesions repair by the use of autologous chondrocytes

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L. De Franceschi

2011-09-01

Full Text Available Promising new therapies based on tissue engineering have been recently developed for cartilage repair. The association of biomaterials with autologous chondrocytes expanded in vitro can represent a useful tool to regenerate this tissue. The scaffolds utilised in such therapeutical applications should provide a pre-formed three-dimensional shape, prevent cells from floating out of the defect, have sufficient mechanical strength, facilitate uniform spread of cells and stimulate the phenotype of transplanted cells. Hyaff®-11 is a hyaluronic-acid based biodegradable polymer, that has been shown to provide successful cell carrier for tissue-engineered repair. From our findings we can state that human chondrocytes seeded on Hyaff®-11 are able to maintain in vitro the characteristic of differentiated cells, expressing and producing collagen type II and aggrecan which are the main markers of cartilage phenotype, down-regulating collagen type I. Moreover, it seems to be a useful scaffold for cartilage repair both in animal models and clinical trials in humans, favouring the formation of a hyaline-like tissue. In the light of these data, we can hypothesise, for the future, the use of autologous chondrocyte transplantation together with gene therapy as a treatment for rheumatic diseases such as osteoarthritis.

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

Osteonecrosis or spontaneous fractures following renal transplantation

International Nuclear Information System (INIS)

Andresen, J.; Nielsen, H.E.; Aarhus Univ.

1981-01-01

31 renal transplant recipients with posttransplant development of osteonecrosis or spontaneous fractures were evaluated with regard to age, duration of dialysis before transplantation. Determination of metacarpal bone mass at the time of transplantation and registration of bone resorption and soft tissue calcification at the time of transplantation and at the time of onset of osteonecrosis and spontaneous fractures were made. Apart from the increased mean age in patients with spontaneous fractures no difference was seen between the groups. Osteonecrosis and spontaneous fractures occurred in areas of trabecular bone. It seems most likely that after renal transplantation the patients show bone complications of different localization. (orig.) [de

Creatinine and cytokines plasma levels related to HLA compatibility in kidney transplant patients

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Lorraine V. Alves

2015-10-01

Full Text Available ABSTRACTIntroduction:The success of kidney transplantation depends on prevention of organ rejection by the recipient’s immune system, which recognizes alloantigens present in transplanted tissue. Human leukocyte antigen (HLA typing is one of the tests used in pre-renal transplantation and represents one of the most important factors for a successful procedure.Objective:The present study evaluated creatinine and cytokines plasma levels in kidney transplant patients according to pre-transplant HLA typing.Methods:We assessed 40 renal transplanted patients selected in two transplant centers in Belo Horizonte (MG.Results:Patients were distributed into three groups according to HLA compatibility and, through statistical analysis, the group with more than three matches (H3 was found to have significantly lower post-transplant creatinine levels, compared to groups with three or fewer matches (H2 and H1, respectively. The median plasma levels of cytokines interleukin 6 (IL-6, tumor necrosis factor alpha (TNF-α, and interleukin 10 (IL-10 were evaluated according to the number of matches. Pro-inflammatory cytokines (IL-6 and TNF-α were significantly higher in groups with lower HLA compatibility. On the other hand, the regulatory cytokine IL-10 had significantly higher plasma levels in the group with greater compatibility between donor and recipient.Conclusion:These findings allow us to infer that pre-transplant HLA typing of donors and recipients can influence post-transplant renal graft function and may contribute to the development and choice of new treatment strategies.

THE ISLAMIC ETHICS OF MITOCHONDRIA TRANSPLANTATION

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Anke Iman Bouzenita

2017-12-01

Full Text Available ABSTRACT: Biotechnology has opened a new chapter with the advent of mitochondria transplantation for cell-based therapy. Mitochondrial transplantation was successfully led to birth; however, cytoplasmic transplantation has caused apprehension, since the mixing of human ooplasm from two different maternal sources may generate mitochondrial DNA (mtDNA heteroplasmy in the offspring. Islamic legal verdicts on human cloning and somatic cell transfer have been overweighing explicit as to its prohibition, due to the change of creation, mixing of lineage and other evaluations. Is mitochondria transplantation equivalent to human cloning in that genetic information is proliferated and does it, therefore, take the same legal rule? Are there possible benefits (masalih for medical treatment that may render mitochondria transplantation permissible, or are possible harms (mafasid overweighing? Or is it a completely different procedure, taking a different rule? The paper will investigate into these questions and discuss the dimensions of Islamic ethics on the issue.

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.

Transplantation of specific human astrocytes promotes functional recovery after spinal cord injury.

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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

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

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.

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...

In vivo evaluation of wound bed reaction and graft performance after cold skin graft storage: new targets for skin tissue engineering.

Science.gov (United States)

Knapik, Alicia; Kornmann, Kai; Kerl, Katrin; Calcagni, Maurizio; Schmidt, Christian A; Vollmar, Brigitte; Giovanoli, Pietro; Lindenblatt, Nicole

2014-01-01

Surplus harvested skin grafts are routinely stored at 4 to 6°C in saline for several days in plastic surgery. The purpose of this study was to evaluate the influence of storage on human skin graft performance in an in vivo intravital microscopic setting after transplantation. Freshly harvested human full-thickness skin grafts and split-thickness skin grafts (STSGs) after storage of 0, 3, or 7 days in moist saline at 4 to 6°C were transplanted into the modified dorsal skinfold chamber, and intravital microscopy was performed to evaluate vessel morphology and angiogenic change of the wound bed. The chamber tissue was harvested 10 days after transplantation for evaluation of tissue integrity and inflammation (hematoxylin and eosin) as well as for immunohistochemistry (human CD31, murine CD31, Ki67, Tdt-mediated dUTP-biotin nick-end labelling). Intravital microscopy results showed no differences in the host angiogenic response between fresh and preserved grafts. However, STSGs and full-thickness skin grafts exhibited a trend toward different timing and strength in capillary widening and capillary bud formation. Preservation had no influence on graft quality before transplantation, but fresh STSGs showed better quality 10 days after transplantation than 7-day preserved grafts. Proliferation and apoptosis as well as host capillary in-growth and graft capillary degeneration were equal in all groups. These results indicate that cells may activate protective mechanisms under cold conditions, allowing them to maintain function and morphology. However, rewarming may disclose underlying tissue damage. These findings could be translated to a new approach for the design of full-thickness skin substitutes.

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...

MSC in clinics: Liver Transplantation

OpenAIRE

DETRY, Olivier

2014-01-01

For several years, mesenchymal stem cells (MSC) have been evaluated in vivo and in vitro for their immunomodulatory, anti-inflammatory, anti- ischemia-reperfusion injury and “tissue repair” properties. These characteristics could make them interesting in various clinical applications, and particularly in organ transplantation. Taking advantage of our centre expertise and experience concerning MSC use in graft-versus-host disease after bone marrow transplantation and using already functioning ...

Alternatives to eye bank native tissue for corneal stromal replacement.

Science.gov (United States)

Brunette, Isabelle; Roberts, Cynthia J; Vidal, François; Harissi-Dagher, Mona; Lachaine, Jean; Sheardown, Heather; Durr, Georges M; Proulx, Stéphanie; Griffith, May

2017-07-01

Corneal blindness is a major cause of blindness in the world and corneal transplantation is the only widely accepted treatment to restore sight in these eyes. However, it is becoming increasingly difficult for eye banks to meet the increasing demand for transplantable tissue, which is in part due to population aging. Donor tissue shortage is therefore a growing concern globally and there is a need for alternatives to human donor corneas. Biosynthetic corneal substitutes offer several significant advantages over native corneas: Large-scale production offers a powerful potential solution to the severe shortage of human donor corneas worldwide; Good manufacturing practices ensure sterility and quality control; Acellular corneal substitutes circumvent immune rejection induced by allogeneic cells; Optical and biomechanical properties of the implants can be adapted to the clinical need; and finally these corneal substitutes could benefit from new advances in biomaterials science, such as surface coating, functionalization and nanoparticles. This review highlights critical contributions from laboratories working on corneal stromal substitutes. It focuses on synthetic inert prostheses (keratoprostheses), acellular scaffolds with and without enhancement of endogenous regeneration, and cell-based replacements. Accent is put on the physical properties and biocompatibility of these biomaterials, on the functional and clinical outcome once transplanted in vivo in animal or human eyes, as well as on the main challenges of corneal stromal replacement. Regulatory and economic aspects are also discussed. All of these perspectives combined highlight the founding principles of the clinical application of corneal stromal replacement, a concept that has now become reality. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

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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.

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

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.

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

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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.

Graft microvascular disease in solid organ transplantation.

Science.gov (United States)

Jiang, Xinguo; Sung, Yon K; Tian, Wen; Qian, Jin; Semenza, Gregg L; Nicolls, Mark R

2014-08-01

Alloimmune inflammation damages the microvasculature of solid organ transplants during acute rejection. Although immunosuppressive drugs diminish the inflammatory response, they do not directly promote vascular repair. Repetitive microvascular injury with insufficient regeneration results in prolonged tissue hypoxia and fibrotic remodeling. While clinical studies show that a loss of the microvascular circulation precedes and may act as an initiating factor for the development of chronic rejection, preclinical studies demonstrate that improved microvascular perfusion during acute rejection delays and attenuates tissue fibrosis. Therefore, preservation of a functional microvasculature may represent an effective therapeutic strategy for preventing chronic rejection. Here, we review recent advances in our understanding of the role of the microvasculature in the long-term survival of transplanted solid organs. We also highlight microvessel-centered therapeutic strategies for prolonging the survival of solid organ transplants.

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...

Immune System and Kidney Transplantation.

Science.gov (United States)

Shrestha, Badri Man

2017-01-01

The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

Radio sterilized human ligaments and their clinical application

International Nuclear Information System (INIS)

Luna Z, D.; Reyes F, M. L.; Diaz M, I.; Hernandez R, G.

2009-10-01

The ligaments are human tissues that are used in the transplantation area. A ligament is an anatomical structure in band form, composed by resistant fibers that connect the tissues that unite the bones with the articulations. In an articulation, the ligaments allow and facilitate the movement inside the natural anatomical directions, while it restricts those movements that are anatomically abnormal, impeding lesions that could arise of this type of movements. The kneecap ligament is a very important tissue in the knee mobility and of walking in the human beings. This ligament can injure it because of automobile accidents, for sport lesions or illnesses, and in many cases the only form of recovering the knee movement is carried out a transplant with the purpose of replacing the damage ligament by allo gen kneecap ligament processed in specialized Tissue Banks where the tissue is sterilized with gamma radiation of 60 Co at very low temperatures, obtaining high quality ligaments for clinical application in injured patients. The kneecap ligaments are processed in the Tissue Banks with a segment of kneecap bone, a segment of tibial bone, the contained ligament between both bones and in some cases a fraction of the quadriceps tendon. In this work is given a description of the selection method of the tissue that includes the donor's serologic control, the kneecap ligament processing in the Radio Sterilized Tissues Bank, its sterilization with gamma radiation of 60 Co, also it is indicated like the clinical application of the allo gen ligament was realized in a hasty patient and whose previous crossed ligament was injured. Finally the results are presented from the tissue obtaining until the clinical application of it is, and in this case is observed a favorable initial evolution of the transplantation patient. (Author)

[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.

Selection, processing and clinical application of muscle-skeletal tissue; Seleccion, Procesamiento y Aplicacion Clinica de Tejido Musculo-Esqueletico

Energy Technology Data Exchange (ETDEWEB)

Luna Z, D.; Reyes F, M.L.; Lavalley E, C.; Castaneda J, G. [ININ, Carretera Mexico-Toluca s/n, 52750 La Marquesa, Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: dlz@nuclear.inin. mx

2007-07-01

Due to the increase in the average of the world population's life, people die each time to more age, this makes that the tissues of support of the human body, as those muscle-skeletal tissues, when increasing the individual's age go weakening, this in turn leads to the increment of the illnesses like the osteoporosis and the arthritis, that undoubtedly gives as a result more injure of the muscle-skeletal tissues joined a greater number of traffic accidents where particularly these tissues are affected, for that the demand of tissues muscle-skeletal for transplant every day will be bigger. The production of these tissues in the Bank of Radio sterilized Tissues, besides helping people to improve its quality of life saved foreign currencies because most of the muscle-skeletal tissues transplanted in Mexico are of import. The use of the irradiation to sterilize tissues for transplant has shown to be one of the best techniques with that purpose for what the International Atomic Energy Agency believes a Technical cooperation program to establish banks of tissues using the nuclear energy, helping mainly to countries in development. In this work the stages that follows the bank of radio sterilized tissues of the National Institute of Nuclear Research for the cadaverous donor's of muscle-skeletal tissue selection are described, as well as the processing and the clinical application of these tissues. (Author)

Transplanting oligodendrocyte progenitors into the adult CNS

International Nuclear Information System (INIS)

Franklin, R.J.M.; Blakemore, W.F.; Cambridge Univ.

1997-01-01

This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate in to astrocytes as will oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oligodendrocyte progenitor cell line CG4) are described. (author)

Bioethics of organ transplantation.

Science.gov (United States)

Caplan, Arthur

2014-03-01

As the ability to transplant organs and tissues has grown, the demand for these procedures has increased as well--to the point at which it far exceeds the available supply creating the core ethical challenge for transplantation--rationing. The gap between supply and demand, although large, is worse than it appears to be. There are two key steps to gaining access to a transplant. First, one must gain access to a transplant center. Then, those waiting need to be selected for a transplant. Many potential recipients do not get admitted to a program. They are deemed too old, not of the right nationality, not appropriate for transplant as a result of severe mental impairment, criminal history, drug abuse, or simply because they do not have access to a competent primary care physician who can refer them to a transplant program. There are also financial obstacles to access to transplant waiting lists in the United States and other nations. In many poor nations, those needing transplants simply die because there is no capacity or a very limited capacity to perform transplants. Although the demand for organs now exceeds the supply, resulting in rationing, the size of waiting lists would quickly expand were there to suddenly be an equally large expansion in the number of organs available for transplantation. Still, even with the reality of unavoidable rationing, saving more lives by increasing organ supply is a moral good. Current public policies for obtaining organs from cadavers are not adequate in that they do not produce the number of organs that public polls of persons in the United States indicate people are willing to donate.

Risk factors for chronic transplant dysfunction and cardiovascular disease are related to accumulation of advanced glycation end-products in renal transplant recipients

NARCIS (Netherlands)

Hartog, Jasper W. L.; de Vries, Aiko P. J.; Bakker, Stephan J. L.; Graaff, Reindert; van Son, Willem J.; van der Heide, Jaap J. Homan; Gans, Reinold O. B.; Wolffenbuttel, Bruce H. R.; de Jong, Paul E.; Smit, Andries J.

Background. Accumulation of advanced glycation end-products (AGEs) has been implicated in the pathogenesis of chronic transplant dysfunction and cardiovascular disease in renal transplant recipients. We aimed to investigate which factors are associated with tissue AGE accumulation in renal

History of Lung Transplantation.

Science.gov (United States)

Dabak, Gül; Şenbaklavacı, Ömer

2016-04-01

History of lung transplantation in the world can be traced back to the early years of the 20 th century when experimental vascular anastomotic techniques were developed by Carrel and Guthrie, followed by transplantation of thoracic organs on animal models by Demikhov and finally it was James Hardy who did the first lung transplantation attempt on human. But it was not until the discovery of cyclosporine and development of better surgical techniques that success could be achieved in that field by the Toronto Lung Transplant Group led by Joel Cooper. Up to the present day, over 51.000 lung transplants were performed in the world at different centers. The start of lung transplantation in Turkey has been delayed for various reasons. From 1998 on, there were several attempts but the first successful lung transplant was performed at Sureyyapasa Hospital in 2009. Today there are four lung transplant centers in Turkey; two in Istanbul, one in Ankara and another one in Izmir. Three lung transplant centers from Istanbul which belong to private sector have newly applied for licence from the Ministry of Health.

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.

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.

Considerations for successful transplantation of encapsulated pancreatic islets

NARCIS (Netherlands)

de Vos, P; Hamel, AF; Tatarkiewicz, K

Encapsulation of pancreatic islets allows for transplantion in the absence of immunosuppression. The technology is based on the principle that transplanted tissue is protected for the host immune system by an artificial membrane. Encapsulation offers a solution to the shortage of donors in clinical

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.

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

Melatonin improves spermatogonial stem cells transplantation efficiency in azoospermic mice

Directory of Open Access Journals (Sweden)

Mohammadreza Gholami

2014-02-01

Conclusion: Administration of melatonin (20 mg/kg simultaneously with transplantation of spermatogonial stem cells in azoospermia mouse testis increases the efficiency of transplantation and improves structural properties of the testes tissue.

Immunological characteristics of human umbilical cord mesenchymal stem cells and the therapeutic effects of their transplantion on hyperglycemia in diabetic rats

Science.gov (United States)

WANG, HONGWU; QIU, XIAOYAN; NI, PING; QIU, XUERONG; LIN, XIAOBO; WU, WEIZHAO; XIE, LICHUN; LIN, LIMIN; MIN, JUAN; LAI, XIULAN; CHEN, YUNBIN; HO, GUYU; MA, LIAN

2014-01-01

Islet transplantation involves the transplantation of pancreatic islets from the pancreas of a donor to another individual. It has proven to be an effective method for the treatment of type 1 diabetes. However, islet transplantation is hampered by immune rejection, as well as the shortage of donor islets. Human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (HUMSCs) are an ideal cell source for use in transplantation due to their biological characteristics and their use does not provoke any ethical issues. In this study, we investigated the immunological characteristics of HUMSCs and their effects on lymphocyte proliferation and the secretion of interferon (IFN)-γ, and explored whether direct cell-to-cell interactions and soluble factors, such as IFN-γ were important for balancing HUMSC-mediated immune regulation. We transplanted HUMSCs into diabetic rats to investigate whether these cells can colonize in vivo and differentiate into pancreatic β-cells, and whether the hyperglycemia of diabetic rats can be improved by transplantation. Our results revealed that HUMSCs did not stimulate the proliferation of lymphocytes and did not induce allogeneic or xenogeneic immune cell responses. qRT-PCR demonstrated that the HUMSCs produced an immunosuppressive isoform of human leukocyte antigen (HLA-I) and did not express HLA-DR. Flow cytometry revealed that the HUMSCs did not express immune response-related surface antigens such as, CD40, CD40L, CD80 and CD86. IFN-γ secretion by human peripheral blood lymphocytes was reduced when the cells were co-cultured with HUMSCs. These results suggest that HUMSCs are tolerated by the host in an allogeneic transplant. We transplanted HUMSCs into diabetic rats, and the cells survived in the liver and pancreas. Hyperglycemia of the diabetic rats was improved and the destruction of pancreatic cells was partly repaired by HUMSC transplantation. Hyperglycemic improvement may be related to the immunomodulatory effects of

Economic 3D-printing approach for transplantation of human stem cell-derived β-like cells.

Science.gov (United States)

Song, Jiwon; Millman, Jeffrey R

2016-12-01

Transplantation of human pluripotent stem cells (hPSC) differentiated into insulin-producing β cells is a regenerative medicine approach being investigated for diabetes cell replacement therapy. This report presents a multifaceted transplantation strategy that combines differentiation into stem cell-derived β (SC-β) cells with 3D printing. By modulating the parameters of a low-cost 3D printer, we created a macroporous device composed of polylactic acid (PLA) that houses SC-β cell clusters within a degradable fibrin gel. Using finite element modeling of cellular oxygen diffusion-consumption and an in vitro culture system that allows for culture of devices at physiological oxygen levels, we identified cluster sizes that avoid severe hypoxia within 3D-printed devices and developed a microwell-based technique for resizing clusters within this range. Upon transplantation into mice, SC-β cell-embedded 3D-printed devices function for 12 weeks, are retrievable, and maintain structural integrity. Here, we demonstrate a novel 3D-printing approach that advances the use of differentiated hPSC for regenerative medicine applications and serves as a platform for future transplantation strategies.