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Sample records for cord blood stem

  1. Cord blood stem cell banking and transplantation.

    Science.gov (United States)

    Dhot, P S; Nair, V; Swarup, D; Sirohi, D; Ganguli, P

    2003-12-01

    Stem cells have the ability to divide for indefinite periods in culture and to give rise to specialized cells. Cord blood as a source of hematopoietic stem cells (HSC) has several advantages as it is easily available, involves non-invasive collection procedure and is better tolerated across the HLA barrier. Since the first cord blood transplant in 1988, over 2500 cord blood HSC transplants have been done world wide. Since then, the advantages of cord blood as a source of hematopietic stem cells for transplantation have become clear. Firstly, the proliferative capacity of HSC in cord blood is superior to that of cells in bone marrow or blood from adults. A 100 ml unit of cord blood contains 1/10th the number of nucleated cells and progenitor cells (CD34+ cells) present in 1000 ml of bone marrow, but because they proliferate rapidly, the stem cell in a single unit of cord blood can reconstitute the entire haematopoietic system. Secondly, the use of cord blood reduces the risk of graft vs host disease. Cord Blood Stem Cell banks have been established in Europe and United States to supply HSC for related and unrelated donors. Currently, more than 65,000 units are available and more than 2500 patients have received transplants of cord blood. Results in children have clearly shown that the number of nucleated cells in the infused cord blood influences the speed of recovery of neutrophils and platelets after myeloablative chemotherapy. The optimal dose is about 2 x 10(7) nucleated cells/kg of body weight. The present study was carried out for collection, separation, enumeration and cryopreservation of cord blood HSC and establishing a Cord Blood HSC Bank. 172 samples of cord blood HSC were collected after delivery of infant prior to expulsion of placenta. The average cord blood volume collected was 101.20 ml. Mononuclear cell count ranged from 7.36 to 25.6 x 10(7)/ml. Viability count of mononuclear cells was 98.1%. After 1 year of cryopreservation, the viability count on

  2. Isolation of mesenchymal stem cells from equine umbilical cord blood

    OpenAIRE

    Thomsen Preben D; Heerkens Tammy; Koch Thomas G; Betts Dean H

    2007-01-01

    Background: There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC) have been isolated from fresh umbilical cord blood of humans collected non-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is lo...

  3. Isolation of mesenchymal stem cells from equine umbilical cord blood

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Heerkens, Tammy; Thomsen, Preben Dybdahl

    2007-01-01

    Background: There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC) have been isolated from fresh umbilical cord blood of humans collected non......-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low......, for the first time, the isolation of mesenchymal-like stem cells from fresh equine cord blood and their differentiation into osteocytes, chondrocytes and adipocytes. This novel isolation of equine cord blood MSCs and their preliminary in vitro differentiation positions the horse as the ideal pre-clinical animal...

  4. Isolation of mesenchymal stem cells from equine umbilical cord blood

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    Thomsen Preben D

    2007-05-01

    Full Text Available Abstract Background There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC have been isolated from fresh umbilical cord blood of humans collected non-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low. The hypothesis of this study was that equine MSCs could be isolated from fresh whole equine cord blood. Results Cord blood was collected from 7 foals immediately after foaling. The mononuclear cell fraction was isolated by Ficoll density centrifugation and cultured in a DMEM low glucose based media at 38.5°C in humidified atmosphere containing 5% CO2. In 4 out of 7 samples colonies with MSC morphology were observed. Cellular morphology varied between monolayers of elongated spindle-shaped cells to layered cell clusters of cuboidal cells with shorter cytoplasmic extensions. Positive Alizarin Red and von Kossa staining as well as significant calcium deposition and alkaline phosphatase activity confirmed osteogenesis. Histology and positive Safranin O staining of matrix glycosaminoglycans illustrated chondrogenesis. Oil Red O staining of lipid droplets confirmed adipogenesis. Conclusion We here report, for the first time, the isolation of mesenchymal-like stem cells from fresh equine cord blood and their differentiation into osteocytes, chondrocytes and adipocytes. This novel isolation of equine cord blood MSCs and their preliminary in vitro differentiation positions the horse as the ideal pre-clinical animal model for proof-of-principle studies of cord blood derived MSCs.

  5. Cord Blood

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    Saeed Abroun

    2014-05-01

    Full Text Available   Stem cells are naïve or master cells. This means they can transform into special 200 cell types as needed by body, and each of these cells has just one function. Stem cells are found in many parts of the human body, although some sources have richer concentrations than others. Some excellent sources of stem cells, such as bone marrow, peripheral blood, cord blood, other tissue stem cells and human embryos, which last one are controversial and their use can be illegal in some countries. Cord blood is a sample of blood taken from a newborn baby's umbilical cord. It is a rich source of stem cells, umbilical cord blood and tissue are collected from material that normally has no use following a child’s birth. Umbilical cord blood and tissue cells are rich sources of stem cells, which have been used in the treatment of over 80 diseases including leukemia, lymphoma and anemia as bone marrow stem cell potency.  The most common disease category has been leukemia. The next largest group is inherited diseases. Patients with lymphoma, myelodysplasia and severe aplastic anemia have also been successfully transplanted with cord blood. Cord blood is obtained by syringing out the placenta through the umbilical cord at the time of childbirth, after the cord has been detached from the newborn. Collecting stem cells from umbilical blood and tissue is ethical, pain-free, safe and simple. When they are needed to treat your child later in life, there will be no rejection or incompatibility issues, as the procedure will be using their own cells. In contrast, stem cells from donors do have these potential problems. By consider about cord blood potency, cord blood banks (familial or public were established. In IRAN, four cord blood banks has activity, Shariati BMT center cord blood bank, Royan familial cord blood banks, Royan public cord blood banks and Iranian Blood Transfusion Organ cord blood banks. Despite 50,000 sample which storage in these banks, but the

  6. CD34+ stem cells from umbilical cord blood

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    Alfio D’Agati

    2011-09-01

    Full Text Available We describe the relation between umbilical cord clamping time and two different enrichment system of CD34+ stem cells from umbilical cord blood with the proliferative ability and bone marrow reconstitution of the stem cells obtained. After an obstetrician performed the cord blood collection, the purification of stem cells was performed either with a combination of monoclonal antibodies (negative selections using the Stem Sep method, or with a positive cells selection based on their surface CD34 antigens using the Mini Macs system. An excellent recovery of haematopoietic progenitors [Burst Forming Unit Erythroids (BFUE; Colony Forming Unit Granulocytes and Macrophages (CFU-GM; and Colony Forming Unit Granulocytes, Erythroids, Monocytes and Macrophages (CFU-GME], inversely related to the increase in clamping time, was performed with the Mini Macs system (54% of colonies, with 90% purity. With Stem Sep method, haematopoietic progenitor’s recovery was 35% (with 80% purity. By applying early clamping of umbilical cord blood we obtained a greater number of CD34+ cells and their clonogenic activity was increased with enrichment. This is a useful technique considering that the number of CD34+ stem cells usually contained from a unit of placental blood is enough for the transplant to a child, but not for an adult. Thus, using these methods, we can get a larger number of CD34+ stem cells which reduces the risk of Graft versus Host Disease also in adult patients, producing survival rates similar to those obtained with transplantation of bone marrow from unrelated donors.

  7. CD34+ stem cells from umbilical cord blood

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    Carlo Pafumi

    2011-10-01

    Full Text Available We describe the relation between umbilical cord clamping time and two different enrichment system of CD34+ stem cells from umbilical cord blood with the proliferative ability and bone marrow reconstitution of the stem cells obtained. After an obstetrician performed the cord blood collection, the purification of stem cells was performed either with a combination of monoclonal antibodies (negative selections using the Stem Sep method, or with a positive cells selection based on their surface CD34 antigens using the Mini Macs system. An excellent recovery of haematopoietic progenitors [Burst Forming Unit Erythroids (BFUE; Colony Forming Unit Granulocytes and Macrophages (CFU-GM; and Colony Forming Unit Granulocytes, Erythroids, Monocytes and Macrophages (CFU-GME], inversely related to the increase in clamping time, was performed with the Mini Macs system (54% of colonies, with 90% purity. With Stem Sep method, haematopoietic progenitor’s recovery was 35% (with 80% purity. By applying early clamping of umbilical cord blood we obtained a greater number of CD34+ cells and their clonogenic activity was increased with enrichment. This is a useful technique considering that the number of CD34+ stem cells usually contained from a unit of placental blood is enough for the transplant to a child, but not for an adult. Thus, using these methods, we can get a larger number of CD34+ stem cells which reduces the risk of Graft versus Host Disease also in adult patients, producing survival rates similar to those obtained with transplantation of bone marrow from unrelated donors.

  8. Saving the leftovers: models for banking cord blood stem cells.

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    Cogdell, Kimberly J

    2009-01-01

    Each year there are over four million live births in the United States. Each birth produces umbilical cord blood stem cells, which are usually discarded. The author argues that rather than discarding the umbilical cord, this valuable resource of cord blood should be banked and used for research and therapeutic purposes. Umbilical cord blood could provide a solution to the critical need to find matching donors for hematopoietic transplants in patients who have no matching bone marrow donors. Creating a system of universal donation to a public bank will greatlyincrease the number of donors and therefore, the number of matches for patients. Such a system will facilitate the development and use of new technologies and transplant procedures, while providing an opportunity for treatment to individuals who would otherwise not be able to find suitable donors.

  9. Expansion of human cord blood hematopoietic stem cells for transplantation.

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    Chou, Song; Chu, Pat; Hwang, William; Lodish, Harvey

    2010-10-08

    A recent Science paper reported a purine derivative that expands human cord blood hematopoietic stem cells in culture (Boitano et al., 2010) by antagonizing the aryl hydrocarbon receptor. Major problems need to be overcome before ex vivo HSC expansion can be used clinically.

  10. Umbilical Cord Blood Stem Cells. Who has the right word?

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    Gisela Laporta

    2014-12-01

    Full Text Available In this article we analyze bioethical and legal aspects related to the cryopreservation of cord blood stem cells in Argentina. To unify definitions, the concept and variety of stem cells, together with the understanding of the means to obtain and store umbilical cord blood stem cells, are provided.  Options that arise in our country, mainly analyzing the conceptual differences underlying legal body and parts by public and private biobanks, are described. Additionally, the current Argentinean legislation and circumstances arising from a resolution which INCUCAI sought to regulate private biobanks, is analyzed. This analysis leads to thoughts on the way conflicts are solved when the health and life of people are judicialized. In this particular case, the appearance of a complex new topic which gives rise to new social and healthcare scenarios, must be further understood.

  11. Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

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    Itır Sirinoglu Demiriz

    2012-01-01

    Full Text Available The introduction of peripheral stem cell (PSC and cord blood (CB as an alternative to bone marrow (BM recently has caused important changes on hematopoietic stem cell transplantation (HSCT practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

  12. Generation of induced pluripotent stem cells from human cord blood.

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    Haase, Alexandra; Olmer, Ruth; Schwanke, Kristin; Wunderlich, Stephanie; Merkert, Sylvia; Hess, Christian; Zweigerdt, Robert; Gruh, Ina; Meyer, Johann; Wagner, Stefan; Maier, Lars S; Han, Dong Wook; Glage, Silke; Miller, Konstantin; Fischer, Philipp; Schöler, Hans R; Martin, Ulrich

    2009-10-02

    Induced pluripotent stem cells (iPSCs) may represent an ideal cell source for future regenerative therapies. A critical issue concerning the clinical use of patient-specific iPSCs is the accumulation of mutations in somatic (stem) cells over an organism's lifetime. Acquired somatic mutations are passed onto iPSCs during reprogramming and may be associated with loss of cellular functions and cancer formation. Here we report the generation of human iPSCs from cord blood (CB) as a juvenescent cell source. CBiPSCs show characteristics typical of embryonic stem cells and can be differentiated into derivatives of all three germ layers, including functional cardiomyocytes. For future therapeutic production of autologous and allogeneic iPSC derivatives, CB could be routinely harvested for public and commercial CB banks without any donor risk. CB could readily become available for pediatric patients and, in particular, for newborns with genetic diseases or congenital malformations.

  13. Cost effectiveness of cord blood versus bone marrow and peripheral blood stem cells

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    Thomas Bart

    2010-10-01

    Full Text Available Thomas BartSwiss Blood Stem Cells, Bern, SwitzerlandAbstract: Umbilical cord blood (CB has become, since its first successful use more than two decades ago, an increasingly important source of blood stem cells. In this light, an overview of current usage of CB in the field of unrelated hematopoietic blood stem cell transplantation (HSCT is given. The three main sources of hematopoietic stem cells: bone marrow (BM, peripheral blood stem cells (PBSC, and cord blood (CB are compared as regards their current quantitative usage in HSCT. A cost analysis of the named three hematopoietic blood stem cell (HSC sources, taking into account various factors, is undertaken. The health economical comparison shows significant differences between CB on the one side, and BM and PBSC on the other. The consequences for the public health side and propositions for a possible health care policy, especially regarding future resource allocation towards the different choices for HSCT products, are discussed. An outlook on the possible future usage of BM, PBSC, and CB and its implications on health systems, donor registries, and CB banks is given.Keywords: health economy, cord blood, hematopoietic stem cell transplantation

  14. [Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank].

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    Barriga, Francisco; Wietstruck, Angélica; Rojas, Nicolás; Bertin, Pablo; Pizarro, Isabel; Carmona, Amanda; Guilof, Alejandro; Rojas, Iván; Oyarzún, Enrique

    2013-08-01

    Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

  15. The treatment of neurodegenerative disorders using umbilical cord blood and menstrual blood-derived stem cells.

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    Sanberg, Paul R; Eve, David J; Willing, Alison E; Garbuzova-Davis, Svitlana; Tan, Jun; Sanberg, Cyndy D; Allickson, Julie G; Cruz, L Eduardo; Borlongan, Cesar V

    2011-01-01

    Stem cell transplantation is a potentially important means of treatment for a number of disorders. Two different stem cell populations of interest are mononuclear umbilical cord blood cells and menstrual blood-derived stem cells. These cells are relatively easy to obtain, appear to be pluripotent, and are immunologically immature. These cells, particularly umbilical cord blood cells, have been studied as either single or multiple injections in a number of animal models of neurodegenerative disorders with some degree of success, including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and Sanfilippo syndrome type B. Evidence of anti-inflammatory effects and secretion of specific cytokines and growth factors that promote cell survival, rather than cell replacement, have been detected in both transplanted cells.

  16. Expression of neurotrophic factors in injured spinal cord after transplantation of human-umbilical cord blood stem cells in rats.

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    Chung, Hyo-jin; Chung, Wook-hun; Lee, Jae-Hoon; Chung, Dai-Jung; Yang, Wo-Jong; Lee, A-Jin; Choi, Chi-Bong; Chang, Hwa-Seok; Kim, Dae-Hyun; Suh, Hyun Jung; Lee, Dong-Hun; Hwang, Soo-Han; Do, Sun Hee; Kim, Hwi-Yool

    2016-03-01

    We induced percutaneous spinal cord injuries (SCI) using a balloon catheter in 45 rats and transplanted human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) at the injury site. Locomotor function was significantly improved in hUCB-MSCs transplanted groups. Quantitative ELISA of extract from entire injured spinal cord showed increased expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Our results show that treatment of SCI with hUCB-MSCs can improve locomotor functions, and suggest that increased levels of BDNF, NGF and NT-3 in the injured spinal cord were the main therapeutic effect.

  17. Differentiation and tumorigenicity of neural stem cells from human cord blood mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Jing Xiang; Changming Wang; Jingzhou Wang

    2009-01-01

    BACKGROUND:Mesenchymal stem cells (MSCs) are capable of differentiating into a variety of tissues and exhibit low immunogenicity.OBJECTIVE:To investigate isolation and in vitro cultivation methods of human cord blood MSCs,to observe expression of neural stem cell (NSC) marker mRNA under induction,and to detect tumorigenicity in animals.DESIGN,TIME AND SETTING:A cell biological,in vitro trial and a randomized,controlled,in vivo experiment were performed at the Department of Neurology,Daping Hospital at the Third Military Medical University of Chinese PLA from August 2006 to May 2008.MATERIALS:Umbilical cord blood was collected from full-term-delivery fetus at the Department of Gynecology and Obstetrics of DapJng Hospital,China.Eighteen BALB/C nu/nu nude mice were randomly assigned to three groups:back subcutaneous,cervical subcutaneous,and control,with 6 mice in each group.METHODS:Monocytes were isolated from heparinized human cord blood samples by density gradient centrifugation and then adherent cultivated in vitro to obtain MSC clones.After the cord blood MSCs were cultured for 7 days with nerve growth factor and retinoic acid to induce differentiation into NSCs,the cells (adjusted density of 1×10~7/mL) were prepared into cell suspension.In the back subcutaneous and cervical subcutaneous groups,nude mice were hypodermically injected with a 0.5-mL cell suspension into the back and cervical regions,respectively.In the control group,nude mice received a subcutaneous injection of 0.5 mL physiological saline into the back or cervical regions,respectively.MAIN OUTCOME MEASURES:Cellular morphology was observed by inverted microscopy,cultured cord blood MSCs were examined by flow cytometry,expression of nestin and musashi-1 mRNA was detected by reverse-transcriptase polymerase chain reaction prior to and after induction,and tumorigenicity following cord blood MSC transplantation was assayed by hematoxylin-eosin staining.RESULTS:Following adherent cultivation

  18. Recent Stem Cell Advances: Cord Blood and Induced Pluripotent Stem Cell for Cardiac Regeneration- a Review.

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    Medhekar, Sheetal Kashinath; Shende, Vikas Suresh; Chincholkar, Anjali Baburao

    2016-05-30

    Stem cells are primitive self renewing undifferentiated cell that can be differentiated into various types of specialized cells like nerve cell, skin cells, muscle cells, intestinal tissue, and blood cells. Stem cells live in bone marrow where they divide to make new blood cells and produces peripheral stem cells in circulation. Under proper environment and in presence of signaling molecules stem cells begin to develop into specialized tissues and organs. These unique characteristics make them very promising entities for regeneration of damaged tissue. Day by day increase in incidence of heart diseases including left ventricular dysfunction, ischemic heart disease (IHD), congestive heart failure (CHF) are the major cause of morbidity and mortality. However infracted tissue cannot regenerate into healthy tissue. Heart transplantation is only the treatment for such patient. Due to limitation of availability of donor for organ transplantation, a focus is made for alternative and effective therapy to treat such condition. In this review we have discussed the new advances in stem cells such as use of cord stem cells and iPSC technology in cardiac repair. Future approach of CB cells was found to be used in tissue repair which is specifically observed for improvement of left ventricular function and myocardial infarction. Here we have also focused on how iPSC technology is used for regeneration of cardiomyocytes and intiating neovascularization in myocardial infarction and also for study of pathophysiology of various degenerative diseases and genetic disease in research field.

  19. Comparison of ectopic bone formation of embryonic stem cells and cord blood stem cells in vivo.

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    Handschel, Jörg; Naujoks, Christian; Langenbach, Fabian; Berr, Karin; Depprich, Rita A; Ommerborn, Michelle A; Kübler, Norbert R; Brinkmann, Matthias; Kögler, Gesine; Meyer, Ulrich

    2010-08-01

    Cell-based reconstruction therapies promise new therapeutic opportunities for bone regeneration. Unrestricted somatic stem cells (USSC) from cord blood and embryonic stem cells (ESCs) can be differentiated into osteogenic cells. The purpose of this in vivo study was to compare their ability to induce ectopic bone formation in vivo. Human USSCs and murine ESCs were cultured as both monolayer cultures and micromasses and seeded on insoluble collagenous bone matrix (ICBM). One week and 1, 2, and 3 months after implanting the constructs in immune-deficient rats, computed tomography scans were performed to detect any calcification. Subsequently, the implanted constructs were examined histologically. The radiological examination showed a steep increase in the mineralized bone-like tissue in the USSC groups. This increase can be considered as statistically significant compared to the basic value. Moreover, the volume and the calcium portion measured by computed tomography scans were about 10 times higher than in the ESC group. The volume of mineralization in the ESC group increased to a much smaller extent over the course of time, and the control group (ICBM without cells) showed almost no alterations during the study. The histological examinations parallel the radiological findings. Cord blood stem cells in combination with ICBM-induced ectopic bone formation in vivo are stronger than ESCs.

  20. Human Umbilical Cord Mesenchymal Stromal Cells Support Viability of Umbilical Cord Blood Hematopoietic Stem Cells but not the "Stemness" of Their Progeny in Co-Culture.

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    Romanov, Yu A; Volgina, N E; Balashova, E E; Kabaeva, N V; Dugina, T N; Sukhikh, G T

    2017-08-01

    Cell-cell interactions and the ability of mesenchymal stromal cells to support the expansion of hematopoietic progenitor cells were studied in co-culture of human umbilical cord tissue-derived mesenchymal stromal cells and nucleated umbilical cord blood cells. It was found that hematopoietic stem cells from the umbilical cord blood are capable to adhere to mesenchymal stromal cells and proliferate during 3-4 weeks in co-culture. However, despite the formation of hematopoietic foci and accumulation of CD34(+) and CD133(+) cells in the adherent cell fraction, the ability of newly generated blood cells to form colonies in semi-solid culture medium was appreciably reduced. These findings suggest that human umbilical cord tissue-derived mesenchymal stromal cells display a weak capability to support the "stemness" of hematopoietic stem cell progeny despite long-term maintenance of their viability and proliferation.

  1. Early human herpes virus type 6 reactivation in umbilical cord blood allogeneic stem cell transplantation.

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    Cirrone, Frank; Ippoliti, Cindy; Wang, Hanhan; Zhou, Xi Kathy; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; van Besien, Koen

    2016-11-01

    Human herpes virus type 6 can reactivate in patients after allogeneic stem cell transplantation and has been associated with serious sequelae such as delayed engraftment and an increased risk of developing acute graft-versus-host disease (GVHD). This study investigated human herpes virus type 6 (HHV-6) reactivation within 60 days of transplantation in stem cell transplants utilizing single umbilical cord blood, double umbilical cord blood, or umbilical cord blood plus haploidentical stem cells. Of 92 patients, 60 (65%) had HHV-6 reactivation. Reactivation was not significantly influenced by any patient characteristics, disease characteristics, or by stem cell source (umbilical cord blood only versus haploidentical plus umbilical cord blood). We did not observe any impact of HHV-6 reactivation on neutrophil or platelet count recovery or on relapse-free survival. HHV-6 reactivation was associated with subsequent development of prerelapse acute GVHD (HR = 3.00; 95% CI, 1.4 to 6.4; p = 0.004).

  2. Differentiation of Human Cord Blood and Stromal Derived Stem Cells into Neuron Cells

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    Özlem Pamukçu Baran

    2007-01-01

    Full Text Available The most basic properties of stem cells are the capacities to self-renew indefinitely and to differentiate into multiple cell or tissue types. Umbilical cord blood has been utilized for human hematopoietic stem cell transplantation as an alternative source to bone marrow.The experiments show that Wharton’s jelly cells are easily attainable and can be expanded in vitro, maintained in culture, and induced to differentiate into neural cells. Almost recent studies it has been discovered that the cord blood-derived cells can differantiate not only to blood cells but also to various somatic cells like neuron or muscle cell with the signals taken from the envoirenment.Interestingly, neural cells obtained from umbilical cord blood show a relatively high spontaneous differentiation into oligodendrocytes, Embryonic stem cells proliferate indefinitely and can differentiate spontaneously into all tissue types.It has been shown that embryonic stem cells can be induced to differentiate into neurons and glia by treatment with retinoic acid or basic fibroblast growth factor. It has been studied that the diseases as Motor Neuron Disease, Parkinson, Alzheimer and degeneration of medulla spinalis and also paralysises could be treated with transplantation of cord blood-dericed stem cells.

  3. Human umbilical cord blood stem cell transplantation for the treatment of chronic spinal cord injury Electrophysiological changes and long-term efficacy

    Institute of Scientific and Technical Information of China (English)

    Liqing Yao; Chuan He; Ying Zhao; Jirong Wang; Mei Tang; Jun Li; Ying Wu; Lijuan Ao; Xiang Hu

    2013-01-01

    Stem cell transplantation can promote functional restoration following acute spinal cord injury (injury time 6 months) were treated with human umbilical cord blood stem cells via intravenous and intrathecal injection. The follow-up period was 12 months after transplantation. Results found that autonomic nerve functions were restored and the latent period of somatosensory evoked potentials was reduced. There were no severe adverse reactions in patients following stem cell transplantation. These experimental findings suggest that the transplantation of human umbilical cord blood stem cells is a safe and effective treatment for patients with traumatic spinal cord injury.

  4. Design guidelines for an umbilical cord blood stem cell therapy quality assessment model

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    Januszewski, Witold S.; Michałek, Krzysztof; Yagensky, Oleksandr; Wardzińska, Marta

    The paper enlists the pivotal guidelines for producing an empirical umbilical cord blood stem cell therapy quality assessment model. The methodology adapted was single equation linear model with domain knowledge derived from MEDAFAR classification. The resulting model is ready for therapeutical application.

  5. Banking cord blood stem cells: attitude and knowledge of pregnant women in five European countries.

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    Katz, Gregory; Mills, Antonia; Garcia, Joan; Hooper, Karen; McGuckin, Colin; Platz, Alexander; Rebulla, Paolo; Salvaterra, Elena; Schmidt, Alexander H; Torrabadella, Marta

    2011-03-01

    This study explores pregnant women's awareness of cord blood stem cells and their attitude regarding banking options in France, Germany, Italy, Spain, and the UK. Questionnaires were distributed in six maternities. This anonymous and self-completed questionnaire included 29 multiple-choice questions based on: 1) sociodemographic factors, 2) awareness and access to information about cord blood banking, 3) banking option preferences, and 4) donating cord blood units (CBUs) to research. A total of 79% of pregnant women had little awareness of cord blood banking (n = 1620). A total of 58% of women had heard of the therapeutic benefits of cord blood, of which 21% received information from midwives and obstetricians. A total of 89% of respondents would opt to store CBUs. Among them, 76% would choose to donate CBUs to a public bank to benefit any patient in need of a cord blood transplant. Twelve percent would choose a mixed bank, and 12%, a private bank. A total of 92% would donate their child's CBU to research when it is not suitable for transplantation. The study reveals a strong preference for public banking in all five countries, based on converging values such as solidarity. Attitudes of pregnant women are not an obstacle to the rapid expansion of allogeneic banking in these EU countries. Banking choices do not appear to be correlated with household income. The extent of commercial marketing of cord blood banks in mass media highlights the importance for obstetric providers to play a central role in raising women's awareness early during their pregnancy with evidence-based medical information about banking options. © 2010 American Association of Blood Banks.

  6. Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

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    Mohammad Reza Nikravesh

    2011-11-01

    Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

  7. Leukemia cell microvesicles promote survival in umbilical cord blood hematopoietic stem cells.

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    Razmkhah, Farnaz; Soleimani, Masoud; Mehrabani, Davood; Karimi, Mohammad Hossein; Kafi-Abad, Sedigheh Amini

    2015-01-01

    Microvesicles can transfer their contents, proteins and RNA, to target cells and thereby transform them. This may induce apoptosis or survival depending on cell origin and the target cell. In this study, we investigate the effect of leukemic cell microvesicles on umbilical cord blood hematopoietic stem cells to seek evidence of apoptosis or cell survival. Microvesicles were isolated from both healthy donor bone marrow samples and Jurkat cells by ultra-centrifugation and were added to hematopoietic stem cells sorted from umbilical cord blood samples by magnetic associated cell sorting (MACS) technique. After 7 days, cell count, cell viability, flow cytometry analysis for hematopoietic stem cell markers and qPCR for P53 gene expression were performed. The results showed higher cell number, higher cell viability rate and lower P53 gene expression in leukemia group in comparison with normal and control groups. Also, CD34 expression as the most important hematopoietic stem cell marker, did not change during the treatment and lineage differentiation was not observed. In conclusion, this study showed anti-apoptotic effect of leukemia cell derived microvesicles on umbilical cord blood hematopoietic stem cells.

  8. Ex Vivo Expansion or Manipulation of Stem Cells to Improve Outcome of Umbilical Cord Blood Transplantation.

    Science.gov (United States)

    Horwitz, Mitchell E

    2016-02-01

    The outcome of umbilical cord blood transplantation for adult patients with hematologic malignancies now rivals that of matched unrelated donor transplantation. However, delayed hematopoietic and immunologic recovery remains a source of significant morbidity and mortality. Multiple strategies are now being studied to overcome these limitations. One strategy involves ex vivo expansion of the umbilical cord blood unit prior to transplantation. A second strategy involves exposure of the umbilical cord blood graft to compounds aimed at improving homing and engraftment following transplantation. Such a strategy may also address the problem of slow hematopoietic recovery as well as the increased risk of graft failure. Many of these strategies are now being tested in late phase multi-center clinical trials. If proven cost-effective and efficacious, they may alter the landscape of donor options for allogeneic stem cell transplantation.

  9. Cord-Blood Banking

    Science.gov (United States)

    ... to Be Smart About Social Media Cord-Blood Banking KidsHealth > For Parents > Cord-Blood Banking Print A ... for you and your family. About Cord-Blood Banking Cord-blood banking basically means collecting and storing ...

  10. Erythropoietic Potential of CD34+ Hematopoietic Stem Cells from Human Cord Blood and G-CSF-Mobilized Peripheral Blood

    Directory of Open Access Journals (Sweden)

    Honglian Jin

    2014-01-01

    Full Text Available Red blood cell (RBC supply for transfusion has been severely constrained by the limited availability of donor blood and the emergence of infection and contamination issues. Alternatively, hematopoietic stem cells (HSCs from human organs have been increasingly considered as safe and effective blood source. Several methods have been studied to obtain mature RBCs from CD34+ hematopoietic stem cells via in vitro culture. Among them, human cord blood (CB and granulocyte colony-stimulating factor-mobilized adult peripheral blood (mPB are common adult stem cells used for allogeneic transplantation. Our present study focuses on comparing CB- and mPB-derived stem cells in differentiation from CD34+ cells into mature RBCs. By using CD34+ cells from cord blood and G-CSF mobilized peripheral blood, we showed in vitro RBC generation of artificial red blood cells. Our results demonstrate that CB- and mPB-derived CD34+ hematopoietic stem cells have similar characteristics when cultured under the same conditions, but differ considerably with respect to expression levels of various genes and hemoglobin development. This study is the first to compare the characteristics of CB- and mPB-derived erythrocytes. The results support the idea that CB and mPB, despite some similarities, possess different erythropoietic potentials in in vitro culture systems.

  11. Interleukin-15 Promotes the Commitment of Cord Blood CD34+ Stem Cells into NK Cells

    Institute of Scientific and Technical Information of China (English)

    张建; 夏青; 孙汭; 田志刚

    2004-01-01

    To explore the effect of rhlL-15 on CB-CD34+ stem cells committing to NK cells, CD34+ stem cells were obtained from cord blood (CB) by magnetic-assisted cell sorting (MACS) method. CD3, CD16 and CD56 molecules expressed on cell surface were detected by flow cytometer. MTF method was used to test the cytotoxicity of NK cells. The results were that stem cell factor (SCF) alone has no effect on CD34+ stem cells. IL-15 stimulated CD34+ stem cells commit to NK cells, and SCF showed strong synergistic effect with IL-15. It was concluded that IL-15 and SCF played different roles during NK cell development, llr15 promoted CD34+ stem cells differentiate to NK cell precursor and SCF improved the effectsof IL-15 on NK cell differentiation.

  12. Time related variations in stem cell harvesting of umbilical cord blood

    Science.gov (United States)

    Mazzoccoli, Gianluigi; Miscio, Giuseppe; Fontana, Andrea; Copetti, Massimiliano; Francavilla, Massimo; Bosi, Alberto; Perfetto, Federico; Valoriani, Alice; De Cata, Angelo; Santodirocco, Michele; Totaro, Angela; Rubino, Rosa; di Mauro, Lazzaro; Tarquini, Roberto

    2016-01-01

    Umbilical cord blood (UCB) contains hematopoietic stem cells and multipotent mesenchymal cells useful for treatment in malignant/nonmalignant hematologic-immunologic diseases and regenerative medicine. Transplantation outcome is correlated with cord blood volume (CBV), number of total nucleated cells (TNC), CD34+ progenitor cells and colony forming units in UCB donations. Several studies have addressed the role of maternal/neonatal factors associated with the hematopoietic reconstruction potential of UCB, including: gestational age, maternal parity, newborn sex and birth weight, placental weight, labor duration and mode of delivery. Few data exist regarding as to how time influences UCB collection and banking patterns. We retrospectively analyzed 17.936 cord blood donations collected from 1999 to 2011 from Tuscany and Apulia Cord Blood Banks. Results from generalized multivariable linear mixed models showed that CBV, TNC and CD34+ cell were associated with known obstetric and neonatal parameters and showed rhythmic patterns in different time domains and frequency ranges. The present findings confirm that volume, total nucleated cells and stem cells of the UCB donations are hallmarked by rhythmic patterns in different time domains and frequency ranges and suggest that temporal rhythms in addition to known obstetric and neonatal parameters influence CBV, TNC and CD34+ cell content in UBC units. PMID:26906327

  13. Stem Cell Transplant (Peripheral Blood, Bone Marrow, and Cord Blood Transplants)

    Science.gov (United States)

    ... cells , they are not the same as the embryos’ stem cells that are studied in cloning and ... March 16, 2016. National Cancer Institute. Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation . August 12, ...

  14. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia

    DEFF Research Database (Denmark)

    Ruggeri, A; Labopin, M; Sanz, G;

    2015-01-01

    Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared ...

  15. Isolation and characterization of in vitro culture of hair follicle cells differentiated from umbilical cord blood mesenchymal stem cells.

    Science.gov (United States)

    Bu, Zhang-Yu; Wu, Li-Min; Yu, Xiao-Hong; Zhong, Jian-Bo; Yang, Ping; Chen, Jian

    2017-07-01

    The present investigation explored the in vitro culture, isolation and characterization of hair follicle cell differentiation from umbilical cord blood mesenchymal stem cells (MSCs). Flow cytometry was used to obtain MSCs from the isolation and purification of human umbilical cord blood MSCs. Culture suspension of hair follicle organ was centrifuged and the supernatant used in the culture medium of MSCs, and the entire process of induced differentiation was recorded by photomicroscopy. The expression level of surface marker CK15 of hair follicle cells obtained from induced differentiation was detected with immunofluorescence. RT-PCR method was used to further detect the difference in expression of CK15 between hair follicle cells and umbilical cord blood MSCs, and statistical analysis was carried out. CD44(+)CD29(+) double-labeled cells accounted for 50.8% of all the samples of umbilical cord blood MSCs in this study. The diameter of hair follicle cells differentiated from umbilical cord blood stem cells reached 800×10(-3) mm after 3 weeks of cell culture. Based on the detection and colocalization of CK15 expression in induced hair follicle cells, the overlap ratio between CK15 and nuclei reached 83% in hair follicle cells, which was obviously higher than that in umbilical cord blood stem cells. The difference had statistical significance (Pumbilical cord blood stem cells by using the supernatant from hair follicle cells. This method can be used for high-speed induced differentiation with high purity, which is promising for clinical application.

  16. Persistence of Yellow Fever vaccine-induced antibodies after cord blood stem cell transplant.

    Science.gov (United States)

    Avelino-Silva, Vivian Iida; Freire, Marcos da Silva; Rocha, Vanderson; Rodrigues, Celso Arrais; Novis, Yana Sarkis; Sabino, Ester C; Kallas, Esper Georges

    2016-04-02

    We report the case of a cord blood haematopoietic stem cell transplant recipient who was vaccinated for Yellow Fever (YF) 7 days before initiating chemotherapy and had persistent YF antibodies more than 3 years after vaccination. Since the stem cell donor was never exposed to wild YF or to the YF vaccine, and our patient was not exposed to YF or revaccinated, this finding strongly suggests the persistence of recipient immunity. We briefly discuss potential consequences of incomplete elimination of recipient's leukocytes following existing haematopoietic cancer treatments.

  17. Umbilical cord blood: a trustworthy source of multipotent stem cells for regenerative medicine.

    Science.gov (United States)

    Jaing, Tang-Her

    2014-01-01

    It is conservatively estimated that one in three individuals in the US might benefit from regenerative medicine therapy. However, the relation of embryonic stem cells (ESCs) to human blastocysts always stirs ethical, political, moral, and emotional debate over their use in research. Thus, for the reasonably foreseeable future, the march of regenerative medicine to the clinic will depend upon the development of non-ESC therapies. Current sources of non-ESCs easily available in large numbers can be found in the bone marrow, adipose tissue, and umbilical cord blood (UCB). UCB provides an immune-compatible source of stem cells for regenerative medicine. Owing to inconsistent results, it is certainly an important and clinically relevant question whether UCB will prove to be therapeutically effective. This review will show that UCB contains multiple populations of multipotent stem cells, capable of giving rise to hematopoietic, epithelial, endothelial, and neural tissues both in vitro and in vivo. Here we raise the possibility that due to unique immunological properties of both the stem cell and non-stem cell components of cord blood, it may be possible to utilize allogeneic cells for regenerative applications without needing to influence or compromise the recipient immune system.

  18. Human Umbilical Cord Blood Stem Cells: Rational for Use as a Neuroprotectant in Ischemic Brain Disease

    Directory of Open Access Journals (Sweden)

    Hadar Arien-Zakay

    2010-09-01

    Full Text Available The use of stem cells for reparative medicine was first proposed more than three decades ago. Hematopoietic stem cells from bone marrow, peripheral blood and human umbilical cord blood (CB have gained major use for treatment of hematological indications. CB, however, is also a source of cells capable of differentiating into various non-hematopoietic cell types, including neural cells. Several animal model reports have shown that CB cells may be used for treatment of neurological injuries. This review summarizes the information available on the origin of CB-derived neuronal cells and the mechanisms proposed to explain their action. The potential use of stem/progenitor cells for treatment of ischemic brain injuries is discussed. Issues that remain to be resolved at the present stage of preclinical trials are addressed.

  19. CD133(+) human umbilical cord blood stem cells enhance angiogenesis in experimental chronic hepatic fibrosis.

    Science.gov (United States)

    Elkhafif, Nagwa; El Baz, Hanan; Hammam, Olfat; Hassan, Salwa; Salah, Faten; Mansour, Wafaa; Mansy, Soheir; Yehia, Hoda; Zaki, Ahmed; Magdy, Ranya

    2011-01-01

    The in vivo angiogenic potential of transplanted human umbilical cord blood (UCB) CD133(+) stem cells in experimental chronic hepatic fibrosis induced by murine schistosomiasis was studied. Enriched cord blood-derived CD133(+) cells were cultured in primary medium for 3 weeks. Twenty-two weeks post-Schistosomiasis infection in mice, after reaching the chronic hepatic fibrotic stage, transplantation of stem cells was performed and mice were sacrificed 3 weeks later. Histopathology and electron microscopy showed an increase in newly formed blood vessels and a decrease in the fibrosis known for this stage of the disease. By immunohistochemical analysis the newly formed blood vessels showed positive expression of the human-specific angiogenic markers CD31, CD34 and von Willebrand factor. Few hepatocyte-like polygonal cells showed positive expression of human vascular endothelial growth factor and inducible nitric oxide synthase. The transplanted CD133(+) human stem cells primarily enhanced hepatic angiogenesis and neovascularization and contributed to repair in a paracrine manner by creating a permissive environment that enabled proliferation and survival of damaged cells rather than by direct differentiation to hepatocytes. A dual advantage of CD133(+) cell therapy in hepatic disease is suggested based on its capability of hematopoietic and endothelial differentiation.

  20. A novel monoclonal antibody of human stem cell factor inhibits umbilical cord blood stem cell ex vivo expansion

    Directory of Open Access Journals (Sweden)

    Fan Jie

    2012-12-01

    Full Text Available Abstract Stem cell factor (SCF activates hematopoietic stem cell (HSC self-renewal and is being used to stimulate the ex vivo expansion of HSCs. The mechanism by which SCF supports expansion of HSCs remains poorly understood. In cord blood ex vivo expansion assays, a newly produced anti-SCF monoclonal antibody (clone 23C8 was found to significantly inhibit the expansion of CD34+ cells. This antibody appears to bind directly to a part of SCF that is critical for biological activity toward expansion of CD34+ cells, which is located in the first 104 amino acids from the NH2-terminus.

  1. Human umbilical cord blood-derived mesenchymal stem cells promote regeneration of crush-injured rat sciatic nerves

    Institute of Scientific and Technical Information of China (English)

    Mi-Ae Sung; Jong-Ho Lee; Hun Jong Jung; Jung-Woo Lee; Jin-Yong Lee; Kang-Mi Pang; Sang Bae Yoo; Mohammad S. Alrashdan; Soung-Min Kim; Jeong Won Jahng

    2012-01-01

    Several studies have demonstrated that human umbilical cord blood-derived mesenchymal stem cells can promote neural regeneration following brain injury. However, the therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells in guiding peripheral nerve regeneration remain poorly understood. This study was designed to investigate the effects of human umbilical cord blood-derived mesenchymal stem cells on neural regeneration using a rat sciatic nerve crush injury model. Human umbilical cord blood-derived mesenchymal stem cells (1 × 106) or a PBS control were injected into the crush-injured segment of the sciatic nerve. Four weeks after cell injection, brain-derived neurotrophic factor and tyrosine kinase receptor B mRNA expression at the lesion site was increased in comparison to control. Furthermore, sciatic function index, Fluoro Gold-labeled neuron counts and axon density were also significantly increased when compared with control. Our results indicate that human umbilical cord blood-derived mesenchymal stem cells promote the functional recovery of crush-injured sciatic nerves.

  2. I-131-Metaiodobenzylguanidine therapy with allogeneic cord blood stem cell transplantation for recurrent neuroblastoma

    Directory of Open Access Journals (Sweden)

    Sato Yuya

    2012-10-01

    Full Text Available Abstract Iodine-131-metaiodiobenzylguanidine (131I-MIBG therapy combined with allogeneic cord blood stem cell transplantation (SCT was used to treat a 4-year-old girl with recurrent neuroblastoma. The patient experienced relapse 2 years after receiving first-line therapies, which included chemotherapy, surgical resection, irradiation, and autologous peripheral SCT. Although 131I-MIBG treatment did not achieve complete remission, the size of the tumor was reduced after treatment. Based on our findings, we suggest that 131I-MIBG treatment with myeloablative allogeneic SCT should be considered as first-line therapy for high-risk neuroblastoma patients when possible.

  3. The umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood.

    Science.gov (United States)

    Zeddou, Mustapha; Briquet, Alexandra; Relic, Biserka; Josse, Claire; Malaise, Michel G; Gothot, André; Lechanteur, Chantal; Beguin, Yves

    2010-07-01

    Many studies have drawn attention to the emerging role of MSC (mesenchymal stem cells) as a promising population supporting new clinical concepts in cellular therapy. However, the sources from which these cells can be isolated are still under discussion. Whereas BM (bone marrow) is presented as the main source of MSC, despite the invasive procedure related to this source, the possibility of isolating sufficient numbers of these cells from UCB (umbilical cord blood) remains controversial. Here, we present the results of experiments aimed at isolating MSC from UCB, BM and UCM (umbilical cord matrix) using different methods of isolation and various culture media that summarize the main procedures and criteria reported in the literature. Whereas isolation of MSC were successful from BM (10:10) and (UCM) (8:8), only one cord blood sample (1:15) gave rise to MSC using various culture media [DMEM (Dulbecco's modified Eagle's medium) +5% platelet lysate, DMEM+10% FBS (fetal bovine serum), DMEM+10% human UCB serum, MSCGM] and different isolation methods [plastic adherence of total MNC (mononuclear cells), CD3+/CD19+/CD14+/CD38+-depleted MNC and CD133+- or LNGFR+-enriched MNC]. MSC from UCM and BM were able to differentiate into adipocytes, osteocytes and hepatocytes. The expansion potential was highest for MSC from UCM. The two cell populations had CD90+/CD73+/CD105+ phenotype with the additional expression of SSEA4 and LNGFR for BM MSC. These results clearly exclude UCB from the list of MSC sources for clinical use and propose instead UCM as a rich, non-invasive and abundant source of MSC.

  4. Survival of cord blood haematopoietic stem cells in a hyaluronan hydrogel for ex vivo biomimicry.

    Science.gov (United States)

    Demange, Elise; Kassim, Yusra; Petit, Cyrille; Buquet, Catherine; Dulong, Virginie; Cerf, Didier Le; Buchonnet, Gérard; Vannier, Jean-Pierre

    2013-11-01

    Haematopoietic stem cells (HSCs) and haematopoietic progenitor cells (HPCs) grow in a specified niche in close association with the microenvironment, the so-called 'haematopoietic niche'. Scaffolds have been introduced to overcome the liquid culture limitations, mimicking the presence of the extracellular matrix (ECM). In the present study the hyaluronic acid scaffold, already developed in the laboratory, has been used for the first time to maintain long-term cultures of CD34⁺ haematopoietic cells obtained from human cord blood. One parameter investigated was the impact on ex vivo survival of CD34⁺ cord blood cells (CBCs) on the hyaluronic acid surface, immobilized with peptides containing the RGD motif. This peptide was conjugated by coating the hyaluronan hydrogel and cultured in serum-free liquid phase complemented with stem cell factor (SCF), a commonly indispensable cytokine for haematopoiesis. Our work demonstrated that these hyaluronan hydrogels were superior to traditional liquid cultures by maintaining and expanding the HPCs without the need for additional cytokines, and a colonization of 280-fold increment in the hydrogel compared with liquid culture after 28 days of ex vivo expansion. Copyright © 2012 John Wiley & Sons, Ltd.

  5. Impact of Umbilical Cord Blood-Derived Mesenchymal Stem Cells on Cardiovascular Research

    Directory of Open Access Journals (Sweden)

    Santiago Roura

    2015-01-01

    Full Text Available Over the years, cell therapy has become an exciting opportunity to treat human diseases. Early enthusiasm using adult stem cell sources has been tempered in light of preliminary benefits in patients. Considerable efforts have been dedicated, therefore, to explore alternative cells such as those extracted from umbilical cord blood (UCB. In line, UCB banking has become a popular possibility to preserve potentially life-saving cells that are usually discarded after birth, and the number of UCB banks has grown worldwide. Thus, a brief overview on the categories of UCB banks as well as the properties, challenges, and impact of UCB-derived mesenchymal stem cells (MSCs on the area of cardiovascular research is presented. Taken together, the experience recounted here shows that UCBMSCs are envisioned as attractive therapeutic candidates against human disorders arising and/or progressing with vascular deficit.

  6. Impact of Umbilical Cord Blood-Derived Mesenchymal Stem Cells on Cardiovascular Research

    Science.gov (United States)

    Roura, Santiago; Pujal, Josep Maria; Gálvez-Montón, Carolina; Bayes-Genis, Antoni

    2015-01-01

    Over the years, cell therapy has become an exciting opportunity to treat human diseases. Early enthusiasm using adult stem cell sources has been tempered in light of preliminary benefits in patients. Considerable efforts have been dedicated, therefore, to explore alternative cells such as those extracted from umbilical cord blood (UCB). In line, UCB banking has become a popular possibility to preserve potentially life-saving cells that are usually discarded after birth, and the number of UCB banks has grown worldwide. Thus, a brief overview on the categories of UCB banks as well as the properties, challenges, and impact of UCB-derived mesenchymal stem cells (MSCs) on the area of cardiovascular research is presented. Taken together, the experience recounted here shows that UCBMSCs are envisioned as attractive therapeutic candidates against human disorders arising and/or progressing with vascular deficit. PMID:25861654

  7. Generation of induced pluripotent stem cells with high efficiency from human umbilical cord blood mononuclear cells.

    Science.gov (United States)

    Wang, Juan; Gu, Qi; Hao, Jie; Bai, Donghui; Liu, Lei; Zhao, Xiaoyang; Liu, Zhonghua; Wang, Liu; Zhou, Qi

    2013-10-01

    Human induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine. Generating iPSCs from immunologically immature newborn umbilical cord blood mononuclear cells (UCBMCs) is of great significance. Here we report generation of human iPSCs with great efficiency from UCBMCs using a dox-inducible lentiviral system carrying four Yamanaka factors. We generated these cells by optimizing the existing iPSC induction protocol. The UCBMC-derived iPSCs (UCB-iPSCs) have characteristics that are identical to pluripotent human embryonic stem cells (hESCs). This study highlights the use of UCBMCs to generate highly functional human iPSCs that could accelerate the development of cell-based regenerative therapy for patients suffering from various diseases.

  8. Differentiation of human umbilical cord blood stem cells into hepatocytes in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    Xiao-Peng Tang; Min Zhang; Xu Yang; Li-Min Chen; Yang Zeng

    2006-01-01

    AIM: To study the condition and potentiality of human umbilical cord blood stem cells (HUCBSC) to differentiate into hepatocytes in vivo or in vitro.METHODS: In a cell culture study of human umbilical cord blood stem cell (HUCBSC) differentiation, human umbilical cord blood mononuclear cells (HUCBMNC) were separated by density gradient centrifugation.Fibroblast growth factor (FGF) and hepatocyte growth factor (HGF) and the supernatant of fetal liver were added in the inducing groups. Only FGF was added in the control group. The expansion and differentiation of HUCBMNC in each group were observed. Human alpha fetoprotein (AFP) and albumin (ALB) were detected by immunohistochemistry. In the animal experiments, the survival SD rats with acute hepatic injury after carbon tetrachloride (CCL4) injection 48 h were randomly divided into three groups. The rats in group A were treated with human umbilical cord blood serum. The rats in group B were treated with HUCBMNC transplantation. The rats in group C were treated with HUCBMNC transplantation followed by intraperitoneal cyclophosphamide for 7 d.The rats were killed at different time points after the treatment and the liver tissue was histopathologically studied and human AFP and ALB detected by immunohistochemistry. The human X inactive-specific transcript gene fragment in the liver tissue was amplified by PCR to find human DNA.RESULTS: The results of cell culture showed that adherent cells were stained negative for AFP or ALB in control group. However, the adherent cells in the inducing groups stained positive for AFP or ALB. The result of animal experiment showed that no human AFP or ALB positive cells present in the liver tissue of group A (control group). However, many human AFP or ALB positive cells were scattered around sinus hepaticus and the central veins of hepatic lobules and in the portal area in group B and group C after one month. The fragment of human X chromagene could be detected in the liver tissue of

  9. The in Vitro Assessment of Biochemical Factors in Hepatocyte like Cells Derived from Umbilical Cord Blood Stem Cells

    Directory of Open Access Journals (Sweden)

    A KHoramroodi

    2009-10-01

    Full Text Available Introduction & Objective: Umbilical cord blood (UCB is a source of Hematopoietic Stem Cells (HSC and progenitor cells that can reconstitute the hematopoietic system in patients with malignant and nonmalignant disorders. Mesenchymal stem cell-derived from umbilical cord blood (UCB have been differentiated to some kind of cells, such as osteobblast, adipoblast and chondroblast in Vitro. This study examined the differentiation of Umbilical Cord Blood (UCB derived stem cells to functional hepatocytes. Materials & Methods: The present study was an experimental study which was carried out in the Payam-e-Noor University of Tehran in cooperation with Hamedan University of Medical Sciences in 2008. Umbilical cord blood (UCB was obtained from Fatemieh hospital (Hamadan, Iran. Stem cells were isolated from the cord blood by combining density gradient centrifugation with plastic adherence. When the isolated cells reached 80% confluence, they differentiated to hepatocyte like cells. The medium which was used was consists of DMEM and 10% Fetal Bovine Serum (FBS supplemented with 20 ng/mL Hepatocyte Growth Factor (HGF, 10 ng/mL basic Fibroblast Growth Factor (bFGF and 20 ng/mL Oncostatin M (OSM.The medium was changed every 3 days and stored for Albumin (ALB, Alpha Fetoprotein (AFP, Alkaline Phosphatase (ALP, and urea assay. Finally PAS stain was done to study Glycogen storage in the differentiated cell. Results: Measurement of biochemical factors in different days showed that concentration of albumin (ALB, alpha fetoprotein (AFP, alkaline phosphatase (ALP, and Urea gradually increased. Also, PAS staining showed the storage of glycogen in these cells. Conclusion: Stem cell-derived from human umbilical cord blood (HUCB is a new source of cell types for cell transplantation therapy of hepatic diseases and under certain conditions these cells can differentiate into liver cells.

  10. Hepatitis B Virus Replication in CD34+ Hematopoietic Stem Cells From Umbilical Cord Blood.

    Science.gov (United States)

    Huang, Yanxin; Yan, Qin; Fan, Rongshan; Song, Shupeng; Ren, Hong; Li, Yongguo; Lan, Yinghua

    2016-05-18

    BACKGROUND Hepatitis B virus (HBV) is a hepatotropic virus that can infect extrahepatic tissue. Whether hematopoietic stem cells (HSCs) can be infected by HBV and serve as a potential virus reservoir is still unknown. In this study, the susceptibility of CD34+ HSCs to HBV was investigated. MATERIAL AND METHODS Cord blood-derived CD34+ HSCs were exposed to HBV in vitro, and immunocytochemistry, transmission electron microscopy, and RT-PCR were used to identify viral-related proteins and specific viral genomic sequences. Then, CD34+ HSCs were challenged by different titers of HBV, and intracellular and supernatant HBV DNA, and hepatitis B surface antigen (HBsAg) levels, were examined. In addition, CD34+ peripheral blood stem cells (PBSCs) from chronic HBV carriers were isolated and cultured, and HBV DNA levels were measured. RESULTS HBV-infected CD34+ cells showed positive signals for HBsAg by DAB staining and TRITC staining, and HBV particles were identified. RT-PCR results showed that the 403 bp PCR products corresponding to the amplified hepatitis B S gene fragment were observed in CD34+ HSCs infected by HBV. In addition, supernatant and intracellular HBV DNA increased with the proliferation of CD34+ HSCs. Similar results were obtained from intracellular HBsAg quantification tests. In addition, HBV DNA levels both in cells and in supernatants of CD34+ PBSCs increased proportionally, and the increments of HBV DNA in the supernatants paralleled those found in cells. CONCLUSIONS HBV can replicate in CD34+ HSCs in cord blood or peripheral blood of chronic HBV carriers.

  11. Cord blood testing

    Science.gov (United States)

    ... is born. The umbilical cord is the cord connecting the baby to the mother's womb. Cord blood ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  12. Are globoseries glycosphingolipids SSEA-3 and -4 markers for stem cells derived from human umbilical cord blood?

    Institute of Scientific and Technical Information of China (English)

    Heli Suila; Jari Natunen; Saara Laitinen; Leena Valmu; Virve Pitk(a)nen; Tia Hirvonen; Annamari Heiskanen; Heidi Anderson; Anita Laitinen; Suvi Natunen; Halina Miller-Podraza; Tero Satomaa

    2011-01-01

    Umbilical cord blood (UCB) is an efficient and valuable source of hematopoietic stem cells (HSCs) for transplantation. In addition to HSCs it harbours low amounts of mesenchymal stem cells (MSCs). No single marker to identify cord blood-derived stem cells, or to indicate their multipotent phenotype, has been characterized so far. SSEA-3 and -4 are cell surface globoseries glycosphingolipid epitopes that are commonly used as markers for human embryonic stem cells, where SSEA-3 rapidly disappears when the cells start to differentiate. Lately SSEA-3 and -4 have also been observed in MSCs. As there is an ongoing discussion and variation of stem-cell markers between laboratories, we have now comprehensively characterized the expression of these epitopes in both the multipotent stem-cell types derived from UCB. We have performed complementary analysis using gene expression analysis, mass spectrometry and immunochemical methods, including both flow cytometry and immunofluoresence microscopy. SSEA-4, but not SSEA-3, was expressed on MSCs but absent from HSCs. Our findings indicate that SSEA-3 and/or -4 may not be optimal markers for multipotency in the case of stem cells derived from cord blood, as their expression may be altered by cell-culture conditions.

  13. Cord blood stem cells: how to get them and what to do with them.

    Science.gov (United States)

    Dracker, R A

    1996-04-01

    This article reviews the means of obtaining cells from the available reservoirs of cord blood, intended as sources of immature hematopoietic stem cells that ultimately could be useful for transplantation, gene therapy, and research. Various issues must be considered when collecting umbilical cord blood regardless of the method employed. One must regard the basic fetal-placental physiology and hemodynamic characteristics prior to and at the time of procurement. Additional concerns exist with the mother, not only at the time of collection but also prenatally, including informed consent, health history, and psychosocial issues. Collection methods may be characterized as either ex utero or in utero, employing either open or closed collections methods. Each of these variables presents limitations and offers specific advantages over the others. Once collected, the cells must be appropriately tested, processed, and prepared for cryopreservation if not used immediately, using good manufacturing practices and acceptable standards of operation. An ideal collection method has yet to be defined that fulfills the need for reliability, reproducibility, and ease of use.

  14. Few single nucleotide variations in exomes of human cord blood induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Rui-Jun Su

    Full Text Available The effect of the cellular reprogramming process per se on mutation load remains unclear. To address this issue, we performed whole exome sequencing analysis of induced pluripotent stem cells (iPSCs reprogrammed from human cord blood (CB CD34(+ cells. Cells from a single donor and improved lentiviral vectors for high-efficiency (2-14% reprogramming were used to examine the effects of three different combinations of reprogramming factors: OCT4 and SOX2 (OS, OS and ZSCAN4 (OSZ, OS and MYC and KLF4 (OSMK. Five clones from each group were subject to whole exome sequencing analysis. We identified 14, 11, and 9 single nucleotide variations (SNVs, in exomes, including untranslated regions (UTR, in the five clones of OSMK, OS, and OSZ iPSC lines. Only 8, 7, and 4 of these, respectively, were protein-coding mutations. An average of 1.3 coding mutations per CB iPSC line is remarkably lower than previous studies using fibroblasts and low-efficiency reprogramming approaches. These data demonstrate that point nucleotide mutations during cord blood reprogramming are negligible and that the inclusion of genome stabilizers like ZSCAN4 during reprogramming may further decrease reprogramming-associated mutations. Our findings provide evidence that CB is a superior source of cells for iPSC banking.

  15. Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury:a biomechanical evaluation

    Institute of Scientific and Technical Information of China (English)

    Zhong-jun Zhang; Ya-jun Li; Xiao-guang Liu; Feng-xiao Huang; Tie-jun Liu; Dong-mei Jiang; Xue-man Lv; Min Luo

    2015-01-01

    Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood stem cells. After 30 days, the maximum load, max-imum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neu-rotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These ifndings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, im-prove biomechanical properties, and contribute to the recovery after injury.

  16. Feasibility of trialling cord blood stem cell treatments for cerebral palsy in Australia.

    Science.gov (United States)

    Crompton, Kylie E; Elwood, Ngaire; Kirkland, Mark; Clark, Pamela; Novak, Iona; Reddihough, Dinah

    2014-07-01

    Umbilical cord blood may have therapeutic benefit in children with cerebral palsy (CP), but further studies are required. On first appearance it seems that Australia is well placed for such a trial because we have excellence in CP research backed by extensive CP registers, and both public and private cord blood banks. We aimed to examine the possibilities of conducting a trial of autologous umbilical cord blood cells (UCBCs) as a treatment for children with CP in Australia. Data linkages between CP registers and cord blood banks were used to estimate potential participant numbers for a trial of autologous UCBCs for children with CP. As of early 2013, one Victorian child with CP had cord blood stored in the public bank, and between 1 and 3 children had their cord blood stored at Cell Care Australia (private cord blood bank). In New South Wales, we counted two children on the CP register who had their stored cord blood available in early 2013. We estimate that there are between 10 and 24 children with CP of any type who have autologous cord blood available across Australia. In nations with small populations like Australia, combined with Australia's relatively low per capita cord blood storage to date, it is not currently feasible to conduct trials of autologous UCBCs for children with CP. Other options must be explored, such as allogeneic UCBCs or prospective trials for neonates at risk of CP. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  17. [Perinatal brain damage--from neuroprotection to neuroregeneration using cord blood stem cells].

    Science.gov (United States)

    Jensen, Arne; Vaihinger, Hans-Martin; Meier, Carola

    2003-12-15

    Per year, approximately 1,000 children in Germany suffer from brain damage due to hypoxic-ischemic insults during the perinatal period. Based on the severity and localization of the insult, these children develop either spastic pareses, choreoathetosis, ataxia, or sensomotoric dysfunctions. A close cooperation between obstetricians, pediatricians, neuropediatricians, physical therapists, developmental psychologists, and other specialists is required, as the strain these disorders have on the children and their families is tremendous. The costs resulting per birthyear for the community are estimated on 1 million Euro. Clinical concepts to decrease the cerebral morbidity in perinatology departments have proven to be effective over the last decade. However, since brain damage cannot be prevented every time, it is essential that therapeutic measures, which have a neuroprotective effect after the insult, are being developed. Experimental pilots regarding these matters are promising. Current experiments are focused on the possible application of cord blood-derived stem cells for neuroregeneration.

  18. Good manufacturing practice-compliant isolation and culture of human umbilical cord blood-derived mesenchymal stem cells

    OpenAIRE

    Van Pham, Phuc; Vu, Ngoc Bich; Pham, Vuong Minh; Truong, Nhung Hai; Pham, Truc Le-Buu; Dang, Loan Thi-Tung; Nguyen, Tam Thanh; Bui, Anh Nguyen-Tu; Phan, Ngoc Kim

    2014-01-01

    Background Mesenchymal stem cells (MSCs) are an attractive source of stem cells for clinical applications. These cells exhibit a multilineage differentiation potential and strong capacity for immune modulation. Thus, MSCs are widely used in cell therapy, tissue engineering, and immunotherapy. Because of important advantages, umbilical cord blood-derived MSCs (UCB-MSCs) have attracted interest for some time. However, the applications of UCB-MSCs are limited by the small number of recoverable U...

  19. Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Di Gioacchino, Mario [Aging Research Center, ' G. d' Annunzio' University Foundation, Via Colle dell' Ara, 66100 Chieti (Italy); Medicine and Science of Ageing University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy)], E-mail: m.digioacchino@unich.it; Petrarca, Claudia; Perrone, Angela [Aging Research Center, ' G. d' Annunzio' University Foundation, Via Colle dell' Ara, 66100 Chieti (Italy); Medicine and Science of Ageing University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy); Farina, Massimo; Sabbioni, Enrico; Hartung, Thomas [Oncology and Neurosciences University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy); Martino, Simone [Department of Experimental Medicine, University La Sapienza, Viale Regina Elena 324, 00161 Rome (Italy); Esposito, Diana L. [Aging Research Center, ' G. d' Annunzio' University Foundation, Via Colle dell' Ara, 66100 Chieti (Italy); Oncology and Neurosciences University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy); Lotti, Lavinia Vittoria [Department of Experimental Medicine, University La Sapienza, Viale Regina Elena 324, 00161 Rome (Italy); Mariani-Costantini, Renato [Aging Research Center, ' G. d' Annunzio' University Foundation, Via Colle dell' Ara, 66100 Chieti (Italy); Oncology and Neurosciences University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy)

    2008-03-15

    Stem cells are a key target of environmental toxicants, but little is known about their toxicological responses. We aimed at developing an in-vitro model based on adult human stem cells to identify biomarkers of heavy metal exposure. To this end we investigated the responses of human CD34+ hematopoietic progenitor cells to hexavalent chromium (Cr[VI]) and cadmium (Cd). Parallel cultures of CD34+ cells isolated from umbilical cord blood were exposed for 48 h to 0.1 {mu}M and 10 {mu}M Cr(VI) or Cd. Cultures treated with 10 {mu}M Cr(VI) or Cd showed marked cell loss. Ultrastructural analysis of surviving cells revealed prominent autophagosomes/autophagolysosomes, which is diagnostic of autophagy, associated with mitochondrial damage and replication, dilatation of the rough endoplasmic reticulum and Golgi complex, cytoplasmic lipid droplets and chromatin condensation. Treated cells did not show the morphologic hallmarks of apoptosis. Treatment with 0.1 {mu}M Cr(VI) or Cd did not result in cell loss, but at the ultrastructural level cells showed dilated endoplasmic reticulum and evidence of mitochondrial damage. We conclude that autophagy is implicated in the response of human hematopoietic stem cells to toxic concentrations of Cr(VI) and Cd. Autophagy, which mediates cell survival and death under stress, deserves further evaluation to be established as biomarker of metal exposure.

  20. Intravitreal transplantation of human umbilical cord blood stem cells protects rats from traumatic optic neuropathy.

    Directory of Open Access Journals (Sweden)

    Bing Jiang

    Full Text Available OBJECTIVES: To treat traumatic optic neuropathy (TON with transplantation of human umbilical cord blood stem cells (hUCBSC and explore how transplanted stem cells participate in the neuron repairing process. METHODS: A total of 195 Sprague-Dawley rats were randomly assigned to three groups: sham-surgery, optic nerve injury, and stem cell transplant group. Optic nerve injury was established in rats by directly clamping the optic nerve for 30 seconds. hUCBSC was microinjected into the vitreous cavity of injured rats. Optic nerve function was evaluated by flash visual evoked potentials (F-VEP. Apoptosis in retina tissues was detected by TUNEL staining. GRP78 and CHOP gene expression was measured by RT-PCR. RESULTS: After injury, transplantation of hUCBSC significantly blunted a reduction in optic nerve function indicated by smaller decreases in amplitude and smaller increases in peak latency of F-VEP waveform compared to the injury alone group. Also, significant more in retinal ganglion cell (RGC count and less in RGC apoptosis were detected after transplantation compared to injured rats. The protective effect correlated with upregulated GRP78 and downregulated CHOP mRNA expression. CONCLUSION: Intravitreal transplantation of hUCBSCs significantly blunted a reduction in optic nerve function through increasing RGC survival and decreasing retinal cell apoptosis. The protective role of transplantation was associated with upregulation of GRP78 expression and downregulation of CHOP expression in retinal cells.

  1. Is there any reason to prefer cord blood instead of adult donors for hematopoietic stem cell transplants?

    Directory of Open Access Journals (Sweden)

    Meral eBeksac

    2016-01-01

    Full Text Available As cord blood (CB enables rapid access and tolerance to HLA mismatches, number of unrelated cord blood transplants have reached 30 000. Such transplant activity has been the result of international accreditation programs maintaining highly qualified CBUs reaching more than 600 000 CBUs stored worldwide. Efforts to increase stem cell content or engraftment rate of the graft by ex vivo expansion, modulation by molecules such as fucose, Prostaglandin E2 derivative, complement, CD26 inhibitors or CXCR4/CXCL12 axis have been able to accelerate engraftment speed and rate. Furthermore introduction of reduced intensity conditioning protocols, better HLA matching and recognition of the importance of HLA-C have improved CBT success by decreasing Transplant Related Mortality (TRM. Cord blood progenitor/stem cell content has been compared with adult stem cells revealing higher long-term repopulating capacity compared to BM-MSC and less oncogenic potential than Induced Progenitor Stem Cells. This chapter summarizes the advantage and disadvantages of CB compared to adult stem cells within the context of stem cell biology and transplantation.

  2. Effects of delayed umbilical cord clamping on peripheral blood hematopoietic stem cells in premature neonates.

    Science.gov (United States)

    Gokmen, Zeynel; Ozkiraz, Servet; Tarcan, Aylin; Kozanoglu, Ilknur; Ozcimen, Emel Ebru; Ozbek, Namik

    2011-05-01

    To investigate the effects of delayed cord clamping (DCC) on peripheral hematopoietic progenitor cells (HPCs) and hematological parameters in premature infants (cord clamping (ICC) at 5-10 s and 21 infants to DCC at 30-45 s. One milliliter blood sample was taken in the first 30 min of life. HPCs were measured by three-color flow cytometry using monoclonal antibodies. There were no significant differences between groups in either maternal or neonatal demographics. All HPC counts were higher in the ICC group, but the difference was not significant. CD34+ cell counts were 45.3 ± 36.6/μL in the ICC and 33.2 ± 26.6/μL in the DCC group (P=0.33); multi-potent progenitor cell counts were 43.2 ± 35/μL in the ICC and 31.1 ± 26.6/μL in the DCC group (P=0.28); and hematopoietic stem cell counts were 2.1 ± 2.1/μL in the ICC and 2.1 ± 3.1/μL in the DCC group (P=0.66). Contrary to our expectation, all HPC counts were lower in the DCC group.

  3. Assessment of Neuroprotective Properties of Melissa officinalis in Combination With Human Umbilical Cord Blood Stem Cells After Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Seyed Ruhollah Hosseini

    2016-10-01

    Full Text Available Introduction The pathophysiology of spinal cord injury (SCI has a classically bad prognosis. It has been demonstrated that human umbilical cord blood stem cells (hUCBSCs and Melissa officinalis (MO are useful for the prevention of neurological disease. Methods Thirty-six adult male rats were randomly divided into intact, sham, control (SCI, MO, hUCBSC, and MO-hUCBSC groups. Intraperitoneal injection of MO (150 mg/kg was commenced 24 hr post-SCI and continued once a day for 14 days. Intraspinal grafting of hUCBSCs was commenced immediately in the next day. The motor and sensory functions of all animals were evaluated once a week after the commencement of SCI. Electromyography (EMG was performed in the last day in order to measure the recruitment index. Immunohistochemistry, reverse transcription-polymerase chain reaction, and transmission electron microscopy evaluations were performed to determine the level of astrogliosis and myelination. Results The results revealed that motor function (MO-hUCBSC: 15 ± 0.3, SCI: 8.2 ± 0.37, p < .001, sensory function (MO-hUCBSC: 3.57 ± 0.19, SCI: 6.38 ± 0.23, p < .001, and EMG recruitment index (MO-hUCBSC: 3.71 ± 0.18, SCI: 1.6 ± 0.1, p < .001 were significantly improved in the MO-hUCBSC group compared with SCI group. Mean cavity area (MO-hUCBSC: 0.03 ± 0.03, SCI: 0.07 ± 0.004, p < .001 was reduced and loss of lower motor neurons (MO-hUCBSC: 7.6 ± 0.43, SCI: 3 ± 0.12, p < .001 and astrogliosis density (MO-hUCBSC: 3.1 ± 0.15, SCI: 6.25 ± 1.42, p < 0.001 in the ventral horn of spinal cord were prevented in MO-hUCBSC group compared with SCI group. Conclusion The results revealed that the combination of MO and hUCBSCs in comparison with the control group has neuroprotective effects in SCI.

  4. Assessment of Neuroprotective Properties of Melissa officinalis in Combination With Human Umbilical Cord Blood Stem Cells After Spinal Cord Injury.

    Science.gov (United States)

    Hosseini, Seyed Ruhollah; Kaka, Gholamreza; Joghataei, Mohammad Taghi; Hooshmandi, Mehdi; Sadraie, Seyed Homayoon; Yaghoobi, Kayvan; Mohammadi, Alireza

    2016-10-01

    The pathophysiology of spinal cord injury (SCI) has a classically bad prognosis. It has been demonstrated that human umbilical cord blood stem cells (hUCBSCs) and Melissa officinalis (MO) are useful for the prevention of neurological disease. Thirty-six adult male rats were randomly divided into intact, sham, control (SCI), MO, hUCBSC, and MO-hUCBSC groups. Intraperitoneal injection of MO (150 mg/kg) was commenced 24 hr post-SCI and continued once a day for 14 days. Intraspinal grafting of hUCBSCs was commenced immediately in the next day. The motor and sensory functions of all animals were evaluated once a week after the commencement of SCI. Electromyography (EMG) was performed in the last day in order to measure the recruitment index. Immunohistochemistry, reverse transcription-polymerase chain reaction, and transmission electron microscopy evaluations were performed to determine the level of astrogliosis and myelination. The results revealed that motor function (MO-hUCBSC: 15 ± 0.3, SCI: 8.2 ± 0.37, p < .001), sensory function (MO-hUCBSC: 3.57 ± 0.19, SCI: 6.38 ± 0.23, p < .001), and EMG recruitment index (MO-hUCBSC: 3.71 ± 0.18, SCI: 1.6 ± 0.1, p < .001) were significantly improved in the MO-hUCBSC group compared with SCI group. Mean cavity area (MO-hUCBSC: 0.03 ± 0.03, SCI: 0.07 ± 0.004, p < .001) was reduced and loss of lower motor neurons (MO-hUCBSC: 7.6 ± 0.43, SCI: 3 ± 0.12, p < .001) and astrogliosis density (MO-hUCBSC: 3.1 ± 0.15, SCI: 6.25 ± 1.42, p < 0.001) in the ventral horn of spinal cord were prevented in MO-hUCBSC group compared with SCI group. The results revealed that the combination of MO and hUCBSCs in comparison with the control group has neuroprotective effects in SCI. © The Author(s) 2016.

  5. Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation

    Institute of Scientific and Technical Information of China (English)

    Chang Dong LI; Wei Yuan ZHANG; He Lian LI; Xiao Xia JIANG; Yi ZHANG; Pei Hsien TANG; Ning MAO

    2005-01-01

    Human placenta-derived mononuclear cells (MNC) were isolated by a Percoll density gradient and cultured in mesenchymal stem cell (MSC) maintenance medium.The homogenous layer of adherent cells exhibited a typical fibroblastlike morphology,a large expansive potential,and cell cycle characteristics including a subset of quiescent cells.In vitro differentiation assays showed the tripotential differentiation capacity of these cells toward adipogenic,osteogenic and chondrogenic lineages.Flow cytometry analyses and immunocytochemistry stain showed that placental MSC was a homogeneous cell population devoid of hematopoietic cells,which uniformly expressed CD29,CD44,CD73,CD 105,CD166,laminin,fibronectin and vimentin while being negative for expression of CD31,CD34,CD45 and α-smooth muscle actin.Most importantly,immuno-phenotypic analyses demonstrated that these cells expressed class I major histocompatibility complex (MHC-Ⅰ),but they did not express MHC-Ⅱ molecules.Additionally these cells could suppress umbilical cord blood (UCB) lymphocytes proliferation induced by cellular or nonspecific mitogenic stimuli.This strongly implies that they may have potential application in allograft transplantation.Since placenta and UCB are homogeneous,the MSC derived from human placenta can be transplanted combined with hematopoietic stem cells (HSC) from UCB to reduce the potential graft-versus-host disease (GVHD) in recipients.

  6. Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Contribute to Chondrogenesis in Coculture with Chondrocytes

    Directory of Open Access Journals (Sweden)

    Xingfu Li

    2016-01-01

    Full Text Available Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs have been shown as the most potential stem cell source for articular cartilage repair. In this study, we aimed to develop a method for long-term coculture of human articular chondrocytes (hACs and hUCB-MSCs at low density in vitro to determine if the low density of hACs could enhance the hUCB-MSC chondrogenic differentiation as well as to determine the optimal ratio of the two cell types. Also, we compared the difference between direct coculture and indirect coculture at low density. Monolayer cultures of hUCB-MSCs and hACs were investigated at different ratios, at direct cell-cell contact groups for 21 days. Compared to direct coculture, hUCB-MSCs and hACs indirect contact culture significantly increased type II collagen (COL2 and decreased type I collagen (COL1 protein expression levels. SRY-box 9 (SOX9 mRNA levels and protein expression were highest in indirect coculture. Overall, these results indicate that low density direct coculture induces fibrocartilage. However, indirect coculture in conditioned chondrocyte cell culture medium can increase expression of chondrogenic markers and induce hUCB-MSCs differentiation into mature chondrocytes. This work demonstrates that it is possible to promote chondrogenesis of hUCB-MSCs in combination with hACs, further supporting the concept of novel coculture strategies for tissue engineering.

  7. Human umbilical cord blood-derived mesenchymal stem cells promote vascular growth in vivo.

    Directory of Open Access Journals (Sweden)

    Santiago Roura

    Full Text Available Stem cell therapies are promising strategies to regenerate human injured tissues, including ischemic myocardium. Here, we examined the acquisition of properties associated with vascular growth by human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs, and whether they promoted vascular growth in vivo. UCBMSCs were induced in endothelial cell-specific growth medium (EGM-2 acquiring new cell markers, increased Ac-LDL uptake, and migratory capacity as assessed by qRT-PCR, Western blotting, indirect immunofluorescence, and invasion assays. Angiogenic and vasculogenic potentials could be anticipated by in vitro experiments showing self organization into Matrigel-mediated cell networks, and activation of circulating angiogenic-supportive myeloid cells. In mice, following subcutaneous co-injection with Matrigel, UCBMSCs modified to co-express bioluminescent (luciferases and fluorescent proteins were demonstrated to participate in the formation of new microvasculature connected with the host circulatory system. Response of UCBMSCs to ischemia was explored in a mouse model of acute myocardial infarction (MI. UCBMSCs transplanted using a fibrin patch survived 4 weeks post-implantation and organized into CD31(+network structures above the infarcted myocardium. MI-treated animals showed a reduced infarct scar and a larger vessel-occupied area in comparison with MI-control animals. Taken together, the presented results show that UCBMSCs can be induced in vitro to acquire angiogenic and vasculogenic properties and contribute to vascular growth in vivo.

  8. The in vivo study of myeloprotection by GST-π gene transfected human cord blood hematopoietic stem cells transplantation

    Institute of Scientific and Technical Information of China (English)

    Yang Xingsheng; Yu Chenghao; Kong Yawei; Jiang Jie; Dong Ruiying; Cui Baoxia; Wang Lijie; Jiang Sen

    2003-01-01

    Objective:To investigate the influence of GST-π gene transfer into human cord blood hematopoietic stem cells on their drug resistance against anti-tumor drugs in vivo.Methods:GST-π gene transfection into human cord blood CD34+ cells was carried out using a retrovirus vector PLJ-GST-π with the aid of fibronectin.Successful gene transfer was confirmed by in vitro colony assay and RT-PCR.GST-π gene transduced human cord blood CD34+ cells were then engrafted into 4-week-old total body irradiated NOD/Scid mice and carboplatin was intraperitoneally administered sequentially at 4 weeks interval 4 weeks after engraftment.Results:Peripheral blood(PB) WBC was significantly higher in GST-π mice than control mice after 2 course of carboplatin.Retroviral GST-π expression in bone marrow hematopoietic progenitor cells of recipient mice was detected by RT-PCR 16 weeks after Xenotransplantation.Conclusion:The transfection of GST-π gene could confer,to some extent,resistance to cord blood stem cells against carboplatin in vivo.

  9. Production of good manufacturing practice-grade human umbilical cord blood-derived mesenchymal stem cells for therapeutic use.

    Science.gov (United States)

    Van Pham, Phuc; Phan, Ngoc Kim

    2015-01-01

    Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) are multipotent stem cells that can be differentiated into several specific cell types such as adipocytes, osteoblasts, and chondroblasts. They also were demonstrated to trans-differentiate into other cell lineages such as muscle cells and neurons. Thus, they are considered a promising stem cell source for therapeutic use. Here, we describe a method for production of good manufacturing practice-grade human UCB-MSCs for therapeutic use. The obtained UCB-MSCs are free of allogenous or xenogenous proteins. In addition, these MSCs could maintain the MSC phenotype in long-term culture.

  10. Intracellular Immunization of Human Fetal Cord Blood Stem/Progenitor Cells with a Ribozyme Against Human Immunodeficiency Virus Type 1

    Science.gov (United States)

    Yu, Mang; Leavitt, Mark C.; Maruyama, Midori; Yamada, Osamu; Young, Dennis; Ho, Anthony D.; Wong-Staal, Flossie

    1995-01-01

    Successful treatment of human immunodeficiency virus infection may ultimately require targeting of hematopoietic stem cells. Here we used retroviral vectors carrying the ribozyme gene to transduce CD34^+ cells from human fetal cord blood. Transduction and ribozyme expression had no apparent adverse effect on cell differentiation and/or proliferation. The macrophage-like cells, differentiated from the stem/progenitor cells in vitro, expressed the ribozyme gene and resisted infection by a macrophage tropic human immunodeficiency virus type 1. These results suggest the feasibility of stem cell gene therapy for human immunodeficiency virus-infected patients.

  11. Novel, high-yield red blood cell production methods from CD34-positive cells derived from human embryonic stem, yolk sac, fetal liver, cord blood, and peripheral blood.

    Science.gov (United States)

    Olivier, Emmanuel; Qiu, Caihong; Bouhassira, Eric E

    2012-08-01

    The current supply of red blood cells expressing rare blood groups is not sufficient to cover all the existing transfusion needs for chronically transfused patients, such as sickle cell disease homozygous carriers, because of alloimmunization. In vitro production of cultured red blood cells is slowly emerging as a possible complement to the existing collection-based red blood cell procurement system. The yield of cultured red blood cells can theoretically be maximized by amplifying the stem, progenitor, or precursor compartment. Here, we combined methods designed to expand these three compartments to optimize the yield of cultured red blood cells and found that exposing CD34(+) cells to a short pulse of cytokines favorable for erythroid differentiation prior to stem cell expansion followed by progenitor expansion produced the highest yield of erythroid cells. This novel serum-free red blood cell production protocol was efficient on CD34(+) cells derived from human embryonic stem cells, 6-8-week yolk sacs, 16-18-week fetal livers, cord blood, and peripheral blood. The yields of cells obtained with these new protocols were larger by an order of magnitude than the yields observed previously. Globin expression analysis by high-performance liquid chromatography revealed that these expansion protocols generally yielded red blood cells that expressed a globin profile similar to that expected for the developmental age of the CD34(+) cells.

  12. Umbilical cord blood transplantation.

    Science.gov (United States)

    Koo, Hong Hoe; Ahn, Hyo Seop

    2012-07-01

    Since the first umbilical cord blood transplantation (CBT) in 1998, cord blood (CB) has now become one of the most commonly used sources of hematopoietic stem cells for transplantation. CBT has advantages of easy procurement, no risk to donor, low risk of transmitting infections, immediate availability and immune tolerance allowing successful transplantation despite human leukocyte antigen disparity. Several studies have shown that the number of cells transplanted is the most important factor for engraftment in CBT, and it limits the wide use of CB in adult patients. New strategies for facilitating engraftment and reducing transplantation-related mortality are ongoing in the field of CBT and include the use of a reduced-intensity conditioning regimen, double-unit CBT, ex vivo expansion of CB, and co-transplantation of CB and mesenchymal stem cells. Recently, the results of two international studies with large sample sizes showed that CB is an acceptable alternative source of hematopoietic stem cells for adult recipients who lack human leukocyte antigen-matched adult donors. Along with the intensive researches, development in banking process of CB will amplify the use of CB and offer the chance for cure in more patients.

  13. Umbilical cord blood transplantation

    Directory of Open Access Journals (Sweden)

    Hong Hoe Koo

    2012-07-01

    Full Text Available Since the first umbilical cord blood transplantation (CBT in 1998, cord blood (CB has now become one of the most commonly used sources of hematopoietic stem cells for transplantation. CBT has advantages of easy procurement, no risk to donor, low risk of transmitting infections, immediate availability and immune tolerance allowing successful transplantation despite human leukocyte antigen disparity. Several studies have shown that the number of cells transplanted is the most important factor for engraftment in CBT, and it limits the wide use of CB in adult patients. New strategies for facilitating engraftment and reducing transplantation-related mortality are ongoing in the field of CBT and include the use of a reduced-intensity conditioning regimen, double-unit CBT, ex vivo expansion of CB, and co-transplantation of CB and mesenchymal stem cells. Recently, the results of two international studies with large sample sizes showed that CB is an acceptable alternative source of hematopoietic stem cells for adult recipients who lack human leukocyte antigen-matched adult donors. Along with the intensive researches, development in banking process of CB will amplify the use of CB and offer the chance for cure in more patients.

  14. Cell differentiation mediated by co-culture of human umbilical cord blood stem cells with murine hepatic cells.

    Science.gov (United States)

    Stecklum, Maria; Wulf-Goldenberg, Annika; Purfürst, Bettina; Siegert, Antje; Keil, Marlen; Eckert, Klaus; Fichtner, Iduna

    2015-02-01

    In the present study, purified human cord blood stem cells were co-cultivated with murine hepatic alpha mouse liver 12 (AML12) cells to compare the effect on endodermal stem cell differentiation by either direct cell-cell interaction or by soluble factors in conditioned hepatic cell medium. With that approach, we want to mimic in vitro the situation of preclinical transplantation experiments using human cells in mice. Cord blood stem cells, cultivated with hepatic conditioned medium, showed a low endodermal differentiation but an increased connexin 32 (Cx32) and Cx43, and cytokeratin 8 (CK8) and CK19 expression was monitored by reverse transcription polymerase chain reaction (RT-PCR). Microarray profiling indicated that in cultivated cord blood cells, 604 genes were upregulated 2-fold, with the highest expression for epithelial CK19 and epithelial cadherin (E-cadherin). On ultrastructural level, there were no major changes in the cellular morphology, except a higher presence of phago(ly)some-like structures observed. Direct co-culture of AML12 cells with cord blood cells led to less incisive differentiation with increased sex-determining region Y-box 17 (SOX17), Cx32 and Cx43, as well as epithelial CK8 and CK19 expressions. On ultrastructural level, tight cell contacts along the plasma membranes were revealed. FACS analysis in co-cultivated cells quantified dye exchange on low level, as also proved by time relapse video-imaging of labelled cells. Modulators of gap junction formation influenced dye transfer between the co-cultured cells, whereby retinoic acid increased and 3-heptanol reduced the dye transfer. The study indicated that the cell-co-cultured model of human umbilical cord blood cells and murine AML12 cells may be a suitable approach to study some aspects of endodermal/hepatic cell differentiation induction.

  15. Development of stem cells from umbilical cord blood and blood banking: "non-controversial" and "free of political and ethical debate"?

    Science.gov (United States)

    Skene, Loane

    2012-03-01

    Opponents of human embryo research have understandably welcomed pluripotent stem cells being derived from body cells including cells from umbilical cords after childbirth. The cord would otherwise be discarded and embryos are not destroyed. However, there are other ethical, legal and political issues in cord blood collection, whether for the child's future use, or a public blood bank. Information and consent procedures may be misleading. Some parents have false hopes about potential outcomes. The right of access to stored blood and other benefits is sometimes uncertain for children and their families. Private stem cell repositories may compete with public ones. People may want to impose conditions on donation. Quality control may be an issue.

  16. A Simple Method to Isolate and Expand Human Umbilical Cord Derived Mesenchymal Stem Cells: Using Explant Method and Umbilical Cord Blood Serum.

    Science.gov (United States)

    Hassan, Ghmkin; Kasem, Issam; Soukkarieh, Chadi; Aljamali, Majd

    2017-08-31

    Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from umbilical cords and are therapeutically used because of their ability to differentiate into various types of cells, in addition to their immunosuppressive and anti-inflammatory properties. Fetal bovine serum (FBS), considered as the standard additive when isolating and culturing MSCs, has a major limitation related to its animal origin. Here, we employed a simple and economically efficient protocol to isolate MSCs from human umbilical cord tissues without using digestive enzymes and replacing FBS with umbilical cord blood serum (CBS). MSCs were isolated by culturing umbilical cord pieces in CBS or FBS supplemented media. Expansion and proliferation kinetics of cells isolated by explant method in the presence of either FBS or CBS were measured, with morphology and multi-differentiation potential of expanded cells characterized by flow cytometry, RT-PCR, and immunofluorescence. MSCs maintained morphology, immunophenotyping, multi-differentiation potential, and self-renewal ability, with better proliferation rates for cells cultured in CBS compared to FBS supplement media. We here present a simple, reliable and efficient method to isolate MSCs from umbilical cord tissues, where cells maintained proliferation, differentiation potential and immunophenotyping properties and could be efficiently expanded for clinical applications.

  17. The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer's disease.

    Science.gov (United States)

    Lee, Hyun Ju; Lee, Jong Kil; Lee, Hyun; Shin, Ji-woong; Carter, Janet E; Sakamoto, Toshiro; Jin, Hee Kyung; Bae, Jae-sung

    2010-08-30

    The neuropathological hallmarks of Alzheimer's disease (AD) include the presence of extracellular amyloid-beta peptide (Abeta) in the form of amyloid plaques in the brain parenchyma and neuronal loss. The mechanism associated with neuronal death by amyloid plaques is unclear but oxidative stress and glial activation has been implicated. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) are being scrutinized as a potential therapeutic tool to prevent various neurodegenerative diseases including AD. However, the therapeutic impact of hUCB-MSCs in AD has not yet been reported. Here we undertook in vitro work to examine the potential impact of hUCB-MSCs treatment on neuronal loss using a paradigm of cultured hippocampal neurons treated with Abeta. We confirmed that hUCB-MSCs co-culture reduced the hippocampal apoptosis induced by Abeta treatment. Moreover, in an acute AD mouse model to directly test the efficacy of hUCB-MSCs treatment on AD-related cognitive and neuropathological outcomes, we demonstrated that markers of glial activation, oxidative stress and apoptosis levels were decreased in AD mouse brain. Interestingly, hUCB-MSCs treated AD mice demonstrated cognitive rescue with restoration of learning/memory function. These data suggest that hUCB-MSCs warrant further investigation as a potential therapeutic agent in AD.

  18. Comparison of the Effects of Different Cryoprotectants on Stem Cells from Umbilical Cord Blood

    Directory of Open Access Journals (Sweden)

    Gecai Chen

    2016-01-01

    Full Text Available Purpose. Cryoprotectants (CPA for stem cells from umbilical cord blood (UCB have been widely developed based on empirical evidence, but there is no consensus on a standard protocol of preservation of the UCB cells. Methods. In this study, UCB from 115 donors was collected. Each unit of UCB was divided into four equal parts and frozen in different kinds of cryoprotectant as follows: group A, 10% ethylene glycol and 2.0% dimethyl sulfoxide (DMSO (v/v; group B, 10% DMSO and 2.0% dextran-40; group C, 2.5% DMSO (v/v + 30 mmol/L trehalose; and group D, without CPA. Results. CD34+, cell viability, colony forming units (CFUs, and cell apoptosis of pre- and postcryopreservation using three cryoprotectants were analyzed. After thawing, significant differences in CD34+ count, CFUs, cell apoptosis, and cell viability were observed among the four groups (P<0.05.  Conclusion. The low concentration of DMSO with the addition of trehalose might improve the cryopreservation outcome.

  19. Hypoxic chondrogenic differentiation of human cord blood stem cells in structurally-graded polycaprolactone scaffolds

    DEFF Research Database (Denmark)

    Munir, Samir; Søballe, Kjeld; Ulrich-Vinther, Michael

    Background: Articular chondrocytes and bone marrow-derived multipotent mesenchymal stromal cells (MSCs) are the favoured cells for cartilage tissue engineering. Umbilical cord blood has proven an alternative source of MSCs and moreover they may be more potent chondroprogenitor cells than bonemarrow...... MSCs. Purpose / Aim of Study: Multilineage progenitor cells (MLPCs) are clonal cord blood-derived MSCs and may therefore provide a cell source with more reproducible outcomes compared to heterogeneous primary MSC cultures. Materials and Methods: We evaluated the chondrogenic potency of MLPCs...

  20. Umbilical Cord Blood Platelet Lysate as Serum Substitute in Expansion of Human Mesenchymal Stem Cells.

    Science.gov (United States)

    Shirzad, Negin; Bordbar, Sima; Goodarzi, Alireza; Mohammad, Monire; Khosravani, Pardis; Sayahpour, Froughazam; Baghaban Eslaminejad, Mohamadreza; Ebrahimi, Marzieh

    2017-10-01

    The diverse clinical applications for human mesenchymal stem cells (hMSCs) in cellular therapy and regenerative medicine warrant increased focus on developing adequate culture supplements devoid of animal-derived products. In the present study, we have investigated the feasibility of umbilical cord blood-platelet lysate (UCB-PL) as a standard substitute for fetal bovine serum (FBS) and human peripheral blood-PL (PB-PL). In this experimental study, platelet concentrates (PC) from UCB and human PB donors were frozen, melted, and sterilized to obtain PL. Quality control included platelet cell counts, sterility testing (viral and microbial), total protein concentrations, growth factor levels, and PL stability. The effects of UCB-PL and PB-PL on hMSCs proliferation and differentiation into osteocytes, chondrocytes, and adipocytes were studied and the results compared with FBS. UCB-PL contained high levels of protein content, platelet-derived growth factor- AB (PDGF-AB), and transforming growth factor (TGF) compared to PB-PL. All growth factors were stable for at least nine months post-storage at -70˚C. hMSCs proliferation enhanced following treatment with UCB-PL. With all three supplements, hMSCs could differentiate into all three lineages. PB-PL and UCB-PL both were potent in hMSCs proliferation. However, PB promoted osteoblastic differentiation and UCB-PL induced chondrogenic differentiation. Because of availability, ease of use and feasible standardization of UCB-PL, we have suggested that UCB-PL be used as an alternative to FBS and PB-PL for the cultivation and expansion of hMSCs in cellular therapy.

  1. Transcriptional activity of telomerase complex in CD34- stem cells of cord blood in dependence of preparation time.

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    M Bojdys-Szyndlar

    2009-12-01

    Full Text Available The aim of the study was to determine whether the expression of telomerase subunits encoding genes changes during the process of cord blood preparation. It should establish if the commonly accepted 24 hours time interval in stem cells kriopreservation procedure significantly influences their immortalization and so decreases the "quality" of cord blood stem cells. Investigation includes 69 women. Spontaneous labour was the inclusion condition. The material was collected at birth after clamping of umbilical cord by direct vasopuncture. CD34- cells were extracted from cord blood (MACS, Miltenyi Biotec; Bisley, Surrey, UK. The expression profile of telomerase activators and inhibitors encoding genes was determined using HG_U133A oligonucleotide microarray (Affymetrix. We used a real-time quantitative RT-PCR assay to quantify the telomerase TERT, hTR and TP1 subunits mRNA copy numbers in CD34- cells in 0, 6, 12 and 24 hours after cord blood collection. We observed significant decrease of numbers of copies of TERTA+B mRNA within the successive hours of observation. Significant decrease of numbers of TERTA mRNA copies was confirmed after 24 hours. However, we observed significant increase of numbers of copies of TERTB mRNA after 6 hours of observation. Similar level was maintained during another 6h. The significantly lower number of copies of TERTB mRNA was observed after 24h. We also observed significant increase of number of copies of TERT mRNA after 6 hours. Number of copies of TERT mRNA significantly decreased after another 6h, remaining, however, on a higher then initial one. The significant lower number of copies of TERT mRNA was observed 24h after delivery. The possible explanation of those results is discussed in the paper.

  2. Proteomic validation of multifunctional molecules in mesenchymal stem cells derived from human bone marrow, umbilical cord blood and peripheral blood.

    Directory of Open Access Journals (Sweden)

    Jumi Kim

    Full Text Available Mesenchymal stem cells (MSCs are one of the most attractive therapeutic resources in clinical application owing to their multipotent capability, which means that cells can differentiate into various mesenchymal tissues such as bone, cartilage, fat, tendon, muscle and marrow stroma. Depending on the cellular source, MSCs exhibit different application potentials according to their different in vivo functions, despite similar phenotypic and cytological characteristics. To understand the different molecular conditions that govern the different application or differentiation potential of each MSC according to cellular source, we generated a proteome reference map of MSCs obtained from bone marrow (BM, umbilical cord blood (CB and peripheral blood (PB. We identified approximately 30 differentially regulated (or expressed proteins. Most up-regulated proteins show a cytoskeletal and antioxidant or detoxification role according to their functional involvement. Additionally, these proteins are involved in the increase of cell viability, engraftment and migration in pathological conditions in vivo. In summary, we examined differentially expressed key regulatory factors of MSCs obtained from several cellular sources, demonstrated their differentially expressed proteome profiles and discussed their functional role in specific pathological conditions. With respect to the field of cell therapy, it may be particularly crucial to determine the most suitable cell sources according to target disease.

  3. Stem Cells in the Umbilical Cord

    Science.gov (United States)

    Weiss, Mark L.; Troyer, Deryl L.

    2012-01-01

    Stem cells are the next frontier in medicine. Stem cells are thought to have great therapeutic and biotechnological potential. This will not only to replace damaged or dysfunctional cells, but also rescue them and/or deliver therapeutic proteins after they have been engineered to do so. Currently, ethical and scientific issues surround both embryonic and fetal stem cells and hinder their widespread implementation. In contrast, stem cells recovered postnatally from the umbilical cord, including the umbilical cord blood cells, amnion/placenta, umbilical cord vein, or umbilical cord matrix cells, are a readily available and inexpensive source of cells that are capable of forming many different cell types (i.e., they are “multipotent”). This review will focus on the umbilical cord-derived stem cells and compare those cells with adult bone marrow-derived mesenchymal stem cells. PMID:17237554

  4. Combination of autologous bone marrow mesenchymal stem cells and cord blood mononuclear cells in the treatment of chronic thoracic spinal cord injury in 27 cases

    Directory of Open Access Journals (Sweden)

    Lian-zhong WANG

    2012-08-01

    Full Text Available Objective To investigate and evaluate therapeutic effects of transplantation of autologous bone marrow mesenchymal stem cells in conjunction with cord blood mononuclear cells for late thoracic spinal cord injury. Methods Data from 27 patients with late thoracic spinal cord injury who received transplantation of autologous bone marrow mesenchymal stem cells in conjunction with cord blood mononuclear cells in Neurosurgery Department of 463rd Hospital of PLA between July 2006 and July 2008 were collected and analyzed. The full treatment course consisted of 4 consecutive injections at one week apart. Indicators for evaluation followed that of the American Spiral Injury Association (ASIA Impairment Scale (AIS grade, ASIA motor and sensory scores, ASIA visual analog score, and the Ashworth score. The follow-up period was 6 months. Evaluations were made 6 weeks and 6 months after the treatment. Results Improvement from AIS A to AIS B was found in 4 patients. In one patient, improvement from AIS A to AIS C and in one patient from AIS B to AIS C was found 6 weeks after the treatment. The AIS improvement rate was 22.2%. In one patient improvement from AIS A to AIS B was found after 6 months. The overall AIS improvement rate was 25.9%. ASIA baseline motor scores of lower extremties were 0.5±1.5, 1.7±2.9, 3.1±3.6 before the treatment, 6 weeks and 6 months after the treatment, respectively, and showed a statistically significant improvement (P < 0.05. ASIA sensory scores including light touch and pinprick were 66.6±13.7 and 67.0±13.6 respectively before treatment, and they became 68.8±14.4, 68.4±14.7 and 70.5±14.4, 70.2±14.4 six weeks and six months after the treatment. The changes were statistically significant (P < 0.05; Modified Ashworth Scale scores were 1.8±1.5, 1.6±1.2,1.1±0.8 respectively at baseline, 6 weeks and 6months after the treatment, and showed a statistically significant descending trend (P < 0.05. Conclusion Transplantation of

  5. Collection, processing and testing of bone, corneas, umbilical cord blood and haematopoietic stem cells by European Blood Alliance members

    DEFF Research Database (Denmark)

    Närhi, M; Natri, O; Desbois, I;

    2013-01-01

    A questionnaire study was carried out in collaboration with the European Blood Alliance (EBA) Tissues and Cells (T&C) working group. The aim was to assess the level of involvement and commonality of processes on the procurement, testing and storage of bone, corneas, umbilical cord blood (UCB...

  6. Business on hope: a case study on private cord blood stem cell banking.

    Science.gov (United States)

    Kiatpongsan, Sorapop

    2008-04-01

    Traditionally, medical practice has been recognized as one of the professional practices with high honors. The interaction between physicians and patients is to provide health care services without the profit orientation. In modernized economy and in today's world of business, the relationship between doctors and patients has been dramatically changed. This transformation is very obvious in the private sector. Health care providers sell their services. Patients have been approached as customers. Decisions to make an investment on new medical technologies or new services would accompany with careful consideration on cost-benefit ratio, on marketing and also on short and long term return of the investment. However most of the medical services available in the past were focusing on the "real" and "tangible" products. This means that the patients or the customers would obtain diagnosis, treatment, palliation or prevention for the fees they paid. They can at least obtain and can feel some direct or indirect health benefits from the services. With the advancement of science and technology, there is recently a new model of business that sells only the hope for future use. Private cord blood stem cell banking is a good example for this business model. Actually, business on hope is not the brand new business model. Insurance is a well-known classical prototype of business on hope. However, when this kind of business model is applied for medical services, there should be some precautions and also intervention including an oversight system from the government sector to make sure that all the information delivered to the clients and family is accurate and unbiased. From the public policy perspective, this business of hope should be appropriately regulated to preserve consumer rights while promoting the advancement of science and technology through sustainable business development.

  7. Human Umbilical Cord Blood-Derived Neural Stem Cell Line as a Screening Model for Toxicity.

    Science.gov (United States)

    Patnaik, Rajashree; Padhy, Rabindra Nath

    2017-04-01

    The aim was to investigate whether a human neural stem cell (NSC) line derived from human umbilical cord blood (hUCB) can be used for toxicity study. Toxicity of both neurotoxic environmental xenobiotics, methyl mercury chloride (CH3HgCl), lead acetate (CH3COOPb), and chlorpyrifos (CP), and non-neurotoxic insecticide, dichlorvos, as well as non-neurotoxic drugs, theophylline and acetaminophen were assessed. Additionally, differentiation of neuronal and glial cell lines derived from hUCB was elucidated. It was observed that CH3HgCl was more toxic to human NSCs in comparison to CH3COOPb and CP. The minimum inhibitory concentration (MIC) value against NSCs was 3, 10, and 300 mg/L, in each staining process, acridine orange/ethidium bromide (AO/EB) staining, 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay, and Hoechst staining, for CH3HgCl, CP, and CH3COOPb, respectively. CH3HgCl had the LC25 value as 10.0, 14.4, and 12.7 mg/L, by staining method mentioned in succession. CP had the LC25 value as 21.9, 23.7, and 18.4 mg/L; similarly, CH3COOPb had LC25 values, successively as 616.9, 719.2, and 890.3 mg/L. LC50 values ranged from 18.2 to 21.7 mg/L for CH3HgCl, 56.4 to 60.2 mg/L for CP, and 1000 to 1460.1 for CH3COOPb. Theophylline, acetaminophen, and dichlorvos had no impact on the viability of NSCs. This work justified that hUCB-NSC model can be used for toxicity study.

  8. Xeno-free culture condition for human bone marrow and umbilical cord matrix-derived mesenchymal stem/stromal cells using human umbilical cord blood serum

    Science.gov (United States)

    Esmaeli, Azadeh; Moshrefi, Mojgan; Shamsara, Ali; Eftekhar-vaghefi, Seyed Hasan; Nematollahi-mahani, Seyed Noureddin

    2016-01-01

    Background: Fetal bovine serum (FBS) is widely used in cell culture laboratories, risk of zoonotic infections and allergic side effects create obstacles for its use in clinical trials. Therefore, an alternative supplement with proper inherent growth-promoting activities is demanded. Objective: To find FBS substitute, we tested human umbilical cord blood serum (hUCS) for proliferation of human umbilical cord matrix derived mesenchymal stem cells (hUC-MSCs) and human bone marrow-derived mesenchymal cells (hBM-MSCs). Materials and Methods: Umbilical cord blood of healthy neonates, delivered by Caesarian section, was collected and the serum was separated. hUC-MSCs and hBM-MSCs were isolated and characterized by assessment of cell surface antigens by flow cytometry, alkaline phosphatase activity and osteogenic/adipogenic differentiation potential. The cells were then cultured in Iscove's Modified Dulbecco's Medium (IMDM) by conventional methods in three preparations: 1- with hUCS, 2- with FBS, and 3- without serum supplements. Cell proliferation was measured using WST-1 assay, and cell viability was assessed by trypan blue staining. Results: The cells cultured in hUCS and FBS exhibited similar morphology and mesenchymal stem cells properties. WST-1 proliferation assay data showed no significant difference between the proliferation rate of either cells following hUCS and FBS supplementation. Trypan blue exclusion dye test also revealed no significant difference for viability between hUCS and FBS groups. A significant difference was detected between the proliferation rate of stem cells cultured in serum-supplemented medium compared with serum-free medium. Conclusion: Our results indicate that human umbilical cord serum can effectively support proliferation of hBM-MSCS and hUC-MSCs in vitro and can be used as an appropriate substitute for FBS, especially in clinical studies. PMID:27738658

  9. Factors inducing human umbilical cord blood-derived mesenchymal stem cells to differentiate into neuron-like cells

    Institute of Scientific and Technical Information of China (English)

    Nawei Zhang; Fengqing Ji

    2006-01-01

    OBJECTIVE:Human umbilical cord blood-derived mesenchymal stem cells (HUCB-derived MSCs)can differentiate into neuron-like cells,which can be used to treat some central nervous system(CNS)diseases.To investigate the factors,which can induce HUCB-derived MSCs to differentiate into neuron-like cells,so as to find effective methods for future clinical application.DATA SOURCES:Using the key terms"human umbilical cord blood"combined with"mesenchymal stem cells,neuron-like cells,neural cells"respectively,the relevant articles in English published during the period from January 1999 to June 2006 were searched from the Medline database.Meanwhile,relevant Chinese articles published from January 1999 to June 2006 were searched Using the same key terms.STUDY SELECTION: All articles associated with the differentiation from human umbilical cord blood into neuron-like cells were selected firstly.Then the full texts were looked up by searchling Ovid medical Journals full-text database and Elsevier Electrical Journals Full-text Database.Articles with full expeiments,enrolled in inducible factors or involved inducible mechanism were retdeved.DATA EXTRACTION:Among 119 collected correlative articles,29 were involved and 90 were excluded.DATA SYNTHESIS:The inducible factors of HUCB-derived MSCs differentiatling into neuron-like cells included renal endothelial growth factors,fibroblasts,β-mercaptoethanol,dimethyl sulfoxide,butyl hydroxyl anisol,brain-derived neurotrophic factor,Danshen,retinoic acid,sodium ferulate and so on,but its mechanism was unclear.CONCLUSION:Human umbilical cord blood-derived MSCs can differentiate into neuron-like cells,with varied inductors.

  10. Establishing a public umbilical cord blood stem cell bank for South Africa: an enquiry into public acceptability.

    Science.gov (United States)

    Meissner-Roloff, Madelein; Pepper, Michael S

    2013-12-01

    South Africa (SA) faces a large unmet need for bone marrow (BM) transplantation, which could be alleviated in part by establishing a public umbilical cord blood stem cell bank (UCB SCB). Umbilical cord blood is an increasingly utilised source of hematopoietic stem cells for BM transplantation in addition to BM or mobilized peripheral blood stem cells. Establishing a public UCB SCB would therefore be a positive step towards improving the quality of health care in SA by providing for an important unmet need. This study takes the form of an enquiry into the acceptability of establishing a public bank through an interview with and questionnaire completed by mothers-to-be in the antenatal clinic of a large public hospital in SA. Initial results are positive, with 85 % of the participants in favour of establishing a public UCB SCB in SA. This initial probe will serve as a model for a more comprehensive national enquiry into public support and acceptability in different clinics, hospitals and provinces in SA.

  11. Distribution of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in canines after intracerebroventricular injection.

    Science.gov (United States)

    Park, Sang Eon; Jung, Na-Yeon; Lee, Na Kyung; Lee, Jeongmin; Hyung, Brian; Myeong, Su Hyeon; Kim, Hyeong Seop; Suh, Yeon-Lim; Lee, Jung-Il; Cho, Kyung Rae; Kim, Do Hyung; Choi, Soo Jin; Chang, Jong Wook; Na, Duk L

    2016-11-01

    In this study, we investigated the distribution of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) administered via intracerebroventricular (ICV) injection in a canine model. Ten beagles (11-13 kg per beagle) each received an injection of 1 × 10(6) cells into the right lateral ventricle and were sacrificed 7 days after administration. Based on immunohistochemical analysis, hUCB-MSCs were observed in the brain parenchyma, especially along the lateral ventricular walls. Detected as far as 3.5 mm from the cortical surface, these cells migrated from the lateral ventricle toward the cortex. We also observed hUCB-MSCs in the hippocampus and the cervical spinal cord. According to real-time polymerase chain reaction results, most of the hUCB-MSCs were found distributed in the brain and the cervical spinal cord but not in the lungs, heart, kidneys, spleen, and liver. ICV administered hUCB-MSCs also enhanced the endogenous neural stem cell population in the subventricular zone. These results highlighted the ICV delivery route as an optimal route to be performed in stem cell-based clinical therapies for neurodegenerative diseases.

  12. Mid-trimester fetal blood-derived adherent cells share characteristics similar to mesenchymal stem cells but full-term umbilical cord blood does not

    Institute of Scientific and Technical Information of China (English)

    MinjunYu; ZhifengXiao; LiShen; LingsongLi

    2005-01-01

    Stem cell transplantation is a promising treatment for many conditions.Although stem cells can be isolated from many tissues, blood is the ideal source of these cells due to the ease of collection. Mesenchymal stem cells (MSCs) have been paid increased attention because of their powerful proliferation and pluripotent differentiating ability. But whether MSCs reside in blood (newborn umbilical cord blood and fetal or adult peripheral blood) is also debatable. The present study showed that MSC-like cells could be isolated and expanded from 16-26 weeks fetal blood but were not acquired efficiently from full-term infants' umbilical cord blood (UCB). Adherent cells separated from postnatal UCB were heterogeneous in cell morphology. Their proliferation capacity was limited and they were mainly CD45+, which indicated their haematopoietic derivation. On the contrary, MSC-like cells shared a similar phenotype to bone marrow MSCs. They were CD34- CD45- CD44+ CD71+ CD90+ CD105+. They could be induced to differentiate into osteogenic, adipogenic and neural lineage cells. Single cell clones also showed similar phenotype and differentiation ability. Our results suggest that early fetal blood is rich in MSCs but term UCB is not.

  13. Hypoxic chondrogenic differentiation of human cord blood stem cells in structurally-graded polycaprolactone scaffolds

    DEFF Research Database (Denmark)

    Munir, Samir; Søballe, Kjeld; Ulrich-Vinther, Michael;

    Background: Articular chondrocytes and bone marrow-derived multipotent mesenchymal stromal cells (MSCs) are the favoured cells for cartilage tissue engineering. Umbilical cord blood has proven an alternative source of MSCs and moreover they may be more potent chondroprogenitor cells than bonemarrow...... MSCs. Purpose / Aim of Study: Multilineage progenitor cells (MLPCs) are clonal cord blood-derived MSCs and may therefore provide a cell source with more reproducible outcomes compared to heterogeneous primary MSC cultures. Materials and Methods: We evaluated the chondrogenic potency of MLPCs...... in standard micromass pellet system, layered on calcium polyphosphate (CPP), and on semi-permeable polytetrafluoroethane membranes with and without collagen type I, II or IV pre-coating. Findings / Results: The MPLC cell line used in this study possessed poor chondrogenic potency overall, but membrane...

  14. Generation of induced pluripotent stem cells from human cord blood cells with only two factors: Oct4 and Sox2.

    Science.gov (United States)

    Giorgetti, Alessandra; Montserrat, Nuria; Rodriguez-Piza, Ignacio; Azqueta, Carmen; Veiga, Anna; Izpisúa Belmonte, Juan Carlos

    2010-04-01

    Induced pluripotent stem cells (iPSC) provide an invaluable resource for regenerative medicine as they allow the generation of patient-specific progenitors with potential value for cell therapy. However, in many instances, an off-the-shelf approach is desirable, such as for cell therapy of acute conditions or when the patient's somatic cells are altered as a consequence of a chronic disease or aging. Cord blood (CB) stem cells appear ideally suited for this purpose as they are young cells expected to carry minimal somatic mutations and possess the immunological immaturity of newborn cells; additionally, several hundred thousand immunotyped CB units are readily available through a worldwide network of CB banks. Here we present a detailed protocol for the derivation of CB stem cells and how they can be reprogrammed to pluripotency by retroviral transduction with only two factors (OCT4 and SOX2) in 2 weeks and without the need for additional chemical compounds.

  15. A Novel Molecular and Functional Stemness Signature Assessing Human Cord Blood-Derived Endothelial Progenitor Cell Immaturity.

    Directory of Open Access Journals (Sweden)

    Oriane Guillevic

    Full Text Available Endothelial Colony Forming Cells (ECFCs, a distinct population of Endothelial Progenitor Cells (EPCs progeny, display phenotypic and functional characteristics of endothelial cells while retaining features of stem/progenitor cells. Cord blood-derived ECFCs (CB-ECFCs have a high clonogenic and proliferative potentials and they can acquire different endothelial phenotypes, this requiring some plasticity. These properties provide angiogenic and vascular repair capabilities to CB-ECFCs for ischemic cell therapies. However, the degree of immaturity retained by EPCs is still confused and poorly defined. Consequently, to better characterize CB-ECFC stemness, we quantified their clonogenic potential and demonstrated that they were reprogrammed into induced pluripotent stem cells (iPSCs more efficiently and rapidly than adult endothelial cells. Moreover, we analyzed the transcriptional profile of a broad gene panel known to be related to stem cells. We showed that, unlike mature endothelial cells, CB-ECFCs expressed genes involved in the maintenance of embryonic stem cell properties such as DNMT3B, GDF3 or SOX2. Thus, these results provide further evidence and tools to appreciate EPC-derived cell stemness. Moreover this novel stem cell transcriptional signature of ECFCs could help better characterizing and ranging EPCs according to their immaturity profile.

  16. Cord Blood-Derived Hematopoietic Stem/Progenitor Cells: Current Challenges in Engraftment, Infection, and Ex Vivo Expansion

    Directory of Open Access Journals (Sweden)

    Katsuhiro Kita

    2011-01-01

    Full Text Available Umbilical cord blood has served as an alternative to bone marrow for hematopoietic transplantation since the late 1980s. Numerous clinical studies have proven the efficacy of umbilical cord blood. Moreover, the possible immaturity of cells in umbilical cord blood gives more options to recipients with HLA mismatch and allows for the use of umbilical cord blood from unrelated donors. However, morbidity and mortality rates associated with hematopoietic malignancies still remain relatively high, even after cord blood transplantation. Infections and relapse are the major causes of death after cord blood transplantation in patients with hematopoietic diseases. Recently, new strategies have been introduced to improve these major problems. Establishing better protocols for simple isolation of primitive cells and ex vivo expansion will also be very important. In this short review, we discuss several recent promising findings related to the technical improvement of cord blood transplantation.

  17. Frozen cord blood hematopoietic stem cells differentiate into higher numbers of functional natural killer cells in vitro than mobilized hematopoietic stem cells or freshly isolated cord blood hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Martha Luevano

    Full Text Available Adoptive natural killer (NK cell therapy relies on the acquisition of large numbers of NK cells that are cytotoxic but not exhausted. NK cell differentiation from hematopoietic stem cells (HSC has become an alluring option for NK cell therapy, with umbilical cord blood (UCB and mobilized peripheral blood (PBCD34(+ being the most accessible HSC sources as collection procedures are less invasive. In this study we compared the capacity of frozen or freshly isolated UCB hematopoietic stem cells (CBCD34(+ and frozen PBCD34(+ to generate NK cells in vitro. By modifying a previously published protocol, we showed that frozen CBCD34(+ cultures generated higher NK cell numbers without loss of function compared to fresh CBCD34(+ cultures. NK cells generated from CBCD34(+ and PBCD34(+ expressed low levels of killer-cell immunoglobulin-like receptors but high levels of activating receptors and of the myeloid marker CD33. However, blocking studies showed that CD33 expression did not impact on the functions of the generated cells. CBCD34(+-NK cells exhibited increased capacity to secrete IFN-γ and kill K562 in vitro and in vivo as compared to PBCD34(+-NK cells. Moreover, K562 killing by the generated NK cells could be further enhanced by IL-12 stimulation. Our data indicate that the use of frozen CBCD34(+ for the production of NK cells in vitro results in higher cell numbers than PBCD34(+, without jeopardizing their functionality, rendering them suitable for NK cell immunotherapy. The results presented here provide an optimal strategy to generate NK cells in vitro for immunotherapy that exhibit enhanced effector function when compared to alternate sources of HSC.

  18. Frozen cord blood hematopoietic stem cells differentiate into higher numbers of functional natural killer cells in vitro than mobilized hematopoietic stem cells or freshly isolated cord blood hematopoietic stem cells.

    Science.gov (United States)

    Luevano, Martha; Domogala, Anna; Blundell, Michael; Jackson, Nicola; Pedroza-Pacheco, Isabela; Derniame, Sophie; Escobedo-Cousin, Michelle; Querol, Sergio; Thrasher, Adrian; Madrigal, Alejandro; Saudemont, Aurore

    2014-01-01

    Adoptive natural killer (NK) cell therapy relies on the acquisition of large numbers of NK cells that are cytotoxic but not exhausted. NK cell differentiation from hematopoietic stem cells (HSC) has become an alluring option for NK cell therapy, with umbilical cord blood (UCB) and mobilized peripheral blood (PBCD34(+)) being the most accessible HSC sources as collection procedures are less invasive. In this study we compared the capacity of frozen or freshly isolated UCB hematopoietic stem cells (CBCD34(+)) and frozen PBCD34(+) to generate NK cells in vitro. By modifying a previously published protocol, we showed that frozen CBCD34(+) cultures generated higher NK cell numbers without loss of function compared to fresh CBCD34(+) cultures. NK cells generated from CBCD34(+) and PBCD34(+) expressed low levels of killer-cell immunoglobulin-like receptors but high levels of activating receptors and of the myeloid marker CD33. However, blocking studies showed that CD33 expression did not impact on the functions of the generated cells. CBCD34(+)-NK cells exhibited increased capacity to secrete IFN-γ and kill K562 in vitro and in vivo as compared to PBCD34(+)-NK cells. Moreover, K562 killing by the generated NK cells could be further enhanced by IL-12 stimulation. Our data indicate that the use of frozen CBCD34(+) for the production of NK cells in vitro results in higher cell numbers than PBCD34(+), without jeopardizing their functionality, rendering them suitable for NK cell immunotherapy. The results presented here provide an optimal strategy to generate NK cells in vitro for immunotherapy that exhibit enhanced effector function when compared to alternate sources of HSC.

  19. Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure.

    Science.gov (United States)

    Sun, Bo; Roh, Kyung-Hwan; Lee, Sae-Rom; Lee, Yong-Soon; Kang, Kyung-Sun

    2007-03-23

    Success in islet-transplantation-based therapies for type I diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Embryonic stem cells (ESCs) have been successfully induced into insulin producing islet-like structure in several studies. However, the source of the ESCs has presented ethical and technical concerns. Here, we isolated a population of stem cells from human cord blood (UCB), which expressed embryo stage specific maker, SSEA-4, and the multi-potential stem cell marker, Oct4. Subsequently, we successfully induced them into insulin-producing islet-like structures, which co-express insulin and C-peptide. These findings might have a significant potential to advance human UCB derived stem-cell-based therapeutics for diabetes.

  20. Ex-Vivo Gene Therapy Using Lentiviral Mediated Gene Transfer Into Umbilical Cord Blood Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Hanieh Jalali

    2016-02-01

    Full Text Available Background Introduction of therapeutic genes into the injured site of nervous system can be achieved using transplantation of cellular vehicles containing desired gene. To transfer exogenous genes into the cellular vehicles, lentiviral vectors are one of interested vectors because of advantages such high transduction efficiency of dividing and non-dividing cells. Unrestricted somatic stem cells are subclasses of umbilical cord blood derived stem cells which are appreciate candidates to use as cellular vehicles for ex vivo gene therapy of nervous system. Objectives In current study we investigated the effect of lentiviral vector transduction on the neuronal related features of unrestricted somatic stem cells to indicate the probable and unwanted changes related to transduction procedure. Materials and Methods In this experimental study, lentiviral vector containing green fluorescent protein (GFP were transduced into unrestricted somatic stem cells and its effect was investigated with using MTT assay, qPCR and immunohistochemistry techniques. For statistical comparison of real time PCR results, REST software (2009, Qiagen was used. Results Obtained results showed lentiviral vector transduction did not have cytotoxic effects on unrestricted somatic stem cells and did not change neuronal differentiation capacity of them as well the expression of some neuronal related genes and preserved them in multilineage situation. Conclusions In conclusion, we suggested that lentiviral vectors could be proper vectors to transfer therapeutic gene into unrestricted somatic stem cells to provide a cellular vehicle for ex vivo gene therapy of nervous system disorders.

  1. Pathogens in Maternal Blood and Fetal Cord Blood Using Q-Pcr Assay

    Directory of Open Access Journals (Sweden)

    Guang Qiong Hou

    2006-06-01

    Conclusion: Our results revealed an unexpectedly high incidence of pathogens in fetal cord blood. Screening for the above pathogens in donor cord blood in cord blood banks using Q-PCR is strongly urged to decrease morbidity and mortality rates in fetal cord blood stem cell transplant recipients.

  2. Vein transplantion using human umbilical cord blood stem cells in the treatment of stroke sequela

    Institute of Scientific and Technical Information of China (English)

    Yong Man; Jianbin Li; Bo Yang; Ji Ma

    2006-01-01

    BACKGROUND: Transplanted mononuclear cell(MNC)of umbilical blood can survive in central nervous system (CNS)of host through blood brain barrier,differentiate into nerver cells,migrate to damaged site and integrate morphological strucgh and function with nerve cells of host so as to improve deficiencies of sensatory function,motor function and cognitive function and influence on stroke sequela.OBJECTIVE: To observe the vein transplantation of human umbilical cord blood stem cells(HUCBSC) for improving neurological function,limb funtion and activity of daily living of patients with stroke and evaluate the reliability.DESIGN: Self-controlled study.SETTING: Department of Neurosurgery,the Second People's Hospital of Zhengzhou City;Red-crossed Blood Center of Henan Province;Department of Neurosurgery,the Fist Affiliated Hospital of Zhenzhou University.PARTICIPANTS:A total of 10 patients with stoke sequela were selected from Department of Cerebral Surgery,the Second People's Hospital of Zhengzhou City from April to December 2005.There were 9males and 1 female aged from 35to 75years with the mean age of 56 years.All of them were diagnosed with CT and MRI examination and coincidence with diagnostic criteria of stroke established by the Fourth National Academic Meeting for Cerebrovascular Disease.All patients provided informed consent. METHODS:80-140 mL umbilical blood of term birth of newborn was selected hermetically and maintained in sterile plastic bag.And then,the blood was centrifugated at the speed of 1500 r/min for 30 minutes at 22℃ in order to separate MNC,i.e.,HUCBSC.In addition,after final diagnosis during hospitalization,stroke patients were perfused with HUCBSC through superficial vein of back of the hand.Each patient was averagely penfused with 6 portions of HUCBSC(cellular numbers≥1×108/portion)and the interval between each portion was 1-7 days with the mean interval of 4 days.MAIN OUTCOME MEASURES: ①Neurological function of stroke patients was

  3. ACOG Committee Opinion No. 648: Umbilical Cord Blood Banking.

    Science.gov (United States)

    2015-12-01

    Once considered a waste product that was discarded with the placenta, umbilical cord blood is now known to contain potentially life-saving hematopoietic stem cells. When used in hematopoietic stem cell transplantation, umbilical cord blood offers several distinct advantages over bone marrow or peripheral stem cells. However, umbilical cord blood collection is not part of routine obstetric care and is not medically indicated. Umbilical cord blood collection should not compromise obstetric or neonatal care or alter routine practice for the timing of umbilical cord clamping. If a patient requests information on umbilical cord blood banking, balanced and accurate information regarding the advantages and disadvantages of public and private umbilical cord blood banking should be provided. The routine storage of umbilical cord blood as "biologic insurance" against future disease is not recommended.

  4. Committee Opinion No. 648 Summary: Umbilical Cord Blood Banking.

    Science.gov (United States)

    2015-12-01

    Once considered a waste product that was discarded with the placenta, umbilical cord blood is now known to contain potentially life-saving hematopoietic stem cells. When used in hematopoietic stem cell transplantation, umbilical cord blood offers several distinct advantages over bone marrow or peripheral stem cells. However, umbilical cord blood collection is not part of routine obstetric care and is not medically indicated. Umbilical cord blood collection should not compromise obstetric or neonatal care or alter routine practice for the timing of umbilical cord clamping. If a patient requests information on umbilical cord blood banking, balanced and accurate information regarding the advantages and disadvantages of public and private umbilical cord blood banking should be provided. The routine storage of umbilical cord blood as "biologic insurance" against future disease is not recommended.

  5. MicroRNAs as markers for neurally committed CD133+/CD34+ stem cells derived from human umbilical cord blood.

    Science.gov (United States)

    Hafizi, Maryam; Atashi, Amir; Bakhshandeh, Behnaz; Kabiri, Mahboubeh; Nadri, Samad; Hosseini, Reza Haji; Soleimani, Masoud

    2013-04-01

    Neural differentiation of the CD133+/CD34+ subpopulation of human umbilical cord blood stem cells was investigated, and neuro-miR (mir-9 and mir-124) expression was examined. An efficient induction protocol for neural differentiation of hematopoietic stem cells together with the exclusion of retinoic acid in this process was also studied. Transcription of some neural markers such as microtubule-associated protein-2, beta-tubulin III, and neuron-specific enolase was evaluated by real-time PCR, immunocytochemistry, and western blotting. Increased expression of neural indicators in the treated cells confirmed the appropriate neural differentiation, which supported the high efficiency of our defined neuronal induction protocol. Verified high expression of neuro-miRNAs along with neuronal specific proteins not only strengthens the regulatory role of miRNAs in determining stem cell fate but also introduces these miRNAs as novel indicators of neural differentiation. These data highlight the prominent therapeutic potential of hematopoietic stem cells for use in cell therapy of neurodegenerative diseases.

  6. Induction of differentiation by down-regulation of Nanog and Rex-1 in cord blood derived unrestricted somatic stem cells.

    Science.gov (United States)

    Langroudi, Lida; Forouzandeh, Mehdi; Soleimani, Masoud; Atashi, Amir; Golestaneh, Azadeh Fahim

    2013-07-01

    Stem cells with high self-renewal and tissue regeneration potentials are the core components of regenerative medicine. Adult stem cells with many available sources, high repairing ability, and also possessing no ethical issues are popular candidates in the clinical field. In this study we looked upon the effects of two transcription factors Nanog and Rex-1 in self-renewal and differentiation abilities of a subpopulation of cord blood stem cells known as unrestricted somatic stem cells (USSCs). USSCs were expanded and transfected in vitro with siRNAs targeting either Nanog, Rex-1, and in combination. Gene suppressions were achieved at both transcript and proteome level. Differentiations were evaluated by specific Real time PCR and differentiating staining. Nanog knock down revealed a significant increase in osteogenic markers, Osteocalcin and Osteopontin expression as well as a positive Alizarin Red staining, which proposes Osteogenesis. This treatment also became positive for Oil Red staining, implying adipogenic differentiation as well. In contrast, Rex-1 knock down showed an increase in MAP II and Nestin expression, which is a hall mark of neural differentiation. Surprisingly, treatment with both siRNAs did not express any changes in any of the assessed markers. Therefore, our results indicated a bilateral mesenchymal differentiation for Nanog and a neural lineage fate for Rex-1 suppression. Considering that both transcription factors are core activators of self-renewal and also are orchestrating with other factors, our results imply a positive feedback in response to changes in the regulatory network of self-renewal.

  7. Stem cells from umbilical cord blood do have myogenic potential, with and without differentiation induction in vitro

    Directory of Open Access Journals (Sweden)

    Gollop Thomaz R

    2009-01-01

    Full Text Available Abstract The dystrophin gene, located at Xp21, codifies dystrophin, which is part of a protein complex responsible for the membrane stability of muscle cells. Its absence on muscle causes Duchenne Muscular Dystrophy (DMD, a severe disorder, while a defect of muscle dystrophin causes Becker Muscular Dystrophy (DMB, a milder disease. The replacement of the defective muscle through stem cells transplantation is a possible future treatment for these patients. Our objective was to analyze the potential of CD34+ stem cells from umbilical cord blood to differentiate in muscle cells and express dystrophin, in vitro. Protein expression was analyzed by Immunofluorescence, Western Blotting (WB and Reverse Transcriptase – Polymerase Chain Reaction (RT-PCR. CD34+ stem cells and myoblasts from a DMD affected patient started to fuse with muscle cells immediately after co-cultures establishment. Differentiation in mature myotubes was observed after 15 days and dystrophin-positive regions were detected through Immunofluorescence analysis. However, WB or RT-PCR analysis did not detect the presence of normal dystrophin in co-cultures of CD34+ and DMD or DMB affected patients' muscle cells. In contrast, some CD34+ stem cells differentiated in dystrophin producers' muscle cells, what was observed by WB, reinforcing that this progenitor cell has the potential to originate muscle dystrophin in vitro, and not just in vivo like reported before.

  8. Differentiating of banked human umbilical cord blood-derived mesenchymal stem cells into insulin-secreting cells.

    Science.gov (United States)

    Phuc, Pham Van; Nhung, Truong Hai; Loan, Dang Thi Tung; Chung, Doan Chinh; Ngoc, Phan Kim

    2011-01-01

    Umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) are multipotent cells. They are able to differentiate into functional cells from not only mesoderm but also endoderm. Many researches showed that cells derived from fresh human UCB could transdifferentiate into insulin-secreting cells. In this study, transdifferentiating potential of cryopreserved human UCB-derived MSCs into insulin-secreting cell was investigated. Fresh human UCB was enriched the mononuclear cells by Ficoll-Paque centrifugation. The mononuclear cell population was cryopreserved in cryo-medium containing Iscove's modified Dulbecco's media (IMDM) with 10% DMSO at -196°C for 1 yr. After thawing, mononuclear cells were cultured to isolate MSCs in medium IMDM with 20% FBS supplemented with growth factors. At the fifth passages, MSCs were confirmed by flow cytometry about expression of CD13, CD14, CD34, CD45, CD166, and HLA-DR markers; after that, they were induced to differentiate into adipocytes and osteoblasts. After inducing with specific medium for islet differentiation, there were many clusters of cell like islet at day 14-28. Using real-time reverse transcription polymerase chain reaction (RT-PCR) to analyze the expression of functional genes, the result showed that Nestin, Pdx-1, Ngn3, Ils-1, Pax6, Pax4, Nkx2.2, Nkx6.1, Glut-2, Insulin genes expressed. The results showed that MSCs derived from banked cord blood can differentiate into functional pancreatic islet-like cells in vitro. If human MSCs, especially MSCs from banked cord blood of diabetes patients themselves can be isolated, proliferated, differentiated into functional pancreatic islet-like cells, and transplanted back into them (autologous transplantation), their high-proliferation potency and rejection avoidance will provide one promising therapy for diabetes.

  9. Cartilage constructs from human cord blood stem cells seeded in structurally-graded polycaprolactone scaffolds

    DEFF Research Database (Denmark)

    Munir, Samir; Koch, Thomas Gadegaard; Foldager, Casper Bindzus

    stimulation. This study demonstrated the chondrogenic potential of human cord blood-derived Multi-Lineage Progenitor Cells (MLPCs) under normoxic and hypoxic culture conditions. Second, MLPCs were seeded in a novel, structurally graded polycaprolactone (SGS-PCL) scaffold and chondrogenesis was evaluated....... MLPCs obtained from BioE Inc (St. Paul, MN, USA) were expanded, and subsequently cultured in a standard micromass pellet system. Pellets were cultured for 21 days in control or chondrogenic induction medium under 5% or 21% oxygen tension. Chondrogenic potential was evaluated by histology (alcian blue......Nano (Aarhus University, Denmark). Micromass pellets cultured in induction medium were larger with a more dense and well-defined spherical structure. GAG production in induced pellets was shown by alcian blue and safranin O staining with most GAG observed centrally in 21%-, and peripherally in 5%-oxygen...

  10. Significance of Establishment of Cord Blood Bank and Its Information Networking Management on Cord Blood Stem Cell Transplantation%脐带血库的建立及其信息网络化管理对脐带血干细胞移植的意义

    Institute of Scientific and Technical Information of China (English)

    刘婷

    2011-01-01

    目的:探讨如何建立脐带血(UCB)库、UCB库信息网络化管理策略及对UCB干细胞移植的意义.方法:通过建立UCB库及UCB库的信息网络化管理,使UCB库在UCB干细胞移植中发挥尽可能大的作用.结果:建立起来的血库切实可行,UCB库信息网络化管理最大限度地发挥了UCB在UCB干细胞移植中的作用.结论:UCB库的建立及其信息网络化管理对UCB干细胞移植意义重大,可最大限度地发挥UCB库的作用.%[ Objective ] To explore how to establish a cord blood bank, information networking management strategies of cord blood bank and its significance on cord blood stem cell transplantation. [ Methods ] In order to make the cord blood bank plays its full role in cord blood stem cell transplantation, the cord blood bank was established and the information networking management was carried out. [ Results]The blood bank is feasible, and umbilical cord blood gets the maximum use in cord blood stem cell transplantation by implementation of information networking management of cord blood bank. [ Conclusion] The establishment of cord blood bank and its information networking management has a great significance on cord blood stem cell transplantation, which can get a maximum effect of cord blood bank.

  11. Human umbilical cord blood derived mesenchymal stem cells were differentiated into pancreatic endocrine cell by Pdx-1 electrotransfer

    Directory of Open Access Journals (Sweden)

    Phuoc Thi-My Nguyen

    2014-02-01

    Full Text Available Diabetes mellitus type 1 is an autoimmune disease with high incidence in adolescents and young adults. A seductive approach overcomes normally obstacles treatment is cell-replacement therapy to endogenous insulin production. At the present, to get enough pancreatic endocrine cells (PECs in cell transplantation, differentiation of mesenchymal stem cells (MSCs into IPCs is an interesting and promising strategy. This study aimed to orient umbilical cord blood-derived MSCs (UCB-MSCs to PECs by Pdx-1 electrotransfer. UCB-MSCs were isolated from human umbilical cord blood according to published protocol. Pdx-1 was isolated and cloned into a plasmid vector. Optimal voltage of an electrotransfer was investigated to improve the cell viability and gene transfection efficacy. The results showed that 200V of the electrotransfer significantly increased in the efficiency of electrotransfer and survival cells compared with other high voltages (350V and 550V. Pdx-1 successfully transfected UCB-MSCs over-expressed pancreatic related genes as Ngn3, Nkx6.1. These results suggested that Pdx-1 transfected UCB-MSCs were successfully oriented PECs. Different to lentiviral vectors, electrotransfer is a safer method to transfer Pdx-1 to UCB-MSCs and a useful tool in translational research. [Biomed Res Ther 2014; 1(2.000: 50-56

  12. Umbilical Cord Blood-Derived Stem Cells Improve Heat Tolerance and Hypothalamic Damage in Heat Stressed Mice

    Directory of Open Access Journals (Sweden)

    Ling-Shu Tseng

    2014-01-01

    Full Text Available Heatstroke is characterized by excessive hyperthermia associated with systemic inflammatory responses, which leads to multiple organ failure, in which brain disorders predominate. This definition can be almost fulfilled by a mouse model of heatstroke used in the present study. Unanesthetized mice were exposed to whole body heating (41.2°C for 1 hour and then returned to room temperature (26°C for recovery. Immediately after termination of whole body heating, heated mice displayed excessive hyperthermia (body core temperature ~42.5°C. Four hours after termination of heat stress, heated mice displayed (i systemic inflammation; (ii ischemic, hypoxic, and oxidative damage to the hypothalamus; (iii hypothalamo-pituitary-adrenocortical axis impairment (reflected by plasma levels of both adrenocorticotrophic-hormone and corticosterone; (iv decreased fractional survival; and (v thermoregulatory deficits (e.g., they became hypothermia when they were exposed to room temperature. These heatstroke reactions can be significantly attenuated by human umbilical cord blood-derived CD34+ cells therapy. Our data suggest that human umbilical cord blood-derived stem cells therapy may improve outcomes of heatstroke in mice by reducing systemic inflammation as well as hypothalamo-pituitary-adrenocortical axis impairment.

  13. Prostaglandin E2 Enhances Human Cord Blood Stem Cell Xenotransplants and Shows Long-Term Safety in Preclinical Nonhuman Primate Transplant Models

    NARCIS (Netherlands)

    Goessling, Wolfram; Allen, Robyn S.; Guan, Xiao; Jin, Ping; Uchida, Naoya; Dovey, Michael; Harris, James M.; Metzger, Mark E.; Bonifacino, Aylin C.; Stroncek, David; Stegner, Joseph; Armant, Myriam; Schlaeger, Thorsten; Tisdale, John F.; Zon, Leonard I.; Donahue, Robert E.; North, Trista E.

    2011-01-01

    Hematopoietic stem cells (HSCs) are used in transplantation therapy to reconstitute the hematopoietic system. Human cord blood (hCB) transplantation has emerged as an attractive alternative treatment option when traditional HSC sources are unavailable; however, the absolute number of hCB HSCE.; tran

  14. Brain-derived neurotrophic factor induces neuron-like cellular differentiation of mesenchymal stem cells derived from human umbilical cord blood cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Lei Chen; Guozhen Hui; Zhongguo Zhang; Bing Chen; Xiaozhi Liu; Zhenlin Liu; Hongliang Liu; Gang Li; Zhiguo Su; Junfei Wang

    2011-01-01

    Human umbilical cord blood was collected from full-term deliveries scheduled for cesarean section. Mononuclear cells were isolated, amplified and induced as mesenchymal stem cells. Isolated mesenchymal stem cells tested positive for the marker CD29, CD44 and CD105 and negative for typical hematopoietic and endothelial markers. Following treatment with neural induction medium containing brain-derived neurotrophic factor for 7 days, the adherent cells exhibited neuron-like cellular morphology. Immunohistochemical staining and reverse transcription-PCR revealed that the induced mesenchymal stem cells expressed the markers for neuron-specific enolase and neurofilament. The results demonstrated that human umbilical cord blood-derived mesenchymal stem cells can differentiate into neuron-like cells induced by brain-derived neurotrophic factor in vitro.

  15. Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells on the radiation-induced GI syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Se Hwan; Jang, Won Suk; Lee, Sun Joo; Park, Eun Young; Kim, Youn Joo; Jin, Sung Ho; Park, Sun Hoo; Lee, Seung Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2011-05-15

    The gastrointestinal (GI) tract is one of the most radiosensitive organ systems in the body. Radiation-induced GI injury is described as destruction of crypt cell, decrease in villous height and number, ulceration, and necrosis of intestinal epithelium. Studies show that mesenchymal stem cells (MSCs) treatment may be useful in the repair or regeneration of damaged organs including bone, cartilage, or myocardium. MSCs from umbilical cord blood (UCB) have many advantages because of the immature nature of newborn cells compared to bone marrow derived MSCs. Moreover, UCB-MSCs provide no ethical barriers for basic studies and clinical applications. In this study, we explore the regeneration capability of human UCB-MSCs after radiation-induced GI injury

  16. Eltrombopag, a thrombopoietin receptor agonist, enhances human umbilical cord blood hematopoietic stem/primitive progenitor cell expansion and promotes multi-lineage hematopoiesis

    OpenAIRE

    2012-01-01

    Umbilical cord blood (UCB) transplantation has emerged as promising therapy, but is challenged by scarcity of stem cells. Eltrombopag is a non-peptide, thrombopoietin (TPO) receptor agonist, which selectively activates c-Mpl in humans and chimpanzees. We investigated eltrombopag’s effects on human UCB hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) expansion, and its effects on hematopoiesis in vivo. Eltrombopag selectively augmented the expansion of human CD45+, CD34+, ...

  17. Optimization of primary culture condition for mesenchymal stem cells derived from umbilical cord blood with factorial design.

    Science.gov (United States)

    Fan, Xiubo; Liu, Tianqing; Liu, Yang; Ma, Xuehu; Cui, Zhanfeng

    2009-01-01

    Mesenchymal stem cells (MSCs) can not only support the expansion of hematopoietic stem cells in vitro, but also alleviate complications and accelerate recovery of hematopoiesis during hematopoietic stem cell transplantation. However, it proved challenging to culture MSCs from umbilical cord blood (UCB) with a success rate of 20-30%. Many cell culture parameters contribute to this outcome and hence optimization of culture conditions is critical to increase the probability of success. In this work, fractional factorial design was applied to study the effect of cell inoculated density, combination and dose of cytokines, and presence of serum and stromal cells. The cultured UCB-MSC-like cells were characterized by flow cytometry and their multilineage differentiation potentials were tested. The optimal protocol was identified achieving above 90% successful outcome: 2 x 10(6) cells/mL mononuclear cells inoculated in Iscove's modified Dulbecco's medium supplied with 10% FBS, 15 ng/mL IL-3, and 5 ng/mL Granulocyte-macrophage colony-stimulating factor (GM-CSF). Moreover, the UCB-MSC-like cells expressed MSC surface markers of CD13, CD29, CD105, CD166, and CD44 positively, and CD34, CD45, and human leukocyte antigens-DR (HLA-DR) negatively. Meanwhile, these cells could differentiate into osteoblasts, chondrocytes, and adipocytes similarly to MSCs derived from bone marrow. In conclusion, we have developed an efficient protocol for the primary culture of UCB-MSCs by adding suitable cytokines into the culture system.

  18. Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

    Science.gov (United States)

    Calatrava-Ferreras, Lucía; Gonzalo-Gobernado, Rafael; Herranz, Antonio S.; Reimers, Diana; Montero Vega, Teresa; Jiménez-Escrig, Adriano; Richart López, Luis Alberto; Bazán, Eulalia

    2012-01-01

    Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders. PMID:23150735

  19. Development of a vascular niche platform for expansion of repopulating human cord blood stem and progenitor cells.

    Science.gov (United States)

    Butler, Jason M; Gars, Eric J; James, Daylon J; Nolan, Daniel J; Scandura, Joseph M; Rafii, Shahin

    2012-08-09

    Transplantation of ex vivo expanded human umbilical cord blood cells (hCB) only partially enhances the hematopoietic recovery after myelosuppressive therapy. Incubation of hCB with optimal combinations of cytokines and niche cells, such as endothelial cells (ECs), could augment the efficiency of hCB expansion. We have devised an approach to cultivate primary human ECs (hECs) in serum-free culture conditions. We demonstrate that coculture of CD34(+) hCB in direct cellular contact with hECs and minimal concentrations of thrombopoietin/Kit-ligand/Flt3-ligand resulted in a 400-fold expansion of total hematopoietic cells, 150-fold expansion of CD45(+)CD34(+) progenitor cells, and 23-fold expansion of CD45(+) Lin(-)CD34(hi+)CD45RA(-)CD49f(+) stem and progenitor cells over a 12-day period. Compared with cytokines alone, coculture of hCB with hECs permitted greater expansion of cells capable of multilineage engraftment and serial transplantation, hallmarks of long-term repopulating hematopoietic stem cells. Therefore, hECs establish a cellular platform for expansion of hematopoietic stem and progenitor cells and treatment of hematologic disorders.

  20. Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

    Directory of Open Access Journals (Sweden)

    Lucía Calatrava-Ferreras

    2012-01-01

    Full Text Available Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders.

  1. Umbilical cord blood transplantation: A review of atricles

    OpenAIRE

    1999-01-01

    Interest in umbilical cord blood as an alternative source of hematopietic stem cells is growing rapidly. Umbilical cord blood offers the clinician a source of hematopoietic stem cells that are readily available and rarely contaminated by latent viruses. Moreover, the collection of umbilical cord blood poses no risk to the donor. There is no need for general anesthesia or blood replacement and the procedure causes no discomfort. Current clinical experience suggests that the incidence of GVHD i...

  2. Cord-Blood Banking

    Science.gov (United States)

    ... blood banks may capitalize on the fears of vulnerable new parents by providing misleading information about the statistics of stem cell transplants. Parents of children of ethnic or racial minorities, adopted children, or ...

  3. Umbilical cord blood transplantation: A review of atricles

    Directory of Open Access Journals (Sweden)

    Asadi Amoly F

    1999-08-01

    Full Text Available Interest in umbilical cord blood as an alternative source of hematopietic stem cells is growing rapidly. Umbilical cord blood offers the clinician a source of hematopoietic stem cells that are readily available and rarely contaminated by latent viruses. Moreover, the collection of umbilical cord blood poses no risk to the donor. There is no need for general anesthesia or blood replacement and the procedure causes no discomfort. Current clinical experience suggests that the incidence of GVHD in umbilical cord blood transplantation is low. These results and associated laboratory findings pose intriguing possibilities for the future of umbilical cord blood stem cells in the setting of unrelated donor transplantation. There are other intriguing possibilities for example cord blood may be an optimal source of pluripotential stem cells for use in genetherapy.

  4. Family-directed umbilical cord blood banking

    Science.gov (United States)

    Gluckman, Eliane; Ruggeri, Annalisa; Rocha, Vanderson; Baudoux, Etienne; Boo, Michael; Kurtzberg, Joanne; Welte, Kathy; Navarrete, Cristina; van Walraven, Suzanna M.

    2011-01-01

    Umbilical cord blood transplantation from HLA-identical siblings provides good results in children. These results support targeted efforts to bank family cord blood units that can be used for a sibling diagnosed with a disease which can be cured by allogeneic hematopoietic stem cell transplantation or for research that investigates the use of allogeneic or autologous cord blood cells. Over 500 patients transplanted with related cord blood units have been reported to the Eurocord registry with a 4-year overall survival of 91% for patients with non-malignant diseases and 56% for patients with malignant diseases. Main hematologic indications in children are leukemia, hemoglobinopathies or inherited hematologic, immunological or metabolic disorders. However, family-directed cord blood banking is not widely promoted; many cord blood units used in sibling transplantation have been obtained from private banks that do not meet the necessary criteria required to store these units. Marketing by private banks who predominantly store autologous cord blood units has created public confusion. There are very few current validated indications for autologous storage but some new indications might appear in the future. Little effort is devoted to provide unbiased information and to educate the public as to the distinction between the different types of banking, economic models and standards involved in such programs. In order to provide a better service for families in need, directed-family cord blood banking activities should be encouraged and closely monitored with common standards, and better information on current and future indications should be made available. PMID:21750089

  5. Generation of human induced pluripotent stem cells from cord blood cells.

    Science.gov (United States)

    Nishishita, Naoki; Takenaka, Chiemi; Fusaki, Noemi; Kawamata, Shin

    2011-01-01

    We report that iPS cells can be safely and effectively generated from fresh human cord blood (CB) cells with Sendai virus (SeV) vector carrying reprogramming factors OCT3/4, SOX2, KLF4, and c-MYC. The SeV vector is a single strand RNA virus having no DNA phase, and selectively infects the freshly isolated CD34+ CD45low+ fraction of CB cells corresponding to hematopoietic progenitors. Approximately twenty ES cell-like colonies emerged from 1 x 104 freshly isolated CD34+ CB cells around 18 days after SeV infection and were selected for passage to reduce the frequency of the remaining SeV-infected cells. The complete elimination of viral constructs was confirmed after several passages by immunostaining with monoclonal antibody against hemagglutinin-neuraminidase (HN) and by RT-PCR analysis. Five ES cell-like clones were selected to examine their in vitro potential for three germ layer differentiation and their capacity for teratoma formation. Generation of non-integrating Sendai virus (SeV) iPS cells from CB cells may be an important step to provide allogeneic iPS cell-derived therapy in the future.

  6. Different strategies to improve the use of the umbilical cord and cord blood for hematopoietic and other regenerative cell therapies

    NARCIS (Netherlands)

    Garde, Mark Paul van der

    2016-01-01

    The umbilical cord and cord blood contain stem cells that can be used for regenerative cell therapies such as hematopoietic stem cell transplantation. However, the application of cord blood is hindered by the slow engraftment of the cells and delayed immune reconstitution compared to stem cells of

  7. Effect of anti-CD52 antibody alemtuzumab on ex-vivo culture of umbilical cord blood stem cells

    Directory of Open Access Journals (Sweden)

    Law Ping

    2008-10-01

    Full Text Available Abstract Background Excessive maturation of hematopoietic cells leads to a reduction of long-term proliferative capability during cord blood (CB expansion. In this study, we report the effects of anit-CD52 (Alemtuzumab, Campath on both short- and long-term ex vivo expansion of CB hematopoietic stem cells (HSC by evaluating the potential role of Alemtuzumab in preserving the repopulating capability in CB HSC and nonlymphoid progenitors. Methods Ex vivo expansion experiments were carried out using freshly purified CB CD34+ cells in StemSpan™ SFEM medium in the presence of stem cell factor, Flt3-Ligand and thrombopoietin at 50 ng/ml. Alemtuzumab (10 μg/ml was used to deplete CD52+ cells during the cultures. Flow cytometry was used to monitor CB HSC and their differentiation. Colony forming unit (CFU assays and long term culture-initiating cell (LTC-IC assays were performed on cells obtained from day 0 (before culture and day 14 after cultures. Secondary cultures was performed using CD34+ cells isolated at 35 days from primary cultures and further cultured in StemSpan™ SFEM medium for another 14 days to confirm the long term effect of alemtuzumab in liquid cultures. Results Compared to cytokines alone, addition of alemtuzumab resulted in a significant increase in total nucleated cells, absolute CD34+ cells, myeloid and megakaryocytic progenitors, multi-lineage and myeloid CFU and LTC-IC. Conclusion The results from current study suggested that the use of alemtuzumab for ex vivo expansion of CBHSC maybe advantageous. Our findings may improve current technologies for CBHSC expansion and increase the availability of CB units for transplantation. However, in vivo studies using animal models are likely needed in further studies to test the hematopoietic effects using such expanded CB products.

  8. Human Umbilical Cord Blood-Derived Serum for Culturing the Supportive Feeder Cells of Human Pluripotent Stem Cell Lines

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    Ruttachuk Rungsiwiwut

    2016-01-01

    Full Text Available Although human pluripotent stem cells (hPSCs can proliferate robustly on the feeder-free culture system, genetic instability of hPSCs has been reported in such environment. Alternatively, feeder cells enable hPSCs to maintain their pluripotency. The feeder cells are usually grown in a culture medium containing fetal bovine serum (FBS prior to coculture with hPSCs. The use of FBS might limit the clinical application of hPSCs. Recently, human cord blood-derived serum (hUCS showed a positive effect on culture of mesenchymal stem cells. It is interesting to test whether hUCS can be used for culture of feeder cells of hPSCs. This study was aimed to replace FBS with hUCS for culturing the human foreskin fibroblasts (HFFs prior to feeder cell preparation. The results showed that HFFs cultured in hUCS-containing medium (HFF-hUCS displayed fibroblastic features, high proliferation rates, short population doubling times, and normal karyotypes after prolonged culture. Inactivated HFF-hUCS expressed important genes, including Activin A, FGF2, and TGFβ1, which have been implicated in the maintenance of hPSC pluripotency. Moreover, hPSC lines maintained pluripotency, differentiation capacities, and karyotypic stability after being cocultured for extended period with inactivated HFF-hUCS. Therefore, the results demonstrated the benefit of hUCS for hPSCs culture system.

  9. Clinical-scale cultures of cord blood CD34(+) cells to amplify committed progenitors and maintain stem cell activity.

    Science.gov (United States)

    Ivanovic, Zoran; Duchez, Pascale; Chevaleyre, Jean; Vlaski, Marija; Lafarge, Xavier; Dazey, Bernard; Robert-Richard, Elodie; Mazurier, Frédéric; Boiron, Jean-Michel

    2011-01-01

    We developed a clinical-scale cord blood (CB) cell ex vivo procedure to enable an extensive expansion of committed progenitors--colony-forming cells (CFCs) without impairing very primitive hematopoietic stem cells (HSCs). CD34(++) cells, selected from previously cryopreserved and thawed CB units, were cultured in two steps (diluted 1:4 after 6 days) in the presence of stem cell factor (SCF), fms-related tyrosine kinase 3 ligand (Flt-3L), megakaryocyte growth and development factor (MGDF) (100 ng/ml each), granulocyte-colony stimulating factor (G-CSF) (10 ng/ml) in HP01 serum-free medium. HSC activity was evaluated in a serial transplantation assay, by detection of human cells (CD45, CD33, CD19 and CFC of human origin) in bone marrow (BM) of primary and secondary recipient NOD/SCID mice 6-8 weeks after transplantation. A wide amplification of total cells (∼350-fold), CD34(+) cells (∼100-fold), and CFC (∼130-fold) without impairing the HSC activity was obtained. The activity of a particular HSC subpopulation (SRC(CFC)) was even enhanced.Thus, an extensive ex vivo expansion of CFCs is feasible without impairing the activity of HSCs. This result was enabled by associating antioxidant power of medium with an appropriate cytokine cocktail (i.e., mimicking physiologic effects of a weak oxygenation in hematopoietic environment).

  10. Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

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    Biaoru Li

    Full Text Available Fetal stem cells isolated from umbilical cord blood (UCB possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1 and 30 TFs were activated by day 56 (Profile-2. Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1 and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34

  11. Umbilical cord blood transplantation: the first 25 years and beyond.

    Science.gov (United States)

    Ballen, Karen K; Gluckman, Eliane; Broxmeyer, Hal E

    2013-07-25

    Umbilical cord blood is an alternative hematopoietic stem cell source for patients with hematologic diseases who can be cured by allogeneic hematopoietic cell transplantation. Initially, umbilical cord blood transplantation was limited to children, given the low cell dose infused. Both related and unrelated cord blood transplants have been performed with high rates of success for a variety of hematologic disorders and metabolic storage diseases in the pediatric setting. The results for adult umbilical cord blood transplantation have improved, with greater emphasis on cord blood units of sufficient cell dose and human leukocyte antigen match and with the use of double umbilical cord blood units and improved supportive care techniques. Cord blood expansion trials have recently shown improvement in time to engraftment. Umbilical cord blood is being compared with other graft sources in both retrospective and prospective trials. The growth of the field over the last 25 years and the plans for future exploration are discussed.

  12. Hypoxia/hypercapnia-induced adaptation maintains functional capacity of cord blood stem and progenitor cells at 4°C.

    Science.gov (United States)

    Vlaski, Marija; Negroni, Luc; Kovacevic-Filipovic, Milica; Guibert, Christelle; Brunet de la Grange, Philippe; Rossignol, Rodrigue; Chevaleyre, Jean; Duchez, Pascale; Lafarge, Xavier; Praloran, Vincent; Schmitter, Jean-Marie; Ivanovic, Zoran

    2014-12-01

    We analyzed the effect of exposure to hypoxic/hypercapnic (HH) gas mixture (5% O2 /9% CO2 ) on the maintenance of functional cord blood CD34(+) hematopoietic stem and progenitor cells in severe hypothermia (4°C) employing the physiological and proteomic approaches. Ten-day exposure to HH maintained the Day 0 (D-0) level of hematopoietic stem cells as detected in vivo on the basis of hematopoietic repopulation of immunodeficient mice-short-term scid repopulating cells (SRC). Conversely, in the atmospheric air (20% O2 /0.05% CO2 ), usual condition used for cell storage at 4°C, stem cell activity was significantly decreased. Also, HH doubled the survival of CD34(+) cells and committed progenitors (CFCs) with respect to the atmospheric air (60% vs. 30%, respectively). Improved cell maintenance in HH was associated with higher proportion of aldehyde dehydrogenase (ALDH) positive cells. Cell-protective effects are associated with an improved maintenance of the plasma and mitochondrial membrane potential and with a conversion to the glycolytic energetic state. We also showed that HH decreased apoptosis, despite a sustained ROS production and a drop of ATP amount per viable cell. The proteomic study revealed that the global protein content was better preserved in HH. This analysis identified: (i) proteins sensitive or insensitive to hypothermia irrespective of the gas phase, and (ii) proteins related to the HH cell-protective effect. Among them are some protein families known to be implicated in the prolonged survival of hibernating animals in hypothermia. These findings suggest a way to optimize short-term cell conservation without freezing.

  13. Efficient Expansion of SALL4–Transduced Umbilical Cord Blood Derived CD133+Hematopoietic Stem Cells

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    Majid Mossahebi-Mohammadi

    2017-07-01

    Full Text Available Hematopoietic stem cells (HSCs were characterized by self-renewal and multilineage potential. Umbilical cord blood-derived (UCB as an alternative source of HSCs is widely used especially in children for stem cells transplant (SCT. The main limitation in using UCB for transplantation especially in adults is low cell dose. To overcome this limitation besides using double dose UCB, ex vivo expansion is the most important way to increase cell number for transplantation. HSCs are mainly isolated using CD133 or CD34. CD133, as the most primitive marker, shows important physiological role in maintenance and expansion of HSCs. SALL4 plays crucial role in the development and maintaining the pluripotency and self-renewal ability of embryonic stem cells (ESCs as well as HSCs. Moreover, SALL4 act as a regulator of HSCs expansion, normal hematopoiesis, and hematological malignancies. In the present study, CD133+ cells positively selected and ex vivo expanded in SALL-4 and GFP-transduced group. CD133 expression assessed using flow cytometry at day 0, 7 and 10. Moreover, multilineage differentiation and proliferation potential of expanded cells in both groups evaluated using colony forming unit (CFU assay, and cells count assay. Karyotyping analysis was performed to assess any chromosomal instability after 7 days of expansion. Obtained results demonstrated that SALL-4 transduced cells showed significant increase in cell number compared to control group. Moreover, immunophenotyping results showed higher expression level of CD133 at day 7 and 10 following expansion in SALL-4 transduced (62 % and 42% compared to control group (51% and 20.6%. Our results illustrated that SALL4 could act as a positive factor for the expansion of CD133+ derived UCB cells besides maintaining self-renewal and differentiation ability of expanded cell without any numerical and structural chromosomal aberrations .

  14. Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older.

    Science.gov (United States)

    Konuma, Takaaki; Tsukada, Nobuhiro; Kanda, Junya; Uchida, Naoyuki; Ohno, Yuju; Miyakoshi, Shigesaburo; Kanamori, Heiwa; Hidaka, Michihiro; Sakura, Toru; Onizuka, Makoto; Kobayashi, Naoki; Sawa, Masashi; Eto, Tetsuya; Matsuhashi, Yoshiko; Kato, Koji; Ichinohe, Tatsuo; Atsuta, Yoshiko; Miyamura, Koichi

    2016-05-01

    Older recipient and donor age were associated with higher incidences of severe graft-versus-host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n = 319), MSD peripheral blood stem cell transplantation (PBSCT) (n = 462), or unrelated CBT (n = 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38-74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P = 0.001) or PBSCT (HR, 2.38; P transplant-related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P = 0.002) compared with CBT, the rates of a composite endpoint of GVHD-free, relapse-free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT.

  15. Pilot social feasibility study for the establishment of a public human umbilical cord blood stem cell bank in South Africa.

    Science.gov (United States)

    Meissner-Roloff, Madelein; Young, Wendy; Rangaka, Isabella; Lombaard, Hennie; Dhai, Ames; Tsotsi, Norma; Pepper, Michael S

    2012-12-01

    There is a large unmet need in South Africa for bone marrow transplantation. Umbilical cord blood (UCB) is an important source of stem cells for the treatment of haematological and non-haematological diseases. Access to the two existing private umbilical cord blood stem cell banks (UCB SCBs) in South Africa is limited to individuals that can afford it, which further aggravates the ever increasing divide between families from different socio-economic classes. The problem is compounded by a severe global shortage of genetically compatible samples, representative of the South African demographics. Establishing a public human UCB SCB in South Africa would provide more South Africans with access to previously unavailable treatment in the form of affordable, genetically compatible stem cells for bone marrow transplantation. A public UCB SCB has many facets to consider, one of which is public preparedness and support for the bank. This was assessed in a social feasibility pilot study which is reported here. In addition to the findings of this social feasibility study, other important considerations for establishing a public human UCB SCB in SA include; (a) testing the samples for HIV and other infectious diseases (required for compliance with international regulatory standards); (b) flow cytometric analysis for enumeration of CD34+ UCB stem cells; (c) mapping of HLA genotypes/alleles; and (d) a study of the economic feasibility of this endeavour.The social feasibility study was conducted to gauge public preparedness and support for a public SCB through patient interviews and questionnaires. The process was dynamic due to its novel nature for interviewers and interviewees alike. Many obstacles were met and dealt with which lead to the compilation of results discussed here in the form of a pilot social feasibility study.In the South African context, we are faced with unique and rich challenges relating to cultural and religious differences that are further augmented by

  16. Efficient generation of multipotent mesenchymal stem cells from umbilical cord blood in stroma-free liquid culture.

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    Rowayda Peters

    Full Text Available BACKGROUND: Haematopoiesis is sustained by haematopoietic (HSC and mesenchymal stem cells (MSC. HSC are the precursors for blood cells, whereas marrow, stroma, bone, cartilage, muscle and connective tissues derive from MSC. The generation of MSC from umbilical cord blood (UCB is possible, but with low and unpredictable success. Here we describe a novel, robust stroma-free dual cell culture system for long-term expansion of primitive UCB-derived MSC. METHODS AND FINDINGS: UCB-derived mononuclear cells (MNC or selected CD34(+ cells were grown in liquid culture in the presence of serum and cytokines. Out of 32 different culture conditions that have been tested for the efficient expansion of HSC, we identified one condition (DMEM, pooled human AB serum, Flt-3 ligand, SCF, MGDF and IL-6; further denoted as D7 which, besides supporting HSC expansion, successfully enabled long-term expansion of stromal/MSC from 8 out of 8 UCB units (5 MNC-derived and 3 CD34(+ selected cells. Expanded MSC displayed a fibroblast-like morphology, expressed several stromal/MSC-related antigens (CD105, CD73, CD29, CD44, CD133 and Nestin but were negative for haematopoietic cell markers (CD45, CD34 and CD14. MSC stemness phenotype and their differentiation capacity in vitro before and after high dilution were preserved throughout long-term culture. Even at passage 24 cells remained Nestin(+, CD133(+ and >95% were positive for CD105, CD73, CD29 and CD44 with the capacity to differentiate into mesodermal lineages. Similarly we show that UCB derived MSC express pluripotency stem cell markers despite differences in cell confluency and culture passages. Further, we generated MSC from peripheral blood (PB MNC of 8 healthy volunteers. In all cases, the resulting MSC expressed MSC-related antigens and showed the capacity to form CFU-F colonies. CONCLUSIONS: This novel stroma-free liquid culture overcomes the existing limitation in obtaining MSC from UCB and PB enabling so far unmet

  17. 脐血造血干细胞移植治疗地中海贫血%Cord Blood Stem Cell Transplantation for Thalassemia Major

    Institute of Scientific and Technical Information of China (English)

    李桥川

    2011-01-01

    造血干细胞移植是目前唯一能治愈地中海贫血(地贫)的治疗方法.本文就脐血造血干细胞移植(Cord blood stem cell transplantation,CBT)的特点,CBT治疗地贫的临床研究和CBT治疗地贫的主要临床问题及对策作一综述.

  18. Comparative Analysis of Human Mesenchymal Stem Cells from Umbilical Cord, Dental Pulp, and Menstrual Blood as Sources for Cell Therapy

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    Huaijuan Ren

    2016-01-01

    Full Text Available Although mesenchymal stem cells (MSCs based therapy has been considered as a promising tool for tissue repair and regeneration, the optimal cell source remains unknown. Umbilical cord (UC, dental pulp (DP, and menstrual blood (MB are easily accessible sources, which make them attractive candidates for MSCs. The goal of this study was to compare the biological characteristics, including morphology, proliferation, antiapoptosis, multilineage differentiation capacity, and immunophenotype of UC-, DP-, and MB-MSCs in order to provide a theoretical basis for clinical selection and application of these cells. As a result, all UC-, DP-, and MB-MSCs have self-renewal capacity and multipotentiality. However, the UC-MSCs seemed to have higher cell proliferation ability, while DP-MSCs may have significant advantages for osteogenic differentiation, lower cell apoptosis, and senescence. These differences may be associated with the different expression level of cytokines, including vascular endothelial growth factor, fibroblast growth factor, keratinocyte growth factor, and hepatocyte growth factor in each of the MSCs. Comprehensively, our results suggest DP-MSCs may be a desired source for clinical applications of cell therapy.

  19. Electrophysiological characterisation of human umbilical cord blood-derived mesenchymal stem cells induced by olfactory ensheathing cell-conditioned medium.

    Science.gov (United States)

    Zeng, Yu; Rong, Mingqiang; Liu, Yunsheng; Liu, Jingfang; Lu, Ming; Tao, Xiaoyu; Li, Zhenyan; Chen, Xin; Yang, Kui; Li, Chuntao; Liu, Zhixiong

    2013-12-01

    Umbilical cord blood-derived marrow stromal cells (UCB-MSCs) with high proliferation capacity and immunomodulatory properties are considered to be a good candidate for cell-based therapies. But until now, little work has been focused on the differentiation of UCB-MSCs. In this work, UCB-MSCs were demonstrated to be negative for CD34 and CD45 expression but positive for CD90 and CD105 expression. The gate values of UCB-MSCs for CD90 and CD105 were 99.3 and 98.6 %, respectively. Two weeks after treatment, the percentage of neuron-like cells differentiated from UCB-MSCs was increased to 84 ± 12 % in the experimental group [treated with olfactory ensheathing cells (OECs)-conditioned medium] and they were neuron-specific enolase positive; few neuron-like cells were found in the control group (without OECs-conditioned medium). Using whole-cell recording, sodium and potassium currents were recorded in UCB-MSCs after differentiation by OECs. Thus, human UCB-MSCs could be differentiated to neural cells by secreted secretion from OECs and exhibited electrophysiological properties similar to mature neurons after 2 weeks post-induction. These results imply that OECs can be used as a new strategy for stem cell differentiation and provide an alternative neurogenesis pathway for generating sufficient numbers of neural cells for cell therapy.

  20. Safety of Allogeneic Umbilical Cord Blood Stem Cells Therapy in Patients with Severe Cerebral Palsy: A Retrospective Study.

    Science.gov (United States)

    Feng, Mei; Lu, Aili; Gao, Hongxia; Qian, Caiwen; Zhang, Jun; Lin, Tongxiang; Zhao, Yuanqi

    2015-01-01

    This retrospective study aimed to assess the safety of patients with severe cerebral palsy (CP), who received allogeneic umbilical cord blood stem cells (UCBSCs) treatment from August 2009 to December 2012 in Guangdong Provincial Hospital of Chinese Medicine. A total of 47 patients with average age of 5.85 ± 6.12 years were evaluated in this study. There was no significant association with allogeneic UCBSCs treatments found in the data of the laboratory index . No casualties occurred. Some adverse events during treatments were found in 26 (55.3%) patients, including fever (42.6%) and vomiting (21.2%). Intrathecal infusion and the ages at the initiation of treatment (≤10 years old) were risk factors for the occurrence of adverse events by logistic regression analysis. However, all adverse events disappeared after symptomatic treatment. No treatment related serious adverse events were found in follow-up visits within 6 months. In conclusion, allogeneic UCBSCs treatment was relatively safe for severe CP patients.

  1. Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model.

    Science.gov (United States)

    Park, Yong-Beom; Song, Minjung; Lee, Choong-Hee; Kim, Jin-A; Ha, Chul-Won

    2015-11-01

    This study was carried out to assess the feasibility of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in articular cartilage repair and to further determine a suitable delivering hydrogel in a rat model. Critical sized full thickness cartilage defects were created. The hUCB-MSCs and three different hydrogel composites (hydrogel A; 4% hyaluronic acid/30% pluronic (1:1, v/v), hydrogel B; 4% hyaluronic acid, and hydrogel C; 4% hyaluronic acid/30% pluronic/chitosan (1:1:2, v/v)) were implanted into the experimental knee (right knee) and hydrogels without hUCB-MSCs were implanted into the control knee (left knee). Defects were evaluated after 8 weeks. The hUCB-MSCs with hydrogels composites resulted in a better repair as seen by gross and histological evaluation compared with hydrogels without hUCB-MSCs. Among the three different hydrogels, the 4% hyaluronic acid hydrogel composite (hydrogel B) showed the best result in cartilage repair as seen by the histological evaluation compared with the other hydrogel composites (hydrogel A and C). The results of this study suggest that hUCB-MSCs may be a promising cell source in combination with 4% hyaluronic acid hydrogels in the in vivo repair of cartilage defects.

  2. Conditioned Media from Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Inhibits Melanogenesis by Promoting Proteasomal Degradation of MITF.

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    Eun Sung Kim

    Full Text Available Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs secrete various beneficial molecules, which have anti-apoptotic activity and cell proliferation. However, the effect of hUCB-MSCs in melanogenesis is largely unclear. In this study, we show that conditioned media (CM derived from hUCB-MSCs inhibit melanogenesis by regulating microphthalmia-associated transcription factor (MITF expression via the ERK signalling pathway. Treatment of hUCB-MSC-CM strongly inhibited the alpha-melanocyte stimulating hormone-induced hyperpigmentation in melanoma cells as well as melanocytes. Treatment of hUCB-MSC-CM induced ERK1/2 activation in melanocytes. In addition, inhibition of ERK1/2 suppressed the anti-pigmentation activity of the hUCB-MSC-CM in melanocytes and in vitro artificial skin models. We also found that the expression of MITF was appreciably diminished while expression of phosphorylated MITF, which leads to its proteasomal degradation, was increased in cells treated with hUCB-MSC-CM. These results suggested that hUCB-MSC-CM significantly suppresses melanin synthesis via MITF degradation by the ERK pathway activation.

  3. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve:viscoelasticity characterization

    Institute of Scientific and Technical Information of China (English)

    Xue-man Lv; Yan Liu; Fei Wu; Yi Yuan; Min Luo

    2016-01-01

    The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery.

  4. Cost-effectiveness of private umbilical cord blood banking.

    Science.gov (United States)

    Kaimal, Anjali J; Smith, Catherine C; Laros, Russell K; Caughey, Aaron B; Cheng, Yvonne W

    2009-10-01

    To investigate the cost-effectiveness of private umbilical cord blood banking. A decision-analytic model was designed comparing private umbilical cord blood banking with no umbilical cord blood banking. Baseline assumptions included a cost of $3,620 for umbilical cord blood banking and storage for 20 years, a 0.04% chance of requiring an autologous stem cell transplant, a 0.07% chance of a sibling requiring an allogenic stem cell transplant, and a 50% reduction in risk of graft-versus-host disease if a sibling uses banked umbilical cord blood. Private cord blood banking is not cost-effective because it cost an additional $1,374,246 per life-year gained. In sensitivity analysis, if the cost of umbilical cord blood banking is less than $262 or the likelihood of a child needing a stem cell transplant is greater than 1 in 110, private umbilical cord blood banking becomes cost-effective. Currently, private umbilical cord blood banking is cost-effective only for children with a very high likelihood of needing a stem cell transplant. Patients considering private blood banking should be informed of the remote likelihood that a unit will be used for a child or another family member. III.

  5. The foetal distress decreases the number of stem cells in umbilical cord blood

    OpenAIRE

    Pafumi, Carlo; PALUMBO, M A; LEANZA, V; TEODORO, M C; COCO, L; RISOLETI, E VI; VIZZINI S; Belvedere, G.; ZARBO, G

    2010-01-01

    The authors evaluated the blood volume of foetal blood remaining in the placenta after giving birth with the foetal distress and after a physiological delivery While the amount of blood collected did non differ between groups, the number of CD34 cells was grater in the physiological may be the foetal distress during labour leads to a shift of blood from the placenta to the foetal circulation compartment.

  6. [Marrow donor registration and cord blood banking: current issues].

    Science.gov (United States)

    Takanashi, Minoko

    2016-03-01

    Marrow donor registration and cord blood banking are essential components of the infrastructure required for unrelated haemopoietic stem cell transplantations. We now have a new law to support and regulate the Marrow Donor Coordination Agency, Cord Blood Banks and the Haematopoietic Stem Cell Provision Support Organization. We also need to have a specific goal for bone marrow and peripheral blood stem cell donor registration, a minimum cord blood bank size, and the demographic data to back the medical needs for unrelated haemopoietic stem cell transplantations. To improve bone marrow and peripheral blood stem cell transplantations, we need to recruit younger adults for marrow registration and make greater efforts to shorten the coordinating period. For cord blood transplantations, uniting and empowering the cord blood collection sites is needed, to encourage and motivate obstetricians and other staff, as the quality of cord blood units is primarily determined during collection. Also, the cord blood banks must work cooperatively to provide cord blood internationally, which includes coordinating with international agencies and their regulations.

  7. An efficient nonviral method to generate integration-free human-induced pluripotent stem cells from cord blood and peripheral blood cells.

    Science.gov (United States)

    Okita, Keisuke; Yamakawa, Tatsuya; Matsumura, Yasuko; Sato, Yoshiko; Amano, Naoki; Watanabe, Akira; Goshima, Naoki; Yamanaka, Shinya

    2013-03-01

    The generation of induced pluripotent stem cells (iPSCs) provides the opportunity to use patient-specific somatic cells, which are a valuable source for disease modeling and drug discovery. To promote research involving these cells, it is important to make iPSCs from easily accessible and less invasive tissues, like blood. We have recently reported the efficient generation of human iPSCs from adult fibroblasts using a combination of plasmids encoding OCT3/4, SOX2, KLF4, L-MYC, LIN28, and shRNA for TP53. We herein report a modified protocol enabling efficient iPSC induction from CD34+ cord blood cells and from peripheral blood isolated from healthy donors using these plasmid vectors. The original plasmid mixture could induce iPSCs; however, the efficiency was low. The addition of EBNA1, an essential factor for episomal amplification of the vectors, by an extra plasmid greatly increased the efficiency of iPSC induction, especially when the induction was performed from αβT cells. This improvement enabled the establishment of blood-derived iPSCs from seven healthy donors ranging in age from their 20s to their 60s. This induction method will be useful for the derivation of patient-specific integration-free iPSCs and would also be applicable to the generation of clinical-grade iPSCs in the future.

  8. In Vivo Efficacy of Umbilical Cord Blood Stem Cell-Derived NK Cells in the Treatment of Metastatic Colorectal Cancer

    Science.gov (United States)

    Veluchamy, John P.; Lopez-Lastra, Silvia; Spanholtz, Jan; Bohme, Fenna; Kok, Nina; Heideman, Daniëlle A. M.; Verheul, Henk M. W.; Di Santo, James P.; de Gruijl, Tanja D.; van der Vliet, Hans J.

    2017-01-01

    Therapeutic monoclonal antibodies against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting a natural killer (NK) cell-mediated antitumor response. The IgG1 mAb cetuximab has been used for treatment of RASwt metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study, we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e., allogeneic activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell-derived NK cells (UCB-NK). While cetuximab monotherapy was not effective against EGFR− RASwt, EGFR+ RASmut, and EGFR+ BRAFmut cells, A-PBNK were able to initiate lysis of EGFR+ colon cancer cells irrespective of RAS or BRAF status. Cytotoxic effects of A-PBNK (but not UCB-NK) were further potentiated significantly by coating EGFR+ colon cancer cells with cetuximab. Of note, a significantly higher cytotoxicity was induced by UCB-NK in EGFR−RASwt (42 ± 8 versus 67 ± 7%), EGFR+ RASmut (20 ± 2 versus 37 ± 6%), and EGFR+ BRAFmut (23 ± 3 versus 43 ± 7%) colon cancer cells compared to A-PBNK and equaled the cytotoxic efficacy of the combination of A-PBNK and cetuximab. The antitumor efficacy of UCB-NK cells against cetuximab-resistant human EGFR+ RASmut colon cancer cells was further confirmed in an in vivo preclinical mouse model where UCB-NK showed enhanced antitumor cytotoxicity against colon cancer independent of EGFR and RAS status. As UCB-NK have been proven safe in a recently conducted phase I clinical trial in acute myeloid leukemia, a fast translation into clinical proof of concept for mCRC could be considered. PMID:28220124

  9. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo

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    Lee, Miyoung; Jeong, Sang Young; Ha, Jueun; Kim, Miyeon; Jin, Hye Jin; Kwon, Soon-Jae [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of); Chang, Jong Wook [Research Institute for Future Medicine Stem Cell and Regenerative Medicine Center, Samsung Medical Center, Seoul 137-710 (Korea, Republic of); Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of); Kim, Jae-Sung [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-709 (Korea, Republic of); Jeon, Hong Bae, E-mail: jhb@medi-post.co.kr [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of)

    2014-04-18

    Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications.

  10. Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue.

    Science.gov (United States)

    Heo, June Seok; Choi, Youjeong; Kim, Han-Soo; Kim, Hyun Ok

    2016-01-01

    Mesenchymal stem cells (MSCs) are clinically useful due to their capacity for self-renewal, their immunomodulatory properties and tissue regenerative potential. These cells can be isolated from various tissues and exhibit different potential for clinical applications according to their origin, and thus comparative studies on MSCs from different tissues are essential. In this study, we investigated the immunophenotype, proliferative potential, multilineage differentiation and immunomodulatory capacity of MSCs derived from different tissue sources, namely bone marrow, adipose tissue, the placenta and umbilical cord blood. The gene expression profiles of stemness-related genes [octamer-binding transcription factor 4 (OCT4), sex determining region Y-box (SOX)2, MYC, Krüppel-like factor 4 (KLF4), NANOG, LIN28 and REX1] and lineage‑related and differentiation stage-related genes [B4GALNT1 (GM2/GS2 synthase), inhibin, beta A (INHBA), distal-less homeobox 5 (DLX5), runt-related transcription factor 2 (RUNX2), proliferator‑activated receptor gamma (PPARG), CCAAT/enhancer-binding protein alpha (C/EBPA), bone morphogenetic protein 7 (BMP7) and SOX9] were compared using RT-PCR. No significant differences in growth rate, colony-forming efficiency and immunophenotype were observed. Our results demonstrated that MSCs derived from bone marrow and adipose tissue shared not only in vitro tri-lineage differentiation potential, but also gene expression profiles. While there was considerable inter-donor variation in DLX5 expression between MSCs derived from different tissues, its expression appears to be associated with the osteogenic potential of MSCs. Bone marrow-derived MSCs (BM-MSCs) significantly inhibited allogeneic T cell proliferation possibly via the high levels of the immunosuppressive cytokines, IL10 and TGFB1. Although MSCs derived from different tissues and fibroblasts share many characteristics, some of the marker genes, such as B4GALNT1 and DLX5 may be useful for

  11. [Ethical aspects of human embryonic stem cell use and commercial umbilical cord blood stem cell banking. Ethical reflections on the occasion of the regulation of the European Council and Parliament on advanced therapy medicinal products].

    Science.gov (United States)

    Virt, G

    2010-01-01

    The regulation of the European Council and Parliament on advanced therapy medicinal products also includes therapies with human embryonic stem cells. The use of these stem cells is controversially and heavily discussed. Contrary to the use of adult stem cells, medical and ethical problems concerning the use of human embryonic stem cells persists, because this use is based on the destruction of human life at the very beginning. The regulation foresees, therefore, subsidiarity within the European Member States. Although there are no ethical problems in principle with the use of stem cells from the umbilical cord blood, there are social ethical doubts with the banking of these stem cells for autologous use without any currently foreseeable medical advantage by commercial blood banks. Also in this case subsidiarity is valid.

  12. Human insulin-like growth factor 1-transfected umbilical cord blood neural stem cell transplantation improves hypoxic-ischemic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dengna Zhu; Yanjie Jia; Jun Wang; Boai Zhang; Guohui Niu; Yazhen Fan

    2011-01-01

    Human insulin-like growth factor 1-transfected umbilical cord blood neural stem cells were transplanted into a hypoxic-ischemic neonatal rat model via the tail vein.BrdU-positive cells at day 7post-transplantation,as well as nestin-and neuron specific enolase-positive cells at day 14 wereincreased compared with those of the single neural stem cell transplantation group.In addition,theproportion of neuronal differentiation was enhanced.The genetically modified cell-transplanted ratsexhibited enhanced performance in correctly crossing a Y-maze and climbing an angled slope compared with those of the single neural stem cell transplantation group.These results showed that human insulin-like growth factor 1-transfected neural stem cell transplantation promotes therecovery of the learning,memory and motor functions in hypoxic-ischemic rats.

  13. Quality of Red Blood Cells Isolated from Umbilical Cord Blood Stored at Room Temperature

    Directory of Open Access Journals (Sweden)

    Mariia Zhurova

    2012-01-01

    Full Text Available Red blood cells (RBCs from cord blood contain fetal hemoglobin that is predominant in newborns and, therefore, may be more appropriate for neonatal transfusions than currently transfused adult RBCs. Post-collection, cord blood can be stored at room temperature for several days before it is processed for stem cells isolation, with little known about how these conditions affect currently discarded RBCs. The present study examined the effect of the duration cord blood spent at room temperature and other cord blood characteristics on cord RBC quality. RBCs were tested immediately after their isolation from cord blood using a broad panel of quality assays. No significant decrease in cord RBC quality was observed during the first 65 hours of storage at room temperature. The ratio of cord blood to anticoagulant was associated with RBC quality and needs to be optimized in future. This knowledge will assist in future development of cord RBC transfusion product.

  14. Mesenchymal stem cells promote a primitive phenotype CD34+c-kit+ in human cord blood-derived hematopoietic stem cells during ex vivo expansion.

    Science.gov (United States)

    Rodríguez-Pardo, Viviana M; Vernot, Jean Paul

    2013-03-01

    The purpose of this study was to evaluate the influence of bone marrow-mesenchymal stem cells (BM-MSC) and exogenously added cytokines on the proliferation, primitive cell subpopulation maintenance (including the c-kit+ marker) and clonogenic capacity of hematopoietic stem cells (HSC). BM-MSC were collected from volunteer donors, isolated and characterized. Umbilical cord blood (UCB) samples were collected from healthy full-term deliveries. UCB-CD34+ cells were cultured in the presence or absence of BM-MSC and/or cytokines for 3 and 7 days. CD34+ cell proliferation was evaluated using the CSFE method and cell phenotype was determined by CD34, c-kit, CD33, CD38, HLA-DR, cyCD22 and cyCD3 detection. Cell clonogenic ability was also assessed. Exogenously added SCF, TPO and FLT3L increased CD34+ cell proliferation in the presence or absence of BM-MSC, but with concomitant cell differentiation. Without any added cytokines, BM-MSC are able to increase the percentage of primitive progenitors as evaluated by c-kit expression and CFU-GEMM increase. Interestingly, this latter effect was dependent on both cell-cell interactions and secreted factors. A 7-day co-culture period will be optimal for obtaining an increased primitive HSC level. Including c-kit as a marker for primitive phenotype evaluation has shown the relevance of BM-MSC and their secreted factors on UCB-HSC stemness function. This effect could be dissociated from that of the addition of exogenous cytokines, which induced cellular differentiation instead.

  15. Optimization of SCF feeding regimen for ex vivo expansion of cord blood hematopoietic stem cells.

    Science.gov (United States)

    Du, Zheng; Cai, Haibo; Ye, Zhaoyang; Tan, Wen-Song

    2012-12-15

    Stem cell factor (SCF) plays important roles in ex vivo expansion of hematopoietic stem cells (HSCs). In this study, the effects of dose and feeding time of SCF on ex vivo expansion of CD34(+) cells were investigated in serum-free medium supplemented with a cytokine cocktail composed of SCF, thrombopoietin (TPO) and flt3-ligand (FL). Among the four tested doses (0, 5, 50 and 500ng/mL), a SCF dose of 50ng/mL was demonstrated to be most favorable for ex vivo expansion of CD34(+) cells, which resulted in 34.22±10.80 and 8.89±1.25 folds of expansion regarding total cells and CD34(+) cells, respectively. Meanwhile, the specific growth rate of cells, the consumption rate of SCF and the percentage of CD34(+)c-kit(+) cells during the 21-day culture process were analyzed. The results indicated that initial 4-day period was a critical stage for SCF functioning on CD34(+) cells during ex vivo expansion. Based on this, a modified SCF feeding regimen was proposed, in which SCF (50ng/mL) was only supplemented on day 0 in the cytokine cocktail and cells were then fed with TPO and FL till the end of culture. It was found that this SCF feeding regimen could expand CD34(+) cells efficiently, thus providing a cost-effect expansion protocol for HSCs.

  16. Comparative outcomes between cord blood transplantation and bone marrow or peripheral blood stem cell transplantation from unrelated donors in patients with hematologic malignancies: a single-institute analysis

    Institute of Scientific and Technical Information of China (English)

    CHEN Yu-hong; XU Lan-ping; LIU Dai-hong; CHEN Huan; ZHANG Xiao-hui; HAN Wei; WANG Feng-rong

    2013-01-01

    Background Umbilical cord blood (UCB) has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients.Our aim was to assess the leukemia-free survival (LFS) and some primary results,such as hematologic recovery,risk of graft-versus-host disease (GVHD),relapse,and long-term survival,after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source.Methods The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood (UCBT) as a primary unrelated stem cell source (n=38),bone marrow (UBMT n=28,transplanted before January 2003),or peripheral blood stem cells (UPBSCT n=46,transplanted after January 2003) between July 2000 and July 2008 were analyzed.Results Except that the patients were much younger in the UCBT group (median age,10.5 years in UCBT,30 years in UPBSCT,and 20 years in UBMT),other pre-transplant parameters,such as gender,diagnosis,and the phase of disease,were comparable.All patients received myeloablative regimens,primarily including BUCY; however,there was less antithymocyte globulin (ATG) used for the UBMT patients (2138 in UCBT,0/46 in UPBSCT,and 8/28 in UBMT did not use ATG,P=0.000).Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets.The cumulative allo-engraftment rates were also significantly lower (87.8% vs.97.8% vs.100% for WBC,P=0.000; 73.0% vs.97.5% vs.89.5% for PLT,P=0.000) for UCBT.The incidence of Grade 2-4 and 3-4 acute graft versus host disease (aGVHD) was much higher in the UBMT group but did not differ among the other groups (51% and 13.2%,40.2% and 10.5%,and 77.4% and 41.2%,respectively,for UCBT,UPBSCT,and UBMT,P=0.000).The occurrence of extensive chronic GVHD (cGVHD)was significantly decreased for recipients of UCBT (4%) compared with that of UPBSCT (39.1%) and UBMT (49.1%,P=0

  17. Mesenchymal Stem Cells and Mononuclear Cells From Cord Blood: Cotransplantation Provides a Better Effect in Treating Myocardial Infarction.

    Science.gov (United States)

    Chen, Gecai; Yue, Aihuan; Yu, Hong; Ruan, Zhongbao; Yin, Yigang; Wang, Ruzhu; Ren, Yin; Zhu, Li

    2016-03-01

    The aim of this study was to evaluate the effect of cotransplanting mononuclear cells from cord blood (CB-MNCs) and mesenchymal stem cells (MSCs) as treatment for myocardial infarction (MI). Transplanting CD34+ cells or MSCs separately has been shown effective in treating MI, but the effect of cotransplanting CB-MNCs and MSCs is not clear. In this study, MSCs were separated by their adherence to the tissue culture. The morphology, immunophenotype, and multilineage potential of MSCs were analyzed. CB-MNCs were separated in lymphocyte separation medium 1.077. CD34+ cell count and viability were analyzed by flow cytometry. Infarcted male Sprague-Dawley rats in a specific-pathogen-free grade were divided into four treatment groups randomly: group I, saline; group II, CB-MNCs; group III, MSCs; and group IV, CB-MNCs plus MSCs. The saline, and CB-MNCs and/or MSCs were injected intramyocardially in infarcted rats. Their cardiac function was evaluated by echocardiography. The myocardial capillary density was analyzed by immunohistochemistry. Both cell types induced an improvement in the left ventricular cardiac function and increased tissue cell proliferation in myocardial tissue and neoangiogenesis. However, CB-MNCs plus MSCs were more effective in reducing the infarct size and preventing ventricular remodeling. Scar tissue was reduced significantly in the CB-MNCs plus MSCs group. MSCs facilitate engraftment of CD34+ cells and immunomodulation after allogeneic CD34+ cell transplantation. Cotransplanting MSCs and CB-MNCs might be more effective than transplanting MSCs or CB-MNCs separately for treating MI. This study contributes knowledge toward effective treatment strategies for MI.

  18. Therapy for Cerebral Palsy by Human Umbilical Cord Blood Mesenchymal Stem Cells Transplantation Combined With Basic Rehabilitation Treatment

    Directory of Open Access Journals (Sweden)

    Che Zhang MD

    2015-03-01

    Full Text Available Background. Cerebral palsy (CP is the most common cause leading to childhood disability. Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs transplantation is a promising alternative considering the safety and efficacy in current reports. This report represents a case of hUCB-MSCs transplantation combined with basic rehabilitation treatment beginning as early as age 6 months with follow-up as long as 5 years. Methods. A 6-year-old female patient was diagnosed with CP at age 6 months. The patient accepted 4 infusions of intravenous hUCB-MSCs in each course and received 4 courses of transplantation totally. A series of assessments were performed before the first transplantation, including laboratory tests, CDCC Infant Mental Development Scale, and Gross Motor Function Measure-88 (GMFM-88. Then annual assessments using the GMFM-88, Ashworth spasm assessment, and comprehensive function assessment scale were made in addition to the annual laboratory tests. In addition, electroencephalography and brain magnetic resonance imaging were conducted before transplantation and in the follow-up phase. Rehabilitation and safety follow-up have been ongoing for 5 years up to date. Results. There was no complaint about adverse effects during hospitalization or postoperative follow-up. Motor function recovered to normal level according to the evaluation of scales. Language function improved significantly. Linguistic rehabilitation therapy was enhanced for further improvement. Conclusions. The clinical application of hUC-MSCs combined with basic rehabilitation treatment was effective and safe for improving motor and comprehensive function in a patient with CP.

  19. Cord blood transplantation: can we make it better?

    Directory of Open Access Journals (Sweden)

    Leland eMetheny

    2013-09-01

    Full Text Available Umbilical cord blood is an established source of hematopoietic stem cells for transplantation. It enjoys several advantages over bone marrow or peripheral blood, including increased tolerance for Human Leukocyte Antigen mismatches, decreased incidence of graft-versus-host disease, and easy availability. Unrelated cord blood does have limitations, however, especially in the treatment of adults. In the 24 years since the first umbilical cord blood transplant was performed, significant progress has been made, but delayed hematopoietic engraftment and increased treatment related mortality remain obstacles to widespread use. Here we summarize the latest results of unrelated cord blood transplants, and review strategies under investigation to improve clinical outcomes.

  20. Molecular and phenotypic characterization of CD133 and SSEA4 enriched very small embryonic-like stem cells in human cord blood.

    Science.gov (United States)

    Shaikh, A; Nagvenkar, P; Pethe, P; Hinduja, I; Bhartiya, D

    2015-09-01

    Very small embryonic-like stem cells (VSELs) are immature primitive cells residing in adult and fetal tissues. This study describes enrichment strategy and molecular and phenotypic characterization of human cord blood VSELs. Flow cytometry analysis revealed that a majority of VSELs (LIN(-)/CD45(-)/CD34(+)) were present in the red blood cell (RBC) pellet after Ficoll-Hypaque centrifugation in contrast to the hematopoietic stem cells (LIN(-)/CD45(+)/CD34(+)) in the interphase layer. Thus, after lyses of RBCs, VSELs were enriched using CD133 and SSEA4 antibodies. These enriched cells were small in size (4-6 μm), spherical, exhibited telomerase activity and expressed pluripotent stem cell (OCT4A, OCT4, SSEA4, NANOG, SOX2, REX1), primordial germ cell (STELLA, FRAGILIS) as well as primitive hematopoietic (CD133, CD34) markers at protein and transcript levels. Heterogeneity was noted among VSELs based on subtle differences in expression of various markers studied. DNA analysis and cell cycle studies revealed that a majority of enriched VSELs were diploid, non-apoptotic and in G0/G1 phase, reflecting their quiescent state. VSELs also survived 5-fluorouracil treatment in vitro and treated cells entered into cell cycle. This study provides further support for the existence of pluripotent, diploid and relatively quiescent VSELs in cord blood and suggests further exploration of the subpopulations among them.

  1. FEASIBILITY OF COLLECTING UMBILICAL CORD BLOOD IN JORDAN AND THE EFFECT OF MATERNAL AND NEONATAL FACTORS ON HEMATOPOIETIC STEM CELL CONTENT

    Directory of Open Access Journals (Sweden)

    Ayad Ahmed Hussein

    2014-02-01

    Conclusion: We conclude that it is feasible to collect cord blood units in Jordan with excellent TNC and CD34+ cell content. The volume of cord blood collected was associated with higher TNC count and CD34+ count. Efforts toward establishing public cord blood banks in our area are warranted.

  2. Association between maternal and fetal factors and quality of cord blood as a source of stem cells

    Directory of Open Access Journals (Sweden)

    Rodrigo Dias Nunes

    2015-02-01

    Full Text Available Objectives: To comparatively analyze maternal and fetal factors and quality markers of blood samples in a public umbilical cord blood bank. Method: This is a cross-sectional descriptive study that revisited 458 records of donations from September 2009 to March 2013 at the Hemocentro de Santa Catarina. The means of markers were used to define cutoff points for the quality of cord blood. Results: Most donations came from women with ages between 18 and 29 years (62.8%, gestational age ≥ 40 weeks (55.2%, vaginal delivery (51.3%, primiparous (41.4%, and with male newborns (54.4% weighing between 3000 and 3499 g (41.8%. The volume of the dona- tions ranged from 71.6 to 275.2 mL, the total nucleated cell count ranged from 4.77 × 108 to 31.0 × 108 cells and CD34+ cells ranged from 0.05 to 1.23%. There were statistically significant differences in the volume with respect to gestation age > 38 weeks (p-value = 0.001, cesarean section (p-value 3500 g (p-value 3500 g (p-value < 0.001. There was no statistically significant difference between the variables and the percentage of CD34+ cells. Conclusions: Delivery route and birth weight influence the volume of cord blood and the total nucleated cell count. Gestational age influences only the volume of cord blood.

  3. Detection of donor-derived CMV-specific T cells in cerebrospinal fluid in a case of CMV meningoencephalitis after cord blood stem cell transplantation.

    Science.gov (United States)

    Ikegame, Kazuhiro; Kato, Ruri; Fujioka, Tatsuya; Okada, Masaya; Kaida, Katsuji; Ishii, Shinichi; Yoshihara, Satoshi; Inoue, Takayuki; Taniguchi, Kyoko; Tamaki, Hiroya; Soma, Toshihiro; Ogawa, Hiroyasu

    2013-02-01

    Cytomegalovirus (CMV) meningoencephalitis is a rather rare complication after allogeneic stem cell transplantation. We describe here the case of a 59-year-old man with acute myeloid leukemia who developed CMV meningoencephalitis after cord blood transplantation. The patient presented with a sudden onset of neurological symptoms, such as convulsion, on day 37. The analysis of cerebrospinal fluid (CSF) sample revealed an increase in the number of cells, which were of donor (cord blood) origin, consisting mainly of T cells. No bacteria were detected in the CSF sample. Real-time PCR analysis revealed that the CSF sample was positive for CMV, but was negative for HHV-6, adenovirus, or BK virus. The patient was diagnosed with CMV meningoencephalitis and received cidofovir. His neurological symptoms were gradually improved and completely disappeared by day 60. CMV-specific dextramer-positive CD8(+) T cells were detected in the peripheral blood and CSF samples, with the frequency being much higher in the CSF. To our knowledge, this is the first report on the appearance of CMV-specific T cells in CSF samples from a patient with CMV meningoencephalitis. Cord blood-derived CMV-specific T cells may develop early after transplantation, enter the intrathecal compartment, and likely contribute to the regulation of CMV-meningoencephalitis.

  4. Human umbilical cord blood-stem cells direct macrophage polarization and block inflammasome activation to alleviate rheumatoid arthritis

    Science.gov (United States)

    Shin, Tae-Hoon; Kim, Hyung-Sik; Kang, Tae-Wook; Lee, Byung-Chul; Lee, Hwa-Yong; Kim, Yoon-Jin; Shin, Ji-Hee; Seo, Yoojin; Won Choi, Soon; Lee, Seunghee; Shin, Kichul; Seo, Kwang-Won; Kang, Kyung-Sun

    2016-01-01

    Rheumatoid arthritis (RA) is a long-lasting intractable autoimmune disorder, which has become a substantial public health problem. Despite widespread use of biologic drugs, there have been uncertainties in efficacy and long-term safety. Mesenchymal stem cells (MSCs) have been suggested as a promising alternative for the treatment of RA because of their immunomodulatory properties. However, the precise mechanisms of MSCs on RA-related immune cells are not fully elucidated. The aim of this study was to investigate the therapeutic potential of human umbilical cord blood-derived MSCs (hUCB-MSCs) as a new therapeutic strategy for patients with RA and to explore the mechanisms underlying hUCB-MSC-mediated immunomodulation. Mice with collagen-induced arthritis (CIA) were administered with hUCB-MSCs after the onset of disease, and therapeutic efficacy was assessed. Systemic delivery of hUCB-MSCs significantly ameliorated the severity of CIA to a similar extent observed in the etanercept-treated group. hUCB-MSCs exerted this therapeutic effect by regulating macrophage function. To verify the regulatory effects of hUCB-MSCs on macrophages, macrophages were co-cultured with hUCB-MSCs. The tumor necrosis factor (TNF)-α-mediated activation of cyclooxygenase-2 and TNF-stimulated gene/protein 6 in hUCB-MSCs polarized naive macrophages toward an M2 phenotype. In addition, hUCB-MSCs down-regulated the activation of nucleotide-binding domain and leucine-rich repeat pyrin 3 inflammasome via a paracrine loop of interleukin-1β signaling. These immune-balancing effects of hUCB-MSCs were reproducible in co-culture experiments using peripheral blood mononuclear cells from patients with active RA. hUCB-MSCs can simultaneously regulate multiple cytokine pathways in response to pro-inflammatory cytokines elevated in RA microenvironment, suggesting that treatment with hUCB-MSCs could be an attractive candidate for patients with treatment-refractory RA. PMID:28005072

  5. 人脐血干细胞体外诱导为肥大细胞的研究进展%Mast cells derived from stem cells of umbilical cord blood

    Institute of Scientific and Technical Information of China (English)

    王海燕; 何韶衡

    2005-01-01

    Mast cells (MCs) play a key role in the pathogenesis of allergic diseases. Tissue MCs are originated from hematopoiefic stem cells in bone marrow. In recent years, it was reported that human mast cells could be differentiated from stem cells of umbilical cord blood. In this review, we summarize the development in this novel area.

  6. Cord blood banking and transplantation: advances and controversies.

    Science.gov (United States)

    Yoder, Mervin C

    2014-04-01

    A review of articles published since January 2012 on the topic of cord blood banking and cord blood stem cell transplantation was conducted for this the 25th anniversary year of the first cord blood transplant performed in a human. Cord blood banking is performed throughout the world. Umbilical cord blood (UCB) transplantation is recognized as an acceptable alternative stem cell source for paediatric and adults requiring a haematopoietic transplant, particularly for patients of racial and ethnic minorities. To further advance the use of UCB, methods to enhance UCB stem cell expansion, engraftment and maintenance may be required. Controversy on the most effective and economically sustainable model for banking and storing an optimal UCB product continues to persist. Cord blood banking and transplantation of cord blood stem cells has advanced rapidly over the initial 25 years, as more than 30 ,000 patients have benefited from the therapy. New concepts on the use of methods to expand UCB stem cells for transplantation and use for nonhaematopoietic indications may increase demand for UCB over the next few decades.

  7. Cord blood banking: 'providing cord blood banking for a nation'.

    Science.gov (United States)

    Querol, Sergio; Rubinstein, Pablo; Marsh, Steven G E; Goldman, John; Madrigal, Jose Alejandro

    2009-10-01

    Transplantation of cord blood (CB) is increasingly used as therapy for patients whose own marrow is affected by genetic mutations that prevent the development of normal cells of the blood or immune tissues, or for patients whose marrow has been destroyed in the course of treatment for leukaemia and other malignancies. CB is a rich source of haematopoietic stem cells, can be easily harvested and stored in frozen aliquots in a CB bank. The first public CB bank was established in 1993 allowing unrelated CB transplantation to become an option for patients lacking a suitable adult donor. Today, the results of CB transplantation are comparable to those of bone marrow transplants with several important advantages: the graft is available 'off the shelf', thereby reducing the waiting time, and the requirements of human lecucoyte antigen (HLA) matching are less restrictive than those of adult sources. The reduced requirement for HLA matching allows transplants between incompletely matched donors and recipients, thus reducing the size of the inventory required at the national level. This also mitigates the disadvantage encountered by persons of rare HLA genotypes or those who do not belong to populations of North Western European descent. Finally, national CB programmes can easily make available for research individual surplus units not meeting minimal criteria for clinical use.

  8. Cord blood mesenchymal stem cells propel human dendritic cells to an intermediate maturation state and boost interleukin-12 production by mature dendritic cells.

    Science.gov (United States)

    van den Berk, Lieke C J; Roelofs, Helene; Huijs, Tonnie; Siebers-Vermeulen, Kim G C; Raymakers, Reinier A; Kögler, Gesine; Figdor, Carl G; Torensma, Ruurd

    2009-12-01

    Pathogen-derived entities force the tissue-resident dendritic cells (DCs) towards a mature state, followed by migration to the draining lymph node to present antigens to T cells. Bone marrow mesenchymal stem cells (MSCs) modulate the differentiation, maturation and function of DCs. In umbilical cord blood an immature MSC population was identified. Remarkably, these immature stem cells modulated DCs in a different way. Marker expression was unchanged during the differentiation of monocytes towards immature DCs (iDCs) when cocultured with cord blood MSC [unrestricted somatic stem cells (USSCs)]. The maturation to mature DCs (mDCs) was enhanced when DCs were co-cultured with USSC, as evidenced by the up-regulation of costimulatory molecules. Endocytosis of dextran by iDCs was hampered in the presence of USSCs, which is indicative for the maturation of iDCs. Despite this maturation, the migration of iDCs cocultured with USSCs appeared to be identical to iDCs cultured alone. However, USSCs increased the migration of mDCs towards CCL21 and boosted interleukin-12 production. So, USSCs mature iDCs, thereby redirecting the antigen-uptake phenotype towards a mature phenotype. Furthermore, DC maturation by lipopolysaccharide (LPS) or USSCs reflects two distinct pathways because migration was unaffected when iDCs were matured by coculture with USSCs, while it was strongly enhanced in the presence of LPS. DCs are able to discriminate the different MSC subtypes, resulting in diverse differentiation programmes.

  9. Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells as assayed by NOD/SCID transplantation.

    Science.gov (United States)

    Zhang, Cheng Cheng; Kaba, Megan; Iizuka, Satoru; Huynh, HoangDinh; Lodish, Harvey F

    2008-04-01

    Hematopoietic stem cells (HSCs) are the basis of bone marrow transplantation and are attractive target cells for hematopoietic gene therapy, but these important clinical applications have been severely hampered by difficulties in ex vivo expansion of HSCs. In particular, the use of cord blood for adult transplantation is greatly limited by the number of HSCs. Previously we identified angiopoietin-like proteins and IGF-binding protein 2 (IGFBP2) as new hormones that, together with other factors, can expand mouse bone marrow HSCs in culture. Here, we measure the activity of multipotent human severe combined immunodeficient (SCID)-repopulating cells (SRCs) by transplantation into the nonobese diabetic SCID (NOD/SCID) mice; secondary transplantation was performed to evaluate the self-renewal potential of SRCs. A serum-free medium containing SCF, TPO, and FGF-1 or Flt3-L cannot significantly support expansion of the SRCs present in human cord blood CD133+ cells. Addition of either angiopoietin-like 5 or IGF-binding protein 2 to the cultures led to a sizable expansion of HSC numbers, as assayed by NOD/SCID transplantation. A serum-free culture containing SCF, TPO, FGF-1, angiopoietin-like 5, and IGFBP2 supports an approximately 20-fold net expansion of repopulating human cord blood HSCs, a number potentially applicable to several clinical processes including HSC transplantation.

  10. Procedure for action in the donation of umbilical cord blood

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    Antonio Herrera Gómez

    2012-05-01

    Full Text Available Stem cells are candidates for donation and transplantation in certain diseases, such as treatment of choice. Stem cells from umbilical cord blood are of particular interest as a gift, for many reasons. It should be noted that the umbilical cord blood is a single, limited source of hematopoietic progenitor cells, and the eventual success of a transplant, cellular viability and retained sample are critical, so the extraction process transport and cryopreservation must be performed under strict quality control criteria. Objective: To describe the procedure extacción umbilical cord blood to be carried out in units of delivery, to ensure quality results.

  11. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells.

    Science.gov (United States)

    Castillo-Melendez, Margie; Yawno, Tamara; Jenkin, Graham; Miller, Suzanne L

    2013-10-24

    In the research, clinical, and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however, this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical, and logistical considerations, together with the propensity for native cells to form teratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs), or umbilical cord blood (UCB) stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs), and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  12. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells

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    Margie eCastillo-Melendez

    2013-10-01

    Full Text Available In the research, clinical and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical and logistical considerations, together with the propensity for native cells to form terratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs, or umbilical cord blood (UCB stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells and mesenchymal stem cells, and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  13. Maternal predictors and quality of umbilical cord blood units.

    Science.gov (United States)

    Bielec-Berek, Beata; Jastrzębska-Stojko, Żaneta; Drosdzol-Cop, Agnieszka; Jendyk, Cecylia; Boruczkowski, Dariusz; Ołdak, Tomasz; Nowak-Brzezińska, Agnieszka; Stojko, Rafał

    2017-08-19

    The aim of the study was to determine the relationship between the maternal age at delivery and selected properties of the cord blood stem cells. The study included 50 pregnant women aged between 18 and 38 years in which spontaneous labors or elective cesarean sections were performed. Umbilical cord blood was collected immediately after the women were delivered of newborns. The samples were analyzed in the Polish Stem Cells Bank in Warsaw. The highest mean WBC level (p umbilical blood collected from patients aged 35 years and more. Similarly, the highest mean cell viability was observed in the umbilical cord blood collected from patients aged 35 and more. There were no statistically significant correlations between the CD34+ cells count and mean cell viability in the umbilical cord blood and the maternal age. With the significance level at p umbilical cord blood of patients aged 35 and more after spontaneous labors. In the same group, the umbilical cord blood was also characterized by the highest mean cell viability (98.72%). The number of nucleated cells in the umbilical cord blood collected in the perinatal period increases together with the maternal age. In the course of physiological spontaneous labors, the collected umbilical cord blood has more nucleated cells as compared with elective caesarian sections.

  14. Percutaneous umbilical cord blood sampling - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100196.htm Percutaneous umbilical cord blood sampling - series—Normal anatomy To use the ... or blood disorder, your doctor may recommend percutaneous umbilical cord blood sampling (PUBS), which is performed at 18 ...

  15. Intrahepatic transplantation of CD34+ cord blood stem cells into newborn and adult NOD/SCID mice induce differential organ engraftment.

    Science.gov (United States)

    Wulf-Goldenberg, Annika; Keil, Marlen; Fichtner, Iduna; Eckert, Klaus

    2012-04-01

    In vivo studies concerning the function of human hematopoietic stem cells (HSC) are limited by relatively low levels of engraftment and the failure of the engrafted HSC preparations to differentiate into functional immune cells after systemic application. In the present paper we describe the effect of intrahepatically transplanted CD34(+) cells from cord blood into the liver of newborn or adult NOD/SCID mice on organ engraftment and differentiation. Analyzing the short and long term time dependency of human cell recruitment into mouse organs after cell transplantation in the liver of newborn and adult NOD/SCID mice by RT-PCR and FACS analysis, a significantly high engraftment was found after transplantation into liver of newborn NOD/SCID mice compared to adult mice, with the highest level of 35% human cells in bone marrow and 4.9% human cells in spleen at day 70. These human cells showed CD19 B-cell, CD34 and CD38 hematopoietic and CD33 myeloid cell differentiation, but lacked any T-cell differentiation. HSC transplantation into liver of adult NOD/SCID mice resulted in minor recruitment of human cells from mouse liver to other mouse organs. The results indicate the usefulness of the intrahepatic application route into the liver of newborn NOD/SCID mice for the investigation of hematopoietic differentiation potential of CD34(+) cord blood stem cell preparations.

  16. Effect of Umbilical Cord Blood Stem Cell Transplantation on Axon Regeneration in Spinal Cord-injured Rats%脐血干细胞移植对大鼠脊髓损伤后轴突再生的影响

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    孙志明; 刘建坤; 闫嶂松; 邓树才; 赵合元; 王雪

    2009-01-01

    Objective: To explore the effect of umbilical cord blood stem cell transplantation on axon regeneration in spinal cord injury (SCl)in rats. Methods: The umbilical cord blood was collected and prepared into suitable concentration of CD34 positive stem cells. Thirty SD rats were divided into two groups randomly. One group served as control, another one was the treatment group. The models of spinal cord contusion injury were made by Allen's weight dropping method. One week later,the treatment group was transplanted with 10x105 umbilical cord blood stem cells with Hamilton micro-syringe at the sites of rostral and caudal to the lesioned zone respectively, while control group received just the same volume of PBS injection. Five rats in each group were sacrificed at 1 w, 2 w and 6 w after this operation. Histological and immunohistochemieal examinations including GAP-43 and NF200 were used to evaluate axon regeneration. Meanwhile, BBB motion scoring and inclined plane test were performed to assess the motion function changes of hindlimbs. Results: Compared to the control group, the area of cavity in the lesioned spinal cord region decreased significantly and the expressions of GAP-43 and NF200 increased markedly in cell transplantation group. Also the motion function had better restoration in the treatment group. Conclusion: Transplantation of umbilical cord blood stem cell may achieve both morphological and behavioral improvement for the injured spinal cord.%目的:探讨脐血千细胞移植对大鼠脊髓损伤后轴突再生的影响.方法:收集脐带血,分离提取,制备成合适浓度的CD34阳性细胞.Allen重物坠击法制作SD大鼠急性脊髓损伤动物模型30只,随机分成2组.A组为损伤对照组,B组为细胞移植组,1周后再次手术,细胞移植组将体外培养的脐血干细胞用微量注射器分别注入于脊髓损伤区域头侧和尾侧各10x105个细胞,损伤对照组予以同样体积的PBS,于移植后1周、2周、6周时分

  17. The problem of cord blood banking

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    Shved A. D.

    2013-03-01

    Full Text Available The review considers the literature data on issues of cord blood (CB banking in different countries and regions. The existing forms of banks are private, mixed and public, the latter is preferred by most clinicians who are experienced in stem cell transplantation. All the researchers admit the need for development of CB banks, but they note that the progress depends on several factors: the deficit of government financial support and poor people’s awareness of the possibilities of stem cell therapy, the appropriateness and relevance of public resources of CB units in National Banks.

  18. Arrest—Individual Treatment with Cord Blood

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    A. Jensen

    2013-01-01

    Full Text Available Each year, thousands of children incur brain damage that results in lifelong sequelae. Therefore, based on experimental evidence, we explored the therapeutic potential of human cord blood, known to contain stem cells, to examine the functional neuroregeneration in a child with cerebral palsy after cardiac arrest. The boy, whose cord blood was stored at birth, was 2.5 years old and normally developed when global ischemic brain damage occurred resulting in a persistent vegetative state. Nine weeks later, he received autologous cord blood (91.7 mL, cryopreserved, 5.75×10e8 mononuclear cells intravenously. Active rehabilitation (physio- and ergotherapy was provided daily, follow-up at 2, 5, 12, 24, 30, and 40 months. At 2-months follow-up the boy’s motor control improved, spastic paresis was largely reduced, and eyesight was recovered, as did the electroencephalogram. He smiled when played with, was able to sit and to speak simple words. At 40 months, independent eating, walking in gait trainer, crawling, and moving from prone position to free sitting were possible, and there was significantly improved receptive and expressive speech competence (four-word sentences, 200 words. This remarkable functional neuroregeneration is difficult to explain by intense active rehabilitation alone and suggests that autologous cord blood transplantation may be an additional and causative treatment of pediatric cerebral palsy after brain damage.

  19. Increased Proportion of Hematopoietic Stem and Progenitor Cell Population in Cord Blood of Neonates Born to Mothers with Gestational Diabetes Mellitus

    Science.gov (United States)

    Hadarits, Orsolya; Zóka, András; Barna, Gábor; Al-Aissa, Zahra; Rosta, Klára; Rigó, János; Kautzky-Willer, Alexandra; Somogyi, Anikó

    2016-01-01

    We assessed the hematopoietic stem and progenitor cell (HSPC) population in the cord blood of neonates born to mothers with gestational diabetes mellitus (GDM) in a hypothesis generating pilot study, due to that, neonatal polycythemia may be the consequence of GDM pregnancy. Forty-five pregnant women with GDM (last trimester mean HbA1C = 33.9 mmol/mol) and 42 (nondiabetic) control pregnant women were enrolled after their routine 75 g oral glucose tolerance test (OGTT) between the 24th and 28th gestational week (with expected differences in their mean routine clinical characteristics: plasma glucose at OGTT: 0′ = 5.07 vs. 4.62 mM, 120′ = 8.9 vs. 5.76 mM, age = 35.07 vs. 31.66 years, prepregnancy body mass index = 27.9 vs. 23.9 kg/m2, GDM vs. control, respectively) on a voluntary basis after signing the informed consent. EDTA-treated cord blood samples were analyzed by flow cytometry and the software Kaluza1.2 using CD45 and CD34-specific fluorescent antibodies to identify the HSPC population (CD34+ cells within the CD45dim blast gate). The proportion of CD34+CD45dim HSPCs among the nucleated cells was significantly (P < 0.05, statistical power = 60.8%) higher in the cord blood samples of neonates born to mothers with GDM (median 0.38%) compared to neonates born to nondiabetic mothers (median 0.32%) and according to treatment types (P < 0.05) median: control 0.32%, GDM-diet only 0.37%, GDM-on insulin 0.45%; control versus GDM on insulin (P < 0.05). The increased proportion of circulating CD34+CD45dim cells in the cord blood may possibly be related to altered fetal stem cell mobilization in GDM pregnancy, yet these results should be interpreted only as preliminary due to the small sample sizes. PMID:26494027

  20. Reversal of type 1 diabetes via islet β cell regeneration following immune modulation by cord blood-derived multipotent stem cells

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    Zhao Yong

    2012-01-01

    Full Text Available Abstract Background Inability to control autoimmunity is the primary barrier to developing a cure for type 1 diabetes (T1D. Evidence that human cord blood-derived multipotent stem cells (CB-SCs can control autoimmune responses by altering regulatory T cells (Tregs and human islet β cell-specific T cell clones offers promise for a new approach to overcome the autoimmunity underlying T1D. Methods We developed a procedure for Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates lymphocytes from the whole blood and briefly co-cultures them with adherent CB-SCs before returning them to the patient's circulation. In an open-label, phase1/phase 2 study, patients (n = 15 with T1D received one treatment with the Stem Cell Educator. Median age was 29 years (range: 15 to 41, and median diabetic history was 8 years (range: 1 to 21. Results Stem Cell Educator therapy was well tolerated in all participants with minimal pain from two venipunctures and no adverse events. Stem Cell Educator therapy can markedly improve C-peptide levels, reduce the median glycated hemoglobin A1C (HbA1C values, and decrease the median daily dose of insulin in patients with some residual β cell function (n = 6 and patients with no residual pancreatic islet β cell function (n = 6. Treatment also produced an increase in basal and glucose-stimulated C-peptide levels through 40 weeks. However, participants in the Control Group (n = 3 did not exhibit significant change at any follow-up. Individuals who received Stem Cell Educator therapy exhibited increased expression of co-stimulating molecules (specifically, CD28 and ICOS, increases in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3 cytokine balance. Conclusions Stem Cell Educator therapy is safe, and in individuals with moderate or severe T1D, a single treatment produces lasting improvement in metabolic control. Initial results indicate Stem Cell

  1. Correlation between Methylation and Expression Level of P15 and P16 Genes during Differentiation of Cord Blood Stem Cells into Erythroid Lineage Mediated by Erythropoietin

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    Mehdi Azad

    2015-02-01

    Full Text Available Background: Several influential factors such as transcription factors and intracellular signaling components are involved in differentiation of stem cells into a specific lineage. P15 and p16 proteins are among these factors. Accumulating evidences has introduced the epigenetic as a master regulator of these factors during lineage specification. The main objective of this study is to determine the correlation between the expression level and methylation pattern of P15 and P16 genes in erythroid lineage after in vitro differentiation by erythropoietin (EPO.Materials and Methods: The purified and expanded CD34+ cord blood stem cells were differentiated into erythroid lineage in the presence of EPO. DNA was isolated from both cord blood stem cells and differentiated cells. The Real-Time PCR performed using cDNA and the isolated DNA was used in methylation Specific PCR (MSP reaction for methylation pattern analysis in both pre and post differentiation stages.Results: The study demonstrated that P15 and P16 genes have partial methylation after erythroid differentiation by EPO. The Expression of P15 gene was higher after differentiation and the expression of P16 gene had a slightly decreased level in post differentiation stage.Conclusion: Significant increase in P15 gene expression after differentiation to erythroid lineage, suggests the remarkable efficacy of this gene in erythroid function. According to upregulation of P15 gene after differentiation despite unchanged methylation status and slight down regulation of P16 gene with slight hyper-methylation of the gene it can be suggested that although the methylation can affects the expression level of P16 gene, the P15 gene is not affected by this mechanism during erythroid differentiation mediated by EPO.

  2. Humoral activity of cord blood-derived stem/progenitor cells: implications for stem cell-based adjuvant therapy of neurodegenerative disorders.

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    Edyta Paczkowska

    Full Text Available BACKGROUND: Stem/progenitor cells (SPCs demonstrate neuro-regenerative potential that is dependent upon their humoral activity by producing various trophic factors regulating cell migration, growth, and differentiation. Herein, we compared the expression of neurotrophins (NTs and their receptors in specific umbilical cord blood (UCB SPC populations, including lineage-negative, CD34(+, and CD133(+ cells, with that in unsorted, nucleated cells (NCs. METHODS AND RESULTS: The expression of NTs and their receptors was detected by QRT-PCR, western blotting, and immunofluorescent staining in UCB-derived SPC populations (i.e., NCs vs. lineage-negative, CD34(+, and CD133(+ cells. To better characterize, global gene expression profiles of SPCs were determined using genome-wide RNA microarray technology. Furthermore, the intracellular production of crucial neuro-regenerative NTs (i.e., BDNF and NT-3 was assessed in NCs and lineage-negative cells after incubation for 24, 48, and 72 h in both serum and serum-free conditions. We discovered significantly higher expression of NTs and NT receptors at both the mRNA and protein level in lineage-negative, CD34(+, and CD133(+ cells than in NCs. Global gene expression analysis revealed considerably higher expression of genes associated with the production and secretion of proteins, migration, proliferation, and differentiation in lineage-negative cells than in CD34(+ or CD133(+ cell populations. Notably, after short-term incubation under serum-free conditions, lineage-negative cells and NCs produced significantly higher amounts of BDNF and NT-3 than under steady-state conditions. Finally, conditioned medium (CM from lineage-negative SPCs exerted a beneficial impact on neural cell survival and proliferation. CONCLUSIONS: Collectively, our findings demonstrate that UCB-derived SPCs highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and

  3. Umbilical cord blood banking: implications for perinatal care providers.

    Science.gov (United States)

    Armson, B Anthony

    2005-03-01

    To evaluate the risks and benefits of umbilical cord blood banking for future stem cell transplantation and to provide guidelines for Canadian perinatal care providers regarding the counselling, procedural, and ethical implications of this potential therapeutic option. Selective or routine collection and storage of umbilical cord blood for future autologous (self) or allogenic (related or unrelated) transplantation of hematopoietic stem cells to treat malignant and nonmalignant disorders in children and adults. Maternal and perinatal morbidity, indications for umbilical cord blood transplantation, short- and long-term risks and benefits of umbilical cord blood transplantation, burden of umbilical cord blood collection on perinatal care providers, parental satisfaction, and health care costs. MEDLINE and PubMed searches were conducted from January 1970 to October 2003 for English-language articles related to umbilical cord blood collection, banking, and transplantation; the Cochrane library was searched; and committee opinions of the Royal College of Obstetricians and Gynaecologists, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists were obtained. The evidence collected was reviewed and evaluated by the Maternal/Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC), and recommendations were made using the evaluation of evidence guidelines developed by the Canadian Task Force on the Periodic Health Exam. Umbilical cord blood is a readily available source of hematopoietic stem cells used with increasing frequency as an alternative to bone marrow or peripheral stem cells for transplantation in the treatment of malignant and nonmalignant conditions in children and adults. Umbilical cord blood transplantation provides a rich source of hematopoietic stem cells with several advantages, including prompt availability, decreased risk of transmissible viral infections and graft

  4. Hematopoietic stem cell transplantation in children with acute leukemia: similar outcomes in recipients of umbilical cord blood versus marrow or peripheral blood stem cells from related or unrelated donors

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    Eun Sang Yi

    2012-03-01

    Full Text Available Purpose : This study compared outcomes in children with acute leukemia who underwent transplantations with umbilical cord blood (UCB, bone marrow, or peripheral blood stem cells from a human leukocyte antigen (HLA-matched related donor (MRD or an unrelated donor (URD. Methods : This retrospective study included consecutive acute leukemia patients who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT at Samsung Medical Center between 2005 and 2010. Patients received stem cells from MRD (n=33, URD (n=46, or UCB (n=41. Results : Neutrophil and platelet recovery were significantly longer after HSCT with UCB than with MRD or URD (P&lt;0.01 for both. In multivariate analysis using the MRD group as a reference, the URD group had a significantly higher risk of grade III to IV acute graft-versushost disease (GVHD; relative risk [RR], 15.2; 95% confidence interval [CI], 1.2 to 186.2; P=0.03 and extensive chronic GVHD (RR, 6.9; 95% CI, 1.9 to 25.2; P&lt;0.01. For all 3 donor types, 5-year event-free survival (EFS and overall survival were similar. Extensive chronic GVHD was associated with fewer relapses (RR, 0.1; 95% CI, 0.04 to 0.6; P&lt;0.01. Multivariate analysis showed that lower EFS was associated with advanced disease at transplantation (RR, 3.2; 95% CI, 1.3 to 7.8; P&lt;0.01 and total body irradiation (RR, 2.1; 95% CI, 1.0 to 4.3; P=0.04. Conclusion : Survival after UCB transplantation was similar to survival after MRD and URD transplantation. For patients lacking an HLA matched donor, the use of UCB is a suitable alternative.

  5. Preliminary evaluation of treatment efficacy of umbilical cord blood-derived mesenchymal stem cell-differentiated cardiac pro-genitor cells in a myocardial injury mouse model

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    Truc Le-Buu Pham

    2015-12-01

    Full Text Available Recently, stem cell therapy has been investigated as a strategy to prevent or reverse damage to heart tissue. Although the results of cell transplantation in animal models and patients with myocardial ischemia are promising, the selection of the appropriate cell type remains an issue that requires consideration. In this study, we aimed to evaluate the effect of cardiac progenitor cell transplantation in a mouse model of myocardial ischemia. The cardiac progenitor cells used for transplantation were differentiated from umbilical cord blood mesenchymal stem cells. Animal models injected with phosphate-buffered saline (PBS and healthy mice were used as controls. Cell grafting was assessed by changes in blood pressure and histological evaluation. After 14 days of transplantation, the results demonstrated that the blood pressure of transplanted mice was stable, similar to healthy mice, whereas it fluctuated in PBS-injected mice. Histological analysis showed that heart tissue had regenerated in transplanted mice, but remained damaged in PBS-injected mice. Furthermore, trichrome staining revealed that the transplanted mice did not generate significant amount of scar tissue compared with PBS-injected control mice. In addition, the cardiac progenitor cells managed to survive and integrate with local cells in cell-injected heart tissue 14 days after transplantation. Most importantly, the transplanted cells did not exhibit tumorigenesis. In conclusion, cardiac progenitor cell transplantation produced a positive effect in a mouse model of myocardial ischemia. [Biomed Res Ther 2015; 2(12.000: 435-445

  6. Human umbilical cord blood-derived mesenchymal stem cells do not differentiate into neural cell types or integrate into the retina after intravitreal grafting in neonatal rats.

    Science.gov (United States)

    Hill, Andrew J; Zwart, Isabel; Tam, Henry H; Chan, Jane; Navarrete, Cristina; Jen, Ling-Sun; Navarrete, Roberto

    2009-04-01

    This study investigated the ability of mesenchymal stem cells (MSCs) derived from full-term human umbilical cord blood to survive, integrate and differentiate after intravitreal grafting to the degenerating neonatal rat retina following intracranial optic tract lesion. MSCs survived for 1 week in the absence of immunosuppression. When host animals were treated with cyclosporin A and dexamethasone to suppress inflammatory and immune responses, donor cells survived for at least 3 weeks, and were able to spread and cover the entire vitreal surface of the host retina. However, MSCs did not significantly integrate into or migrate through the retina. They also maintained their human antigenicity, and no indication of neural differentiation was observed in retinas where retinal ganglion cells either underwent severe degeneration or were lost. These results have provided the first in vivo evidence that MSCs derived from human umbilical cord blood can survive for a significant period of time when the host rat response is suppressed even for a short period. These results, together with the observation of a lack of neuronal differentiation and integration of MSCs after intravitreal grafting, has raised an important question as to the potential use of MSCs for neural repair through the replacement of lost neurons in the mammalian retina and central nervous system.

  7. Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

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    Wang, Z.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Li, X.L. [Department of Dermatology, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); He, X.J. [Department of Orthopedics, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Wu, B.J.; Xu, M. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Chang, H.M. [Department of Otolaryngology - Head and Neck Surgery, Affiliated Hospital of Xi' an Medical University, Xi' an (China); Zhang, X.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Xing, Z. [Department of Clinical Dentistry, Faculty of Dentistry, Center for Clinical Dental Research, University of Bergen, Bergen (Norway); Jing, X.H.; Kong, D.M.; Kou, X.H.; Yang, Y.Y. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China)

    2014-03-18

    SRY-related high-mobility-group box 9 (Sox9) gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs). After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering.

  8. Cord blood banking activity in Iran National Cord Blood Bank: a two years experience.

    Science.gov (United States)

    Jamali, Mostafa; Atarodi, Kamran; Nakhlestani, Mozhdeh; Abolghasemi, Hasan; Sadegh, Hosein; Faranoosh, Mohammad; Golzade, Khadije; Fadai, Razieh; Niknam, Fereshte; Zarif, Mahin Nikougoftar

    2014-02-01

    Today umbilical cord blood (UCB) has known as a commonly used source of hematopoietic stem cells for allogeneic transplantation and many cord blood banks have been established around the world for collection and cryopreservation of cord blood units. Herein, we describe our experience at Iran National Cord Blood Bank (INCBB) during 2 years of activity. From November 2010 to 2012, UCBs were collected from 5 hospitals in Tehran. All the collection, processing, testing, cryopreservation and storage procedures were done according to standard operation procedures. Total nucleated cells (TNC) count, viability test, CD34+ cell count, colony forming unit (CFU) assay, screening tests and HLA typing were done on all banked units. Within 3770 collected units, only 32.9% fulfilled banking criteria. The mean volume of units was 105.2 ml and after volume reduction the mean of TNC, viability, CD34+ cells and CFUs was 10.76×10(8), 95.2%, 2.99×10(6) and 7.1×10(5), respectively. One unit was transplanted at Dec 2012 to a 5-year old patient with five of six HLA compatibilities. In our country banking of UCB is new and high rate of hematopoietic stem cell transplants needs expanding CB banks capacity to find more matching units, optimization of methods and sharing experiences to improve biological characterization of units.

  9. Effect of Human WEE1 and Stem Cell Factor on Human CD34+ Umbilical Cord Blood Cell Damage Induced by Chemotherapeutic Agents

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    Ping LEI; Yong HE; Wenfang SHI; Jilin PENG; Sha WU; Huifen ZHU; Jianguo CHEN; Guanxin SHEN

    2007-01-01

    Myelosuppression is one of the major side-effects of most anticancer drugs. To achieve myeloprotection, one bicistronic vector encoding anti-apoptotic protein human WEE1 (WEE1Hu) and proliferation-stimulating stem cell factor (SCF) was generated. In this study, we selected human umbilical cord blood CD34+ cells as the in vitro model in an attempt to investigate whether WEE1Hu, rather than conventional drug-resistant genes, can be introduced to rescue cells from the damage by chemotherapeutic agents such as cisplatin, adriamycin, mitomycin-c and 5-fluorouracil. Cell viability and cytotoxicity assay,colony-forming units in culture assay and externalization of phospholipid phosphatidylserine analysis showed that the expression of WEE1Hu and SCF in CD34+ cells provided the cells with some protection. These findings suggest that the expression of WEE1Hu and SCF might rescue CD34+ cells from chemotherapyinduced myelosuppression.

  10. Inhibition by miR-410 facilitates direct retinal pigment epithelium differentiation of umbilical cord blood-derived mesenchymal stem cells

    Science.gov (United States)

    Choi, Soon Won; Kim, Jae-Jun; Seo, Min-Soo; Park, Sang-Bum; Shin, Tae-Hoon; Shin, Ji-Hee; Seo, Yoojin; Kim, Hyung-Sik

    2017-01-01

    Retinal pigment epithelium (RPE) is a major component of the eye. This highly specialized cell type facilitates maintenance of the visual system. Because RPE loss induces an irreversible visual impairment, RPE generation techniques have recently been investigated as a potential therapeutic approach to RPE degeneration. The microRNA-based technique is a new strategy for producing RPE cells from adult stem cell sources. Previously, we identified that antisense microRNA-410 (anti-miR-410) induces RPE differentiation from amniotic epithelial stem cells. In this study, we investigated RPE differentiation from umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) via anti-miR-410 treatment. We identified miR-410 as a RPE-relevant microRNA in UCB-MSCs from among 21 putative human RPE-depleted microRNAs. Inhibition of miR-410 induces overexpression of immature and mature RPE-specific factors, including MITF, LRAT, RPE65, Bestrophin, and EMMPRIN. The RPE-induced cells were able to phagocytize microbeads. Results of our microRNA-based strategy demonstrated proof-of-principle for RPE differentiation in UCB-MSCs by using anti-miR-410 treatment without the use of additional factors or exogenous transduction. PMID:27297412

  11. Eltrombopag, a thrombopoietin receptor agonist, enhances human umbilical cord blood hematopoietic stem/primitive progenitor cell expansion and promotes multi-lineage hematopoiesis.

    Science.gov (United States)

    Sun, Hongliang; Tsai, Ying; Nowak, Irena; Liesveld, Jane; Chen, Yuhchyau

    2012-09-01

    Umbilical cord blood (UCB) transplantation has emerged as a promising therapy, but it is challenged by scarcity of stem cells. Eltrombopag is a non-peptide, thrombopoietin (TPO) receptor agonist, which selectively activates c-Mpl in humans and chimpanzees. We investigated eltrombopag's effects on human UCB hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) expansion, and its effects on hematopoiesis in vivo. Eltrombopag selectively augmented the expansion of human CD45+, CD34+, and CD41+ cells in bone marrow compartment without effects on mouse bone marrow cells in the NOD/SCID mice xenotransplant model. Consequently, eltrombopag increased peripheral human platelets and white blood cells. We further examined effects in the STAT and AKT signaling pathways in serum-free cultures. Eltrombopag expanded human CD34+ CD38-, CD34+, and CD41+ cells. Both eltrombopag and recombinant human TPO (rhTPO) induced phosphorylation of STAT5 of CD34+ CD41-, CD34- CD41+, and CD34- CD41- cells. rhTPO preferentially induced pSTAT3, pAKT, and more pSTAT5 in CD34- C41+ cells, while eltrombopag had no effects on pSTAT3. In conclusion, eltrombopag enhanced expansion of HSCs/HPCs of human UCB in vivo and in vitro, and promoted multi-lineage hematopoiesis through the expansion of bone marrow HSCs/HPCs of human UCB in vivo. Eltrombopag differed somewhat from rhTPO in the signal transduction pathways by favoring earlier HSC/HPC populations.

  12. How to improve cord blood engraftment?

    Directory of Open Access Journals (Sweden)

    Meral eBeksac

    2016-02-01

    Full Text Available Various factors make cord blood (CB a significant source of hematopoietic stem cells (HSC, including ease of procurement and lack of donor attrition, with the ability to process and store the donor cells long term. Importantly, high proliferative potential of the immature HSCs allows one log less use of cells compared to bone marrow (BM or peripheral blood stem cells. As total nucleated cell (TNC and CD34 + cell content of CB grafts are correlated with engraftment rate and speed, strategies to expand HSC and homing have been developed. This chapter will focus on modalities such as intra-bone administration, fucosylation, CD26 inhibition, Prostaglandin G2 derivative or complement 3 exposure and SDF-1/CXCR4/CXCL-12 pathway interventions that have been experimented successfully. Furthermore increasing evidence in line with better recognition of CB progenitors that are involved in engraftment and homing will also be addressed.

  13. Mesenchymal stem/progenitor cells in human umbilical cord blood as support for ex vivo expansion of CD34+ hematopoietic stem cells and for chondrogenic differentiation

    Institute of Scientific and Technical Information of China (English)

    JIN-FUWANG; LI-JUANWANG; YI-FANWU; YINGXIANG; CHUN-GANGXIE; BING-BINGJIA; JENNYHARRINGTON; IANK.MCNIECE

    2005-01-01

    Background and Objectives. Human mesenchymal stem/progenitor cells (MSPC) ar pluripotent, being the precursors for marrow stroma, bone, cartilage, muscle and connective tissues. Although the presence of hematopoietic stem/progenitor cells (HSPC) in umbilical cord blood (UCB) is well known, that of MSPC has been not fully evaluated. Design and Methods. In this study, we examined the immunophenotype, the supporting function in relation to exvivo expansion of hematopoietic stem progenitor cells and the chondrogenic differentiation of cultured cells with characteristics of MSPC from UCB. When UCB nucleated cells were isolated and 107 cells cultured in IMDM with 20% fetal bovine serum, the mean number of adherent fibroblastlike colonies was 3.5±0.7/106 monuclear cells. Results. UCB-derived MSPC could be expanded for at least 15 passages. In their undifferentiated state, UCB-derived MSPC were CD 13+, CD29+, CD90+, CD105+, CD166+, SH2+,SH3+, SH4+, CD45-, CD34-, and CD14-; they produced stem cell factor, interleukin 6 and tumor necrosis factor α.UCB-derived MSPC cultured in chondrogenic media differentiated into chondrogenic cells. UCB-derived MSPC supported the proliferation and differentiation of CD34+ cells from UCB in vitro. Interpretation and Conclusions. UCB-derived MSPC have the potential to support ex vivo expansion of HSPC and chondrogenic differentiation. UCB should not be regarded as medical waste. It can serve as an alternative source of mesenchymal stem cells and may provide a unique source of fetal cells for cellular and gene therapy.

  14. Bloodstream infection after umbilical cord blood transplantation using reduced-intensity stem cell transplantation for adult patients.

    Science.gov (United States)

    Narimatsu, Hiroto; Matsumura, Tomoko; Kami, Masahiro; Miyakoshi, Shigesaburo; Kusumi, Eiji; Takagi, Shinsuke; Miura, Yuji; Kato, Daisuke; Inokuchi, Chiho; Myojo, Tomohiro; Kishi, Yukiko; Murashige, Naoko; Yuji, Koichiro; Masuoka, Kazuhiro; Yoneyama, Akiko; Wake, Atsushi; Morinaga, Shinichi; Kanda, Yoshinobu; Taniguchi, Shuichi

    2005-06-01

    Bloodstream infection (BSI) is a significant problem after cord blood transplantation (CBT). However, little information has been reported on BSI after reduced-intensity CBT (RI-CBT). We retrospectively reviewed the medical records of 102 patients. The median age of the patients was 55 years (range, 17-79 years). Preparative regimens comprised fludarabine 125 to 150 mg/m 2 , melphalan 80 to 140 mg/m 2 , or busulfan 8 mg/kg and total body irradiation 2 to 8 Gy. Prophylaxis against graft-versus-host disease comprised cyclosporin or tacrolimus. BSI developed within 100 days of RI-CBT in 32 patients. The cumulative incidence of BSI was 25% at day 30 and 32% at day 100. The median onset was day 15 (range, 1-98 days). Causative organisms included Pseudomonas aeruginosa (n = 12), Staphylococcus epidermidis (n = 11), Staphylococcus aureus (n = 6), Enterococcus faecium (n = 4), Enterococcus faecalis (n = 4), Stenotrophomonas maltophilia (n = 4), and others (n = 7). Of the 32 patients with BSI, 25 (84%) died within 100 days after RI-CBT. BSI was the direct cause of death in 8 patients (25%). Univariate analysis failed to identify any significant risk factors. BSI clearly represents a significant and fatal complication after RI-CBT. Further studies are warranted to determine clinical characteristics, identify patients at high risk of BSI, and establish therapeutic strategies.

  15. 脐带血造血干细胞移植的伦理学问题浅析%The Ethical Analysis of the Umbilical Cord Blood Stem Cell Transplantation

    Institute of Scientific and Technical Information of China (English)

    于波海; 高春波; 张萌; 柴淼; 苏丽菊

    2013-01-01

    the umbilical cord blood stem cell transplantation is gradually widespread used, and becoming very important in cure of malignant hematologic disease. the umbilical cord blood bank was established in different country and area in order to more effectively use of the technology. With the gradual development of umbilical cord blood stem cell transplantation, the exposure of the ethic problems also more attention. this article examines and discusses ethical considerations that arise from the umbilical cord blood stem cell transplantation.%脐带血造血干细胞移植在临床上越来越广泛的应用,并且在血液疾病治疗中取得喜人成果,为血液病患者带来新的希望。为了更有效地应用这一新技术,许多国家纷纷建立起了脐带血库。然而,随着脐带血造血干细胞移植应用深度与广度的逐渐展开,其伦理上所暴露的问题也日见受到人们的重视。本文拟就脐带血造血干细胞移植伦理学方面的问题做一探讨。

  16. Ex vivo expansion of hematopoietic stem- and progenitor cells from cord blood in coculture with mesenchymal stroma cells from amnion, chorion, Wharton's jelly, amniotic fluid, cord blood, and bone marrow.

    Science.gov (United States)

    Klein, Caroline; Strobel, Julian; Zingsem, Jürgen; Richter, Richard H; Goecke, Tamme W; Beckmann, Matthias W; Eckstein, Reinhold; Weisbach, Volker

    2013-12-01

    In most cases, the amount of hematopoietic stem and progenitor cells (HSPCs) in a single cord blood (CB) unit is not sufficient for allogenic transplantation of adults. Therefore, two CB units are usually required. The ex vivo expansion of HSPCs from CB in coculture with mesenchymal stroma cells (MSCs) might be an alternative. It was investigated, whether bone marrow-derived MSCs, which have to be obtained in an invasive procedure, introduce a further donor and increases the risk of transmissible infectious diseases for the patient can be replaced by MSCs from amnion, chorion, Wharton's jelly, amniotic fluid, and CB, which can be isolated from placental tissue which is readily available when CB is sampled. In a two-step ex vivo coculture mononuclear cells from cryopreserved CB were cultured with different MSC-feederlayers in a medium supplemented with cytokines (stem cell factor, thrombopoietin [TPO], and granulocyte colony-stimulating factor). Expansion rates were analyzed as well, by long-term culture-initiating cell (LTC-IC) and colony-forming unit (CFU) assays, as by measuring CD34(+)- and CD45(+)-cells. Due to the comparably low number of 5×10(2) to 1×10(4) CD34(+)-cells per cm(2) MSC-monolayer, we observed comparably high expansion rates from 80 to 391,000 for CFU, 70 to 313,000 for CD34(+)-, and 200 to 352,000 for CD45(+)-cells. Expansion of LTC-IC was partly observed. Compared to the literature, we found a better expansion rate of CD34(+)-cells with MSCs from all different sources. This is probably due to the comparably low number of 5×10(2) to 1×10 CD34(+)-cells per cm(2) MSC-monolayer we used. Comparably, high expansion rates were observed from 80 to 391,000 for CFUs, 70 to 313,000 for CD34(+)-, and 200 to 352,000 for CD45(+)-cells. However, the expansion of CD34(+)-cells was significantly more effective with MSCs from bone marrow compared to MSCs from amnion, chorion, and Wharton's jelly. The comparison of MSCs from bone marrow with MSCs from CB and

  17. Cord Blood Transplantation Study (COBLT): cord blood bank standard operating procedures.

    Science.gov (United States)

    Fraser, J K; Cairo, M S; Wagner, E L; McCurdy, P R; Baxter-Lowe, L A; Carter, S L; Kernan, N A; Lill, M C; Slone, V; Wagner, J E; Wallas, C H; Kurtzberg, J

    1998-12-01

    In 1995, the National Heart Lung and Blood Institute (NHLBI) solicited requests for a proposal (RFP) entitled "Transplant Centers for Clinical Research on Transplantation of Umbilical Cord Stem and Progenitor Cells." Three banks, six transplant centers, and one medical coordinating center (MCC) (Table 1) were funded with the overall goal of banking cord blood units (CBU) using a single manual of operations. Furthermore, the clinical protocols to evaluate the transplant outcome for adult and pediatric recipients of these well-characterized CBU would be analyzed in a uniform fashion. Because of the intense interest of the transplantation community in the policies and procedures for cord blood collection and processing, the principal investigators of the cord blood banks (CBB) and NHLBI elected to submit for publication the rationale and an abridged, but detailed, version of the standard operating procedures (SOP) developed between October 1996 and July 1998 prior to the initiation of the clinical protocols to be performed with these CBU. As the SOP will be refined over time, the complete SOP and subsequent amendments will be published and continually updated on the websites from the MCC-The EMMES Corporation (www.EMMES.com). All forms referred to in this document may be obtained from the EMMES website. It is hoped that the publication of this document will lay down a framework that will not only facilitate the development of other CBB but also help us more rapidly define what constitutes an "acceptable" CBU product.

  18. Distribution of human umbilical cord blood-derived mesenchymal stem cells in the Alzheimer's disease transgenic mouse after a single intravenous injection.

    Science.gov (United States)

    Park, Sang Eon; Lee, Na Kyung; Lee, Jeongmin; Hwang, Jung Won; Choi, Soo Jin; Hwang, Hyeri; Hyung, Brian; Chang, Jong Wook; Na, Duk L

    2016-03-02

    The aim of this study was to track the migration of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) administered through a single intravenous injection and to observe the consequential therapeutic effects in a transgenic Alzheimer's disease mouse model. Ten-month-old APP/PS1 mice received a total injection of 1×10 cells through the lateral tail vein and were killed 1, 4, and 7 days after administration. On the basis of immunohistochemical analysis, hUCB-MSCs were not detected in the brain at any of the time points. Instead, most of the injected mesenchymal stem cells were found to be distributed in the lung, heart, and liver. In terms of the molecular effects, statistically significant differences in the amyloid β protein, neprilysin, and SOX2 levels were not observed among the groups. On the basis of the results from this study, we suggest that single intravenously administered hUCB-MSCs are not delivered to the brain and also do not have a significant influence on Alzheimer's disease pathology.

  19. Roles of db-cAMP, IBMX and RA in aspects of neural differentiation of cord blood derived mesenchymal-like stem cells.

    Directory of Open Access Journals (Sweden)

    Murni Tio

    Full Text Available Mesenchymal stem cells (MSCs have multilineage differentiation potential which includes cell lineages of the central nervous system; hence MSCs might be useful in the treatment of neurodegenerative diseases such as Parkinson's disease. Although mesenchymal stem cells have been shown to differentiate into the neural lineage, there is still little knowledge about the underlying mechanisms of differentiation particularly towards specialized neurons such as dopaminergic neurons. Here, we show that MSCs derived from human umbilical cord blood (MSC(hUCBs are capable of expressing tyrosine hydroxylase (TH and Nurr1, markers typically associated with DA neurons. We also found differential phosphorylation of TH isoforms indicating the presence of post-translational mechanisms possibly activating and modifying TH in MSC(hUCB. Furthermore, functional dissection of components in the differentiation medium revealed that dibutyryl-cAMP (db-cAMP, 3-isobutyl-1-methylxanthine (IBMX and retinoic acid (RA are involved in the regulation of Nurr1 and Neurofilament-L expression as well as in the differential phosphorylation of TH. We also demonstrate a possible inhibitory role of the protein kinase A signaling pathway in the phosphorylation of specific TH isoforms.

  20. Lead exposure induces changes in 5-hydroxymethylcytosine clusters in CpG islands in human embryonic stem cells and umbilical cord blood.

    Science.gov (United States)

    Sen, Arko; Cingolani, Pablo; Senut, Marie-Claude; Land, Susan; Mercado-Garcia, Adriana; Tellez-Rojo, Martha M; Baccarelli, Andrea A; Wright, Robert O; Ruden, Douglas M

    2015-01-01

    Prenatal exposure to neurotoxicants such as lead (Pb) may cause stable changes in the DNA methylation (5mC) profile of the fetal genome. However, few studies have examined its effect on the DNA de-methylation pathway, specifically the dynamic changes of the 5-hydroxymethylcytosine (5hmC) profile. Therefore, in this study, we investigate the relationship between Pb exposure and 5mC and 5hmC modifications during early development. To study the changes in the 5hmC profile, we use a novel modification of the Infinium™ HumanMethylation450 assay (Illumina, Inc.), which we named HMeDIP-450K assay, in an in vitro human embryonic stem cell model of Pb exposure. We model Pb exposure-associated 5hmC changes as clusters of correlated, adjacent CpG sites, which are co-responding to Pb. We further extend our study to look at Pb-dependent changes in high density 5hmC regions in umbilical cord blood DNA from 48 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort. For our study, we randomly selected umbilical cord blood from 24 male and 24 female children from the 1st and 4th quartiles of Pb levels. Our data show that Pb-associated changes in the 5hmC and 5mC profiles can be divided into sex-dependent and sex-independent categories. Interestingly, differential 5mC sites are better markers of Pb-associated sex-dependent changes compared to differential 5hmC sites. In this study we identified several 5hmC and 5mC genomic loci, which we believe might have some potential as early biomarkers of prenatal Pb exposure.

  1. MiRNAs and piRNAs from bone marrow mesenchymal stem cell extracellular vesicles induce cell survival and inhibit cell differentiation of cord blood hematopoietic stem cells: a new insight in transplantation.

    Science.gov (United States)

    De Luca, Luciana; Trino, Stefania; Laurenzana, Ilaria; Simeon, Vittorio; Calice, Giovanni; Raimondo, Stefania; Podestà, Marina; Santodirocco, Michele; Di Mauro, Lazzaro; La Rocca, Francesco; Caivano, Antonella; Morano, Annalisa; Frassoni, Francesco; Cilloni, Daniela; Del Vecchio, Luigi; Musto, Pellegrino

    2016-02-01

    Hematopoietic stem cells (HSC), including umbilical cord blood CD34+ stem cells (UCB-CD34+), are used for the treatment of several diseases. Although different studies suggest that bone marrow mesenchymal stem cells (BM-MSC) support hematopoiesis, the exact mechanism remains unclear. Recently, extracellular vesicles (EVs) have been described as a novel avenue of cell communication, which may mediate BM-MSC effect on HSC. In this work, we studied the interaction between UCB-CD34+ cells and BM-MSC derived EVs. First, by sequencing EV derived miRNAs and piRNAs we found that EVs contain RNAs able to influence UCB-CD34+ cell fate. Accordingly, a gene expression profile of UCB-CD34+ cells treated with EVs, identified about 100 down-regulated genes among those targeted by EV-derived miRNAs and piRNAs (e.g. miR-27b/MPL, miR-21/ANXA1, miR-181/EGR2), indicating that EV content was able to modify gene expression profile of receiving cells. Moreover, we demonstrated that UCB-CD34+ cells, exposed to EVs, significantly changed different biological functions, becoming more viable and less differentiated. UCB-CD34+ gene expression profile also identified 103 up-regulated genes, most of them codifying for chemokines, cytokines and their receptors, involved in chemotaxis of different BM cells, an essential function of hematopoietic reconstitution. Finally, the exposure of UCB-CD34+ cells to EVs caused an increased expression CXCR4, paralleled by an in vivo augmented migration from peripheral blood to BM niche in NSG mice. This study demonstrates the existence of a powerful cross talk between BM-MSC and UCB-CD34+ cells, mediated by EVs, providing new insight in the biology of cord blood transplantation.

  2. Concise review: ex vivo expansion of cord blood-derived hematopoietic stem and progenitor cells: basic principles, experimental approaches, and impact in regenerative medicine.

    Science.gov (United States)

    Flores-Guzmán, Patricia; Fernández-Sánchez, Verónica; Mayani, Hector

    2013-11-01

    Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play key roles in the production of mature blood cells and in the biology and clinical outcomes of hematopoietic transplants. The numbers of these cells, however, are extremely low, particularly in umbilical cord blood (UCB); thus, ex vivo expansion of human UCB-derived HSCs and HPCs has become a priority in the biomedical field. Expansion of progenitor cells can be achieved by culturing such cells in the presence of different combinations of recombinant stimulatory cytokines; in contrast, expansion of actual HSCs has proved to be more difficult because, in addition to needing recombinant cytokines, HSCs seem to deeply depend on the presence of stromal cells and/or elements that promote the activation of particular self-renewal signaling pathways. Hence, there is still controversy regarding the optimal culture conditions that should be used to achieve this. To date, UCB transplants using ex vivo-expanded cells have already been performed for the treatment of different hematological disorders, and although results are still far from being optimal, the advances are encouraging. Recent studies suggest that HSCs may also give rise to nonhematopoietic cells, such as neural, cardiac, mesenchymal, and muscle cells. Such plasticity and the possibility of producing nonhematopoietic cells at the clinical scale could bring new alternatives for the treatment of neural, metabolic, orthopedic, cardiac, and neoplastic disorders. Once standardized, ex vivo expansion of human HSCs/HPCs will surely have a positive impact in regenerative medicine.

  3. Combination of low O(2) concentration and mesenchymal stromal cells during culture of cord blood CD34(+) cells improves the maintenance and proliferative capacity of hematopoietic stem cells.

    Science.gov (United States)

    Hammoud, Mohammad; Vlaski, Marija; Duchez, Pascale; Chevaleyre, Jean; Lafarge, Xavier; Boiron, Jean-Michel; Praloran, Vincent; Brunet De La Grange, Philippe; Ivanovic, Zoran

    2012-06-01

    The physiological approach suggests that an environment associating the mesenchymal stromal cells (MSC) and low O(2) concentration would be most favorable for the maintenance of hematopoietic stem cells (HSCs) in course of ex vivo expansion of hematopoietic grafts. To test this hypothesis, we performed a co-culture of cord blood CD34(+) cells with or without MSC in presence of cytokines for 10 days at 20%, 5%, and 1.5% O(2) and assessed the impact on total cells, CD34(+) cells, committed progenitors (colony-forming cells-CFC) and stem cells activity (pre-CFC and Scid repopulating cells-SRC). Not surprisingly, the expansion of total cells, CD34(+) cells, and CFC was higher in co-culture and at 20% O(2) compared to simple culture and low O(2) concentrations, respectively. However, co-culture at low O(2) concentrations provided CD34(+) cell and CFC amplification similar to classical culture at 20% O(2) . Interestingly, low O(2) concentrations ensured a better pre-CFC and SRC preservation/expansion in co-culture. Indeed, SRC activity in co-culture at 1.5% O(2) was higher than in freshly isolated CD34(+) cells. Interleukin-6 production by MSC at physiologically low O(2) concentrations might be one of the factors mediating this effect. Our data demonstrate that association of co-culture and low O(2) concentration not only induces sufficient expansion of committed progenitors (with respect to the classical culture), but also ensures a better maintenance/expansion of hematopoietic stem cells (HSCs), pointing to the oxygenation as a physiological regulatory factor but also as a cell engineering tool.

  4. Cord blood mesenchymal stem cells propel human dendritic cells to an intermediate maturation state and boost interleukin-12 production by mature dendritic cells.

    NARCIS (Netherlands)

    Berk, L.C.J. van den; Roelofs, H.; Huijs, T.; Siebers-Vermeulen, K.G.C.; Raymakers, R.A.P.; Kogler, G.; Figdor, C.G.; Torensma, R.

    2009-01-01

    Pathogen-derived entities force the tissue-resident dendritic cells (DCs) towards a mature state, followed by migration to the draining lymph node to present antigens to T cells. Bone marrow mesenchymal stem cells (MSCs) modulate the differentiation, maturation and function of DCs. In umbilical cord

  5. Conditioned Medium from Placental Mesenchymal Stem Cells Reduces Oxidative Stress during the Cryopreservation of Ex Vivo Expanded Umbilical Cord Blood Cells.

    Science.gov (United States)

    Kadekar, Darshana; Rangole, Sonal; Kale, Vaijayanti; Limaye, Lalita

    2016-01-01

    The limited cell dose in umbilical cord blood (UCB) necessitates ex vivo expansion of UCB. Further, the effective cryopreservation of these expanded cells is important in widening their use in the clinics. During cryopreservation, cells experience oxidative stress due to the generation of reactive oxygen species (ROS). Conditioned medium from mesenchymal stem cells (MSCs-CM) has been shown to alleviate the oxidative stress during wound healing, Alzheimer's disease and ischemic disease. This premise prompted us to investigate the influence of MSCs-CM during cryopreservation of expanded UCB cells. CM-was collected from cord/placental MSCs(C-MSCs-CM, P-MSC-CM). UCB CD34+cells were expanded as suspension cultures in serum free medium containing cytokines for 10 days. Cells were frozen with/without C-MSCs-CM and or P-MSCs-CM in the conventional freezing medium containing 20%FCS +10%DMSO using a programmable freezer and stored in liquid nitrogen. Upon revival, cells frozen with MSCs-CM were found to be superior to cells frozen in conventional medium in terms of viability, CD34+content and clonogenecity. Priming of revived cells for 48 hrs with MSCs-CM further improved their transplantation ability, as compared to those cultured without MSCs-CM. P-MSCs-CM radically reduced the oxidative stress in cryopreserved cells, resulting in better post thaw functionality of CD34+ cells than with C-MSCs-CM. The observed cryoprotective effect of MSCs-CM was primarily due to anti-oxidative and anti-apoptotic properties of the MSCs-CM and not because of the exosomes secreted by them. Our data suggest that MSCs-CM can serve as a valuable additive to the freezing or the priming medium for expanded UCB cells, which would increase their clinical applicability.

  6. Alginate/PEG based microcarriers with cleavable crosslinkage for expansion and non-invasive harvest of human umbilical cord blood mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chunge [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, No. 92, Weijin Road, Tianjin 300072 (China); Qian, Yufeng [Department of Chemistry and Biochemistry, University of Texas at Austin, 2500 Speedway, Austin, TX 78712 (United States); Zhao, Shuang [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, No. 92, Weijin Road, Tianjin 300072 (China); Yin, Yuji, E-mail: yinyuji@tju.edu.cn [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, No. 92, Weijin Road, Tianjin 300072 (China); Li, Junjie, E-mail: li41308@tju.edu.cn [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, No. 92, Weijin Road, Tianjin 300072 (China); Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, No. 27, Taiping Road, Beijing 100850 (China)

    2016-07-01

    Porous microcarriers are increasingly used to expand and harvest stem cells. Generally, the cells are harvested via proteolytic enzyme treatment, which always leads to damages to stem cells. To address this disadvantage, a series of alginate/PEG (AL/PEG) semi-interpenetrating network microcarriers are prepared in this study. In this AL/PEG system, the chemically cross-linked alginate networks are formed via the reaction between carboxylic acid group of alginate and di-terminated amine groups of cystamine. PEG is introduced to modulate the degradation of microcarriers, which does not participate in this cross-linked reaction, while it interpenetrates in alginate network via physical interactions. In addition, chitosan are coated on the surface of AL/PEG to improve the mechanical strength via the electrostatic interactions. Biocompatible fibronectin are also coated on these microcarriers to modulate the biological behaviors of cells seeded in microcarriers. Results suggest that the size of AL/PEG microcarriers can be modulated via adjusting the contents and molecular weight of PEG. Moreover, the microcarriers are designed to be degraded with cleavage of disulfide crosslinkage. By changing the type and concentration of reductant, the ratio of AL to PEG, and the magnitude of chitosan coating, the degradation ability of AL/PEG microcarriers can be well controlled. In addition, AL/PEG microcarriers can support the attachment and proliferation of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). More importantly, the expanded hUCB-MSCs can be detached from microcarriers after addition of reductant, which indeed reduce the cell damage caused by proteolytic enzyme treatment. Therefore, it is convinced that AL/PEG based microcarriers will be a promising candidate for large-scale expansion of hUCB-MSCs. - Graphical abstract: Alginate/PEG IPN microcarriers can support the attachment and expansion of hUCB-MSCs. More importantly, the expanded cells can be harvested

  7. Private Cord Blood Banking: Experiences And Views Of Pediatric Hematopoietic Cell Transplantation Physicians

    Science.gov (United States)

    Thornley, Ian; Eapen, Mary; Sung, Lillian; Lee, Stephanie J.; Davies, Stella M.; Joffe, Steven

    2011-01-01

    Objective Private cord blood banks are for-profit companies that facilitate storage of umbilical cord blood for personal or family use. Pediatric hematopoietic cell transplantation (HCT) physicians are currently best situated to use cord blood therapeutically. We sought to describe the experiences and views of these physicians regarding private cord blood banking. Participants and Methods Emailed cross-sectional survey of pediatric HCT physicians in the United States and Canada. 93/152 potentially eligible physicians (93/130 confirmed survey recipients) from 57 centers responded. Questions addressed the number of transplants performed using privately banked cord blood, willingness to use banked autologous cord blood in specific clinical settings, and recommendations to parents regarding private cord blood banking. Results Respondents reported having performed 9 autologous and 41 allogeneic transplants using privately banked cord blood. In 36/40 allogeneic cases for which data were available, the cord blood had been collected because of a known indication in the recipient. Few respondents would choose autologous cord blood over alternative stem cell sources for treatment of acute lymphoblastic leukemia in second remission. In contrast, 55% would choose autologous cord blood to treat high-risk neuroblastoma, or to treat severe aplastic anemia in the absence of an available sibling donor. No respondent would recommend private cord blood banking for a newborn with one healthy sibling when both parents were of Northern European descent; 11% would recommend banking when parents were of different minority ethnicities. Conclusions Few transplants have been performed using cord blood stored in the absence of a known indication in the recipient. Willingness to use banked autologous cord blood varies depending on disease and availability of alternative stem cell sources. Few pediatric HCT physicians endorse private cord blood banking in the absence of an identified recipient

  8. Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study

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    Isaac Perea-Gil

    2015-01-01

    Full Text Available Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs to comparatively assess the immunomodulatory properties of cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs. Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune response in vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells.

  9. Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study

    Science.gov (United States)

    Perea-Gil, Isaac; Monguió-Tortajada, Marta; Gálvez-Montón, Carolina; Bayes-Genis, Antoni; Borràs, Francesc E.; Roura, Santiago

    2015-01-01

    Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs) with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) to comparatively assess the immunomodulatory properties of cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs). Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ) was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune response in vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells. PMID:25861626

  10. Chondrogenic Differentiation of Human Umbilical Cord Blood-Derived Unrestricted Somatic Stem Cells on A 3D Beta-Tricalcium Phosphate-Alginate-Gelatin Scaffold

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    Masoud Soleimani

    2014-03-01

    Full Text Available Objective: Finding cell sources for cartilage tissue engineering is a critical procedure. The purpose of the present experimental study was to test the in vitro efficacy of the beta-tricalcium phosphate-alginate-gelatin (BTAG scaffold to induce chondrogenic differentiation of human umbilical cord blood-derived unrestricted somatic stem cells (USSCs. Materials and Methods: In this experimental study, USSCs were encapsulated in BTAG scaffold and cultured for 3 weeks in chondrogenic medium as chondrogenic group and in Dulbecco’s Modified Eagle’s Medium (DMEM as control group. Chondrogenic differentiation was evaluated by histology, immunofluorescence and RNA analyses for the expression of cartilage extracellular matrix components. The obtain data were analyzed using SPSS version 15. Results: Histological and immunohistochemical staining revealed that collagen II was markedly expressed in the extracellular matrix of the seeded cells on scaffold in presence of chondrogenic media after 21 days. Reverse transcription-polymerase chain reaction (RT-PCR showed a significant increase in expression levels of genes encoded the cartilage-specific markers, aggrecan, type I and II collagen, and bone morphogenetic protein (BMP-6 in chondrogenic group. Conclusion: This study demonstrates that BTAG can be considered as a suitable scaffold for encapsulation and chondrogenesis of USSCs.

  11. Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer's disease mouse model through modulation of neuroinflammation.

    Science.gov (United States)

    Lee, Hyun Ju; Lee, Jong Kil; Lee, Hyun; Carter, Janet E; Chang, Jong Wook; Oh, Wonil; Yang, Yoon Sun; Suh, Jun-Gyo; Lee, Byoung-Hee; Jin, Hee Kyung; Bae, Jae-Sung

    2012-03-01

    Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) have a potential therapeutic role in the treatment of neurological disorders, but their current clinical usage and mechanism of action has yet to be ascertained in Alzheimer's disease (AD). Here we report that hUCB-MSC transplantation into amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice significantly improved spatial learning and memory decline. Furthermore, amyloid-β peptide (Aβ) deposition, β-secretase 1 (BACE-1) levels, and tau hyperphosphorylation were dramatically reduced in hUCB-MSC transplanted APP/PS1 mice. Interestingly, these effects were associated with reversal of disease-associated microglial neuroinflammation, as evidenced by decreased microglia-induced proinflammatory cytokines, elevated alternatively activated microglia, and increased anti-inflammatory cytokines. These findings lead us to suggest that hUCB-MSC produced their sustained neuroprotective effect by inducing a feed-forward loop involving alternative activation of microglial neuroinflammation, thereby ameliorating disease pathophysiology and reversing the cognitive decline associated with Aβ deposition in AD mice.

  12. Comparative Analysis of Human Mesenchymal Stem Cells from Bone Marrow, Adipose Tissue, and Umbilical Cord Blood as Sources of Cell Therapy

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    Yoon Sun Yang

    2013-09-01

    Full Text Available Various source-derived mesenchymal stem cells (MSCs have been considered for cell therapeutics in incurable diseases. To characterize MSCs from different sources, we compared human bone marrow (BM, adipose tissue (AT, and umbilical cord blood-derived MSCs (UCB-MSCs for surface antigen expression, differentiation ability, proliferation capacity, clonality, tolerance for aging, and paracrine activity. Although MSCs from different tissues have similar levels of surface antigen expression, immunosuppressive activity, and differentiation ability, UCB-MSCs had the highest rate of cell proliferation and clonality, and significantly lower expression of p53, p21, and p16, well known markers of senescence. Since paracrine action is the main action of MSCs, we examined the anti-inflammatory activity of each MSC under lipopolysaccharide (LPS-induced inflammation. Co-culture of UCB-MSCs with LPS-treated rat alveolar macrophage, reduced expression of inflammatory cytokines including interleukin-1α (IL-1α, IL-6, and IL-8 via angiopoietin-1 (Ang-1. Using recombinant Ang-1 as potential soluble paracrine factor or its small interference RNA (siRNA, we found that Ang-1 secretion was responsible for this beneficial effect in part by preventing inflammation. Our results demonstrate that primitive UCB-MSCs have biological advantages in comparison to adult sources, making UCB-MSCs a useful model for clinical applications of cell therapy.

  13. Efficient reprogramming of human cord blood CD34+ cells into induced pluripotent stem cells with OCT4 and SOX2 alone.

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    Meng, Xianmei; Neises, Amanda; Su, Rui-Jun; Payne, Kimberly J; Ritter, Linda; Gridley, Daila S; Wang, Jun; Sheng, Matilda; Lau, K-H William; Baylink, David J; Zhang, Xiao-Bing

    2012-02-01

    The reprogramming of cord blood (CB) cells into induced pluripotent stem cells (iPSCs) has potential applications in regenerative medicine by converting CB banks into iPSC banks for allogeneic cell replacement therapy. Therefore, further investigation into novel approaches for efficient reprogramming is necessary. Here, we show that the lentiviral expression of OCT4 together with SOX2 (OS) driven by a strong spleen focus-forming virus (SFFV) promoter in a single vector can convert 2% of CB CD34(+) cells into iPSCs without additional reprogramming factors. Reprogramming efficiency was found to be critically dependent upon expression levels of OS. To generate transgene-free iPSCs, we developed an improved episomal vector with a woodchuck post-transcriptional regulatory element (Wpre) that increases transgene expression by 50%. With this vector, we successfully generated transgene-free iPSCs using OS alone. In conclusion, high-level expression of OS alone is sufficient for efficient reprogramming of CB CD34(+) cells into iPSCs. This report is the first to describe the generation of transgene-free iPSCs with the use of OCT4 and SOX2 alone. These findings have important implications for the clinical applications of iPSCs.

  14. Incidence of human herpes virus-6 and human cytomegalovirus infections in donated bone marrow and umbilical cord blood hematopoietic stem cells

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    Behzad-Behbahani A

    2008-01-01

    Full Text Available This study examined the incidence of human herpes virus-6 (HHV-6 and human cytomegalovirus (HCMV infections that are potentially transmitted to haematopoietic stem cells (HSC transplant recipients via bone marrow (BM or umbilical cord blood (UCB. Bone marrow progenitor cells were collected from 30 allogenic BM donors. UCB HSC were collected from 34 subjects. The extracted DNA was then processed using nested polymerase chain reaction (nPCR technique. HCMV and HHV-6 serological status were determined by enzyme immunoassay (EIA. Nested PCR identified HCMV in 22 (73% of 30 samples of BM progenitor cells but in only eight (23.5% of 34 samples of UBC HSC ( P = 0.001. HHV-6 DNA was detected in 11 (36.6% of 30 BM progenitor cells and in only one (2.9% of 34 UBC cells ( P = 0.002. Both HHV-6 and HCMV infections were determined in nine (26.5% of 34 bone marrow samples. The results indicate that, the risk of HCMV and HHV-6 via BM progenitor cells is higher than transmission by UCB cells ( P= 0.04.

  15. [A Nude Mouse Model for Human Umbilical Cord Blood Transplantation

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    Lan, Jiongcai; Liu, Hongyu; Chen, Qiang; Yang, Chongli; Zhang, Zhimei

    2000-03-01

    To evaluate the hematopoietic potentiality and the migration and homing routine of separated as well as cryopreserved umbilical cord blood hematopoietic cells, the BALB/cnu(+) mice were used to establish a murine model. This can prepare for the clinical transplantation and the establishment of a large-scale cord blood bank. The result indicated that the hydroxyethyl starch (HES) sedimentation and DMSO step-by-step cryopreservation procedure resulted in only less losses of hematopoietic progenitor cells and also unharmful to the hematopietic potentiality. We can found evidence for successful transplantation in each mouse which received (1.0 - 2.0) x 10(7) separated or cryopresered hematopoietic cells from cord blood, which lasted for about fifty days. The results demonstrated that (1) HES sedimentation and DMSO cryopreservation procedure can keep the hematopoietic potentiality of cord blood, and so can be used to clinical transplantation or establishment of a cord blood bank; (2) Rich hematopoietic stem cells in human cord blood can cross the xenogenetic barriers and successfully engraft mice; (3) The hematopoietic cells migrated among bone marrow, liver, spleen, lung and kidney in the mice and homed to bone marrow by the end. Cryopreservation may influence the adhesion molecule on the hematopoietic cells and the homing behaviour, but not influence their hematopoietic potentiality.

  16. GDF-15 secreted from human umbilical cord blood mesenchymal stem cells delivered through the cerebrospinal fluid promotes hippocampal neurogenesis and synaptic activity in an Alzheimer's disease model.

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    Kim, Dong Hyun; Lee, Dahm; Chang, Eun Hyuk; Kim, Ji Hyun; Hwang, Jung Won; Kim, Ju-Yeon; Kyung, Jae Won; Kim, Sung Hyun; Oh, Jeong Su; Shim, Sang Mi; Na, Duk Lyul; Oh, Wonil; Chang, Jong Wook

    2015-10-15

    Our previous studies demonstrated that transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the hippocampus of a transgenic mouse model of Alzheimer's disease (AD) reduced amyloid-β (Aβ) plaques and enhanced cognitive function through paracrine action. Due to the limited life span of hUCB-MSCs after their transplantation, the extension of hUCB-MSC efficacy was essential for AD treatment. In this study, we show that repeated cisterna magna injections of hUCB-MSCs activated endogenous hippocampal neurogenesis and significantly reduced Aβ42 levels. To identify the paracrine factors released from the hUCB-MSCs that stimulated endogenous hippocampal neurogenesis in the dentate gyrus, we cocultured adult mouse neural stem cells (NSCs) with hUCB-MSCs and analyzed the cocultured media with cytokine arrays. Growth differentiation factor-15 (GDF-15) levels were significantly increased in the media. GDF-15 suppression in hUCB-MSCs with GDF-15 small interfering RNA reduced the proliferation of NSCs in cocultures. Conversely, recombinant GDF-15 treatment in both in vitro and in vivo enhanced hippocampal NSC proliferation and neuronal differentiation. Repeated administration of hUBC-MSCs markedly promoted the expression of synaptic vesicle markers, including synaptophysin, which are downregulated in patients with AD. In addition, in vitro synaptic activity through GDF-15 was promoted. Taken together, these results indicated that repeated cisterna magna administration of hUCB-MSCs enhanced endogenous adult hippocampal neurogenesis and synaptic activity through a paracrine factor of GDF-15, suggesting a possible role of hUCB-MSCs in future treatment strategies for AD.

  17. 脐血干细胞和脐带间充质干细胞联合移植治疗自闭症%Umbilical blood stem cell and umbilical cord mesenchymal stem cell combination transplantation on autism

    Institute of Scientific and Technical Information of China (English)

    杨华强; 张荣环; 李贞艳; 杜玲; 李东升; 张琼

    2012-01-01

    目的 探讨干细胞移植治疗自闭症的可行性、疗效和安全性.方法 将脐血干细胞和脐带间充质干细胞分别通过静脉输注和腰穿鞘内注射途径移植到自愿接受干细胞移植的2例自闭症患者体内.术后随访6个月定期观察患者临床症状及各项指标的变化,并采用儿童自闭症评定量表(CARS)和临床总体评定量表(CGIS)进行综合分析.结果 治疗后患者临床症状较治疗前明显好转,并且随访半年症状持续缓解无复发.2例患者CARS较治疗前明显降低、CGIS较治疗前明显好转,移植过程中及治疗后未出现严重的并发症和明显的不良反应.结论 脐血干细胞和脐带间充质干细胞联合移植治疗自闭症患者是一种值得借鉴的方法.%Objective It is to approach the feasibility, clinical effect and safety of stem cell transplantation in the treatment of autism. Methods Two patients with autism were received umbilical blood stem cell and umbilical cord mesenchymal stem cell combination transplantation by intravenous infusion and lumbar puncture intrathecal injections respectively. The patients were followed up for six months after transplantation, and the clinical symptoms and various indexes were observed. Childhood Autism Rating Scale ( CARS ) and Clinical Global Impression Scale ( CGIS ) were employed to assess the children of autism. Results The clinical symptoms of the two patients were improved obviously after transplantation treatment, and the patient ' s conditions were continuously relieved and no recurrence after six months was followed up. CARS were markedly decreased and CGIS were markedly improved than before treatment for all two patients. Various biochemical indicators were normal and the patient had no severe complications and clear side effects after transplantation. Conclusion The combination transplantation of umbilical blood stem cell and umbilical cord mesenchymal stem cell can be a new hope for autism

  18. [Effects of human mesenchymal stem cells and fibroblastoid cell line as feeder layers on expansion of umbilical cord blood CD34(+) cells in vitro].

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    Ma, Li-Jun; Gao, Lei; Zhou, Hong; Qiu, Hui-Ying; Hu, Xiao-Xia; Xie, Lin-Na; Wang, Jian-Min

    2006-10-01

    To investigate the effects of human mesenchymal stem cells (MSC) and human fibroblastoid cell line (HFCL) as feeder layer on expansion of umbilical cord blood CD34(+) cells in vitro, (60)Co gamma-ray irradiated MSC and HFCL were used as feeder layer to expand cord blood CD34(+) cells in culture. The efficiencies of MSC and HFCL on expansion of CD34(+) cells in culture with or without cytokines were compared. The results showed that no matter whether cytokines (rhFL, rhSCF, rhTPO) were added, the proliferation of nucleated cells after expansion for 12 days in HFCL group was statistically higher than that in MSC group, i.e. with cytokines (9797 +/- 361)% vs (7061 +/- 418)%; without cytokines (5305 +/- 354)% vs (1992 +/- 247)%, when the cell numbers at day 0 was accounted as 100%), P 0.05. However, in the presence of cytokines, the propagating rate of MSC group was lower than that of HFCL group (939 +/- 212)% vs (1617 +/- 222)%, P < 0.01. MSC was better than HFCL in maintaining the LTC-IC of UCB CD34(+) cells, i.e. the number of CFU-GM colonies in the fifth week was (129.95 +/- 8.73) /10(5) seeded cells vs (89.81 +/- 10.29) colonies/10(5) cells, P < 0.05; with addition of cytokines, the effect was more obvious, i.e. the number of CFU-GM colonies in the fifth week (192.93 +/- 4.95)/10(5) seeded cells vs (90.47 +/- 14.28) colonies/10(5) seeded cells, P < 0.01. MSC mixed with a certain proportion of HFCL facilitated maintaining the LTC-IC of UCB CD34(+) cells. When the proportion was 4:1, the number of CFU-GM colonies was the highest (186.89 +/- 11.11)/10(5) seeded cells, which was higher than that of both 3:2 group [(138.92 +/- 14.84) colonies/10(5) seeded cells] and MSC only group, i.e. (64.63 +/- 6.11) colonies/10(5) seeded cells, both P < 0.01. It is concluded that HFCL is better than MSC in maintaining the expansion of CD34(+) cells and cytokines can enhance this effect, while MSC are stronger than HFCL in maintaining the LTC-IC of UCB CD34(+) cells in vitro. MSC

  19. Fibroblast growth factor-4 and hepatocyte growth factor induce differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Xin-Qin Kang; Wei-Jin Zang; Li-Jun Bao; Dong-Ling Li; Tu-Sheng Song; Xiao-Li Xu; Xiao-Jiang Yu

    2005-01-01

    AIM: To investigate the differentiation of human umbilical cord blood (HUCB)-derived mesenchymal stem cells (MSCs) into hepatocytes by induction of fibroblast growth factor-4 (FGF-4) and hepatocyte growth factor (HGF), and to find a new source of cell types for therapies of hepatic diseases.METHODS: vSCs were isolated by combining gradient density centrifugation with plastic adherence. When HUCB-derived MSCs reached 70% confluence, they were cultured in Iscove modified Dulbecco medium (IMDM) supplemented with 10 mL/L FBS, 20 ng/mL HGF and 10 ng/mL FGF-4. The medium was changed every 4 d and stored for albumin, alpha-fetoprotein (AFP) and urea assay. Expression of CK-18 was detected by immunocytochemistry. Glycogen storage in hepatocytes was determined by PAS staining.RESULTS: By combining gradient density centrifugation with plastic adherence, we could isolate MSCs from 25.6% of human umbilical cord blood. When MSCs were cultured with FGF-4 and HGF, approximately 63.6% of cells became small, round and epithelioid on d 28 by morphology. Compared with the control, the level of AFP increased significantly from d 12 to 18.20±1.16 μg/L (t = 2.884, P<0.05) in MSCs cultured with FGF-4 and HGF, and was higher (54.28±3.11 μg/L) on d 28 (t = 13.493, P<0.01). Albumin increased significantly on d 16 (t = 6.68, P<0.01) to 1.02±0.15 μg/mL, and to 3.63±0.30 μg/mL on d 28 (t = 11.748, P<0.01). Urea(4.72±1.03 μmol/L) was detected on d 20 (t = 4.272,P<0.01), and continued to increase to 10.28±1.06 μmol/L on d 28 (t = 9.276, P<0.01). Cells expressed CK-18 on d 16. Glycogen storage was observed on d 24. CONCLUSION: HUCB-derived MSCs can differentiate into hepatocytes by induction of FGF-4 and HGF. HUCBderived MSCs are a new source of cell types for cell transplantation therapy of hepatic diseases.

  20. Platelet gene therapy corrects the hemophilic phenotype in immunocompromised hemophilia A mice transplanted with genetically manipulated human cord blood stem cells.

    Science.gov (United States)

    Shi, Qizhen; Kuether, Erin L; Chen, Yingyu; Schroeder, Jocelyn A; Fahs, Scot A; Montgomery, Robert R

    2014-01-16

    Our previous studies have demonstrated that platelet FVIII (2bF8) gene therapy can improve hemostasis in hemophilia A mice, even in the presence of inhibitory antibodies, but none of our studies has targeted human cells. Here, we evaluated the feasibility for lentivirus (LV)-mediated human platelet gene therapy of hemophilia A. Human platelet FVIII expression was introduced by 2bF8LV-mediated transduction of human cord blood (hCB) CD34(+) cells followed by xenotransplantation into immunocompromised NSG mice or NSG mice in an FVIII(null) background (NSGF8KO). Platelet FVIII was detected in all recipients that received 2bF8LV-transduced hCB cells as long as human platelet chimerism persisted. All NSGF8KO recipients (n = 7) that received 2bF8LV-transduced hCB cells survived tail clipping if animals had greater than 2% of platelets derived from 2bF8LV-transduced hCB cells, whereas 5 of 7 survived when human platelets were 0.3% to 2%. Whole blood clotting time analysis confirmed that hemostasis was improved in NSGF8KO mice that received 2bF8LV-transduced hCB cells. We demonstrate, for the first time, the feasibility of 2bF8LV gene delivery to human hematopoietic stem cells to introduce FVIII expression in human platelets and that human platelet-derived FVIII can improve hemostasis in hemophilia A.

  1. Preliminary evaluation of intravenous infusion and intrapancreatic injection of human umbilical cord blood-derived mesenchymal stem cells for the treatment of diabetic mice

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    Ngoc Kim Phan

    2014-03-01

    Full Text Available Type 1 diabetes mellitus is characterized by the destruction of pancreatic islet beta cells, which leads to insulin insufficiency, hyperglycemia, and reduced metabolic glucose level. Insulin replacement is the current standard therapy for type 1 diabetes mellitus but has several limitations. Pancreatic islet transplantation can result in the production of exogenous insulin, but its use is limited by immune-rejection and donor availability. Recent studies have shown that mesenchymal stem cells (MSCs can transdifferentiate into insulin-producing cells (IPCs, which could be utilized for diabetes mellitus treatment. Previously published reports have demonstrated that MSC or IPC transplantation could produce significant improvement in mouse models of diabetes mellitus. This study was aimed at determining the effects of two different methods of MSC transplantation on the efficacy of diabetes mellitus treatment in mouse models. The MSCs were isolated from umbilical cord blood and were proliferated following a previously published procedure. Diabetes mellitus was induced in mice by streptozotocin (STZ injection. Thirty days after transplantation, the weight of the mice treated by intra-venous infusion and intra-pancreatic injection was found to be 22% and 14% higher than that of the un-treated mice. The blood glucose concentrations in both intra-venous infusion and intra-pancreatic injection groups decreased and remained more stable than those in the control group. Moreover, insulin was detected in the serum of the treated mice, and the pancreas also showed gradual recovery. Based on the results of this preliminary investigation, intra-venous infusion seems more suitable than intra-pancreatic injection for MSC transplantation for diabetes mellitus treatment. [Biomed Res Ther 2014; 1(3.000: 98-105

  2. The Role of Amnion Membrane-Derived Mesenchymal Stem Cells on Differentiation and Expansion of Natural Killer Cell Progenitors Originated From Umbilical Cord Blood Mononuclear Cells

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    Ahmadi

    2015-11-01

    Full Text Available Background Natural killer (NK cells are members of the innate immune system. Their unique properties, including recognition of viral infected and tumor cells without major histocompatibility complex (MHC restriction or prior sensitization, make them a suitable choice for immunotherapy. Low numbers of NK cells in circulating blood is the most important obstacle for this goal. Objectives The aim of this study was to make an optimum in vitro condition to proliferate and differentiate cord blood (CB-NK cell progenitors to mature NK cells, which can be used for cell therapy. Materials and Methods In our study, CB-Mononuclear Cells’ (MNCs CD3+ lymphocytes were positive depleted using immunomagnetic microbeads. This CD3-depleted (CD3-dep CB - MNCs compartment was used for in vitro expansion with or without a layer of amnion membrane mesenchymal stem cells (MSCs in combination with cytokines that are essential for NK cells expansion (IL-2, IL-3, IL-15, and FLT3 ligand. The expansion period lasted for one week. On day seven, immunophenotype and fold expansion of differentiated cells were measured. Results Combination of cytokines and MSC layer yielded significant fold expansion in comparison with cytokines without feeder conditions (day 7: 5.2 ± 1.12 and 2 ± 0.78, respectively, P < 0.05. CD3-/CD56+ cells percentage increased during the culture period in MSCs/with cytokine and cytokine/without feeder, respectively (day 0: 4.4 ± 0.42% and day 7: 22.9 ± 3.6% and 13.9 ± 1.92 % for MSC/with cytokine and cytokine without feeder, respectively. Conclusions Our results suggested that CB-NK cells progenitors could proliferate and differentiate on feeder layer of amnion membrane MSCs in combination with specific cytokines to produce NK cells for immunotherapy.

  3. The Validity of the Umbilical Cord Blood Stem Cells Deposit Contracts%脐带血干细胞捐赠与自存契约之效力分析

    Institute of Scientific and Technical Information of China (English)

    刘颖

    2012-01-01

    与脐带血储存相关的契约以其储存目的为标准,称当事人以自存脐带血干细胞为目的所缔结的为"自存契约",而以他捐为目的者,称之为"捐赠契约"。基于脐带血干细胞所有权归属解释上的差异,比照法律行为之生效要件,检视我国现有的脐带血捐赠与自存契约的效力,并得出结论即宜以母亲为脐带血所有权人以及契约当事人的地位订立契约,借此契约的订立,能让母亲为子女预存脐带血的意志得以完整实现,脐带血干细胞的利用也会更有效。%Umbilical cord blood stem cells, or the storage of the motivation tor the use ot the possible tuture for me purpose called "save", or the charity gift for public use and for the purpose is called "the contributed". According to the storage purpose the umbilical cord blood stem cells with a party for the purpose of that concluded as "the deposit contract", and he contributed to for purposes, called it "donation contract". In this paper, the umbilical cord blood stem cell ownership on the interpretation of differences, and combine with validity of civil juristic act actually, examine our country's existing cord blood donation and save the effectiveness of the contract. And concluded that is appropriate to mother as ownership of umbilical cord blood to sign a contract. By this way, it can let mother for children stored umbilical cord blood.

  4. Cord Blood Banking Standards: Autologous Versus Altruistic.

    Science.gov (United States)

    Armitage, Sue

    2015-01-01

    Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as "biological insurance" should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards.

  5. Cord blood transplants for SCID: better B-cell engraftment?

    Science.gov (United States)

    Chan, Wan-Yin; Roberts, Robert Lloyd; Moore, Theodore B; Stiehm, E Richard

    2013-01-01

    Hematopoietic stem-cell transplantation is the treatment of choice for severe combined immunodeficiency (SCID). Despite successful T-cell engraftment in transplanted patients, B-cell function is not always achieved; up to 58% of patients require immunoglobulin therapy after receiving haploidentical transplants. We report 2 half-sibling males with X-linked γ-chain SCID treated with different sources of stem cells. Sibling 1 was transplanted with T-cell-depleted haploidentical maternal bone marrow and sibling 2 was transplanted with 7/8 human leukocyte antigen-matched unrelated umbilical cord blood. Both patients received pretransplant conditioning and posttransplant graft-versus-host-disease prophylaxis. B-cell engraftment and function was achieved in sibling 1 but not in sibling 2. This disparate result is consistent with a review of 19 other SCID children who received cord blood transplants. B-cell function, as indicated by no need for immunoglobulin therapy, was restored in 42% of patients given haploidentical transplants and in 68% of patients given matched unrelated donor transplants compared with 80% of patients given cord blood transplants. Cord blood is an alternative source of stem cells for transplantation in children with SCID and has a higher likelihood of B-cell reconstitution.

  6. 'Two's company--Three's a crowd': the collection of umbilical cord blood for commercial stem cell banks in England and the midwifery profession.

    Science.gov (United States)

    Machin, Laura L; Brown, Nik; McLeod, Danae

    2012-06-01

    to explore how lay and professional stakeholders within umbilical cord blood banking discussed midwives' and privately employed phlebotomists' roles in light of commercial UCB collection, and what insights this offers of midwifery authority and power. qualitative study using face-to-face, semi-structured interviews that were digitally recorded, transcribed and coded according to themes relating to the research aims. across England. 61 interviews were conducted between April 2009 and August 2010 with lay and professional stakeholders within umbilical cord blood banking. the space and access requirements for privately employed phlebotomists to conduct their work were discussed and highlighted the discursive and spatial boundary-work conducted by, or on behalf of, midwives to retain their authority over the umbilical cord blood and labour rooms. midwives were portrayed as accommodating privately employed phlebotomists to some extent. It was implied that midwives did so because phlebotomists conformed to implicit boundaries, which required respecting midwives' authority over the labour ward, room and the umbilical cord blood. In turn, midwives' power was protected. the findings highlight the important role of spatial boundaries and the significance of the organisation of spaces when implementing new services within health care. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Immunoregulation and human umbilical cord blood-derived mesenchymal stem cells transplantation%脐血间充质干细胞移植与免疫调节

    Institute of Scientific and Technical Information of China (English)

    焦保良; 王景川; 高炳华; 王新生

    2012-01-01

    BACKGROUND: Research in recent years suggests that the self-renewal and multi-directional differentiation potency of human umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) offer basic condition to cell transplantation treatment. Moreover, their immunoloregulation function enormously expands the direction and limits cell transplantation treatment. OBJECTIVE: To retrospectively analyze the immunoloregulation and human UCB-MSCs transplantation. METHODS: The key word "umbilical cord blood-derived mesenchymal stem cells" was used to search in Pubmed database and CNKI database from January 2008 to June 2011 in English and Chinese using computer. The preliminary screening was made through reading the title and abstract. The articles with unrelated contents, repetitive and Meta analysis were excluded. 30 papers of pertinent literature to be published in the near future or published in the authority magazine were selected to review. RESULTS AND CONCLUSION: Human UCB-MSCs have the similar self-renewal and multi-directional differentiation potency with the bone marrow derived mesenchymal stem cells. Through cell transplantation technique, human UCB-MSCs show powerful potentiality in diabetes mellitus treatment, neural degeneration disease like Alzheimer's disease and Parkinson's disease and injury of nerve retreatment. Meanwhile, human UCB-MSCs have immunoregulatory ettects, they can lower immune reaction through down regulation of T-cells. We also get some advancements on several immunological diseases such as cell therapy of graft versus host disease and lupus nephritis.%背景:近年研究显示,脐血间充质干细胞的自我更新和多向分化潜能为细胞移植治疗提供了基础条件,而其免疫调节功能也极大地拓展了细胞治疗的方向和范围. 目的:就近期脐血间充质干细胞的免疫调节和细胞移植研究进行回顾分析. 摘要进行初筛,排除研究内容与此文无关的文献、重复性研究及Meta分析,

  8. Pluripotent stem cells isolated from umbilical cord form embryonic like bodies in a mesenchymal layer culture.

    Science.gov (United States)

    Tsagias, Nikos; Kouzi-Koliakos, Kokkona; Karagiannis, Vasileios; Tsikouras, P; Koliakos, George G

    2015-03-01

    Recently the matrix of umbilical cord began to use as an alternative source of stem cells additionally to the blood of umbilical cord. Umbilical cord has been used mainly for mesenchymal stem cell banking. The immunological characteristics of mesenchymal stem cells in combination with their ability to avoid rejection make them an attractive biological material for transplantations. In this study the isolation of small in size pluripotent stem cells from umbilical cord expressing early transcription factors with characteristics that resemble to embryonic stem cells is investigated. Pluripotent stem cells were isolated from human umbilical cords, by a new strategy method based on unique characteristics such as the small size and the positivity on early transcription factors OCT and Nanog. An enriched population of CXCR4(+) OCT(+) Nanog(+) CD45(-) small stem cells from the cord was isolated. This fraction was able to create alkaline phosphatase positive like spheres forms in a mesenchymal layer with multilineage differentiation capacity. Our results were assessed by RT PCR and electophoresis for the pluripotent genes. These data suggest that umbilical cord provides an attractive source not only of mesenchymal stem cells but moreover of pluripotent stem cells. The method described herein should be applied in the field of stem cell banking in addition to the classical umbilical cord harvesting method. Isolation of a population of cells with pluripotent characteristics from umbilical cord. Adoption of a second centrifugation step for the pluripotent stem isolation. Increasing the value of the cord and explaining the pluripotency. This work will enhance the value of umbilical cord harvesting.

  9. Implication of NOD1 and NOD2 for the differentiation of multipotent mesenchymal stem cells derived from human umbilical cord blood.

    Directory of Open Access Journals (Sweden)

    Hyung-Sik Kim

    Full Text Available Toll-like receptors (TLRs and Nod-like receptors (NLRs are known to trigger an innate immune response against microbial infection. Although studies suggest that activation of TLRs modulate the function of mesenchymal stem cells (MSCs, little is known about the role of NLRs on the MSC function. In this study, we investigated whether NOD1 and NOD2 regulate the functions of human umbilical cord blood-derived MSCs (hUCB-MSCs. The genes of TLR2, TLR4, NOD1, and NOD2 were expressed in hUCB-MSCs. Stimulation with each agonist (Pam(3CSK(4 for TLR2, LPS for TLR4, Tri-DAP for NOD1, and MDP for NOD2 led to IL-8 production in hUCB-MSC, suggesting the expressed receptors are functional in hUCB-MSC. CCK-8 assay revealed that none of agonist influenced proliferation of hUCB-MSCs. We next examined whether TLR and NLR agonists affect osteogenic-, adipogenic-, and chondrogenic differentiation of hUCB-MSCs. Pam(3CSK(4 and Tri-DAP strongly enhanced osteogenic differentiation and ERK phosphorylation in hUCB-MSCs, and LPS and MDP also slightly did. Treatment of U0126 (MEK1/2 inhibitor restored osteogenic differentiation enhanced by Pam(3CSK(4. Tri-DAP and MDP inhibited adipogenic differentiation of hUCB-MSCs, but Pam(3CSK(4 and LPS did not. On chondrogenic differentiation, all TLR and NLR agonists could promote chondrogenesis of hUCB-MSCs with difference in the ability. Our findings suggest that NOD1 and NOD2 as well as TLRs are involved in regulating the differentiation of MSCs.

  10. Extracellular matrix gel is necessary for in vitro cultivation of insulin producing cells from human umbilical cord blood derived mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    GAO Feng; WU De-quan; HU Yan-hua; JIN Guang-xin

    2008-01-01

    Background Pancreatic islet cell transplantation is an effective approach to treat type 1 diabetes. However, this therapy is not widely used because of the severe shortage of transplantable donor islets. This study investigated whether mesenchymal stem cells (MSCs) derived from human umbilical cord blood (UCB) could be transdifferentiated into insulin producing cells in vitro and the role of extracellular matrix (ECM) gel in this procedure.Methods Human UCB samples were collected and MSCs were isolated. MSCs specific marker proteins were analyzed by a flow cytometer. The capacities of osteoblast and adipocyte to differentiate were tested. Differentiation into islet like cell was induced by a 15-day protocol with or without ECM gel. Pancreatic characteristics were evaluated with immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. Insulin content and release in response to glucose stimulation were detected with chemiluminescent immunoassay system.Results Sixteen MSCs were isolated from 42 term human UCB units (38%). Human UCB-MSCs expressed MSCs specific markers and could be induced in vitro into osteoblast and adipocyte. Islet like cell clusters appeared about 9 days after pancreatic differentiation in the inducing system with ECM gel. The insulin positive cells accounted for (25.2±3.4)% of the induced cells. The induced cells expressed islet related genes and hormones, but were not very responsive to glucose challenge. When MSCs were induced without ECM gel, clusters formation and secretion of functional islet proteins could not be observed.Conclusions Human UCB-MSCs can differentiate into islet like cells in vitro and ECM gel plays an important role in pancreatic endocrine cell maturation and formation of three dimensional structures.

  11. Kinetics of versican-expressing macrophages in bone marrow after cord blood stem cell transplantation for treatment of acute myelogenous leukaemia

    Science.gov (United States)

    Senda, Miho; Fukuyama, Ryuichi; Nagasaka, Tetsuro

    2016-01-01

    Aims To determine versican-producing cells in normocellular bone marrow and to evaluate chronological alteration in the number of versican-producing macrophages in bone marrow of patients with acute myelogenous leukaemia (AML) after cord blood stem cell transplantation (CBSCT) to gain insight in the significance of versican in recovery of haematopoiesis. Methods We enrolled seven age-matched unrelated patients with normocellular bone marrow for determining versican-producing cells in bone marrow, CBSCT-treated patients with AML, 18 with fine and other four with poor engraftment, for determining chronological alteration of versican-expressing and CD68-expressing cells in transplanted bone marrow in reference to the total cells. Clot samples of patients with AML were collected from the +16 to +55 day after transplantation and separated into four groups. We included an AML case whose specimen was obtained on the +9 day. Cells positive in immunohistochemistry using antibodies to versican and CD68 were counted to obtain the mean±SD in a unit area of the bone marrow, plotted chronologically and compared with the numbers from the age-matched normocellular group. Results We determined by a double immunohistochemistry that the versican-expressing cells in bone marrow are macrophages. The time-course curve demonstrated an inverse relationship between the versican-positive macrophages and the total cells in the transplanted bone marrow for over 55 days. In bone marrow of poor engraftment cases, versican-positive macrophages appeared to be decreased in comparison with age-matched and sampling day-matched patients. Conclusions These results suggest that versican and/or versican-expressing macrophages positively contribute to bone marrow regeneration of patients with AML after CBSCT. PMID:26951084

  12. Therapy for Cerebral Palsy by Human Umbilical Cord Blood Mesenchymal Stem Cells Transplantation Combined With Basic Rehabilitation Treatment: A Case Report.

    Science.gov (United States)

    Zhang, Che; Huang, Li; Gu, Jiaowei; Zhou, Xihui

    2015-01-01

    Background. Cerebral palsy (CP) is the most common cause leading to childhood disability. Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) transplantation is a promising alternative considering the safety and efficacy in current reports. This report represents a case of hUCB-MSCs transplantation combined with basic rehabilitation treatment beginning as early as age 6 months with follow-up as long as 5 years. Methods. A 6-year-old female patient was diagnosed with CP at age 6 months. The patient accepted 4 infusions of intravenous hUCB-MSCs in each course and received 4 courses of transplantation totally. A series of assessments were performed before the first transplantation, including laboratory tests, CDCC Infant Mental Development Scale, and Gross Motor Function Measure-88 (GMFM-88). Then annual assessments using the GMFM-88, Ashworth spasm assessment, and comprehensive function assessment scale were made in addition to the annual laboratory tests. In addition, electroencephalography and brain magnetic resonance imaging were conducted before transplantation and in the follow-up phase. Rehabilitation and safety follow-up have been ongoing for 5 years up to date. Results. There was no complaint about adverse effects during hospitalization or postoperative follow-up. Motor function recovered to normal level according to the evaluation of scales. Language function improved significantly. Linguistic rehabilitation therapy was enhanced for further improvement. Conclusions. The clinical application of hUC-MSCs combined with basic rehabilitation treatment was effective and safe for improving motor and comprehensive function in a patient with CP.

  13. Identification of cord blood-derived mesenchymal stem/stromal cell populations with distinct growth kinetics, differentiation potentials, and gene expression profiles.

    Science.gov (United States)

    Markov, Vladimir; Kusumi, Kenro; Tadesse, Mahlet G; William, Dilusha A; Hall, Dorian M; Lounev, Vitali; Carlton, Arlene; Leonard, Jay; Cohen, Rick I; Rappaport, Eric F; Saitta, Biagio

    2007-02-01

    Phenotypic heterogeneity has been observed among mesenchymal stem/stromal cell (MSC) populations, but specific genes associated with this variability have not been defined. To study this question, we analyzed two distinct isogenic MSC populations isolated from umbilical cord blood (UCB1 and UCB2). The use of isogenic populations eliminated differences contributed by genetic background. We characterized these UCB MSCs for cell morphology, growth kinetics, immunophenotype, and potential for differentiation. UCB1 displayed faster growth kinetics, higher population doublings, and increased adipogenic lineage differentiation compared to UCB2. However, osteogenic differentiation was stronger for the UCB2 population. To identify MSC-specific genes and developmental genes associated with observed phenotypic differences, we performed expression analysis using Affymetrix microarrays and compared them to bone marrow (BM) MSCs. We compared UCB1, UCB2, and BM and identified distinct gene expression patterns. Selected clusters were analyzed demonstrating that genes of multiple developmental pathways, such as transforming growth factor-beta (TGF-beta) and wnt genes, and markers of early embryonic stages and mesodermal differentiation displayed significant differences among the MSC populations. In undifferentiated UCB1 cells, multiple genes were significantly up-regulated (p < 0.0001): peroxisome proliferation activated receptor gamma (PPARG), which correlated with adipogenic differentiation capacities, hepatocyte growth factor (HGF), and stromal-derived factor 1 (SDF1/CXCL12), which could both potentially contribute to the higher growth kinetics observed in UCB1 cells. Overall, the results confirmed the presence of two distinct isogenic UCB-derived cell populations, identified gene profiles useful to distinguish MSC types with different lineage differentiation potentials, and helped clarify the heterogeneity observed in these cells.

  14. Kinetics of versican-expressing macrophages in bone marrow after cord blood stem cell transplantation for treatment of acute myelogenous leukaemia.

    Science.gov (United States)

    Senda, Miho; Fukuyama, Ryuichi; Nagasaka, Tetsuro

    2016-10-01

    To determine versican-producing cells in normocellular bone marrow and to evaluate chronological alteration in the number of versican-producing macrophages in bone marrow of patients with acute myelogenous leukaemia (AML) after cord blood stem cell transplantation (CBSCT) to gain insight in the significance of versican in recovery of haematopoiesis. We enrolled seven age-matched unrelated patients with normocellular bone marrow for determining versican-producing cells in bone marrow, CBSCT-treated patients with AML, 18 with fine and other four with poor engraftment, for determining chronological alteration of versican-expressing and CD68-expressing cells in transplanted bone marrow in reference to the total cells. Clot samples of patients with AML were collected from the +16 to +55 day after transplantation and separated into four groups. We included an AML case whose specimen was obtained on the +9 day. Cells positive in immunohistochemistry using antibodies to versican and CD68 were counted to obtain the mean±SD in a unit area of the bone marrow, plotted chronologically and compared with the numbers from the age-matched normocellular group. We determined by a double immunohistochemistry that the versican-expressing cells in bone marrow are macrophages. The time-course curve demonstrated an inverse relationship between the versican-positive macrophages and the total cells in the transplanted bone marrow for over 55 days. In bone marrow of poor engraftment cases, versican-positive macrophages appeared to be decreased in comparison with age-matched and sampling day-matched patients. These results suggest that versican and/or versican-expressing macrophages positively contribute to bone marrow regeneration of patients with AML after CBSCT. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. The Probability of Umbilical Cord Blood Stem Cell Transplantation for Vascular Dementia%脐血干细胞移植治疗血管性痴呆的可能性

    Institute of Scientific and Technical Information of China (English)

    李莹; 王景周

    2008-01-01

    Vascular dementia iS one of the common forms of dementia,and its occurrence is closely associated with cerebrovascular disease.There are abundant stem cells in cord blood that differentiate into neural stem cells.The studies of stem cell transplantation in the treatment of ischemic cerebrovascular disease and neurodegenerative diseases have achieved some results. Cord blood stem cells may also he used in the treatment of vascular dementia.%血管性痴呆足常见的痴呆类型之一,其发生与脑血管病密切相关.脐血中含有丰富的可向神经细胞方向分化的干细胞.干细胞移植治疗缺血性脑血管病和神经系统变性疾病的研究已取得了一些成果,脐血干细胞也有可能用于血管性痴呆的治疗.

  16. Nursing for patients with multiple system atrophy treated with mesenchymal stem cells in umbilical cord blood therapy%脐血间充质干细胞治疗多系统萎缩患者的护理

    Institute of Scientific and Technical Information of China (English)

    许梅

    2011-01-01

    目的 观察护理对脐血间充质干细胞治疗多系统萎缩疗效的作用.方法 脐血间充质干细胞治疗(静脉输注结合鞘内注射)2例多系统萎缩患者,辅以心理护理、专科护理、健康宣教等.结果 2例患者脐血间充质干细胞治疗后,临床症状显著改善.结论 脐血间充质干细胞治疗是一种新型有效的治疗多系统萎缩的方法,而护理在其中起重要作用.%Objective To observe the effect of nursing for patients with multiple system atrophy treated with mesenchymal stem cells in umbilical cord blood therapyMethods Two patients with multiple system atrophy were treated by mesenchymal stem cells in umbilical cord blood (intravenous and intrathecal injection). Results The mesenchymal stem cell therapy improved clinical symptoms. Conclusion The mesenchymal stem cell therapy is a novel and effective therapy for multiple system atrophy. Nursing plays a key role in the process.

  17. Cotransplantation of human umbilical cord-derived mesenchymal stem cells and umbilical cord blood-derived CD34⁺ cells in a rabbit model of myocardial infarction.

    Science.gov (United States)

    Li, Tong; Ma, Qunxing; Ning, Meng; Zhao, Yue; Hou, Yuelong

    2014-02-01

    The objective of the study is to investigate the effect of hypoxic preconditioning on the immunomodulatory properties of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and the effect of cotransplantation of hUC-MSCs and human umbilical cord blood (hUCB)-derived CD34(+) cells in a rabbit model of myocardial infarction. hUC-MSCs with or without hypoxic preconditioning by cobalt chloride were plated in a 24-well plate, and then cocultured with hUCB-CD34(+) cells and PBMCs for 96 h at 37 °C in a 5% CO₂ incubator. For the negative control, hUC-MSCs were omitted. The groups were divided as follows: A1 = HP-MSCs + hUCB-CD34(+) cells + PBMC, A2 = hUC-MSCs + hUCB-CD34(+) cells + PBMC, Negative Control = hUCB-CD34(+) cells + PBMC. Culture supernatants of each group were collected, and the IL-10 and IFN-γ levels were measured by ELISA. A rabbit model of MI was established using a modified Fujita method. The animals were then randomized into three groups and received intramyocardial injections of 0.4 ml of PBS alone (n = 8, PBS group), hUC-MSCs in PBS (n = 8, hUC-MSCs group), or hUC-MSCs + CD34(+) cells in PBS (n = 8, Cotrans group), at four points in the infarct border zone. Echocardiography was performed at baseline, 4 weeks after MI induction, and 4 weeks after cell transplantation, respectively. Stem cell differentiation and neovascularization in the infracted area were characterized for the presence of cardiac Troponin I (cTnI) and CD31 by immunohistochemical staining, and the extent of myocardial fibrosis was evaluated by hematoxylin and eosin (H&E) and Masson's trichrome. IFN-γ was 27.00 ± 1.11, 14.20 ± 0.81, and 7.22 ± 0.14 pg/ml, and IL-10 was 31.68 ± 3.08, 61.42 ± 1.08, and 85.85 ± 1.80 pg/ml for the Control, A1 and A2 groups, respectively, which indicated that hUCB-CD34(+) cells induced immune reaction of peripheral blood mononuclear cells, whereas both hUC-MSCs and HP-MSCs showed an immunosuppressive effect, which, however, was attenuated

  18. Experimental Study on Osmotic Properties of Human Cord Blood Stem Cell%脐带血干细胞渗透特性实验研究

    Institute of Scientific and Technical Information of China (English)

    张绍志; 王葳; 周新丽; 陈光明; 胡军祥; 王金福; 项盈; 殷华波

    2004-01-01

    The transport of water during freezing directly influences the resultof cryopreservation of biological materials. Measurement of the osmotic properties ofcells will help the design of cryopreservation protocols. In this paper, the osmoticproperties of human cord blood stem cells (HCBSCs) are experimentally studied witha diffusion-chamber method. The inactive volume ratio of HCBSCs is determined to be0.52 + 0.07. The average diameter of HCBSCs is 9.9 + 1.0μm. The water permeabilityWith an Arrhemius relationship, the activation energy is calculated to be 58.6k J/mol.The data obtained are compared to those of stem cell from other sources.%冷冻过程中水的输运直接影响生物材料低温保存的效果.对细胞渗透特性的测量将有助于低温保存方案的设计.本文采用渗透腔法,对脐带血干细胞的渗透性能或特性进行了实验研究.实验测得脐带血干细胞的不变体积比例为0.52土0.07,平均直径为9.9士1,0μm,25℃下对水的渗透系数为4.394×10-13m3/N.s,10℃下对水的渗透系数为1.256×10-13m3/N·s.根据Arrhemius关系式,得到渗透系数的活化能为58 6kJ/mol.文中将脐带血干细胞的这些性能数据与从其它文章得到的干细胞的类似性能数据进行了对比.

  19. Effect on umbilical cord blood platelet - rich plasma promoting proliferation of umbilical cord blood mesenchymal stem cells%脐血来源富血小板血浆对脐血间充质干细胞增殖的影响

    Institute of Scientific and Technical Information of China (English)

    胡资兵; 孙杰聪; 刘田丰

    2016-01-01

    Objective To explore the best concentration of umbilical cord blood derived platelet rich plasma for promoting the proliferation and proliferation of umbilical cord blood mesenchymal stem cells. Method Umbilical cord blood was collected in term health cesarean selection newborn. Separation of umbilical cord blood mesenchymal stem cells was performed by using the tissue pieces culture. Platelet - rich plasma from umbilical cord blood was extracted with the use of secondary centrifuga-tion. Transforming growth factor - beta 1 in platelet - rich plasma was detected with the method of ELISA. In this experiment, platelet rich plasma combined 10% fetal bovine serum was used to cultivate umbilical cord blood mesenchymal stem cells. According to the concentration of TGF - beta 1 in platelet - rich plasma,the experiment was divided into 6 groups:2 000 pg/ ml,1 000 pg/ ml,750 pg/ ml,500 pg/ ml,250 pg/ ml,10% fetal bovine serum group. Umbilical cord blood mesenchy-mal stem cells were incubated in 96 - well plates,and cultured for 7 days. After 1,3,5,and 7 days later,CCK8 kit was used to determinate the proliferation effect of mesenchymal stem cells. Meanwhile,statistical analysis was performed to select the best concentration. Results Different concentrations of platelet - rich plasma combined 10% fetal bovine serum resulted in varied proliferation rate from umbilical cord blood mesenchymal stem cells. The findings suggested that the proliferation rate in 500 ~1 000 pg/ ml concentration groups was superior to that of other groups. It was not 5 - day cultured until there was statistically significant(P ﹤ 0. 05). Conclusion Platelet - rich plasma can improve proliferation of the umbilical cord blood mesenchymal stem cells. Furthermore,the activity shows a dose dependent.%目的:初步探讨脐血来源富血小板血浆促进脐血间充质干细胞增殖及增殖最佳浓度。方法:收集足月健康剖宫产新生儿脐带血,采用组织块培养法进行脐血间

  20. Enhancing endogenous stem cells in the newbornvia delayed umbilical cord clamping

    Institute of Scientific and Technical Information of China (English)

    Christopher Lawton; Sandra Acosta; Nate Watson; Chiara Gonzales-Portillo; hTeo Diamandis; Naoki Tajiri; Yuji Kaneko; Paul R. Sanberg; Cesar V. Borlongan

    2015-01-01

    There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal beneifts including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deifciency anemia in term infants. Human umbilical cord blood con-tains signiifcant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it en-hances blood lfow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant’s susceptibility to both neonatal and age-related diseases.

  1. Enhancing endogenous stem cells in the newborn via delayed umbilical cord clamping

    Directory of Open Access Journals (Sweden)

    Christopher Lawton

    2015-01-01

    Full Text Available There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal benefits including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deficiency anemia in term infants. Human umbilical cord blood contains significant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it enhances blood flow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant′s susceptibility to both neonatal and age-related diseases.

  2. Enhancing endogenous stem cells in the newborn via delayed umbilical cord clamping.

    Science.gov (United States)

    Lawton, Christopher; Acosta, Sandra; Watson, Nate; Gonzales-Portillo, Chiara; Diamandis, Theo; Tajiri, Naoki; Kaneko, Yuji; Sanberg, Paul R; Borlongan, Cesar V

    2015-09-01

    There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal benefits including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deficiency anemia in term infants. Human umbilical cord blood contains significant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it enhances blood flow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant's susceptibility to both neonatal and age-related diseases.

  3. Optimal Route for Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation to Protect Against Neonatal Hyperoxic Lung Injury: Gene Expression Profiles and Histopathology.

    Directory of Open Access Journals (Sweden)

    Dong Kyung Sung

    Full Text Available The aim of this study was to determine the optimal route of mesenchymal stem cell (MSC transplantation. To this end, gene expression profiling was performed to compare the effects of intratracheal (i.t. versus intravenous (i.v. MSC administration. Furthermore, the therapeutic efficacy of each route to protect against neonatal hyperoxic lung injury was also determined. Newborn Sprague-Dawley rats were exposed to hyperoxia (90% oxygen from birth for 14 days. Human umbilical cord blood-derived MSCs labeling with PKH26 were transplanted through either the i.t. (5×10(5 or i.v. (2×10(6 route at postnatal day (P 5. At P14, lungs were harvested for histological, biochemical and microarray analyses. Hyperoxic conditions induced an increase in the mean linear intercept and mean alveolar volume (MAV, indicative of impaired alveolarization. The number of ED-1 positive cells was significantly decreased by both i.t. and i.v. transplantations. However, i.t. administration of MSCs resulted in a greater decrease in MAV and ED-1 positive cells compared to i.v. administration. Moreover, the number of TUNEL-positive cells was significantly decreased in the i.t. group, but not in the i.v. group. Although the i.t. group received only one fourth of the number of MSCs that the i.v. group did, a significantly higher number of donor cell-derived red PKH 26 positivity were recovered in the i.t. group. Hyperoxic conditions induced the up regulation of genes associated with the inflammatory response, such as macrophage inflammatory protein-1 α, tumor necrosis factor-α and inter leukin-6; genes associated with cell death, such as p53 and caspases; and genes associated with fibrosis, such as connective tissue growth factor. In contrast, hyperoxic conditions induced the dwon-regulation of vascular endothelial growth factor and hepatocyte growth factor. These hyperoxia-induced changes in gene expression were decreased in the i.t. group, but not in the i.v. group. Thus

  4. Notch signaling: a novel regulating differentiation mechanism of human umbilical cord blood-derived mesenchymal stem cells into insulin-producing cells in vitro

    Institute of Scientific and Technical Information of China (English)

    HU Yan-hua; WU De-quan; GAO Feng; LI Guo-dong; ZHANG Xin-chen

    2010-01-01

    Background Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) could be induced to differentiate into insulin producing cells (IPCs) in vitro, which have good application potential in the cell replacement treatment of type-1 diabetes. However, the mechanisms regulating this differentiation have remained largely unknown. Notch signaling is critical in cell differentiation. This study investigated whether Notch signaling could regulate the IPCs differentiation of human UCB-MSCs. Methods Using an interfering Notch signaling protocol in vitro, we studied the role of Notch signaling in differentiation of human UCB-MSCs into IPCs. In a control group the induction took place without interfering Notch signaling. Results Human UCB-MSCs expressed the genes of Notch receptors (Notch 1 and Notch 2) and ligands (Jagged 1 and Deltalike 1). Human UCB-MSCs with over-expressing Notch signaling in differentiation resulted in the down-regulation of insulin gene level, proinsulin protein expression, and insulin-positive cells percentage compared with the control group. These results showed that over-expressing Notch signaling inhibited IPCs differentiation. Conversely, when Notch signaling was attenuated by receptor inhibitor, the induced cells increased on average by 3.06-fold (n=4, P<0.001) in insulin gene level, 2.60-fold (n=3, P <0.02) in proinsulin protein expression, and 1.62-fold (n=6, P <0.001) in the rate of IPCs compared with the control group. Notch signaling inhibition significantly promoted IPCs differentiation with about 40% of human UCB-MSCs that converted to IPCs, but these IPCs were not responsive to glucose challenge very well both in vitro and in vivo. Hence, further research has to be carried out in the future. Conclusions Notch signaling may be an important mechanism regulating IPCs differentiation of human UCB-MSCs in vitro and Notch signaling inhibition may be an efficient way to increase the number of IPCs, which may resolve the shortage of

  5. Institutional Knots: A Comparative Analysis of Cord Blood Policy in Canada and the United States.

    Science.gov (United States)

    Denburg, Avram

    2016-02-01

    Umbilical cord blood is a rich source of blood stem cells, which are of critical clinical importance in the treatment of a variety of malignant and genetic conditions requiring stem cell transplantation. Many countries have established national public cord blood banks; such banks often coexist with a panoply of private options for cord blood banking. Until recently, Canada was the only G8 country without a national cord blood bank. This differs markedly from the United States, which years ago established a national cord blood bank policy and inventory. This article investigates potential reasons for this discrepancy through a comparative analysis of the evolution of programs and policies on national cord blood banking in Canada and the United States. My analysis suggests that cross-national discrepancies in policy on public cord blood banking were determined primarily by institutional factors, principal among them formal governmental structure and the legacy of past policies. Institutional entrepreneurialism in the health sector played a constitutive role in the earlier evolution of national cord blood policy in the United States as compared to Canada.

  6. Umbilical cord blood stem cells treatment for central pain: one case report%异体脐带血干细胞治疗中枢性疼痛一例

    Institute of Scientific and Technical Information of China (English)

    岳宝玲; 范亚林; 李香社; 郑丽; 侯会荣; 高丽昕

    2012-01-01

    Objective To study the effective of stem cell transplantation in a central pain patient. Methods There was a central pain case who had suffered central pain which resulted in brain ischemia-hypoxia. The patient was given 6 packets of umbilical cord blood stem cells transplantation ( 2 intravenous injection and 4 lumber puncture ). She was received stem cell treatment every 5 days. We observed the condition of central pain for 2 months. Result There was some improvement of pain and life quality from the 2rd stem cells transplantation. But patient felt pain after the 2rd month. Conclusion Umbilical cord blood stem cell transplantation was a new treatment method for central pain.%目的 探讨1例中枢性疼痛患者接受脐带血干细胞移植后症状转归.方法 随访我院1例脑缺血缺氧后中枢性疼痛患者给予2次静脉、4次腰穿鞘内注射途径移植干细胞,每次移植间隔5天,治疗后随访患者疼痛变化情况2个月.结果 从第2次脐带血干细胞移植开始,患者的疼痛情况及生活质量均有一定改善,移植结束后2个月患者疼痛又开始反复.结论 脐带血干细胞移植可能为中枢性疼痛的治疗提供新的治疗途径.

  7. US Public Cord Blood Banking Practices: Recruitment, Donation, and the Timing of Consent

    Science.gov (United States)

    Broder, Sherri; Ponsaran, Roselle; Goldenberg, Aaron

    2012-01-01

    BACKGROUND Cord blood has moved rapidly from an experimental stem cell source to an accepted and important source of hematopoietic stem cells. There has been no comprehensive assessment of US public cord blood banking practices since the Institute of Medicine study in 2005. STUDY DESIGN AND METHODS Of 34 US public cord blood banks identified, 16 participated in our qualitative survey of public cord blood banking practices. Participants took part in in-depth telephone interviews in which they were asked structured and open-ended questions regarding recruitment, donation, and the informed consent process at these banks. RESULTS 13 of 16 participants reported a variably high percentage of women who consented to public cord blood donation. 15 banks offered donor registration at the time of hospital admission for labor and delivery. 7 obtained full informed consent and medical history during early labor and 8 conducted some form of phased consent and/or phased medical screening and history. 9 participants identified initial selection of the collection site location as the chief mode by which they recruited minority donors. CONCLUSION Since 2005, more public banks offer cord blood donor registration at the time of admission for labor and delivery. That, and the targeted location of cord blood collection sites, are the main methods used to increase access to donation and HLA diversity of banked units. Currently, the ability to collect and process donations, rather than donor willingness, is the major barrier to public cord blood banking. PMID:22803637

  8. Toxoplasmosis in cord blood transplantation recipients.

    Science.gov (United States)

    Bautista, G; Ramos, A; Forés, R; Regidor, C; Ruiz, E; de Laiglesia, A; Navarro, B; Bravo, J; Portero, F; Sanjuan, I; Fernández, M N; Cabrera, R

    2012-10-01

    Toxoplasmosis is a devastating opportunistic infection that can affect immunocompromised patients such as cord blood transplantation (CBT) recipients. The clinical characteristics of 4 toxoplasmosis CBT patients treated at our institution are reviewed, together with 5 cases collected from the literature. The rate of toxoplasmosis in our hospital was 6% in CBT recipients and 0.2% in other types of allogeneic hematopoietic stem cell transplantation (P < 0.001). Five patients (56%) presented disseminated toxoplasmosis and 4 patients (44%) had localized infection in the central nervous system. In 5 of the 9 patients considered (56%), cytomegalovirus viral replication had been detected before the clinical onset of toxoplasmosis. Seven patients (78%) had previously developed graft-versus-host disease. All patients who exhibited disseminated disease died due to Toxoplasma infection. Pre-transplant serology was positive in 1 patient, negative in 3 patients, and not performed in another. Only 1 of these 5 patients with disseminated disease had received Toxoplasma prophylaxis with cotrimoxazole. It could be concluded that mortality in CBT patients with disseminated toxoplasmosis is unacceptably high. The negative results of serology in the majority of these cases, and its unspecific clinical presentation, makes diagnosis exceedingly difficult. Better diagnostic tests and prophylaxis strategy are needed in CBT recipients.

  9. Age, Sex, and Religious Beliefs Impact the Attitude towards Cord Blood Banking.

    Science.gov (United States)

    Sundell, Inger Birgitta; Setzer, Teddi J

    2015-01-01

    In this study, a self-administered questionnaire was used to assess opinions about stem cell research and cord blood banking. Three attitudes were examined: willingness to accept cord blood banking, willingness to accept embryonic stem cell research, and religious belief system. A total of 90 Wayne State University students enrolled in the study in response to an invitation posted on a web page for the university. Sex distribution among study participants was 79 females and eight males; three declined to state their sex. Support for cord blood banking was high (> 70%) among students. Students over the age of 25 years of age were more (85%) positive than students 18 to 24 years old (57%). They prefered a public cord blood bank over a private cord blood bank. Atheist/agnostic or spiritual/not religious students (> 90%), Catholic students (78%) and Christian students (58%) support cord blood banking. Age, sex and religion seems influence the student's attitude towards stem cell research and cord blood banking.

  10. Effect of Single and Double Administration of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Following Focal Cerebral Ischemia in Rats

    Science.gov (United States)

    Park, Hyung Woo; Kim, Yona; Chang, Jong Wook; Yang, Yoon Sun; Oh, Wonil; Lee, Jae Min; Park, Hye Ran; Kim, Dong Gyu

    2017-01-01

    Stem cell therapies are administered during the acute phase of stroke to preserve the penumbral tissues from ischemic injury. However, the effect of repeated cell therapy during the acute phase remains unclear. In this study, we investigated and compared the functional outcome of single (two days post-injury) and repeated (two and nine days post-injury) treatment with human umbilical cord derived mesenchymal stem cells (hUCB-MSCs) after middle cerebral artery occlusion (MCAO). The rotarod and limb placement tests were utilized to investigate functional outcomes, while infarct volume and tissue damage were measured by immunofluorescent staining for neovascularization, neurogenesis, apoptosis, and inflammation in the penumbral zones. We observed notable motor dysfunction and a significant decrease in infarcted brain volume, as well as increases in neurons and vessels in both single and repeated hUCB-MSC treatments compared to the control group. Interestingly, repeated administration of hUCB-MSCs was not found to elicit additional or synergistic improvements over monotherapy. This study suggests that a clearer understanding of the therapeutic window after stroke will facilitate the development of more efficient treatment protocols in the clinical application of stem cell therapy. PMID:28243167

  11. Ethical considerations in umbilical cord blood banking.

    Science.gov (United States)

    Fox, Nathan S; Chervenak, Frank A; McCullough, Laurence B

    2008-01-01

    Pregnant patients have the option at delivery of having their cord blood collected and stored for future use. At many hospitals, they have the option of donating their cord blood to the public banking system for future use by anyone who is an appropriate match (public banking). Patients also have the option of having their cord blood stored for a fee with a commercial/private company for future use within their family (private banking). Currently, private banking is not recommended by major obstetric and pediatric professional organizations. We applied current evidence of the risks and benefits of private and public cord blood banking and accepted ethical principles to answer the following two related questions: 1) Do obstetricians have an ethical obligation to comply with a request for private banking? and 2) Do obstetricians have an ethical obligation to routinely offer private banking to women who do not request it? The only situation where there is a known benefit to private banking is when public banking is not available and the patient currently has an affected family member who may benefit from cord blood therapy. We conclude that when presented with a request for private banking, obstetricians have an ethical obligation to explain the lack of proven benefit of this procedure. If the patient still requests private banking, it would be appropriate to comply, because there is minimal or no risk to the procedure. However, obstetricians are not ethically obligated to offer private banking, even when public banking is not available, except in the limited circumstance when the patient currently has an affected family member who may benefit from cord blood therapy.

  12. Stem cell transplantation for treating spinal cord injury A literature comparison between studies of stem cells obtained from various sources

    Institute of Scientific and Technical Information of China (English)

    Liangbi Xiang; Yu Chen

    2012-01-01

    OBJECTIVE: To identify global research trends of stem cell transplantation for treating spinal cord injury using a bibliometric analysis of the Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating spinal cord injury from 2002 to 2011 using the Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed articles on stem cell transplantation for treating spinal cord injury that were published and indexed in the Web of Science; (b) type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and (c) year of publication: 2002–2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) a number of corrected papers from the total number of articles.MAIN OUTCOME MEASURES: (1) Annual publication output; (2) distribution according to country; (3) distribution according to institution; (4) distribution according to journals; (5) distribution according to funding agencies; and (6) top cited articles over the last 10 years.RESULTS: Bone marrow mesenchymal stem cells and embryonic stem cells have been widely used for treating spinal cord injury. In total, 191 studies of bone marrow mesenchymal stem cell transplantation and 236 studies of embryonic stem cell transplantation for treating spinal cord injury appeared in the Web of Science from 2002 to 2011, and almost half of which were derived from American or Japanese authors and institutes. The number of studies of stem cell transplantation for treating spinal cord injury has gradually increased over the past 10 years. Most papers on stem cell transplantation for treating spinal cord injury appeared in journals with a particular focus on stem cell research, such as Stem Cells and Cell Transplantation. Although umbilical cord blood stem cells and adipose

  13. OCT4A contributes to the stemness and multi-potency of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs)

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Kwang-Won; Lee, Sae-Rom; Bhandari, Dilli Ram; Roh, Kyoung-Hwan; Park, Sang-Bum; So, Ah-Young; Jung, Ji-Won; Seo, Min-Soo [Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University 151-742, Seoul (Korea, Republic of); Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University 151-742, Seoul (Korea, Republic of); Kang, Soo-Kyung [Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University 151-742, Seoul (Korea, Republic of); Laboratory of Biotechnology, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University 151-742, Seoul (Korea, Republic of); Lee, Yong-Soon [Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University 151-742, Seoul (Korea, Republic of); Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University 151-742, Seoul (Korea, Republic of); Kang, Kyung-Sun, E-mail: kangpub@snu.ac.kr [Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University 151-742, Seoul (Korea, Republic of); Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University 151-742, Seoul (Korea, Republic of)

    2009-06-19

    The OCT4A gene, a POU homeodomain transcription factor, has been shown to be expressed in embryonic stem cells (ESC) as well as hUCB-MSCs. In this study, the roles played by OCT4A in hUCB-MSCs were determined by stably inhibiting OCT4A with lenti-viral vector-based small hairpin RNA (shRNA). A decreased rate of cell proliferation was observed in OCT4-inhibited hUCB-MSCs. Down-regulation of CCNA2 expression in OCT4-inhibited hUCB-MSCs was confirmed by RT-PCR and real-time RT-PCR analysis in three genetically independent hUCB-MSC clones. Adipogenic differentiation was also suppressed in OCT4-inhibited hUCB-MSCs. The up-regulation of DTX1 and down-regulation of HDAC1, 2, and 4 expressions may be related to this differentiation deformity. The expression of other transcription factors, including SOX2, REX1 and c-MYC, was also affected by OCT4 inhibition in hUCB-MSCs. In conclusion, these finding suggest that OCT4A performs functionally conserved roles in hUCB-MSCs, making its expression biologically important for ex vivo culture of hUCB-MSCs.

  14. Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization.

    Science.gov (United States)

    Anand, Sarah; Thomas, Samantha; Hyslop, Terry; Adcock, Janet; Corbet, Kelly; Gasparetto, Cristina; Lopez, Richard; Long, Gwynn D; Morris, Ashley K; Rizzieri, David A; Sullivan, Keith M; Sung, Anthony D; Sarantopoulos, Stefanie; Chao, Nelson J; Horwitz, Mitchell E

    2017-07-01

    Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared with historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared with 86 standard UCB recipients at our institution. The median time to neutrophil engraftment was shorter in NiCord recipients compared with standard UCB recipients (12.5 days versus 26 days; P < .001). Compared with standard UCB recipients, NiCord recipients had a significantly reduced risk for total infection (RR, 0.69; P = .01), grade 2-3 (moderate to severe) infection (RR, 0.36; P < .001), bacterial infection (RR, 0.39; P = .003), and grade 2-3 bacterial infection (RR, 0.21; P = .003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II-IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days post-transplantation after adjustment for age and Karnofsky Performance Status (69.9 days versus 49.7 days; P = .005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, fewer total and bacterial infections, and shorter hospitalization in the first 100 days compared with standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  15. Prevalence of Medical Conditions Potentially Amenable to Cellular Therapy among Families Privately Storing Umbilical Cord Blood.

    Science.gov (United States)

    Mazonson, Peter; Kane, Mark; Colberg, Kelin; Harris, Heather; Brown, Heather; Mohr, Andrew; Ziman, Alyssa; Santas, Chris

    2017-01-01

    Introduction Little is known about the prevalence of conditions potentially amenable to cellular therapy among families storing umbilical cord blood in private cord blood banks. Methods A cross-sectional study of families with at least one child who stored umbilical cord blood in the largest private cord blood bank in the United States was performed. Respondent families completed a questionnaire to determine whether children with stored cord blood or a first-degree relative had one or more of 16 conditions amenable primarily to allogeneic stem cell transplant ("transplant indications") or 16 conditions under investigation for autologous stem cell infusion ("regenerative indications"), regardless of whether they received a transplant or infusion. Results 94,803 families responded, representing 33.3 % of those surveyed. Of respondent families, 16.01 % indicated at least one specified condition. 1.64 % reported at least one first-degree member with a transplant indication potentially treatable with an allogeneic stem cell transplant. The most common transplant indications reported among first-degree family members were Non-Hodgkin's Lymphoma (0.33 %), Hodgkin's Lymphoma (0.30 %), and Acute Lymphoblastic Leukemia (0.28 %). 4.23 % reported at least one child with a regenerative indication potentially treatable with an autologous stem cell infusion. The most common regenerative indications among children with stored umbilical cord blood were Autism/Autism Spectrum Disorder/Apraxia (1.93 %), Other Developmental Delay (1.36 %), and Congenital Heart Defect (0.87 %). Discussion Among families storing umbilical cord blood in private cord blood banks, conditions for which stem cell transplant or infusion may be indicated, or are under investigation, appear to be prevalent, especially for regenerative medicine indications.

  16. Efficient generation of transgene-free induced pluripotent stem cells from normal and neoplastic bone marrow and cord blood mononuclear cells.

    Science.gov (United States)

    Hu, Kejin; Yu, Junying; Suknuntha, Kran; Tian, Shulan; Montgomery, Karen; Choi, Kyung-Dal; Stewart, Ron; Thomson, James A; Slukvin, Igor I

    2011-04-07

    Reprogramming blood cells to induced pluripotent stem cells (iPSCs) provides a novel tool for modeling blood diseases in vitro. However, the well-known limitations of current reprogramming technologies include low efficiency, slow kinetics, and transgene integration and residual expression. In the present study, we have demonstrated that iPSCs free of transgene and vector sequences could be generated from human BM and CB mononuclear cells using non-integrating episomal vectors. The reprogramming described here is up to 100 times more efficient, occurs 1-3 weeks faster compared with the reprogramming of fibroblasts, and does not require isolation of progenitors or multiple rounds of transfection. Blood-derived iPSC lines lacked rearrangements of IGH and TCR, indicating that their origin is non-B- or non-T-lymphoid cells. When cocultured on OP9, blood-derived iPSCs could be differentiated back to the blood cells, albeit with lower efficiency compared to fibroblast-derived iPSCs. We also generated transgene-free iPSCs from the BM of a patient with chronic myeloid leukemia (CML). CML iPSCs showed a unique complex chromosomal translocation identified in marrow sample while displaying typical embryonic stem cell phenotype and pluripotent differentiation potential. This approach provides an opportunity to explore banked normal and diseased CB and BM samples without the limitations associated with virus-based methods.

  17. Histamine release from cord blood basophils

    DEFF Research Database (Denmark)

    Nielsen, Bent Windelborg; Damsgaard, Tine Engberg; Herlin, Troels

    1990-01-01

    The histamine release (HR) after challenge with anti-IgE, concanavalin A, N-formyl-met-leu-phe and the calcium ionophore A23187 from 97 cord blood samples was determined by a microfiber-based assay. Maximum HR with anti-IgE showed great inter-individual variation (median: 20.5; range: 1-104 ng...

  18. Histamine release from cord blood basophils

    DEFF Research Database (Denmark)

    Nielsen, Bent Windelborg; Damsgaard, Tine Engberg; Herlin, Troels

    1990-01-01

    The histamine release (HR) after challenge with anti-IgE, concanavalin A, N-formyl-met-leu-phe and the calcium ionophore A23187 from 97 cord blood samples was determined by a microfiber-based assay. Maximum HR with anti-IgE showed great inter-individual variation (median: 20.5; range: 1-104 ng...

  19. Feasibility of stem cells from umbilical cord blood as seed cells for tooth regeneration%脐血干细胞作为牙再生种子细胞的可行性

    Institute of Scientific and Technical Information of China (English)

    计宝辉; 陈娇; 王杭

    2010-01-01

    背景:近年来牙再生成为组织工程领域一项重要课题,但目前还没有最合适的种子细胞,迫切需要探索新的种子细胞.目的:综述脐血干细胞作为牙再生种子细胞的可行性.方法:应用计算机检索1998-01/2009-01 PubMed数据库相关文章,检索词为"tooth regeneration, seed cells, tissue engineering, umbilical cord blood,mesenchymal stem cells",并限定文章语言种类为English.同时计算机检索1998-01/2009-01中国期刊网全文数据库、万方数据库、中文科技期刊全文数据库相关文章,检索词为"组织工程,种子细胞,间充质干细胞,脐带血,牙再生",并限定文章语言种类为中文.共检索到文献40篇.结果与结论:各类种子细胞,如牙胚来源的成牙本质细胞,牙髓和乳牙来源的干细胞,以及第一腮弓来源的外胚层间充质干细胞都已经在基础研究中显示出了成牙分化潜能.但是,在临床实验中这些种子细胞很难获取.骨髓间充质干细胞虽然也显示出了成牙潜能,但是它们的分化能力随供体年龄的增长显著下降.脐血干细胞和骨髓间充质干细胞相比,拥有很多优势,并且呈现出典型的间充质干细胞的特点.所以,推测脐血干细胞可能被诱导成成牙细胞系,并且可能成为合适的牙再生的种子细胞来修复牙缺失.%BACKGROUND: With the development of tissue engineering, more attention has been paid to tooth regeneration. However, the resource of best seed cells is still uncertain. Therefore, alternative sources should be attached to intensive investigation. OBJECTIVE: To review the feasibility of stem cells from umbilical cord blood as seed cells for tooth regeneration. METHODS: A PubMed search was performed for articles published between January 1998 and January 2009. Key words were "tooth regeneration, seed cells, tissue engineering, umbilical cord blood, mesenchymal stem cells". Only studies written in English were included. Simultaneously

  20. Therapeutic effect of allogeneic cord blood stem cells transplantation on ataxia patients%异体脐血干细胞移植治疗共济失调患者疗效观察

    Institute of Scientific and Technical Information of China (English)

    周艳辉; 王琦; 余丹; 林珍

    2012-01-01

    Objective To observe the effect of allogeneic cord blood stem cells transplantation on ataxia patients. Methods A retrospective analysis of the effect of allogeneic cord blood stem cells transplantation on 3 ataxia patients,using ICARS and Berg Balance Scale.ReSUltS The ICARS score of 3 patients' after treatment dropped by 2.30El?.65,and Berg Balance Scale score rised about 9.00 ?3.00, showing significant difference (P<0.05 = . Conclusion The stem cells transplantation is effective in treatment of ataxia patients, while a followup of long - term effect and side effects is indicated.%目的 探讨异体脐血干细胞移植治疗共济失调患者的疗效.方法 回顾性分析3例共济失调患者经异体脐血干细胞移植治疗后的疗效,使用世界神经病联合会国际合作共济失调量表(ICARS)及Berg平衡量表评分.结果 3例患者治疗后ICARS评分下降2.30E1±2.65,Berg平衡量表评分升高9.00±3.00,P< 0.05.结论 异体脐血干细胞移植治疗共济失调疗效明确,但长期疗效及副作用尚需继续观察.

  1. In vivo differentiation of human amniotic epithelial cells into cardiomyocyte-like cells and cell transplantation effect on myocardial infarction in rats: comparison with cord blood and adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Fang, Cheng-Hu; Jin, Jiyong; Joe, Jun-Ho; Song, Yi-Sun; So, Byung-Im; Lim, Sang Moo; Cheon, Gi Jeong; Woo, Sang-Keun; Ra, Jeong-Chan; Lee, Young-Yiul; Kim, Kyung-Soo

    2012-01-01

    Human amniotic epithelial cells (h-AECs), which have various merits as a cell source for cell therapy, are known to differentiate into cardiomyocytes in vitro. However, the ability of h-AECs to differentiate into cardiomyocytes in vivo and their cell transplantation effects on myocardial infarction are still unknown. In this study, we assessed whether h-AECs could differentiate into cardiomyocytes in vivo and whether h-AECs transplantation can decrease infarct size and improve cardiac function, in comparison to transplantation of cord blood-derived mesenchymal stem cells (MSCs) or adipose tissue-derived MSCs. For our study, we injected h-AECs, cord blood-derived MSCs, adipose tissue-derived MSCs, and saline into areas of myocardial infarction in athymic nude rats. After 4 weeks, 3% of the surviving h-AECs expressed myosin heavy chain, a marker specific to the myocardium. Compared with the saline group, all cell-implanted groups showed a higher ejection fraction, lower infarct area by positron emission tomography and histology, and more abundant myocardial gene and protein expression in the infarct area. We showed that h-AECs can differentiate into cardiomyocyte-like cells, decrease infarct size, and improve cardiac function in vivo. The beneficial effects of h-AECs were comparable to those of cord blood and adipose tissue-derived MSCs. These results support the need for further studies of h-AECs as a cell source for myocardial regeneration due to their plentiful availability, low immunity, and lack of ethical issues related to their use.

  2. Targeted expansion and regulation of genetically modified cord blood stem/progenitor cells in vitro%靶基因调控的脐血干/祖细胞体外长期扩增与调控

    Institute of Scientific and Technical Information of China (English)

    赵声明; 彭明婷; 顾惜春; 常乃柏

    2008-01-01

    BACKGROUND: Cord blood stem cells are one of ideal target cells for gene therapy, but low gene transferring rate is the main difficulty at recent. Janus kinase tyrosine 2 (JAK2) plays an important role in self-renewing of cord blood stem/progenitor cell12s. Therefore, cord blood CD34+ cell line modified by target-amplified JAK2 genes has been developed yet by using gene regulating expression technique in order to overcome low transferring rate of cord blood genes.OBJECTIVE: To investigate the feasibility and reliability of a long-term amplified regulation for cord blood stem/progenitor cells mediated by transgene JAK2. SETTING: Department of Hematology, Beijing Hospital, Ministry of Health.MATERIALS: The experiment was carried out in the Laboratory of Hematological Department, Beijing Hospital, Ministry of Health from June 2003 to April 2006. Cord blood was derived from umbilical cord which was immediately cut from healthy, full-term and natural-parturition infants and was provided by Department of Obstetrics & Gynecology, Beijing Hospital. The experiment was approved by the local ethical committee, and informed consent was obtained from expectant mothers and their relatives for the use of cord blood cells. MiniMACS magnetic separation apparatus and immunomagnetic beads adsorbing CD34 single antibody were provided by Miltenyi Biotec Company, Germany; flow cytometer by FACScalibur, USA; recombinant human stem cell factor (rhSCF), Flt3 ligand (FL), human interleukin-6 (hIL-6), granulocyte macrophage colony stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and thrombopoeitin (TPO) by PeproTec Company; nude mice of the SPF level by Animal Center of Beijing Medical University.METHODS: Retroviral vector MGI-F2JAK2, which was composed of functional catalytic domain of JAK2 genes and two site proteins (2xF36v, F2) combined with synthetic drug (AP20187) of target gene of small molecules, was constructed. AP20187 might specially combine with F36v to

  3. Human umbilical cord mesenchymal stem cells and the treatment of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    CAO Fu-jiang; FENG Shi-qing

    2009-01-01

    Objective To review the recent studies about human umbilical cord mesenchymal stem cells (hUCMSCs) and advances in the treatment of spinal cord injury, Data sources Published articles (1983-2007) about hUCMSCs and spinal cord injury were selected using Medline. Study selection Articles selected were relevant to development of mesenchymal stem cells (MSCs) for transplantation in spinal cord injury therapy. Of 258 originally identifiied arises 51 were selected that specifically addressed the stated purpose. Results Recent work has revealed that hUCMSCs share most of the characteristics with MSCs derived from bone marrow and are more appropriate to transplantation for cell based therapies. Conclusions Human umbilical cord could be regarded as a source of MSCs for experimental and clinical needs. In addition, as a peculiar source of stem cells, hUCMSCs may play an important role in the treatment of spinal cord injury.

  4. Transplante de sangue de cordão umbilical - SCU Umbilical cord blood transplantation

    Directory of Open Access Journals (Sweden)

    Celso A. Rodrigues

    2010-05-01

    Full Text Available A frequente utilização de sangue de cordão umbilical - SCU como fonte de células- tronco hematopoéticas - CTH, tanto em crianças, como em adultos, que não dispõem de doador na família, tem levado ao estabelecimento da padronização de critérios em sua seleção, objetivando a obtenção de melhores resultados. A escolha da unidade de SCU deve basear-se no número total de células nucleadas e no número de diferenças de antígenos leucocitários humanos (HLA. Diante de uma unidade com celularidade mínima, deve-se considerar a possibilidade da utilização de duplo cordão. Frente a mais de uma unidade com características semelhantes, a realização da contagem de células CD34 e da compatibilidade ABO, assim como a qualidade e a rapidez para obtenção da unidade, podem definir a escolha.The frequent use of umbilical cord blood as the source of hematopoietic stem cells, both in children and adults who do not have related donors, has led to the establishment of a better standardization of selection criteria aiming at improving the results. The choice of the umbilical cord blood unit should be based on the total number of nucleated cells and the number of differences in the human leukocyte antigen (HLA system. When a unit has minimal cellularity, the use of a double cord blood transplant should be considered. When two or more units have similar characteristics, the choice may be determined by the CD34 count, ABO compatibility and the quality and speed to obtain the unit.

  5. Isolation and characterization of mesenchymal stem cells from caprine umbilical cord tissue matrix.

    Science.gov (United States)

    Kumar, Kuldeep; Agarwal, Pranjali; Das, Kinsuk; Mili, Bhabesh; Madhusoodan, A P; Kumar, Ajay; Bag, Sadhan

    2016-12-01

    Cord tissue fills the umbilical cord around the blood vessels and contains types of stem cells (mesenchymal stem cells or MSCs) that are not generally found in cord blood. MSCs are the stem cells that give rise to many of the "support tissues" in the body, including bone, cartilage, fat and muscle. Umbilical Cord Tissue cells (UCTs) possessing the capacity to differentiate into various cell types such as osteoblasts, chondrocytes and adipocytes have been previously isolated from different species including human, canine, murine, avian species etc. The present study documents the existence of similar multipotential stem cells in caprine UCTs having similar growth and morphological characteristics. The cells were isolated from caprine umbilical cord and cultivated in DMEM (low glucose) supplemented with 15% FBS, L-glutamine and antibiotics. Primary culture achieved confluence in 5-7days having spindle shaped morphology. The cells were morphologically homogeneous, showed robust proliferation ability with a population doubled time of 92.07h as well as normal karyotype. In vitro self-renewal capacity was demonstrated by colony-forming unit assay (CFU). The cells expressed MSC specific markers and showed multi-differentiation capability into adipogenic and osteogeneic. The results indicated that caprine UCTs (cUCTs) were isolated and characterized from umbilical cord tissue which can be used for tissue regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. 脐血干细胞治疗1型糖尿病3例%Umbilical Cord Blood Stem Cell in the Treatment of Type 1 Diabetes-3 cases with Report

    Institute of Scientific and Technical Information of China (English)

    李孔龙; 段志胜; 徐勉; 柯亭羽

    2013-01-01

    Umbilical cord blood stem cells in certain conditions can be differentiated into isletβcells in the treatment of type 1 diabetes is a safe, effective-therapy. Objective Umbilical cord blood mesenchymal stem cell therapy T1DM, observe the efficacy and safety. Methods Two T1DM patients, age 16 and 20 years old respectively, and body mass index were in the patient and family under the condition of informed consent in our room behavior intervention in art, umbilical cord blood mesenchymal stem cells injected intravenously dorsal pancreatic artery. Transplant patients were followed up the clinical symptoms and the change of the index, and make comprehensive analysis. Results Two patients required to insulin from islet function is improved significantly, glycated hemoglobin from to, diabetic ketoacidosis fewer happened. Conclusion Umbilical cord blood mesenchymal stem cells as a new way of treatment is T1DM, in clinical application shows its unique effect.%研究证实,干细胞具有趋向分化作用,可分化为胰岛β细胞,在治疗T1DM中是一种安全、有效的治疗手段。目的脐血间充质干细胞治疗T1DM,观察其疗效和安全性。方法3例T1DM患者,年龄分别16岁、20岁、28岁。体质量指数分别是22.3、21.5、21.6。在患者及家属知情同意的情况下于我院介入室行为介入术,脐血间充质干细胞静脉注入胰背动脉。术后随访其临床症状及各项指标的变化,进行综合分析。结果3例患者胰岛素需要量较前下降30%~50%,胰岛功能较前明显改善,糖化血红蛋白从9.85%~13.26%下降到6.7%~7.8%,糖尿病酮症随访期间未发生。结论脐血间充质干细胞作为干细胞的一种是治疗T1DM的新途径,在临床应用中显示出其特有的效应。

  7. Umbilical cord blood graft enhancement strategies: has the time come to move these into the clinic?

    Science.gov (United States)

    Norkin, M; Lazarus, H M; Wingard, J R

    2013-07-01

    Umbilical cord blood (UCB) is an attractive stem cell graft option for patients who need allogeneic hematopoietic stem cell support, but lack a suitable HLA-matched donor. However, the limited number of hematopoietic progenitor cells in a single cord blood unit can lead to an increased risk of graft failure, delayed hematological recovery and prolonged immunosuppression, particularly in adult patients. Several strategies to overcome these potential limitations are being evaluated. In this review, we discuss promising ex vivo manipulations to enhance cord blood engraftment capacity such as culture of UCB cells with stimulatory cytokines and growth factors, mesenchymal cells, Notch ligand, copper chelators, prostaglandins, complement components, nicotinamide and CD26/DPPIV inhibitors. All these approaches are now in early clinical trials. However, despite the fact that several cord blood enhancement strategies have resulted in increased numbers of progenitor cells and faster neutrophil recovery, the ability of these techniques to significantly shorten engraftment time and permit the use of cord units with low numbers of total nucleated cells, or accomplish reliable engraftment with a single cord, have yet to be convincingly demonstrated. The ultimate clinical value of ex vivo cord blood expansion or manipulation has not been defined yet, and the current data do not permit predicting which technology will prove to be the optimal strategy. Nevertheless, expectations remain high that eventually ex vivo enhancement will be able to improve clinical outcomes and significantly extend the applicability of UCB transplantation.

  8. Percutaneous ultrasound guided umbilical cord blood sampling

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Hyup; Choi, B. I.; Kim, C. W.; Youn, B. H.; Shin, H. C.; Kim, S. O. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1989-12-15

    This report describes a technique and the result of percutaneous ultrasound-guided umbilical cord blood sampling and its potential use in the management of diagnostic problems in the second and third trimester of pregnancy. This method has been employed in the prenatal assessment of 19 fetuses at risk for chromosomal disorders, fetal hypoxia and hematologic disorders. This simple and rapid procedure offers a safe access to the fetal circulation

  9. Sibling cord blood donor program for hematopoietic cell transplantation: the 20-year experience in the Rome Cord Blood Bank.

    Science.gov (United States)

    Screnci, Maria; Murgi, Emilia; Valle, Veronica; Tamburini, Anna; Pellegrini, Maria Grazia; Strano, Sabrina; Corona, Francesca; Ambrogi, Eleonora Barbacci; Girelli, Gabriella

    2016-03-01

    Umbilical cord blood (UCB) represents a source of hematopoietic stem cells for patients lacking a suitably matched and readily available related or unrelated stem cell donor. As UCB transplantation from compatible sibling provides good results in children therefore directed sibling UCB collection and banking is indicated in family who already have a child with a disease potentially treatable with an allogeneic hematopoietic stem cell transplantation. Particularly, related UCB collection is recommended when the patients urgently need a transplantation. To provide access to all patients in need, we developed a "Sibling cord blood donor program for hematopoietic cell transplantation". Here we report results of this project started 20years ago. To date, in this study a total of 194 families were enrolled, a total of 204 UCB samples were successfully collected and 15 pediatric patients have been transplanted. Recently, some authors have suggested novel role for UCB other than in the transplantation setting. Therefore, future studies in the immunotherapy and regenerative medicine areas could expand indication for sibling directed UCB collection.

  10. Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective.

    Science.gov (United States)

    Beak, Carla Pereira; Chargé, Sophie B; Isasi, Rosario; Knoppers, Bartha M

    2015-05-01

    In 2013 Canadian Blood Services (CBS) launched the National Public Cord Blood Bank (NPCBB), a program to collect, process, test, and store cord blood units donated for use in transplantation. A key component of the creation of the NPCBB is the establishment of a program that enables cord blood not suitable for banking or transplantation to be used for biomedical research purposes. Along with the development of processes and policies to manage the NPCBB and the cord blood research program, CBS-in collaboration with researchers from the Stem Cell Network-have also developed educational tools to provide relevant information for target audiences to aid implementation and operation. We describe here one of these tools, the REB Primer on Research and Cord Blood Donation (the Primer), which highlights key ethical and legal considerations and identifies Canadian documents that are relevant to the use of cord blood in biomedical research. The Primer also introduces the NPCBB and describes the systems CBS is implementing to address ethical issues. The Primer is intended to assist research ethics boards in evaluating the ethical acceptability of research protocols, to facilitate harmonized decision-making by providing a common reference, and to highlight the role of research ethics boards in governance frameworks. With the Primer we hope to illustrate how the development of such educational tools can facilitate the ethical implementation and governance of programs related to stem cell research in Canada and abroad.

  11. Umbilical cord blood mercury levels in China

    Institute of Scientific and Technical Information of China (English)

    Meiqin Wu,; Chonghuai Yan; Jian Xu; Wei Wu; Hui Li; Xin Zhou

    2013-01-01

    Mercury (Hg) is a well-known neurotoxicant.Hg exposure at high levels can harm individuals of all ages.Even low level exposure to Hg can damage the brain of fetuses and young children,and affect their central nervous system and cognitive development.The aims of our study were to measure total Hg levels in infant umbilical cord blood and to investigate the risk factors associated with total Hg cord blood levels in various cities in China.Our goal was to provide clues for the prevention of Hg exposure in utero.The results indicated that the average cord blood mercury levels (CBMLs) were (1.81 ± 1.93) μg/L,which were lower than those found in most previous studies.The concentrations also differed according to geographic region.The CBMLs were not only associated with family economic and living conditions,but also with diet in pregnant women,especially the intake of marine fish,shellfish,poultry,formula milk and fruits.

  12. Induced Pluripotent Stem Cells for Traumatic Spinal Cord Injury

    Science.gov (United States)

    Khazaei, Mohamad; Ahuja, Christopher S.; Fehlings, Michael G.

    2017-01-01

    Spinal cord injury (SCI) is a common cause of mortality and neurological morbidity. Although progress had been made in the last decades in medical, surgical, and rehabilitation treatments for SCI, the outcomes of these approaches are not yet ideal. The use of cell transplantation as a therapeutic strategy for the treatment of SCI is very promising. Cell therapies for the treatment of SCI are limited by several translational road blocks, including ethical concerns in relation to cell sources. The use of iPSCs is particularly attractive, given that they provide an autologous cell source and avoid the ethical and moral considerations of other stem cell sources. In addition, different cell types, that are applicable to SCI, can be created from iPSCs. Common cell sources used for reprogramming are skin fibroblasts, keratinocytes, melanocytes, CD34+ cells, cord blood cells and adipose stem cells. Different cell types have different genetic and epigenetic considerations that affect their reprogramming efficiencies. Furthermore, in SCI the iPSCs can be differentiated to neural precursor cells, neural crest cells, neurons, oligodendrocytes, astrocytes, and even mesenchymal stromal cells. These can produce functional recovery by replacing lost cells and/or modulating the lesion microenvironment.

  13. Stem cell-based therapies for spinal cord injury.

    Science.gov (United States)

    Nandoe Tewarie, Rishi S; Hurtado, Andres; Bartels, Ronald H; Grotenhuis, Andre; Oudega, Martin

    2009-01-01

    Spinal cord injury (SCI) results in loss of nervous tissue and consequently loss of motor and sensory function. There is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. Transplantation of stem cells or progenitors may support spinal cord repair. Stem cells are characterized by self-renewal and their ability to become any cell in an organism. Promising results have been obtained in experimental models of SCI. Stem cells can be directed to differentiate into neurons or glia in vitro, which can be used for replacement of neural cells lost after SCI. Neuroprotective and axon regeneration-promoting effects have also been credited to transplanted stem cells. There are still issues related to stem cell transplantation that need to be resolved, including ethical concerns. This paper reviews the current status of stem cell application for spinal cord repair.

  14. Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks.

    Science.gov (United States)

    Rafii, Hanadi; Bernaudin, Françoise; Rouard, Helene; Vanneaux, Valérie; Ruggeri, Annalisa; Cavazzana, Marina; Gauthereau, Valerie; Stanislas, Aurélie; Benkerrou, Malika; De Montalembert, Mariane; Ferry, Christele; Girot, Robert; Arnaud, Cecile; Kamdem, Annie; Gour, Joelle; Touboul, Claudine; Cras, Audrey; Kuentz, Mathieu; Rieux, Claire; Volt, Fernanda; Cappelli, Barbara; Maio, Karina T; Paviglianiti, Annalisa; Kenzey, Chantal; Larghero, Jerome; Gluckman, Eliane

    2017-06-01

    Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had a previous child diagnosed with homozygous sickle cell disease. Participation was voluntary and free of charge. All mothers underwent mandatory serological screening. Cord blood units were collected in different hospitals, but processed and stored in two public banks. A total of 338 units were stored for 302 families. Median recipient age was six years (11 months-15 years). Median collected volume and total nucleated cell count were 91 mL (range 23-230) and 8.6×10(8) (range 0.7-75×10(8)), respectively. Microbial contamination was observed in 3.5% (n=12), positive hepatitis B serology in 25% (n=84), and homozygous sickle cell disease in 11% (n=37) of the collections. Forty-four units were HLA-identical to the intended recipient, and 28 units were released for transplantation either alone (n=23) or in combination with the bone marrow from the same donor (n=5), reflecting a utilization rate of 8%. Engraftment rate was 96% with 100% survival. Family cord blood banking yields good quality units for sibling transplantation. More comprehensive banking based on close collaboration among banks, clinical and transplant teams is recommended to optimize the use of these units. Copyright© Ferrata Storti Foundation.

  15. Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks

    Science.gov (United States)

    Rafii, Hanadi; Bernaudin, Françoise; Rouard, Helene; Vanneaux, Valérie; Ruggeri, Annalisa; Cavazzana, Marina; Gauthereau, Valerie; Stanislas, Aurélie; Benkerrou, Malika; De Montalembert, Mariane; Ferry, Christele; Girot, Robert; Arnaud, Cecile; Kamdem, Annie; Gour, Joelle; Touboul, Claudine; Cras, Audrey; Kuentz, Mathieu; Rieux, Claire; Volt, Fernanda; Cappelli, Barbara; Maio, Karina T.; Paviglianiti, Annalisa; Kenzey, Chantal; Larghero, Jerome; Gluckman, Eliane

    2017-01-01

    Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had a previous child diagnosed with homozygous sickle cell disease. Participation was voluntary and free of charge. All mothers underwent mandatory serological screening. Cord blood units were collected in different hospitals, but processed and stored in two public banks. A total of 338 units were stored for 302 families. Median recipient age was six years (11 months-15 years). Median collected volume and total nucleated cell count were 91 mL (range 23–230) and 8.6×108 (range 0.7–75×108), respectively. Microbial contamination was observed in 3.5% (n=12), positive hepatitis B serology in 25% (n=84), and homozygous sickle cell disease in 11% (n=37) of the collections. Forty-four units were HLA-identical to the intended recipient, and 28 units were released for transplantation either alone (n=23) or in combination with the bone marrow from the same donor (n=5), reflecting a utilization rate of 8%. Engraftment rate was 96% with 100% survival. Family cord blood banking yields good quality units for sibling transplantation. More comprehensive banking based on close collaboration among banks, clinical and transplant teams is recommended to optimize the use of these units. PMID:28302713

  16. Human Umbilical Cord Blood for Transplantation Therapy in Myocardial Infarction.

    Science.gov (United States)

    Acosta, Sandra A; Franzese, Nick; Staples, Meaghan; Weinbren, Nathan L; Babilonia, Monica; Patel, Jason; Merchant, Neil; Simancas, Alejandra Jacotte; Slakter, Adam; Caputo, Mathew; Patel, Milan; Franyuti, Giorgio; Franzblau, Max H; Suarez, Lyanne; Gonzales-Portillo, Chiara; Diamandis, Theo; Shinozuka, Kazutaka; Tajiri, Naoki; Sanberg, Paul R; Kaneko, Yuji; Miller, Leslie W; Borlongan, Cesar V

    2013-07-01

    Cell-based therapy is a promising therapy for myocardial infarction. Endogenous repair of the heart muscle after myocardial infarction is a challenge because adult cardiomyocytes have a limited capacity to proliferate and replace damaged cells. Pre-clinical and clinical evidence has shown that cell based therapy may promote revascularization and replacement of damaged myocytes after myocardial infarction. Adult stem cells can be harvested from different sources including bone marrow, skeletal myoblast, and human umbilical cord blood cells. The use of these cells for the repair of myocardial infarction presents various advantages over other sources of stem cells. Among these are easy harvesting, unlimited differentiation capability, and robust angiogenic potential. In this review, we discuss the milestone findings and the most recent evidence demonstrating the therapeutic efficacy and safety of the transplantation of human umbilical cord blood cells as a stand-alone therapy or in combination with gene therapy, highlighting the importance of optimizing the timing, dose and delivery methods, and a better understanding of the mechanisms of action that will guide the clinical entry of this innovative treatment for ischemic disorders, specifically myocardial infarction.

  17. Human Umbilical Cord Blood Cell Transplantation in Neuroregenerative Strategies

    Directory of Open Access Journals (Sweden)

    Luisa R. Galieva

    2017-09-01

    Full Text Available At present there is no effective treatment of pathologies associated with the death of neurons and glial cells which take place as a result of physical trauma or ischemic lesions of the nervous system. Thus, researchers have high hopes for a treatment based on the use of stem cells (SC, which are potentially able to replace dead cells and synthesize neurotrophic factors and other molecules that stimulate neuroregeneration. We are often faced with ethical issues when selecting a source of SC. In addition to precluding these, human umbilical cord blood (hUCB presents a number of advantages when compared with other sources of SC. In this review, we consider the key characteristics of hUCB, the results of various studies focused on the treatment of neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, ischemic (stroke and traumatic injuries of the nervous system and the molecular mechanisms of hUCB-derived mononuclear and stem cells.

  18. Free erythrocyte porphyrins in cord blood.

    Science.gov (United States)

    Gottuso, M A; Oski, B F; Oski, F A

    1978-05-01

    Red cell free erythrocyte porphyrin determinations were performed on cord blood specimens from 236 term infants and on capillary blood specimens from 63 preterm infants weighing less than 1,500 gm, during the first week of life. These results were contrasted with those obtained from 398 normal infants and children ages 1 to 6 years. The mean FEP value for the infants was significantly higher than that observed in the normal control subjects. In 10.5% of the term infants and 15.9% of the preterm infants, values in excess of 120 microgram/dl RBCs, the highest value recorded in the normal subjects, were observed. Elevations in FEP values were not related to either blood lead concentration or hematocrit levels in the infants. Infants with elevated FEP values were found to have lower serum iron and transferrin saturation values than did infants with low FEP values. These findings suggest that elevations in cord blood FEP values may indicate a state of relative iron deficiency present at birth.

  19. Quantification of viral genome in cord blood donors by real time PCR to investigate human herpesvirus type 8 active infection.

    Science.gov (United States)

    Golchin, Neda; Kheirandish, Maryam; Sharifi, Zohreh; Samiee, Shahram; Kokhaei, Parviz; Pourpak, Zahra

    2015-12-01

    Umbilical cord blood (UCB) is one of the most important sources of hematopoietic stem cells which can be used for transplantation. The transplanted CB stem cells might cause infections in recipients. The aim of this study is to evaluate Human Herpes Virus8 (HHV8) as a Rhadinovirus among CB samples in order to assess safety of cord blood stem cells transplantation. To assess this aim, we surveyed 800 cord blood specimens by Real Time PCR.The overall HHV8 incidence in cord blood mononuclear cells was 1.38% and none of them was in lytic phase of HHV8. The authors suggest further HHV8 study on CB samples for transplantation.

  20. Cord Blood as a Source of Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Rohtesh S Mehta

    2016-01-01

    Full Text Available Cord blood (CB offers several unique advantages as a graft source for hematopoietic stem cell transplantation (HSCT. The risk of relapse and graft-versus-host disease (GVHD after cord blood transplantation (CBT are lower than what is typically observed after other graft sources with a similar degree of human leukocyte antigen (HLA mismatch. Natural killer (NK cells have a well-defined role in both innate and adaptive immunity and as the first lymphocytes to reconstitute after HSCT and CBT, they play a significant role in protection against early relapse. In this article, we highlight the uses of CB NK cells in transplantation and adoptive immunotherapy. First, we will describe differences in the phenotype and functional characteristics of NK cells in CB as compared with peripheral blood. Then, we will review some of the obstacles we face in using resting CB NK cells for adoptive immunotherapy, and discuss methods to overcome them. We will review the current literature on killer-cell immunoglobulin-like receptors (KIR-ligand mismatch and outcomes after CBT. Finally, we will touch on current strategiesfor the use of CB NK cells in cellular immunotherapy.

  1. Double cord blood transplantation: co-operation or competition?

    Directory of Open Access Journals (Sweden)

    Nikolaos Neokleous

    2011-06-01

    Full Text Available Over the last two decades umbilical cord blood (UCB transplantation (UCBT is increasingly used for a variety of malignant and benign hematological and other diseases. The main factor that limits the use of UCB to low weight recipients, mainly children and adolescents, is its low progenitor cell content. Various alternatives have been exploited to overcome this difficulty, including the transplantation of two UCB units (double umbilical cord blood transplantation, dUCBT. Following dUCBT, donor(s hematopoietic stem cells (HSC can be detected in the peripheral blood of the recipient as soon as 14 days post-transplantation. Sustained engraftment of HSC from one or both donors can be observed- dominance or mixed chimerism respectively, although single donor unit dominance has been observed in over 85% of patients. The underlying biology, which accounts for the interactions both between the two infused UCB units- cooperative or competitive, and with the recipient’s immune system, has not been elucidated.

  2. Cord Blood as a Source of Natural Killer Cells

    Science.gov (United States)

    Mehta, Rohtesh S.; Shpall, Elizabeth J.; Rezvani, Katayoun

    2016-01-01

    Cord blood (CB) offers several unique advantages as a graft source for hematopoietic stem cell transplantation (HSCT). The risk of relapse and graft vs. host disease after cord blood transplantation (CBT) is lower than what is typically observed after other graft sources with a similar degree of human leukocyte antigen mismatch. Natural killer (NK) cells have a well-defined role in both innate and adaptive immunity and as the first lymphocytes to reconstitute after HSCT and CBT, and they play a significant role in protection against early relapse. In this article, we highlight the uses of CB NK cells in transplantation and adoptive immunotherapy. First, we will describe differences in the phenotype and functional characteristics of NK cells in CB as compared with peripheral blood. Then, we will review some of the obstacles we face in using resting CB NK cells for adoptive immunotherapy, and discuss methods to overcome them. We will review the current literature on killer-cell immunoglobulin-like receptors ligand mismatch and outcomes after CBT. Finally, we will touch on current strategies for the use of CB NK cells in cellular immunotherapy. PMID:26779484

  3. Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy.

    Science.gov (United States)

    Ding, Dah-Ching; Chang, Yu-Hsun; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2015-01-01

    The human umbilical cord is a promising source of mesenchymal stem cells (HUCMSCs). Unlike bone marrow stem cells, HUCMSCs have a painless collection procedure and faster self-renewal properties. Different derivation protocols may provide different amounts and populations of stem cells. Stem cell populations have also been reported in other compartments of the umbilical cord, such as the cord lining, perivascular tissue, and Wharton's jelly. HUCMSCs are noncontroversial sources compared to embryonic stem cells. They can differentiate into the three germ layers that promote tissue repair and modulate immune responses and anticancer properties. Thus, they are attractive autologous or allogenic agents for the treatment of malignant and nonmalignant solid and soft cancers. HUCMCs also can be the feeder layer for embryonic stem cells or other pluripotent stem cells. Regarding their therapeutic value, storage banking system and protocols should be established immediately. This review critically evaluates their therapeutic value, challenges, and future directions for their clinical applications.

  4. Effect of human umbilical cord blood stem cells on nerve growth factor levels and nerve function in rats with focal cerebral ischemia%人脐血干细胞对局灶性脑缺血大鼠神经生长因子水平及神经功能的影响

    Institute of Scientific and Technical Information of China (English)

    王强; 汪青松; 张云静; 项倩彤; 刘学春; 黄海丽

    2013-01-01

    Objective To explore the efficacy of the intravenous transplantation of umbilical cord blood stem cells on cerebral ischemia in rats and its nerve function. Methods Ludmila Belayev method was used to establish middle cerebral artery occlusion and reperfusion model. Thirty - three rats were randomly divided into edaravone group and transplantation group. One day after modeling the intravenous injection of saline, edaravone and umbilical cord blood stem cell line was performed respectively, and the effect was observed. Results Before modeling the serum NGF ( OD value ) in three groups showed no significant difference ( P > 0. 05 ); three to forty days after modeling, the decrease of serum NGF levels ( OD value ) in edaravone group and umbilical cord blood stem cell group showed a significant difference compared with that of the physiological saline group ( P < 0. 05 ); the serum NGF ( OD value ) of the umbilical cord blood stem cell group was significantly higher than that of edaravone group 7, 14, 21, 28 , 40 days after treatment ( P < 0. 05 ). At the same time, the nerve function score of three groups before modeling was 0, while that after treatment was improved; there were significant differences in edaravone group and umbilical cord blood stem cell group compared with the saline group ( P < 0. 05 ); the neurological score difference was not statistically significant between edaravone group and umbilical cord blood stem cell group 3, 5 and 7 days after treatment, ( P > 0. 05 ); however, 14, 21, 28 , 40 days after treatment, the neurological score of the umbilical cord blood stem cell group was better than that of edaravone group ( P < 0. 05 ). Conclusion The experiments suggest that intravenous transplantation of cord blood stem cells can migrate to focal ischemic brain tissue, which improves the level of nerve growth factor in rats and the neurological function significantly.%目的 探讨经静脉移植脐血干细胞治疗大鼠脑缺血模型的

  5. Improving engraftment and immune reconstitution in umbilical cord blood transplantation

    Directory of Open Access Journals (Sweden)

    Robert eDanby

    2014-02-01

    Full Text Available Umbilical cord blood (UCB is an important source of haematopoietic stem cells (HSC for allogeneic transplantation when HLA-matched sibling and unrelated donors (MUD are unavailable. Although the overall survival rates of UCB transplantation are comparable to the results with MUD, UCB transplants are associated with slow engraftment, delayed immune reconstitution, and increased opportunistic infections. While this may be a consequence of the lower cell dose in UCB grafts, it also reflects the relative immaturity of cellular immunity within cord blood. Furthermore, the limited number of cells and the non-availability of donor lymphocyte infusions (DLI currently prevent the use of post-transplant cellular immunotherapy to boost donor-derived immunity to treat infection, mixed chimerism and disease relapse. Therefore, to further develop UCB transplantation, many strategies to enhance engraftment and immune reconstitution are currently under investigation. This review summarises our current understanding of engraftment and immune recovery following UCB transplantation and why this differs from allogeneic transplants using other sources of HSC. It also provides an comprehensive overview of the promising techniques being used to improve myeloid and lymphoid recovery, including expansion, homing, and delivery of UCB HSC; combined use of UCB with third party donors; isolation and expansion of NK cells, pathogen specific T cells, and regulatory T cells; methods to protect and/or improve thymopoiesis. As many of these strategies are now in clinical trials, it is anticipated that UCB transplantation will continue to advance, further expanding our understanding of UCB biology and HSC transplantation.

  6. Generation, Expansion, and Differentiation of Human Induced Pluripotent Stem Cells (hiPSCs) Derived From the Umbilical Cords of Newborns.

    Science.gov (United States)

    Song, Richard S; Carroll, Jeanne M; Acevedo, Lisette; Wu, Dongmei; Liu, Yang; Snyder, Evan Y

    2014-05-16

    The umbilical cord is tissue that is normally discarded after the delivery of the infant, but it has been shown to be a rich source of stem cells from the cord blood, Wharton's jelly, and umbilical endothelial cells. Patient-specific human induced pluripotent stem cells (hiPSCs) reprogrammed from patient specific human umbilical vein endothelial cells in the neonatal intensive care unit (NICU) population (specifically, premature neonates) have not been shown in the literature. This unit describes a protocol for the generation and expansion of hiPSCs originating from umbilical cords collected from patients in the NICU.

  7. Molecular Imaging in Stem Cell Therapy for Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Fahuan Song

    2014-01-01

    Full Text Available Spinal cord injury (SCI is a serious disease of the center nervous system (CNS. It is a devastating injury with sudden loss of motor, sensory, and autonomic function distal to the level of trauma and produces great personal and societal costs. Currently, there are no remarkable effective therapies for the treatment of SCI. Compared to traditional treatment methods, stem cell transplantation therapy holds potential for repair and functional plasticity after SCI. However, the mechanism of stem cell therapy for SCI remains largely unknown and obscure partly due to the lack of efficient stem cell trafficking methods. Molecular imaging technology including positron emission tomography (PET, magnetic resonance imaging (MRI, optical imaging (i.e., bioluminescence imaging (BLI gives the hope to complete the knowledge concerning basic stem cell biology survival, migration, differentiation, and integration in real time when transplanted into damaged spinal cord. In this paper, we mainly review the molecular imaging technology in stem cell therapy for SCI.

  8. Cord blood is the optimal graft source for the treatment of pediatric patients with lysosomal storage diseases : Clinical outcomes and future directions

    NARCIS (Netherlands)

    Aldenhoven, Mieke|info:eu-repo/dai/nl/304815365; Kurtzberg, Joanne

    2015-01-01

    Initially used as an alternative hematopoietic stem cell source for patients without a human leukocyte antigen-matched bone marrow or peripheral blood stem cell donor, unrelated cord blood (UCB) is now the preferred donor source when hematopoietic stem cell transplantation (HSCT) is used to treat pa

  9. Cord blood is the optimal graft source for the treatment of pediatric patients with lysosomal storage diseases : Clinical outcomes and future directions

    NARCIS (Netherlands)

    Aldenhoven, Mieke; Kurtzberg, Joanne

    Initially used as an alternative hematopoietic stem cell source for patients without a human leukocyte antigen-matched bone marrow or peripheral blood stem cell donor, unrelated cord blood (UCB) is now the preferred donor source when hematopoietic stem cell transplantation (HSCT) is used to treat

  10. Successful second transplantation from haploidentical donor for graft failure following unrelated cord blood cell transplantation or mismatched related transplantation: 2cases report

    Institute of Scientific and Technical Information of China (English)

    XU Lan-ping; HUANG Xiao-jun

    2006-01-01

    @@ Cord blood transplantation (CBT) from unrelated donors has increasingly been performed worldwide during the last decade. The immaturity of lymphocytes in cord blood permits HLA-mismatching between donors and recipients and reduces the severity of graft-versus-host disease (GVHD).However, the relatively small dose of the cord blood nucleated cells is associated with a high frequency of engraftment failure.1-5 But re-transplantation with stem cells from the original donor is impossible.

  11. Short-Lived Human Umbilical Cord-Blood-Derived Neural Stem Cells Influence the Endogenous Secretome and Increase the Number of Endogenous Neural Progenitors in a Rat Model of Lacunar Stroke.

    Science.gov (United States)

    Jablonska, Anna; Drela, Katarzyna; Wojcik-Stanaszek, Luiza; Janowski, Miroslaw; Zalewska, Teresa; Lukomska, Barbara

    2016-11-01

    Stroke is the leading cause of severe disability, and lacunar stroke is related to cognitive decline and hemiparesis. There is no effective treatment for the majority of patients with stroke. Thus, stem cell-based regenerative medicine has drawn a growing body of attention due to the capabilities for trophic factor expression and neurogenesis enhancement. Moreover, it was shown in an experimental autoimmune encephalomyelitis (EAE) model that even short-lived stem cells can be therapeutic, and we have previously observed that phenomenon indirectly. Here, in a rat model of lacunar stroke, we investigated the molecular mechanisms underlying the positive therapeutic effects of short-lived human umbilical cord-blood-derived neural stem cells (HUCB-NSCs) through the distinct measurement of exogenous human and endogenous rat trophic factors. We have also evaluated neurogenesis and metalloproteinase activity as cellular components of therapeutic activity. As expected, we observed an increased proliferation and migration of progenitors, as well as metalloproteinase activity up to 14 days post transplantation. These changes were most prominent at the 7-day time point when we observed 30 % increases in the number of bromodeoxyuridine (BrdU)-positive cells in HUCB-NSC transplanted animals. The expression of human trophic factors was present until 7 days post transplantation, which correlated well with the survival of the human graft. For these 7 days, the level of messenger RNA (mRNA) in the analyzed trophic factors was from 300-fold for CNTF to 10,000-fold for IGF, much higher compared to constitutive expression in HUCB-NSCs in vitro. What is interesting is that there was no increase in the expression of rat trophic factors during the human graft survival, compared to that in non-transplanted animals. However, there was a prolongation of a period of increased trophic expression until 14 days post transplantation, while, in non-transplanted animals, there was a

  12. Cord blood transplantation for the treatment of acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Meerim Park; Young-ho Lee

    2013-01-01

    Objective This review discussed the available data on treatment outcomes of cord blood transplantation (CBT) for acute leukemia.Data sources The data cited in this review were obtained from articles listed in Medline and Pubmed.Study selection We reviewed the articles of clinical results from various registries and institutions,as well as our experiences with CBT in children,adolescents and adults.Results This research has clearly shown that cord blood (CB) has several unique characteristics resulting in distinct advantage and disadvantages when compared to transplantation with unrelated donor bone marrow or peripheral blood stem cells.The field of CBT has advanced from investigating its safety and feasibility to addressing more specific issues such as accelerating engraftment,extending access,and examining outcomes in specific subgroups of patients.Many approaches have been investigated in the attempt to improve engraftment and survival.Variable factors have been identified,such as factors related to donor choice (human leukocyte antigen (HLA) compatibility,cell dose,and others) and transplantation (conditioning and graft-versus-host disease prophylaxis regimen).Data support that CB should be considered a reasonable option in those that do not have HLA matched sibling donor and for those in whom the time to transplant is critical.Conclusions CB is a reasonable alternative to unrelated donor bone marrow or peripheral blood progenitor cells for transplantation.Recently developed strategies aimed at improving hematopoietic recovery and reducing early transplantation-related mortality could further improve treatment outcomes of CBT for patients with acute leukemia.

  13. Epithelial and mesenchymal stem cells from the umbilical cord lining membrane.

    Science.gov (United States)

    Lim, Ivor J; Phan, Toan Thang

    2014-01-01

    mesenchymal and epithelial stem cells can be isolated from the umbilical cord lining membrane, usefully regenerating not only mesenchymal tissue, such as bone, cartilage, and cardiac and striated muscle, but also epithelial tissue, such as skin, cornea, and liver. Both mesenchymal and epithelial CLSCs are immune privileged and resist rejection. Clinically, CLSCs have proved effective in the treatment of difficult-to-heal human wounds, such as diabetic ulcers, recalcitrant chronic wounds, and even persistent epithelial defects of the cornea. Heart and liver regeneration has been shown to be successful in animal studies and await human trials. CLSCs have also been shown to be an effective feeder layer for cord blood hematopoietic stem cells and, more recently, has been recognized as an abundant and high-quality source of cells for iPSC production. Banking of CLSCs by cord blood banks in both private and public settings is now available in many countries, so that individuals may have their personal stores of CLSCs for future translational applications for both themselves and their families. Cord lining stem cells are strongly positioned to be the future of cell therapy and regenerative medicine.

  14. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Loading... Unsubscribe from NCIcancertopics? Cancel Unsubscribe ... Ever considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  15. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Loading... Unsubscribe from NCIcancertopics? Cancel Unsubscribe ... Ever considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  16. Blood-Forming Stem Cell Transplants

    Science.gov (United States)

    ... to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... Considering becoming a bone marrow or a blood stem cell donor? View this video on YouTube. Follow a ...

  17. Becoming a Blood Stem Cell Donor

    Science.gov (United States)

    ... total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Loading... Unsubscribe from NCIcancertopics? Cancel Unsubscribe ... Ever considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  18. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Loading... Unsubscribe from NCIcancertopics? Cancel Unsubscribe ... considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  19. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Loading... Unsubscribe from NCIcancertopics? Cancel Unsubscribe ... considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  20. Use of cost-effectiveness analysis to determine inventory size for a national cord blood bank.

    Science.gov (United States)

    Howard, David H; Meltzer, David; Kollman, Craig; Maiers, Martin; Logan, Brent; Gragert, Loren; Setterholm, Michelle; Horowitz, Mary M

    2008-01-01

    Transplantation with stem cells from stored umbilical cord blood units is an alternative to living unrelated bone marrow transplantation. The larger the inventory of stored cord units, the greater the likelihood that transplant candidates will match to a unit, but storing units is costly. The authors present the results of a study, commissioned by the Institute of Medicine, as part of a report on the establishment of a national cord blood bank, examining the optimal inventory level. They emphasize the unique challenges of undertaking cost-effectiveness analysis in this field and the contribution of the analysis to policy. The authors estimate the likelihood that transplant candidates will match to a living unrelated marrow donor or a cord blood unit as a function of cord blood inventory and then calculate the life-years gained for each transplant type by match level using historical data. They develop a model of the cord blood inventory level to estimate total costs as a function of the number of stored units. The cost per life-year gained associated with increasing inventory from 50,000 to 100,000 units is $44,000 to $86,000 and from 100,000 to 150,000 units is $64,000 to $153,000, depending on the assumption about the degree to which survival rates for cord transplants vary by match quality. Expanding the cord blood inventory above current levels is cost-effective by conventional standards. The analysis helped shape the Institute of Medicine's report, but it is difficult to determine the extent to which the analysis influenced subsequent congressional legislation.

  1. Ethical issues relating the the banking of umbilical cord blood in Mexico

    Directory of Open Access Journals (Sweden)

    Valdez-Martinez Edith

    2009-08-01

    Full Text Available Abstract Background Umbilical cord banks are a central component, as umbilical cord tissue providers, in both medical treatment and scientific research with stem cells. But, whereas the creation of umbilical cord banks is seen as successful practice, it is perceived as a risky style of play by others. This article examines and discusses the ethical, medical and legal considerations that arise from the operation of umbilical cord banks in Mexico. Discussion A number of experts have stated that the use of umbilical cord goes beyond the mere utilization of human tissues for the purpose of treatment. This tissue is also used in research studies: genetic studies, studies to evaluate the effectiveness of new antibiotics, studies to identify new proteins, etc. Meanwhile, others claim that the law and other norms for the functioning of cord banks are not consistent and are poorly defined. Some of these critics point out that the confidentiality of donor information is handled differently in different places. The fact that private cord banks offer their services as "biological insurance" in order to obtain informed consent by promising the parents that the tissue that will be stored insures the health of their child in the future raises the issue of whether the consent is freely given or given under coercion. Another consideration that must be made in relation to privately owned cord banks has to do with the ownership of the stored umbilical cord. Summary Conflicts between moral principles and economic interests (non-moral principles cause dilemmas in the clinical practice of umbilical cord blood storage and use especially in privately owned banks. This article presents a reflection and some of the guidelines that must be followed by umbilical cord banks in order to deal with these conflicts. This reflection is based on the fundamental notions of ethics and public health and seeks to be a contribution towards the improvement of umbilical cord banks

  2. Bilirubin dosage in cord blood: could it predict neonatal hyperbilirubinemia?

    Directory of Open Access Journals (Sweden)

    Adélia Jeha Nasser Bernaldo

    Full Text Available CONTEXT: With early discharge, many newborns have to be readmitted to hospital for hyperbilirubinemia to be treated, and this has been held responsible for the reappearance of kernicterus. OBJECTIVE: To evaluate whether bilirubin levels in cord blood could predict neonatal hyperbilirubinemia that would require treatment, in full-term newborns up to their third day of life. TYPE OF STUDY: Prospective study. SETTING: Neonatal Unit of Hospital Israelita Albert Einstein, São Paulo, Brazil. PARTICIPANTS: 380 full-term newborns considered normal: with or without ABO/Rh blood group incompatibility and without other complications. PROCEDURES: Blood was taken from the umbilical cord for analysis of conjugated, unconjugated and total bilirubin serum levels. The newborns were followed up until discharge, and unconjugated bilirubin that required phototherapy was compared to the cord bilirubin assay. Discriminant analysis was used to classify newborns: with or without risk of needing phototherapy by the third day of life. MAIN MEASUREMENTS: Bilirubin assay in cord blood; mother's and newborn's blood groups; phototherapy indication. RESULTS: The mean value for unconjugated bilirubin in cord blood was significantly higher in newborns whose unconjugated bilirubin required phototherapy. The presence of ABO blood group incompatibility was a significant variable in relation to unconjugated bilirubin that required phototherapy. The most useful cutoff point for unconjugated bilirubin in cord blood was 2.0 mg/100 ml. DISCUSSION: Cord blood could be collected, stored and used for further analysis of unconjugated bilirubin levels as a means for considering whether or not to discharge a moderately jaundiced child from hospital, in association with other resources. CONCLUSIONS: Blood incompatibility between mother and child was a predictor for the appearance of hyperbilirubinemia that required treatment. Considering a cutoff point of 2.0 mg/100 ml, it could be concluded

  3. Stem cell-based therapies for spinal cord injury.

    NARCIS (Netherlands)

    Nandoe, R.D.S.; Hurtado, A.; Bartels, R.H.M.A.; Grotenhuis, A.; Oudega, M.

    2009-01-01

    Spinal cord injury (SCI) results in loss of nervous tissue and consequently loss of motor and sensory function. There is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. Transplantation of stem cells or progenitors may s

  4. Syrinx of the Spinal Cord and Brain Stem

    Science.gov (United States)

    ... Prompt Healthier Eating Scientists Working on Solar-Powered Prosthetic Limbs Health Highlights: March 23, 2017 Fruit Juice for Kids: A Serving a Day OK ALL NEWS > Resources ... may extend downward to affect the entire cord. Syrinxes that extend into or begin in the lower part of the brain stem may compress pathways ...

  5. Preliminary evaluation of intravenous infusion and intrapancreatic injection of human umbilical cord blood-derived mesenchymal stem cells for the treatment of diabetic mice

    OpenAIRE

    Ngoc Kim Phan; Thuy Thanh Duong; Truc Le-Buu Pham; Loan Thi-Tung Dang; Anh Nguyen-Tu Bui; Vuong Minh Pham; Nhat Chau Truong; and Phuc Van Pham

    2014-01-01

    Type 1 diabetes mellitus is characterized by the destruction of pancreatic islet beta cells, which leads to insulin insufficiency, hyperglycemia, and reduced metabolic glucose level. Insulin replacement is the current standard therapy for type 1 diabetes mellitus but has several limitations. Pancreatic islet transplantation can result in the production of exogenous insulin, but its use is limited by immune-rejection and donor availability. Recent studies have shown that mesenchymal stem cells...

  6. Delayed clamping of the umbilical cord after delivery and implications for public cord blood banking.

    Science.gov (United States)

    Allan, David S; Scrivens, Nicholas; Lawless, Tiffany; Mostert, Karen; Oppenheimer, Lawrence; Walker, Mark; Petraszko, Tanya; Elmoazzen, Heidi

    2016-03-01

    Public banking of umbilical cord blood units (CBUs) containing higher numbers of cells ensures timely engraftment after transplantation for increasing numbers of patients. Delayed clamping of the umbilical cord after birth may benefit some infants by preventing iron deficiency. Implications of delayed cord clamping for public cord blood banking remains unclear. CBUs collected by Canadian Blood Services at one collection site between November 1, 2014, and March 17, 2015, were analyzed. The delay in cord clamping after birth was timed and classified as "no delay," 20 to 60 seconds, more than 60 seconds, or more than 120 seconds. Of 367 collections, 100 reported no delay in clamping while clamping was delayed by 20 to 60 seconds (n = 69), more than 60 seconds (n = 98), or more than 120 seconds (n = 100) in the remaining cases. The mean volume and total nucleated cells (TNCs) in units with no delay in clamping were significantly greater than mean volumes for all categories of delayed clamping (Tukey's test, p clamping was delayed (p = 5.5 × 10(-8) ). The difference was most marked for cords that were clamped more than 120 seconds after delivery (6.2% compared with 39%). Delayed cord clamping greatly diminishes the volume and TNC count of units collected for a public cord blood bank. Creating an inventory of CBUs with high TNC content may take more time than expected. © 2015 AABB.

  7. Paracrine proangiopoietic effects of human umbilical cord blood-derived purified CD133+ cells--implications for stem cell therapies in regenerative medicine.

    Science.gov (United States)

    Ratajczak, Janina; Kucia, Magda; Mierzejewska, Kasia; Marlicz, Wojciech; Pietrzkowski, Zbigniew; Wojakowski, Wojciech; Greco, Nicholas J; Tendera, Michal; Ratajczak, Mariusz Z

    2013-02-01

    CD133+ cells purified from hematopoietic tissues are enriched mostly for hematopoietic stem/progenitor cells, but also contain some endothelial progenitor cells and very small embryonic-like stem cells. CD133+ cells, which are akin to CD34+ cells, are a potential source of stem cells in regenerative medicine. However, the lack of convincing donor-derived chimerism in the damaged organs of patients treated with these cells suggests that the improvement in function involves mechanisms other than a direct contribution to the damaged tissues. We hypothesized that CD133+ cells secrete several paracrine factors that play a major role in the positive effects observed after treatment and tested supernatants derived from these cells for the presence of such factors. We observed that CD133+ cells and CD133+ cell-derived microvesicles (MVs) express mRNAs for several antiapoptotic and proangiopoietic factors, including kit ligand, insulin growth factor-1, vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8. These factors were also detected in a CD133+ cell-derived conditioned medium (CM). More important, the CD133+ cell-derived CM and MVs chemoattracted endothelial cells and display proangiopoietic activity both in vitro and in vivo assays. This observation should be taken into consideration when evaluating clinical outcomes from purified CD133+ cell therapies in regenerative medicine.

  8. [Knockdown of Puma protects cord blood CD34(+) cells against γ- irradiation].

    Science.gov (United States)

    Zhao, Lei; Zhang, Hong-Yan; Pang, Ya-Kun; Gu, Hai-Hui; Xu, Jing; Yuan, Wei-Ping; Cheng, Tao

    2014-04-01

    Puma (P53 upregulated modulator of apoptosis) is a BCL-2 homology 3 (BH3)-only BCL-1 family member and a critical mediator of P53-dependent and -independent apoptosis. Puma plays an essential role in the apoptosis of hematopoietic stem cells exposed to irradiation without an increased risk of malignancies. This study was purposed to develop an effective lentiviral vector to target Puma in human hematopoietic cells and to investigate the effect of Puma gene knockdown on the biological function of human cord blood CD34(+) cells. SF-LV-shPuma-EGFP and control vectors were constructed, and packaged with the pSPAX2/pMD2.G packaging plasmids via 293T cells to produce pseudo-type lentiviruses. SF-LV-shPuma-EGFP or control lentiviruses were harvested within 72 hours after transfection and then were used to transduce human cord blood CD34(+) cells. GFP(+) transduced cells were sorted by flow cytometry (FCM) for subsequent studies. Semi-quantitative real time RT PCR, Western blot, FCM with Annexin V-PE/7-AAD double staining, Ki67 staining, colony forming cell assay (CFC), CCK-8 assay and BrdU incorporation were performed to determine the expression of Puma and its effect on the cord blood CD34(+) cells. The results showed that Puma was significantly knocked down in cord blood CD34(+) cells and the low expression of Puma conferred a radio-protective effect on the cord blood CD34(+) cells. This effect was achieved through reduced apoptosis and sustained quiescence after irradiation due to Puma knockdown. It is concluded that knockdown of puma gene in CD34(+) hematopoietic stem cells of human cord blood possesses the radioprotective effect, maintains the cells in silence targeting Puma in human hematopoietic cells may have a similar effect with that on mouse hematopoietic cells as previously shown, and our lentiviral targeting system for Puma provides a valuable tool for future translational studies with human cells.

  9. File list: His.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  11. File list: His.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. 胰岛干细胞和脐血间充质干细胞体外分离培养的形态学特征观察%Morphological observation of pancreatic stem cells and umbilical cord blood mesenchymal stem cells cultured in vitro

    Institute of Scientific and Technical Information of China (English)

    刘素芳; 李长生; 鄢文海; 韩雪飞; 邢莹

    2006-01-01

    在体外分离和培养,用于进一步相关实验工作.%BACKGROUND: Stem cells are relatively primitive cells possessing the capabilities of self-renewal, high proliferation and multi-potential differentiation in vivo under certain conditions. Pancreatic stem cells and umbilical cord blood mesenchymal stem cells (MSCs) may serve therapeutic purpose clinically, but they are still difficult to culture in vitro at present.OBJECTIVE: To explore the method for isolation, purification and culture of pancreatic stem cells and umbilical cord blood MSCs in vitro and observe their morphological changes during culture in vitro.DESIGN: Completely randomized experiment with repeated measurement.SETTING: Stem Cell Research Center, Teaching and Research Division of Physiology, Medical School of Zhengzhou University.MATERIALS: This experiment was conducted in the Stem Cell Research Center, Teaching and Research Division of Physiology, Medical College of Zhengzhou University, between April 2004 and January 2005. Ten to fifteen newborn SD rats (1-3 days) were selected for culture in vitro of pancreatic stem cells, and fresh umbilical cord blood was collected from healthy woman (24-35 years old, with informed consent) at full-term delivery for culture in vitro of umbilical blood SMCs.METHODS: The abdomen of the newborn SD rat was opened under aseptic condition to obtain the pancreas, which was cut into small tissue blocks and digested with type-V collagenase for islet isolation. The isolated islets were purified in continuous roller-bottle culture. Umbilical cord blood was freshly collected for isolating the monocytes by means of density gradient centrifugation in lymphocyte separation medium (with density of 1.077 g/cm3). The islet cells and umbilical cord blood monocytes were cultured in the incubator at 37 ℃ with 5% CO2. The morphological changes of the cells were observed at designed time points and flow cytometry was used to determine the expression of cell surface molecules.MAIN OUTCOME MEASURES: The

  13. Therapeutic potential of umbilical cord blood cells for type 1 diabetes mellitus.

    Science.gov (United States)

    He, Binbin; Li, Xia; Yu, Haibo; Zhou, Zhiguang

    2015-11-01

    Type 1 diabetes mellitus (T1DM) is a chronic disorder that results from autoimmune-mediated destruction of pancreatic islet β-cells. However, to date, no conventional intervention has successfully treated the disease. The optimal therapeutic method for T1DM should effectively control the autoimmunity, restore immune homeostasis, preserve residual β-cells, reverse β-cell destruction, and protect the regenerated insulin-producing cells against re-attack. Umbilical cord blood is rich in regulatory T (T(reg)) cells and multiple types of stem cells that exhibit immunomodulating potential and hold promise in their ability to restore peripheral tolerance towards pancreatic islet β-cells through remodeling of immune responses and suppression of autoreactive T cells. Recently, reinfusion of autologous umbilical cord blood or immune cells from cord blood has been proposed as a novel therapy for T1DM, with the advantages of no risk to the donors, minimal ethical concerns, a low incidence of graft-versus-host disease and easy accessibility. In this review, we revisit the role of autologous umbilical cord blood or immune cells from cord blood-based applications for the treatment of T1DM.

  14. Analysis of risk factors of cord blood transplantation for children.

    Science.gov (United States)

    Goldstein, Gal; Bielorai, Bella; Stein, Jerry; Stepensky, Polina; Elhasid, Ronit; Zaidman, Irena; Chetrit, Angela; Yaniv, Isaac; Nagler, Arnon; Toren, Amos

    2013-12-01

    As cord blood (CB) is being used frequently as a source for heamtopoetic stem cell transplantation defining risk factors for transplantation outcome is an important issue. The data of all single unit CB transplantation preformed in Israel from 1992 to 2011 were collected. The risk factors for myeloid engraftment, event free survival (EFS) and overall survival (OS) were studied in 87 children. There were 49 children with hematological malignancies and 38 with non-malignant diseases. Cumulative rate of neutrophil recovery was 78.3%, while median time to myeloid recovery was 26 days. The incidence of platelet engraftment at 150 days was 53%, and the median time to platelet recovery was 36 days. ABO blood group matching between CB unit and recipient was associated with superior myeloid engraftment. Acute graft versus host disease of grades II-IV occurred in 33% of the patients. Chronic graft versus host disease occurred in 16% of patients. Probabilities of EFS and OS at 1 year were 45% and 57%, respectively. Factors associated with inferior OS were Rh major mismatch versus matched Rh and transplantation from unrelated donor versus related donor. These results indicate that matching of ABO blood groups is an important factor that affects engraftment, and also that Rh matching seem to have an impact on OS, which was not previously described in the setting of CB transplantation. © 2013 Wiley Periodicals, Inc.

  15. Interleukin-3 and granulocyte-macrophage colony-stimulating factor levels of cord blood plasma in term neonates

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ AIM: Umbilical cord blood plasma contain higher hematopoietic stimulatory activities than adult peripheral blood plasma. IL-3 is regarded as multilineage hematopoietic growth factor that acts on primitive pluripotential stem cells and progenitor cells of every lineage except T and B-lymphoid lineage.

  16. Cord blood banking in France: reorganising the national network.

    Science.gov (United States)

    Katz, Gregory; Mills, Antonia

    2010-06-01

    Paradoxically, France is one of the leading exporters of cord blood units worldwide, but ranks only 17th in terms of cord blood units per inhabitant, and imports 64% of cord blood grafts to meet national transplantation demands. With three operational banks in 2008, the French allogeneic cord blood network is now entering an important phase of development with the creation of seven new banks collecting from local clusters of maternities. Although the French network of public banks is demonstrating a strong commitment to reorganise and scale up its activities, the revision of France's bioethics law in 2010 has sparked a debate concerning the legalisation of commercial autologous banking. The paper discusses key elements for a comprehensive national plan that would strengthen the allogeneic banking network through which France could meet its national medical needs and guarantee equal access to healthcare. Copyright 2010. Published by Elsevier Ltd.

  17. Induced pluripotent stem cell-derived neural stem cell therapies for spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Corinne A Lee-Kubli; Paul Lu

    2015-01-01

    The greatest challenge to successful treatment of spinal cord injury is the limited regenerative capacity of the central nervous system and its inability to replace lost neurons and severed axons following injury. Neural stem cell grafts derived from fetal central nervous system tissue or embryonic stem cells have shown therapeutic promise by differentiation into neurons and glia that have the potential to form functional neuronal relays across injured spinal cord segments. However, implementation of fetal-derived or embryonic stem cell-derived neural stem cell ther-apies for patients with spinal cord injury raises ethical concerns. Induced pluripotent stem cells can be generated from adult somatic cells and differentiated into neural stem cells suitable for therapeutic use, thereby providing an ethical source of implantable cells that can be made in an autologous fashion to avoid problems of immune rejection. This review discusses the therapeutic potential of human induced pluripotent stem cell-derived neural stem cell transplantation for treatment of spinal cord injury, as well as addressing potential mechanisms, future perspectives and challenges.

  18. Comparison of umbilical cord blood allogeneic stem cell transplantation vs. auto-SCT for adult acute myeloid leukemia patients in second complete remission at transplant: a retrospective study on behalf of the SFGM-TC.

    Science.gov (United States)

    Chevallier, Patrice; Labopin, Myriam; Socie, Gerard; Rubio, Marie-There; Blaise, Didier; Vigouroux, Stephane; Huynh, Anne; Michallet, Mauricette; Bay, Jacques-Olivier; Maury, Sébastien; Yakoub-Agha, Ibrahim; Fegueux, Nathalie; Deconinck, Eric; Contentin, Nathalie; Maillard, Natacha; Bulabois, Claude-Eric; Francois, Sylvie; Oumedaly, Reman; Raus, Nicole; Mohty, Mohamad

    2015-05-01

    This retrospective study considered the outcomes of 181 patients with acute myeloid leukemia (AML) transplanted in second complete remission (CR2) between January 2005 and April 2012 and who received either a myeloablative autologous stem cell transplant (Auto-SCT; n = 82; median age: 48 years; median follow-up: 45 months) or an umbilical cord blood (UCB) allogeneic SCT (n = 99, median age: 46 years; median follow-up: 36 months; conditioning regimens: myeloablative n = 21, reduced n = 78; single unit n = 37, double units n = 62). Although the Auto group showed a significant better prognostic profile at transplant, with longer median interval between diagnosis and time of graft, higher incidence of good-risk cytogenetics and lower number of previously transplanted patients, 3-year OS and LFS were similar between both groups (Auto: 59 ± 6% vs. 50 ± 6%, P = 0.45; and 57 ± 6% vs. 46 ± 6%, P = 0.37). In multivariate analysis, UCB allo-SCT was associated with lower relapse incidence (HR: 0.3, 95% CI: 0.11-0.82, P = 0.02), but higher non-relapse mortality (NRM) (HR: 4.16; 95% CI: 1.46-11.9, P = 0.008). Results from this large study suggest that UCB allo-SCT provides better disease control than auto-SCT, which is especially important in the setting of high-risk disease. However, this disease control advantage is counterbalanced by higher toxicity, highlighting the need for novel approaches aiming to decrease NRM after UCB allo-SCT.

  19. Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

    Zhi Li; Wei Zhao; Wei Liu; Ye Zhou; Jingqiao Jia; Lifeng Yang

    2014-01-01

    Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the ifeld of nerve damage repair. In the present study, human placenta-derived mesenchymal stem cells were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the resto-ration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury.

  20. Cord Blood Cells Responses to IL2, IL7 and IL15 Cytokines for mTOR Expression

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    Anahita Mohammadian

    2017-04-01

    Full Text Available Purpose: Mammalian target of rapamycin (mTORis important in hematopoiesis and affect cell growth,differentiation and survival. Although previous studies were identified the effect of cytokines on the mononuclear cells development however the cytokines effect on mTOR in cord blood mononuclear cells was unclear. The aim of this study was to evaluate mTOR expression in cord blood mononuclear and cord blood stem cells (CD34+ cells in culture conditions for lymphoid cell development. Methods: Isolation of The mononuclear cells (MNCs from umbilical cord blood were done with use of Ficollpaque density gradient. We evaluated cultured cord blood mononuclear and CD34+ cells in presece of IL2, IL7 and IL15 at distinct time points during 21 days by using flow cytometry. In this study, we presented the role of IL2, IL7 and IL15 on the expression of mTOR in cord blood cells. Results: mTOR expression were increased in peresence of IL2, IL7 and IL15 in day 14 and afterword reduced. However in persence of IL2 and IL15 expression of mTOR significantly reduced. mTOR expression in CD34+ cells decreased significantly from day7 to day 21 in culture. Conclusion: cytokines play important role in mTOR expression during hematopoiesis and development of cord blood mononuclear cells.

  1. Effect of delayed umbilical cord clamping on blood gas analysis.

    Science.gov (United States)

    Valero, Javier; Desantes, Domingo; Perales-Puchalt, Alfredo; Rubio, Juan; Diago Almela, Vicente J; Perales, Alfredo

    2012-05-01

    To ascertain if there are differences in umbilical cord blood gas analysis between immediate and delayed cord clamping. In a prospective observational study on 60 vaginally delivered healthy term newborns, we sampled umbilical cord blood immediately after delivery and at the time umbilical cord pulsation spontaneously ceased. There were significant decreases in pH, oxygen saturation (sO(2)), glycemia, oxygen content (ctO(2)), bicarbonate (HCO(3)(-)) and base excess (BE). Lactate and [Formula: see text] increased. Delayed cord clamping pH correlated with immediate cord clamping pH, [Formula: see text] , ctHb, sO(2) and time (r(2)=0.77, pcord clamping lactate was associated with immediate cord clamping lactate and time (r(2)=0.83, pcord clamping alters acid-base parameters and lactate values compared to immediate cord clamping. Those variations depend mainly on time, prior pH and lactate. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Effects and mechanism of the transplantation of human umbilical cord blood msenchymal stem cells to treat spinal cord injury%人脐血MSCs移植修复大鼠脊髓损伤的效果及机制的初步探讨

    Institute of Scientific and Technical Information of China (English)

    孙丽; 于丽; 张华芳; 王力; 魏志新

    2011-01-01

    Objective To explore the therapeutic effect and mechanism of mesenchymal stem cells (MSCs) derived from human umbilical cord blood on rat spinal cord injury. Methods MSCs were separated and purified from human umbilical cord blood. The spinal cord semi-transection was done on adult rats and then the animals were randomly divided into three groups which were treated with BrdU labeled MSCs, culture medium or saline respectively. Functional outcome was measured using the Basso-Beattie-Bresnehan (BBB) score method periodically up to 28 days post-surgery. MSCs survival and migration were observed by immunofluorescence double labeling techniques. The expression pattern of HMGB1 and NF-K B were detected by immunohistochemical techniques. Results BBB score showed that locomotor improvement in MSCs transplantation groups was much better than that of normal saline group and culture medium group at 28 days post-transplantation (P<0.05). BrdU-labeled MSCs could be detected in the lesion area at 7, 14 and 21 days post-transplantation. 53.3% of transplanted BrdU-positive cells were GFAP-positive, and 22.15% of them were NSE-positive. The positive rate of HMGB1 and NF-κB expression in MSCs transplantation group were lower than that in saline group and culture medium group, and there was a significant differences among three groups (P<0.05). Conclusions MSCs could promote functional recovery of the injuried spinal cord by replacing damaged nerve cells and alleviating inflammatory reaction.%目的 探讨人脐血间充质干细胞(MSCs)移植修复大鼠脊髓损伤的作用及机制.方法 分离纯化人脐血MSCs;制备大鼠脊髓半横断损伤模型,随机分为三组,分别在术后3 d经尾静脉注射生理盐水、培养液和BrdU标记的MSCs.移植后7、14、21、28 d,采用BBB评分法评估各组大鼠脊髓功能恢复情况;免疫荧光双标法检测MSCs在脊髓内的迁移、存活和分化,免疫组织化学法检测炎症因子高迁移率族蛋白B1

  3. 脐血间充质干细胞移植治疗低血糖昏迷1例%Umbilical cord blood mesenchymal stem cells transplantation for treating hypoglycemic coma in one case

    Institute of Scientific and Technical Information of China (English)

    李平; 周瑞; 晏小琼; 余勇飞; 阮清源

    2011-01-01

    背景:成体干细胞可以跨系跨胚层分化为所有的组织细胞类型,在特定的条件下,可分化为骨、软骨、脂肪、肌肉和神经细胞等,替代、修复已受损的组织、细胞,达到功能修复的目的.目的:观察脐血间充质干细胞治疗低血糖昏迷并发缺氧缺血性脑病的疗效.方法:对收治的1 例低血糖昏迷并发缺氧缺血性脑病及肺部感染的患者,给予抗自由基、营养神经、促醒、抗感染、康复理疗等综合治疗的同时,从静脉滴注进行脐血间充质干细胞治疗.观察住院期间意识恢复情况、脑电图、日常生活能力评分及随访结果.结果与结论:治疗近1个月后患者运动、认知功能明显恢复,复查脑电图可及a波,日常生活活动能力评分50分,70 d后随访,患者未出现不良反应,表明干细胞治疗近期疗效安全.提示脐血间充质干细胞治疗低血糖昏迷并发缺氧缺血性脑病安全有效.%BACKGROUND: Adult stem cells can differentiate into all kinds of cell type. Under special conditions, adult stem cells can differentiate into osteoblasts, chond rocytes, adipocytes, muscle cells and neural cells to replace and to repair damaged tissues and cells, to achieve functional recovery purposes.OBJECTIVE: To observe the effect of umbilical cord blood mesenchymal stem cells (UCB-MSCs) therapy in hypoglycemic coma combined with hypoxic ischemic encephalopathy.METHODS: One case of hypoglycemic coma combined with hypoxic ischemic encephalopathy and pulmonary infection was admitted. This patient received a combined treatment, including anti-free radical, nerve-nurturing, consciousness-regaining,anti-infective therapy, rehabilitation and physiotherapy. At the same time, we also gave him the UCB-MSCs therapy by intravenous infusion. The recovery of consciousness, electroencephalogram, activity of daily living and follow-up results were observed during hospital stay.RESULTS AND CONCLUSION: One month later, the

  4. 补阳还五汤生物碱有效部位对人脐血干细胞体外增殖的影响%Alkaloids of Buyang Huanwu decoction promote the in vitro proliferation of human umbilical cord blood stem cells

    Institute of Scientific and Technical Information of China (English)

    蔡咏; 林金丽; 布林白乙拉

    2013-01-01

      背景:研究表明补阳还五汤对各种细胞均有保护作用,但机制尚不清楚,有研究推测是它的生物碱有效部位起作用。目的:观察补阳还五汤生物碱有效部位对人脐血干细胞体外增殖的影响。方法:获取临床健康产妇的新鲜脐血,制备人脐血干细胞悬液,将纯化的人脐血干细胞接种于40个培养皿中进行传代。分组:川芎嗪组给予100 g/L川芎嗪,阿魏酸组给予50 g/L阿魏酸,生物碱有效部位组(川芎嗪+阿魏酸组)给予100 g/L川芎嗪+50 g/L阿魏酸;对照组:继续用含体积分数为20%小牛血清的DMEM培养液培养。培养2,4,6,8,10 d观察人脐血干细胞增殖情况;24,72 h后流式细胞仪测定S期细胞的比例,培养10 d后电流钳模式记录细胞静息膜电位变化。结果与结论:川芎嗪组和阿魏酸组人脐血干细胞的增殖作用不明显,培养10 d时生物碱有效部位组细胞增殖情况明显高于川芎嗪组、阿魏酸组和对照组(P<0.01)。生物碱有效部位组在培养24,72 h后处于S期的人脐血干细胞明显增多;川芎嗪+阿魏酸组细胞静息膜电位高于川芎嗪组、阿魏酸组和对照组(P<0.01)。提示补阳还五汤生物碱有效部位能促进人脐血干细胞的体外增殖。%BACKGROUND:Studies have shown that Buyang Huanwu decoction has protection effect on various cel s, but the mechanism is unclear. Some studies have speculated that the alkaloids of Buyang Huanwu decoction play a role. OBJECTIVE:To observe the effect of alkaloid of Buyang Huanwu decoction on the in vitro proliferation of human umbilical cord blood stem cel s. METHODS:Fresh umbilical cord blood was obtained from healthy puerperant to prepare the human umbilical cord blood stem cel s suspension, then the purified human umbilical cord blood stem cel s were seeded into 40 culture dishes for passage. The cel s were divided into four groups. The cel s in the

  5. Cultivo de células mesenquimais do sangue de cordão umbilical com e sem uso do gradiente de densidade Ficoll-Paque Blood mesenchymal stem cell culture from the umbilical cord with and without Ficoll-Paque density gradient method

    Directory of Open Access Journals (Sweden)

    Rosa Sayoko Kawasaki-Oyama

    2008-03-01

    Full Text Available OBJETIVOS: Implantação de técnicas de isolamento e cultivo de células-tronco mesenquimais do sangue de cordão umbilical humano, com e sem uso de gradiente de densidade Ficoll-Paque (d=1,077g/ml. MÉTODOS: Dez amostras de sangue de cordão umbilical humano de gestação a termo foram submetidas a dois procedimentos de cultivo de células-tronco mesenquimais: sem gradiente de densidade Ficoll-Paque e com gradiente de densidade. As células foram semeadas em frascos de 25cm² a uma densidade de 1x10(7células nucleadas/cm² (sem Ficoll e 1,0x10(6 células mononucleares/cm² (com Ficoll. As células aderentes foram submetidas a marcação citoquímica com fosfatase ácida e reativo de Schiff. RESULTADOS: No procedimento sem gradiente de densidade Ficoll, foram obtidas 2,0-13,0x10(7 células nucleadas (mediana=2,35x10(7 e, no procedimento com gradiente de densidade Ficoll, foram obtidas 3,7-15,7x10(6 células mononucleares (mediana=7,2x10(6. Em todas as culturas foram observadas células aderentes 24 horas após o início de cultivo. As células apresentaram morfologias fibroblastóides ou epitelióides. Na maioria das culturas houve proliferação celular nas primeiras semanas de cultivo, mas após a segunda semana, somente três culturas provenientes do método sem gradiente de densidade Ficoll-Paque mantiveram crescimento celular, formando focos confluentes de células. Essas culturas foram submetidas a várias etapas de tripsinização para espalhamento ou subdivisão e permaneceram em cultivo por períodos que variaram de dois a três meses. CONCLUSÃO: Nas amostras estudadas, o isolamento e cultivo de células-tronco mesenquimais do sangue de cordão umbilical humano pelo método sem gradiente de densidade Ficoll-Paque foi mais eficiente do que o método com gradiente de densidade Ficoll-Paque.OBJECTIVES: Implantation of cell separation and mesenchymal stem cell culture techniques from human umbilical cord blood with and without using the

  6. Spinal Cord Blood Flow after Ischemic Preconditioning in a Rat Model of Spinal Cord Ischemia

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    David Zvara

    2004-01-01

    Full Text Available Spinal cord blood flow after ischemic preconditioning is poorly characterized. This study is designed to evaluate spinal cord blood flow patterns in animals after acute ischemic preconditioning. Experiment 1: After a laminectomy and placement of a laser Doppler probe over the lumbar spinal cord to measure spinal cord blood flow, 16 male Sprague-Dawley rats were randomized into two groups: ischemic preconditioning (IPC, n = 8, and control (CTRL, n = 8. Rats in the CTRL and the IPC groups were subjected to 12 min of ischemia directly followed by 60 min of reperfusion. IPC rats received 3 min of IPC and 30 min of reperfusion prior to the 12-min insult period. Experiment 2: After instrumentation, the rats were randomized into three groups: control (CTRL, n = 7, ischemic preconditioning (IPC, n = 7, and time control (TC, n = 4. Rats in the CTRL and the IPC groups were subjected to the same ischemia and reperfusion protocol as above. The TC group was anesthetized for the same time period as the CTRL and the IPC groups, but had no ischemic intervention. Microspheres were injected at baseline and at 15 and 60 min into the final reperfusion. All rats were euthanized and tissue harvested for spinal cord blood flow analysis. In Experiment 1, there was a slight, significant difference in spinal cord blood flow during the ischemic period; however, this difference soon disappeared during reperfusion. In experiment 2, there was no difference in blood flow at any experimental time. The results of these experiments demonstrate that IPC slightly enhances blood flow to the spinal cord during ischemia; however, this effect is not sustained during the reperfusion period.

  7. Evaluation of the expansion of umbilical cord blood derived from CD133+ cells on biocompatible microwells

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    Mina Soufizomorrod

    2016-05-01

    Full Text Available Background: Hematopoietic stem cell transplantation (HSCT is a therapeutic approach for treatment of hematological malignancies and incompatibility of Bone marrow. Umbilical cord blood (UCB has known as an alternative for hematopoietic stem/progenitor cells (HPSC in allogeneic transplantation. The low volume of collected samples is the main hindrance in application of HPSC derived from umbilical cord blood. So, ex vivo expansion of HPSCs is the useful approach to overcome this restriction. The goal of using this system is to produce appropriate amount of hematopoietic stem cells, which have the ability of transplantation and long term haematopoiesis. Material & Methods: In current study CD133+ cells were isolated from cord blood (CB. Isolated cells were seeded on microwells. Then expanded cells proliferation rate and ability in colony formation were assessed and finally were compared with 2 Dimensional (2D culture systems. Results: Our findings demonstrated that CD133+ cells derived from UCB which were cultivated on microwells had significantly higher rate of proliferation in compared with routine cell culture systems. Conclusion: In Current study, it was shown that CD133+ cells’ proliferations which were seeded on PDMS microwells coated with collagen significantly increased. We hope that 3 dimensional (3D microenvironment which mimics the 3D structure of bone marrow can solve the problem of using UCB as an alternative source of bone marrow.

  8. Phenotypic and functional characterization of cytokine-induced killer cells derived from preterm and term infant cord blood.

    Science.gov (United States)

    Zhang, Qian; Wang, Lili; Luo, Chenghan; Shi, Zanyang; Cheng, Xinru; Zhang, Zhen; Yang, Yi; Zhang, Yi

    2014-11-01

    Cord blood has gradually become an important source for hematopoietic stem cell transplantation (HSCT) in the human, particularly in pediatric patients. Adoptive cellular immunotherapy of patients with hematologic malignancies after umbilical cord blood transplant is crucial. Cytokine‑induced killer (CIK) cells derived from cord blood are a new type of antitumor immune effector cells in tumor prevention and treatment and have increasingly attracted the attention of researchers. On the other hand, it has been suggested that preterm infant cord blood retains an early differentiation phenotype suitable for immunotherapy. Therefore, we determined the phenotypic and functional characterization of CIK cells derived from preterm infant cord blood (PCB-CIK) compared with CIK cells from term infant cord blood (TCB-CIK). Twenty cord blood samples were collected and classified into two groups based on gestational age. Cord blood mononuclear cells (CBMCs) were isolated, cultured and induced to CIK cells in vitro. We used flow cytometry to detect cell surface markers, FlowJo software to analyze the proliferation profile and intracellular staining to test the secretion of cytokines. Finally, we evaluated the antitumor activity of CIK cells against K562 in vitro. Compared with TCB-CIK, PCB-CIK cells demonstrated faster proliferation and higher expression of activated cell surface markers. The secretion of IL-10 was lower in PCB-CIK cells while the expression of perforin and CD107a had no significant difference between the two cell groups. PCB-CIK cells exhibited a high proliferation rate while the cytotoxic activity had no difference between the PCB-CIK and TCB-CIK cells. Hence preterm infant cord blood may be a potential source for immunotherapy.

  9. In delicate balance: stem cells and spinal cord injury advocacy.

    Science.gov (United States)

    Parke, Sara; Illes, Judy

    2011-09-01

    Spinal cord injury (SCI) is a major focus for stem cell therapy (SCT). However, the science of SCT has not been well matched with an understanding of perspectives of persons with SCI. The online advocacy community is a key source of health information for primary stakeholders and their caregivers. In this study, we sought to characterize the content of SCI advocacy websites with respect to their discussion of SCT and stem cell tourism. We performed a comprehensive analysis of SCI advocacy websites identified through a web search and verified by expert opinion. Two independent researchers coded the information for major themes (e.g., scientific & clinical facts, research & funding, policy, ethics) and valence (positive, negative, balanced, neutral). Of the 40 SCI advocacy websites that met inclusion criteria, 50% (N=20) contained information about SCT. Less than 18% (N=7) contained information on stem cell tourism. There were more than ten times as many statements about SCT with a positive valence (N=67) as with a negative valence (N=6). Ethics-related SCT information comprised 20% (N=37) of the total content; the largest proportion of ethics-related content was devoted to stem cell tourism (80%, N=30 statements). Of those, the majority focused on the risks of stem cell tourism (N=16). Given the still-developing science behind SCT, the presence of cautionary information about stem cell tourism at advocacy sites is ethically appropriate. The absence of stem cell tourism information at the majority of advocacy sites represents a lost educational opportunity.

  10. Neural differentiation of brain-derived neurotrophic factor-expressing human umbilical cord blood-derived mesenchymal stem cells in culture via TrkB-mediated ERK and β-catenin phosphorylation and following transplantation into the developing brain.

    Science.gov (United States)

    Lim, Jung Yeon; Park, Sang In; Kim, Seong Muk; Jun, Jin Ae; Oh, Ji Hyeon; Ryu, Chung Hun; Jeong, Chang Hyun; Park, Sun Hwa; Park, Soon A; Oh, Wonil; Chang, Jong Wook; Jeun, Sin-Soo

    2011-01-01

    The ability of mesenchymal stem cells (MSCs) to differentiate into neural cells makes them potential replacement therapeutic candidates in neurological diseases. Presently, overexpression of brain-derived neurotrophic factor (BDNF), which is crucial in the regulation of neural progenitor cell differentiation and maturation during development, was sufficient to convert the mesodermal cell fate of human umbilical cord blood-derived MSCs (hUCB-MSCs) into a neuronal fate in culture, in the absence of specialized induction chemicals. BDNF overexpressing hUCB-MSCs (MSCs-BDNF) yielded an increased number of neuron-like cells and, surprisingly, increased the expression of neuronal phenotype markers in a time-dependent manner compared with control hUCB-MSCs. In addition, MSCs-BDNF exhibited a decreased labeling for MSCs-related antigens such as CD44, CD73, and CD90, and decreased potential to differentiate into mesodermal lineages. Phosphorylation of the receptor tyrosine kinase B (TrkB), which is a receptor of BDNF, was increased significantly in MSC-BDNF. BDNF overexpression also increased the phosphorylation of β-catenin and extracellular signal-regulated kinases (ERKs). Inhibition of TrkB availability by treatment with the TrkB-specific inhibitor K252a blocked the BDNF-stimulated phosphorylation of β-catenin and ERKs, indicating the involvement of both the β-catenin and ERKs signals in the BDNF-stimulated and TrkB-mediated neural differentiation of hUCB-MSCs. Reduction of β-catenin availability using small interfering RNA-mediated gene silencing inhibited ERKs phosphorylation. However, β-catenin activation was maintained. In addition, inhibition of β-catenin and ERKs expression levels abrogated the BDNF-stimulated upregulation of neuronal phenotype markers. Furthermore, MSC-BDNF survived and migrated more extensively when grafted into the lateral ventricles of neonatal mouse brain, and differentiated significantly into neurons in the olfactory bulb and

  11. Cord blood banking - bio-objects on the borderlands between community and immunity.

    Science.gov (United States)

    Brown, Nik; Williams, Rosalind

    2015-01-01

    Umbilical cord blood (UCB) has become the focus of intense efforts to collect, screen and bank haematopoietic stem cells (HSCs) in hundreds of repositories around the world. UCB banking has developed through a broad spectrum of overlapping banking practices, sectors and institutional forms. Superficially at least, these sectors have been widely distinguished in bioethical and policy literature between notions of the 'public' and the 'private', the commons and the market respectively. Our purpose in this paper is to reflect more critically on these distinctions and to articulate the complex practical and hybrid nature of cord blood as a 'bio-object' that straddles binary conceptions of the blood economies. The paper draws upon Roberto Esposito's reflections on biopolitics and his attempt to transcend the dualistic polarisations of immunity and community, or the private and the public. We suggest that his thoughts on immunitary hospitality resonate with many of the actual features and realpolitik of a necessarily internationalised and globally distributed UCB 'immunitary regime'.

  12. Risk Factors and Options to Improve Engraftment in Unrelated Cord Blood Transplantation

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    Anna D. Petropoulou

    2011-01-01

    Full Text Available Use of umbilical unrelated cord-blood (UCB cells as an alternative source of hematopoietic cell transplantation has been widely used mainly for patients lacking an HLA-matched donor. UCB present many advantages over bone marrow or mobilized peripheral blood from volunteer donors, such as rapid availability, absence of risk for the donor, and decreased incidence of acute graft-versus-host disease. However, a significant clinical problem is delayed engraftment that is directly correlated with the number of hematopoietic stem cells in a cord-blood unit. The identification of prognostic factors associated with engraftment that can be easily modified (e.g., strategies for donor choice and the development of new approaches including use of multiple donors, intrabone injection of UCB, ex vivo expansion, and cotransplantation with accessory cells are of crucial importance in order to circumvent the problem of delayed engraftment after UCB transplantation. Those approaches may increase the quality and availability of UCB for transplantation.

  13. Mesenchymal stem cells from human umbilical cord ameliorate testicular dysfunction in a male rat hypogonadism model

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    Zhi-Yuan Zhang

    2017-01-01

    Full Text Available Androgen deficiency is a physical disorder that not only affects adults but can also jeopardize children′s health. Because there are many disadvantages to using traditional androgen replacement therapy, we have herein attempted to explore the use of human umbilical cord mesenchymal stem cells for the treatment of androgen deficiency. We transplanted CM-Dil-labeled human umbilical cord mesenchymal stem cells into the testes of an ethane dimethanesulfonate (EDS-induced male rat hypogonadism model. Twenty-one days after transplantation, we found that blood testosterone levels in the therapy group were higher than that of the control group (P = 0.037, and using immunohistochemistry and flow cytometry, we observed that some of the CM-Dil-labeled cells expressed Leydig cell markers for cytochrome P450, family 11, subfamily A, polypeptide 1, and 3-β-hydroxysteroid dehydrogenase. We then recovered these cells and observed that they were still able to proliferate in vitro. The present study shows that mesenchymal stem cells from human umbilical cord may constitute a promising therapeutic modality for the treatment of male hypogonadism patients.

  14. Immunitary bioeconomy: the economisation of life in the international cord blood market.

    Science.gov (United States)

    Brown, Nik; Machin, Laura; McLeod, Danae

    2011-04-01

    This paper examines an emerging bioeconomy centred on the international banking and trade in cord blood. Since the late 1980s cord blood has been used in an expanding range of treatments and as an alternative to the use of bone marrow stem cells. This is particularly the case in treating ethnic minority populations who have historically been under-represented in bone marrow registries. The paper explores the mobilisation and commercialisation of an increasingly important bioeconomic resource with cord blood units trading internationally at high prices. This is a market mediated through a sophisticated global network of immunologically typed and matched bodily matter in which immunity has become a form of 'corporeal currency'. Based on recent international figures we reflect upon the balance of trade between imports and exports across the world's cord blood bioeconomy. Theoretically, this case is, we suggest, an extension of what Roberto Esposito (2008) has termed an 'immunitary paradigm' in which immunity has become the basis for new forms of bioeconomic flow, circulation and exchange. Esposito (2008). Bios: Biopolitics and Philosophy. Minnesota, MN: University of Minnesota Press. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Adult spinal cord ependymal layer: A promising pool of quiescent stem cells to treat spinal cord injury

    OpenAIRE

    Stavros eMalas; Elena ePanayiotou

    2013-01-01

    Spinal cord injury is a major health burden and currently there is no effective medical intervention. Research performed over the last decade revealed that cells surrounding the central canal of the adult spinal cord and forming the ependymal layer acquire stem cell properties either in vitro or in response to injury. Following spinal cord injury activated ependymal cells generate progeny cells which migrate to the injury site but fail to produce the appropriate type of cells in sufficient nu...

  16. Neuron-specific enolase: reference values in cord blood.

    Science.gov (United States)

    Kintzel, K; Sonntag, J; Strauss, E; Obladen, M

    1998-04-01

    With foetal sonography prenatal detection of tumours has become more frequent. To evaluate and treat these infants it is necessary to identify the tumour postnatally. Elevated neuron-specific enolase is a biochemical marker of neuroblastoma. Since conditions during birth may influence neuron-specific enolase concentration in foetal serum, specific reference values in cord blood are required. Cord blood samples were taken from 192 healthy term newborns and concentration of neuron-specific enolase was measured by enzyme immunoassay (EIA). Median neuron-specific enolase concentration in the reference group was 8.0 micrograms/l and the 5th-95th percentiles were 4.8-19.4 micrograms/l. No differences between male and female newborns were detected (p = 0.13). Measurement of neuron-specific enolase in cord blood, in comparison with our reference values, offers an early postnatal possibility of confirming the diagnosis of neuroblastoma.

  17. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... 53 PBSC (Peripheral blood stem cell) Harvest - Duration: 2:55. bmdpsg 4,554 views 2:55 Introduction To Stem Cells – Manipal Hospital - Duration: ... in Germany. #priceless - Duration: 1:04. Jacque Brohawn 2,548 views 1:04 Stem Cell Basics - How ...

  18. Impact of C-rel inhibition of cord blood-derived B-, T-, and NK cells.

    Science.gov (United States)

    Fallahi, Shirin; Mohammadi, Seyede Momeneh; Tayefi Nasrabadi, Hamid; Alihemmati, Alireza; Samadi, Naser; Gholami, Sanaz; Shanehbandi, Dariush; Nozad Charoudeh, Hojjatollah

    2017-12-01

    The c-Rel transcription factor is a unique member of the nuclear factor (NF)-κB family that has a role in curtailing the proliferation, differentiation, cytokine production, and overall activity of B- and T-cells. In addition, c-Rel is a key regulator of apoptosis in that it influences the expression of anti-apoptotic genes such as Bcl-2 and Bcl-xL; conversely, inhibition of c-Rel increases cell apoptosis. To better understand the relationship between c-Rel expression and effects on B- and T-cell expansion, the current study evaluated c-Rel expression in cord blood mononuclear cells. This particular source was selected as cord blood is an important source of cells used for transplantation and immunotherapy, primarily in treating leukemias. As stem cell factor (SCF) and FLT3 are important agents for hematopoietic stem cell expansion, and cytokines like interleukin (IL)-2, -7, and -15 are essential for T- and B- (and also NK) cell development and proliferation, the current study evaluated c-Rel expression in cord blood mononuclear cells and CD34(+ )cells, as well as effects on B-, T-, and NK cells associated with alterations in c-Rel expression, using flow cytometry and PCR. The results showed c-Rel expression increased among cells cultured in the presence of SCF and FLT3 but was reduced when IL-2, IL-7, and IL-15 were used all together. Further, inhibition of c-Rel expression by siRNA reduced cord blood-derived B-, T-, and NK cell differentiation and expansion. These results indicated that with cells isolated from cord blood, c-Rel has an important role in B-, T-, and NK cell differentiation and, further, that agents (select cytokines/growth factors) that could impact on its expression might not only affect immune cell profiles in a host but could potentially also limit apoptotic activities in (non-)immune cells in that host. In the context of cancer (immuno)therapy, in particular, when cord blood is used an important source in stem cell transplantation in

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  1. File list: ALL.Bld.50.AllAg.Umbilical_cord_blood [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. [Pooled Umbilical Cord Blood Plasma for Culturing UCMSC and Ex Vivo Expanding Umbilical Cord Blood CD34⁺ Cells].

    Science.gov (United States)

    Wu, Jie-Ying; Lu, Yan; Chen, Jin-Song; Wu, Shao-Qing; Tang, Xue-Wei; Li, Yan

    2015-08-01

    To investigate the feasibility of umbilical cord blood plasma (UCP) as a replacement for fetal bovine serum (FBS) for culturing mesenchymal stem cells (MSC) derived from umbilical cord, and to observe the supporting effects of these cells (served as a feeder layer) on ex vivo expanding of human umbilical cord blood CD34(+) cells. Umbilical cord blood (UCB) units were suitable if the Guangzhou cord blood bank donor selection criteria strictly were fulfilled. UCP were ready to use after the collection from the plasma depletion/reduction during the processing and pooling of suitable UCB units (at least 30 units were screened for pathogens and microorganisms, and qualified). Umbilical cord mesenchymal stem cells (UCMSC) were harvested from the umbilical cord tissue of health full-term newborns after delivery by enzyme digestion and divided into 3 groups: group 1 and 2 were cultured in the presence of DMEM/F12 containing either FBS or UCP; and group 3 was cultured in serum-free medium (StemPro® MSC SFM CTS™). Morphology, proliferation and surface marker expression were examined by flow cytometry, and the differentiation toward adipogenic and osteogenic lineages was used for investigating the effect of media on UCMSC after 3-5 passages. Next, the cells cultured in the three different media were cryopreserved and thawed, then prepared as feeder layers with the name of UCMSC(FBS), UCMSC(UCP), and UCMSC(SFM), respectively. The CD34⁺ cells were separated from UCB by magnetic activated cell sorting (MACS) and divided into 4 groups cultured in StemPro(-34) SFM medium added with hematopoietic cytokine combination (StemSpan® CC100). The control group included only CD34⁺ cells as group A (blank control) and experimental groups included UCMSC(FBS) + CD34⁺ cells as group B, UCMSC(UCP) + CD34⁺ cells as group C, UCMSC(SFM) + CD34⁺ cells as group D, and cells in all groups were cultured ex vivo for 7 days. The nucleated cell (NC) number was counted by cell counter, CD34

  3. Umbilical Cord Blood Lead Levels and Neonatal Behaviour

    Directory of Open Access Journals (Sweden)

    M. L. de Cáceres

    1995-01-01

    Full Text Available Negative correlations have been found between cord blood lead levels and scores on the Brazelton Neonatal Behaviour Assessment in 30 otherwise healthy newborns. Items in the Habituation, Orientation and Regulation of state clusters, particularly those items related to self-regulatory, self-quieting and auditory habituation, showed lower scores (worse performance in those newborns with higher cord blood lead levels. These disturbances are potentially important since this type of behavior may interfere with the normal process of adaptation to their environment, leading to a less than optimal bonding between newborns and their carers.

  4. Repair of calvarial defects with human umbilical cord blood derived mesenchymal stem cells and demineralized bone matrix in athymic rats%人脐血间充质干细胞修复颅骨缺损的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘广鹏; 李宇琳; 孙剑; 崔磊; 张文杰; 曹谊林

    2010-01-01

    Objective To investigate the feasibility of using human umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) and demineralized bone matrix (DBM) scaffolds to repair critical-sized calvarial defects in athymic rats. Methods Human UCB-MSCs were isolated, expanded and osteogenically induced in vitro. Osteogenic differentiation of UCB-MSCs was evaluated by Alizarin Red staining and measurement of calcium content respectively, and then the cells were seeded onto DBM scaffolds. Bilateral full-thickness defects (5 mm in diameter) of parietal bone were created in an athymic rat model. The defects were either repaired with UCB-MSC/DBM constructs (experimental group) or with DBM scaffolds alone (control group). Animals were harvested at 6 and 12 weeks post-implantation respectively, and defect repair was evaluated with gross observation, micro-CT measurement and histological analysis. Results Micro-CT showed that new bone was formed in the experimental group at 6 weeks post-implantation, while no sign of new bone formation was observed in the control group. At 12 weeks post-transplantation, scaffolds had been degraded almost completely in both sides. It was shown that an average of (78.19±6.45)% of each defect volume had been repaired in experimental side; while in the control side, only limited bone formed at the periphery of the defect. Histological examination revealed that the defect was repaired by trabecular bone tissue in experimental side at 12 weeks, while only fibrous connection was observed in the control group. Conclusions Tissue-engineered bone composed of osteogenically-induced human UCB-MSCs on DBM scaffolds could successfully repair the critical-sized calvarial defects in athymic rat models.%目的 应用人脐血间充质干细胞(umbilical cord blood derived mesenchymal stem cells,UCB-MSCs)复合脱钙骨材料构建组织工程化骨,修复裸大鼠颅骨标准缺损.方法 体外扩增培养、成骨诱导人UCB-MSCs,采用Alizarin Red染色

  5. 脐血干细胞移植对帕金森病大鼠旋转行为的影响%Effect of human umbilical cord blood mesenchymal stem cells transplantation on rotational behavior of Parkinson's disease rats

    Institute of Scientific and Technical Information of China (English)

    樊志刚; 刘芳

    2012-01-01

    背景:目前帕金森病的临床治疗还是以药物为主,细胞移植实验也多见于骨髓间充质干细胞,脐血来源干细胞移植能否改善帕金森病的旋转行为报道较少.目的:观察脐血间充质干细胞移植对帕金森病大鼠旋转行为的影响.方法:帕金森病模型大鼠随机分成实验组和对照组.实验组大鼠纹状体内植入用Hoechst33258标记的第4代脐血间充质干细胞,对照组注射PBS.此后每周腹腔注射阿扑吗啡以观察大鼠的旋转行为;并在移植后3,6,9周用免疫荧光双标法检测间充质干细胞的存活、迁移情况以及胶质纤维酸性蛋白、神经元特异性烯醇化酶、酪氨酸羟化酶和突触素的表达.结果与结论:移植脐血间充质干细胞后大鼠的旋转行为与对照组相比有明显改善(P < 0.05);间充质干细胞可在大鼠脑内存活,随时间延长迁移范围扩大,分布于纹状体、胼胝体和皮质;胶质纤维酸性蛋白、神经元特异性烯醇化酶、酪氨酸羟化酶都有表达,突触素无表达.结果可见移植脐血间充质干细胞后能明显改善帕金森病大鼠旋转行为,有望成为治疗帕金森病的种子细胞.%BACKGROUND: To date, the clinical treatment of Parkinson's disease (PD) mainly depends on drug, and as for celltransplantation experiment, bone marrow mesenchymal stem cells (BMSCs) transplantation is the common method. The reportsabout whether umbilical cord blood mesenchymal stem cells (UCBMSCs) transplantation can improve the rotational behavior arerare.OBJECTIVE: To explore the effect of human UCBMSCs transplantation on rotational behavior of PD rats.METHODS: The PD rat models were divided into the experimental group (n=20) and the control group (n=20). The fourthgeneration of MSCs were marked by Hoechst33258 and then transplanted into rat striatum in experimental group, and the rats incontrol group were given PBS. Apomorphine was injected intraperitoneally to examine the rotational

  6. Markers infectious agent in the cord blood samples public register of donors

    Directory of Open Access Journals (Sweden)

    A. B. Smoljaninov

    2014-01-01

    Full Text Available Objective. To evaluate the distribution of markers of infectious agents in umbilical cord blood samples Pokrovskij public stem cell bank donor registry for five years (2009 – 2013.Materials and Methods. 3533 plasma samples were investigatedafter selection during cord blood processing procedure for allogeneic use in Pokrovskij stem cell bank. All plasma samples were investigated in accordance with the Order of the Ministry of Health № 325 – 2003 by enzymelinked immunoassay method. In addition, during the period from November 2011 to December 2013 1030 plasma samples of umbilical cord blood were examined for the presence of HCV RNA, the RNA of HIV and HBV DNA.Results. Markers of the agents above have not been found in the plasma of 481 samples (13.6%. During the described period, no significant change in the share of samples containing antibodies to cytomegalovirus and toxoplasmosis (cytomegalovirus – 1978 samples (56%, Toxoplasma gondii – 112 samples (3.2%, 825 samples (23.4% cytomegalovirus and Toxoplasma gondii simultaneously were registered. 137 samples (3.9% were subjected to utilization in connection with detection of antibodies to HbcorAg – 116 samples (3.3%, antibodies to HCV – five samples (0.14%, and antibodies to Treponema pallidum – 16 samples (0.45%.Conclusion. The introduction of an additional method of polymerase chain reaction for the detection of nucleic acids of hepatitis viruses B, C, human immunodeficiency virus, along with study of cord blood samples by enzyme-linked immunoassay improve the quality of the control of the transmission of blood-borne infections.

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

    Directory of Open Access Journals (Sweden)

    Gong D

    2013-08-01

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

  8. Acellular spinal cord scaffold seeded with mesenchymal stem cells promotes long-distance axon regeneration and functional recovery in spinal cord injured rats.

    Science.gov (United States)

    Liu, Jia; Chen, Jian; Liu, Bin; Yang, Cuilan; Xie, Denghui; Zheng, Xiaochen; Xu, Song; Chen, Tianyu; Wang, Liang; Zhang, Zhongmin; Bai, Xiaochun; Jin, Dadi

    2013-02-15

    The stem cell-based experimental therapies are partially successful for the recovery of spinal cord injury (SCI). Recently, acellular spinal cord (ASC) scaffolds which mimic native extracellular matrix (ECM) have been successfully prepared. This study aimed at investigating whether the spinal cord lesion gap could be bridged by implantation of bionic-designed ASC scaffold alone and seeded with human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) respectively, and their effects on functional improvement. A laterally hemisected SCI lesion was performed in adult Sprague-Dawley (SD) rats (n=36) and ASC scaffolds seeded with or without hUCB-MSCs were implanted into the lesion immediately. All rats were behaviorally tested using the Basso-Beattie-Bresnahan (BBB) test once a week for 8weeks. Behavioral analysis showed that there was significant locomotor recovery improvement in combined treatment group (ASC scaffold and ASC scaffold+hUCB-MSCs) as compared with the SCI only group (pspinal cord cavity and promote long-distance axon regeneration and functional recovery in SCI rats.

  9. Good practices in collecting umbilical cord and placental blood

    Directory of Open Access Journals (Sweden)

    Lauren Auer Lopes

    Full Text Available Abstract Objective: to identify the factors related to the quality of umbilical cord and placental blood specimens, and define best practices for their collection in a government bank of umbilical cord and placental blood. Method: this was a descriptive study, quantitative approach, performed at a government umbilical cord and placental blood bank, in two steps: 1 verification of the obstetric, neonatal and operational factors, using a specific tool for gathering data as non-participant observers; 2 definition of best practices by grouping non-conformities observed before, during and after blood collection. The data was analyzed using descriptive statistics and the following statistical software: Statistica(r and R(r. Results: while there was a correlation with obstetrical and neonatal factors, there was a larger correlation with operational factors, resulting in the need to adjust the professional practices of the nursing staff and obstetrical team involved in collecting this type of blood. Based on these non-conformities we defined best practices for nurses before, during and after blood collection. Conclusion: the best practices defined in this study are an important management tool for the work of nurses in obtaining blood specimens of high cell quality.

  10. Umbilical cord blood banking: from personal donation to international public registries to global bioeconomy

    Directory of Open Access Journals (Sweden)

    Petrini C

    2014-06-01

    Full Text Available Carlo Petrini Italian National Institute of Health, Rome, Italy Abstract: The procedures for collecting voluntarily and freely donated umbilical cord blood (UCB units and processing them for use in transplants are extremely costly, and the capital flows thus generated form part of an increasingly pervasive global bioeconomy. To place the issue in perspective, this article first examines the different types of UCB biobank, the organization of international registries of public UCB biobanks, the optimal size of national inventories, and the possibility of obtaining commercial products from donated units. The fees generally applied for the acquisition of UCB units for transplantation are then discussed, and some considerations are proposed regarding the social and ethical implications raised by the international network for the importation and exportation of UCB, with a particular emphasis on the globalized bioeconomy of UCB and its commerciality or lack thereof. Keywords: cord blood banking, economy, ethics, stem cells, transplantation

  11. Pharmacokinetic studies on fenoterol in maternal and cord blood.

    Science.gov (United States)

    von Mandach, U; Huch, A; Huch, R

    1989-04-01

    Fenoterol plasma concentrations were measured by radioimmunoassay in 38 pregnant women at different stages of preterm labor and in cord blood. Eight women were treated intravenously until delivery with 1.0 to 4 micrograms/min of fenoterol for periods ranging from 27 hours to 27 days; blood samples were taken at the same time as cord blood. In these women the fenoterol concentrations in cord blood ranged from 18 to 53% of the maternal concentrations. In eight women treated intravenously with 1.2 to 4.0 micrograms/min for 2 to 15 days, the infusion was stopped 1.3 to 38 hours before delivery. In these instances the concentrations in cord blood reached as much as 90% of the maternal, meaning that the rate of elimination from fetal plasma is lower than that from maternal plasma. Five women were treated daily with 20 to 30 mg per os for 3 to 17 days (three of these women had also had intravenous treatment before). The ratio of cord to maternal blood concentrations was higher than in women receiving the drug intravenously, the relative times of sampling being the same. The findings suggest that: (1) the placental transfer of fenoterol is higher than that found in previous studies in humans and animals with tritium-labeled substances; (2) the rate of fenoterol elimination from fetal plasma after intravenous and oral long-term therapy is lower than that from maternal plasma; (3) after oral administration, the ratios of fetal to maternal fenoterol concentrations are higher than after intravenous infusion.

  12. SCREENING CORD BLOOD FOR HEMOGLOBINOPATHIES AND THALASSEMIA BY HPLC

    NARCIS (Netherlands)

    VANDERDIJS, FPL; VANDENBERG, GA; SCHERMER, JG; MUSKIET, FD; LANDMAN, H; MUSKIET, FAJ

    1992-01-01

    We evaluated the use of an HPLC method for screening hemoglobins in cord blood. We studied the genotype frequencies of the structural hemoglobin variants HbS and HbC and the synthesis variants alpha- and beta+-thalassemia in babies born on Curacao. During three months, 67.2% of all (748) newborns we

  13. SCREENING CORD BLOOD FOR HEMOGLOBINOPATHIES AND THALASSEMIA BY HPLC

    NARCIS (Netherlands)

    VANDERDIJS, FPL; VANDENBERG, GA; SCHERMER, JG; MUSKIET, FD; LANDMAN, H; MUSKIET, FAJ

    We evaluated the use of an HPLC method for screening hemoglobins in cord blood. We studied the genotype frequencies of the structural hemoglobin variants HbS and HbC and the synthesis variants alpha- and beta+-thalassemia in babies born on Curacao. During three months, 67.2% of all (748) newborns

  14. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Ya-jing Zhou

    2015-01-01

    Full Text Available Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  15. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Ya-jing Zhou; Jian-min Liu; Shu-ming Wei; Yun-hao Zhang; Zhen-hua Qu; Shu-bo Chen

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administrationvia the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve ifbers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and lfuorogold-labeled nerve ifbers were increased and hindlimb motor function of spinal cord-injured rats was mark-edly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  16. Current status of cord blood banking during first two years of 'National Government-Assigned Public Cord Blood Banks Operation' in Korea.

    Science.gov (United States)

    Roh, Eun Youn; Lee, Jung Lim; Yoon, Jong Hyun; Kim, Su Yeon; Lee, Kyung Eun; Song, Do Young; Kim, Tai Gyu; Shin, Sue

    2014-10-01

    Cord blood (CB) has become a viable stem cell source for hematopoietic stem cell transplantation (HSCT), and public cord blood banks (CBBs) have been established to manage donated cord blood units (CBUs) for unrelated HSCT. As the potential uses for CB continue to grow, there is a global tendency to encourage public CBBs. The aim of this study was to investigate the current status of public CBBs that were designated and supported by the Korean national government. We analyzed 6,168 CBUs preserved at the 3 Government-Assigned Public CBBs during their first two years of operation (2012-2013) and the standard operating procedures for CB processing at each CBB. CBU inventories at ALLCORD, Catholic HSC Bank and Fatima Public CBB were 4,022, 1,207 and 939 units, respectively. Total nucleated cell (TNC) counts per unit were 11.0 × 10(8) at ALLCORD, 10.7 × 10(8) at Fatima and 9.8 × 10(8) at Catholic, and all far exceeded the requirement for cryopreservation under the law (7.0 × 10(8)). CD34(+) cell counts and % were as follows: 3.5 × 10(6) (0.31 %) in ALLCORD, 2.2 × 10(6) (0.20 %) in Fatima and 2.2 × 10(6) (0.22 %) in Catholic. All the three banks observed the 'CB Act' in dealing with CBUs, including collection, processing, laboratory tests and cryopreservation. Government supported and strictly law-abiding public CBBs in Korea have considerable CBU inventories of high quality in terms of efficacy and safety. Legislation and accompanying government-support will be helpful for establishing CB standardization, vitalizing CBT and improving clinical outcomes.

  17. Methods of isolation, expansion, differentiating induction and preservation of human umbilical cord mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    LI Dong-rui; CAI Jian-hui

    2012-01-01

    Objective This literature review aims to summarize the methods of isolation,expansion,differentiation and preservation of human umbilical cord mesenchymal stem cells (hUCMSCs),for comprehensive understanding and practical use in preclinical research and clinical trials.Data sources All the literature reviewed was published over the last 10 years and is listed in PubMed and Chinese National Knowledge Infrastructure (CNKI).Studies were retrieved using the key word "human umbilical cord mesenchymal stem cells".Results Explants culture and enzymatic digestion are two methods to isolate hUCMSCs from WJ and there are modifications to improve these methods.Culture conditions may affect the expansion and differentiating orientations of hUCMSCs.In addition,hUCMSCs can maintain their multi-potential effects after being properly frozen and thawed.Conclusion Considering their multi-potential,convenient and non-invasive accessibility,low immunogenicity and the reported therapeutic effects in several different preclinical animal models,hUCMSCs have immense scope in regeneration medicine as a substitute for MSCs derived from bone marrow or umbilical cord blood.

  18. 脐血干细胞移植结合常规药物治疗终末期肝硬化的临床研究%The Clinical Research of Umbilical Cord Blood Stem Cell Transplantation Combined with Conventional Drug as Treatment of End-stage Liver Cirrhosis

    Institute of Scientific and Technical Information of China (English)

    赵义萍; 徐黎鸣

    2013-01-01

    Objective To observe the clinical curative effect of the umbilical cord blood stem cell transplantation combining routine therapy for end-stage liver cirrhosis. Methods Fifty patients with volunteers receivingumbilical cord blood stem cells for cirrhosis of the liver decompensation period( Child grade C )were selected. All patients were given intravenous and umbilical cord blood stem cells in femoral artery and conventional drugs. Regularly after 3,6,9 and 12 weeks the changes of liver function,serum albumin and pro-thrombin time were observed. Results Clinical symptoms and signs started to be improved obviously 3 weeks after treatment, including ascites reduction 30 cases( 60% ), double lower limb swelling relief 40 cases ( 80% ),better stamina 35 cases( 70% ),and appetite improvement 30 cases ( 60% ). After three weeks of umbilical cord stem cell therapy, all indexes were significantly improved from before the treatment. Six weeks after treatment, AST,ALT, ALB and PT were not obviously improved,after 9 weeks of treatment, all indexes were obviously improved( P < 0.05 ), 12 weeks later, each index was improved more obviously( P < 0. 05 ). Conclusion Umbilical cord blood stem cell therapy combined with routine medication therapy for end-stage liver cirrhosis is a simple,safe and effective treatment. Its curative effect is significant, which can solve the problem of donor shortage and immune rejection, and significantly improve the quality of life of the patients.%目的 观察脐血干细胞移植结合常规药物治疗终末期肝硬化的临床疗效.方法 选取湖北医药学院附属太和医院于2012年1 ~7月收治的50例自愿接受脐血干细胞移植患者为肝硬化失代偿期(Child C级),全部患者均给予静脉输注及股动脉介入脐血干细胞,同时进行常规药物治疗.定期观察术后3、6、9、12周肝功能、血清白蛋白(ALB)及凝血酶原时间(PT)的变化.结果 治疗第3周开始多数患者的临床症状、体征

  19. In vitro differentiation of human umbilical cord blood mesenchymal ...

    African Journals Online (AJOL)

    May H. Hasan

    2016-08-05

    Aug 5, 2016 ... hepatocyte-like cells were detected on day 21 and increased on day 28. Protein ... MSCs can be a promising source of cell therapy for intractable liver diseases. ..... blood-derived mesenchymal stem cells by DNA microarray.

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  7. 脐血间充质干细胞移植治疗儿童型脊肌萎缩症1例%Umbilical cord blood mesenchymal stem cell transplantation for treatment of a child with spinal muscular atrophy

    Institute of Scientific and Technical Information of China (English)

    杜玲; 杨华强; 王娜; 罗国君

    2011-01-01

    BACKGROUND: Many animal and clinical studies have reported that the safe and effective usage of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) transplantation for treatment of neurological genetic diseases.OBJECTIVE: To investigate the feasibility and effect of UCB-MSCs transplantation in the treatment of spinal muscular atrophy (SMA).METHODS: A child admitted at January 2010 had been confirmed as having SMA, and drug and rehabilitation therapies were invalid. Then, the child received UCB-MSCs transplantation via the first intravenous infusion and three times of subarachnoid injection, once a week, (4-6)×107 cells once and four times as a course. Neurological physical examination, biochemical test, muscle enzymes detection, FIM scoring and electromyography (EMG) examination were conducted. RESULTS AND CONCLUSION: Compared with prior to transplantation, the level of muscle enzymes decreased, FIM scores were increased from 68 to 93 points, EMG results showed that the motor units with re-contraction in each 10.0 ms were increased that the motor function was improved, the lower extremity muscle strength elevated, and the self-care ability was improved in the SMA child at 6 months after transplantation. During the 10-month follow-up, the child had no adverse effects. It is indicated that UCB-MSCs transplantation is effective to treat SMA, and the neurological function has a remarkable restoration.%背景:国内外已有实验动物和临床应用脐血间充质干细胞移植治疗神经系统遗传性疾病安全、有效的诸多报道.目的:探讨脐血间充质干细胞移植治疗儿童进行性脊髓性肌肉萎缩症的可行性及效果.方法:2010-01收治1例确诊为儿童进行性脊髓性肌肉萎缩症患儿,经药物及康复治疗无效,行脐血间充质干细胞移植治疗.移植途径采取首次静脉输注,后3次蛛网膜下腔注入,1次/周,每次细胞数量达(4~6)×107个,4次为1个疗程.治疗前和治疗后半年均需

  8. Umbilical Cord Blood: Counselling, Collection, and Banking.

    Science.gov (United States)

    Armson, B Anthony; Allan, David S; Casper, Robert F

    2015-09-01

    Objectif : Analyser les données probantes actuelles sur le counseling, le prélèvement et la mise en banque, en ce qui a trait au sang de cordon ombilical, et fournir des lignes directrices aux professionnels canadiens de la santé en ce qui concerne la sensibilisation des patientes, le consentement éclairé, les aspects techniques et les options pour la mise en banque de sang de cordon au Canada. Options : Prélèvement sélectif ou systématique et mise en banque du sang de cordon ombilical, en vue de futures greffes autologues (chez le patient même) ou allogéniques (lien de parenté ou non) de cellules souches visant la prise en charge de troubles malins et bénins chez les enfants et les adultes. Le sang de cordon peut être prélevé au moyen de techniques in utero ou ex utero. Issues : Counseling, prélèvement et mise en banque en ce qui a trait au sang de cordon ombilical, formation des professionnels de la santé, indications du prélèvement de sang de cordon, risques et avantages à court et à long terme, morbidité maternelle et périnatale, satisfaction parentale et coûts de santé. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans Medline et PubMed à partir de septembre 2013, au moyen d’un vocabulaire contrôlé (p. ex. « fetal blood », « pregnancy », « transplantation », « ethics ») et de mots clés (p. ex. « umbilical cord blood », « banking », « collection », « pregnancy », « transplantation », « ethics », « public », « private ») MeSH appropriés. Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs. Aucune limite n’a été imposée en matière de date, mais les résultats ont été limités aux articles publiés en anglais ou en français. Les recherches ont été mises à jour de façon régulière et int

  9. Could cord blood cell therapy reduce preterm brain injury?

    Science.gov (United States)

    Li, Jingang; McDonald, Courtney A; Fahey, Michael C; Jenkin, Graham; Miller, Suzanne L

    2014-01-01

    Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP). Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain. Nearly 90% of preterm infants who later develop spastic CP have evidence of periventricular white matter injury. There are currently no treatments targeted at protecting the immature preterm brain. Umbilical cord blood (UCB) contains a diverse mix of stem and progenitor cells, and is a particularly promising source of cells for clinical applications, due to ethical and practical advantages over other potential therapeutic cell types. Recent studies have documented the potential benefits of UCB cells in reducing brain injury, particularly in rodent models of term neonatal hypoxia-ischemia. These studies indicate that UCB cells act via anti-inflammatory and immuno-modulatory effects, and release neurotrophic growth factors to support the damaged and surrounding brain tissue. The etiology of brain injury in preterm-born infants is less well understood than in term infants, but likely results from episodes of hypoperfusion, hypoxia-ischemia, and/or inflammation over a developmental period of white matter vulnerability. This review will explore current knowledge about the neuroprotective actions of UCB cells and their potential to ameliorate preterm brain injury through neonatal cell administration. We will also discuss the characteristics of UCB-derived from preterm and term infants for use in clinical applications.

  10. Could cord blood cell therapy reduce preterm brain injury?

    Directory of Open Access Journals (Sweden)

    Jingang eLi

    2014-10-01

    Full Text Available Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP. Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain. Nearly 90% of preterm infants who later develop spastic CP have evidence of periventricular white matter injury. There are currently no treatments targeted at protecting the immature preterm brain. Umbilical cord blood (UCB contains a diverse mix of stem and progenitor cells, and is a particularly promising source of cells for clinical applications, due to ethical and practical advantages over other potential therapeutic cell types. Recent studies have documented the potential benefits of UCB cells in reducing brain injury, particularly in rodent models of term neonatal hypoxia-ischemia. These studies indicate that UCB cells act via anti-inflammatory and immuno-modulatory effects, and release neurotrophic growth factors to support the damaged and surrounding brain tissue. The etiology of brain injury in preterm-born infants is less well understood than in term infants, but likely results from episodes of hypoperfusion, hypoxia-ischemia, and/or inflammation over a developmental period of white matter vulnerability. This review will explore current knowledge about the neuroprotective actions of UCB cells and their potential to ameliorate preterm brain injury through neonatal cell administration. We will also discuss the characteristics of UCB derived from preterm and term infants for use in clinical applications.

  11. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... Queue __count__/__total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Loading... Unsubscribe from ... later? Sign in to add this video to a playlist. Sign in Share More Report Need to ...

  12. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... takes you through her blood stem cell donation experience at the National Institutes of Health Clinical Center ... views 11:58 Sara's filgrastim and PBSC donation experience - Duration: 10:58. Be The Match 24,944 ...

  13. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... Queue __count__/__total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Loading... Unsubscribe from ... later? Sign in to add this video to a playlist. Sign in Share More Report Need to ...

  14. Comparison of Umbilical Cord Milking and Delayed Cord Clamping on Cerebral Blood Flow in Term Neonates.

    Science.gov (United States)

    Jaiswal, Prateek; Upadhyay, Amit; Gothwal, Sunil; Chaudhary, Hema; Tandon, Ashutosh

    2015-10-01

    To compare the effect of umbilical cord milking (UCM) and delayed cord clamping (DCC) on cerebral blood flow in term neonates. This randomized controlled trial was conducted at a teaching hospital in India during 2012 to 2013. Two hundred newborns (>36wk) were randomized to UCM and DCC groups. UCM was done on 25cm of cord length. In DCC group, clamping was delayed by 60 to 90s. Resistive Index (RI), Pulsatility Index (PI) and cerebral blood flow velocities of middle cerebral artery (MCA) were measured at 24 to 48h of life. Baseline characteristics and hemodynamic parameters were comparable. Mean PI [1.18 (0.26)] and RI [0.65 (0.08)] in UCM group was comparable to mean PI [1.18 (0.25)] and RI [0.65 (0.08)] in DCC group. The peak systolic velocity and end diastolic velocity (cm/s) of blood flow in MCA for UCM group were 34.94 (11.82) and 11.71 (4.75) respectively, while in DCC group they were 37.24 (12.63) and 13.07 (4.78) (p 0.23 and 0.07) respectively. Indices among growth retarded babies were not different. DCC and UCM had similar effect on cerebral blood flow velocities and Doppler indices in MCA, in term neonates.

  15. Potential of human dental stem cells in repairing the complete transection of rat spinal cord

    Science.gov (United States)

    Yang, Chao; Li, Xinghan; Sun, Liang; Guo, Weihua; Tian, Weidong

    2017-04-01

    Objective. The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering. Approach. Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored. Main results. The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth. Significance. Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.

  16. Arylsulfatase-A in umbilical cord blood: gestational age and mode of delivery do not influence enzyme activity.

    Science.gov (United States)

    Georgeson, G D; Szöny, B J; Streitman, K; Sallay, E; Kovács, A; Kovács, L; László, A

    2002-03-01

    The possibility of using umbilical cord blood for transplantation in several enzyme deficiencies has received increasing attention because of the availability of cord blood, the reduced incidence of post-transplantation complications, such as graft-versus-host disease and the possible accomplishment of good corrective results following transplantation, even in cases of greater HLA disparity. The use of hematopoietic stem cells from unrelated donors is even more highly recommended for the treatment of inherited enzyme deficiencies, because it might reduce the risk of the transplanted cells originating from a carrier of the defect, which might have an inadequate corrective ability. Our study was designed to elucidate whether the gestational age and mode of delivery influences the arylsulfatase-A activity in the umbilical cord blood. Enzyme activities proved to be similar in the four populations studied (full-term normal spontaneous vaginal delivery, full-term caesarean section, preterm normal spontaneous vaginal delivery and preterm caesarean section). Therefore, umbilical cord blood samples seem to be suitable for transplantation in metachromatic leukodystrophy, regardless of gestational age and mode of delivery. Moreover, our results are the first published data on normal values for arylsulfatase-A activity in human umbilical cord blood.

  17. In-vitro stem cell derived red blood cells for transfusion: are we there yet?

    Science.gov (United States)

    Kim, Hyun Ok

    2014-03-01

    To date, the use of red blood cells (RBCs) produced from stem cells in vitro has not proved practical for routine transfusion. However, the perpetual and widespread shortage of blood products, problems related to transfusion-transmitted infections, and new emerging pathogens elicit an increasing demand for artificial blood. Worldwide efforts to achieve the goal of RBC production through stem cell research have received vast attention; however, problems with large-scale production and cost effectiveness have yet to prove practical usefulness. Some progress has been made, though, as cord blood stem cells and embryonic stem cells have shown an ability to differentiate and proliferate, and induced pluripotent stem cells have been shown to be an unlimited source for RBC production. However, transfusion of stem cell-derived RBCs still presents a number of challenges to overcome. This paper will summarize an up to date account of research and advances in stem cell-derived RBCs, delineate our laboratory protocol in producing RBCs from cord blood, and introduce the technological developments and limitations to current RBC production practices.

  18. Adult spinal cord ependymal layer: a promising pool of quiescent stem cells to treat spinal cord injury

    OpenAIRE

    Panayiotou, Elena; Malas, Stavros

    2013-01-01

    Spinal cord injury (SCI) is a major health burden and currently there is no effective medical intervention. Research performed over the last decade revealed that cells surrounding the central canal of the adult spinal cord and forming the ependymal layer acquire stem cell properties either in vitro or in response to injury. Following SCI activated ependymal cells generate progeny cells which migrate to the injury site but fail to produce the appropriate type of cells in sufficient number to l...

  19. Isolation and Characterisation of Mesenchymal Stem Cells from Different Regions of the Human Umbilical Cord

    Directory of Open Access Journals (Sweden)

    Claire Mennan

    2013-01-01

    Full Text Available Umbilical cords as a source of stem cells are of increasing interest for cell therapies as they present little ethical consideration and are reported to contain immune privileged cells which may be suitable for allogeneic based therapies. Mesenchymal stem cells (MSCs sourced from several different cord regions, including artery, vein, cord lining, and Wharton’s jelly, are described in the literature. However, no one study has yet isolated and characterised MSCs from all regions of the same cord to determine the most suitable cells for cell based therapeutics.

  20. Isolation and Characterisation of Mesenchymal Stem Cells from Different Regions of the Human Umbilical Cord

    Science.gov (United States)

    Wright, Karina; Bhattacharjee, Atanu; Balain, Birender; Richardson, James; Roberts, Sally

    2013-01-01

    Umbilical cords as a source of stem cells are of increasing interest for cell therapies as they present little ethical consideration and are reported to contain immune privileged cells which may be suitable for allogeneic based therapies. Mesenchymal stem cells (MSCs) sourced from several different cord regions, including artery, vein, cord lining, and Wharton's jelly, are described in the literature. However, no one study has yet isolated and characterised MSCs from all regions of the same cord to determine the most suitable cells for cell based therapeutics. PMID:23984420

  1. Rat hair follicle stem cells differentiate and promote recovery following spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Nowruz Najafzadeh; Maliheh Nobakht; Bagher Pourheydar; Mohammad Ghasem Golmohammadi

    2013-01-01

    Emerging studies of treating spinal cord injury (SCI) with adult stem cells led us to evaluate the effects of transplantation of hair fol icle stem cells in rats with a compression-induced spinal cord lesion. Here, we proposed a hypothesis that rat hair fol icle stem celltransplantation can promote the recovery of injured spinal cord. Compression-induced spinal cord injury was induced in Wistar rats in this study. The bulge area of the rat vibrissa fol icles was isolated, cultivated and characterized with nestin as a stem cellmarker. 5-Bromo-2′-deoxyuridine (BrdU) labeled bulge stem cells were transplanted into rats with spinal cord injury. Immunohistochemical staining results showed that some of the grafted cells could survive and differentiate into oligodendrocytes (receptor-interacting protein positive cells) and neuronal-like cells (βIII-tubulin positive cells) at 3 weeks after transplantation. In addition, recovery of hind limb locomotor function in spinal cord injury rats at 8 weeks fol owing celltransplantation was assessed using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. The results demon-strate that the grafted hair fol icle stem cells can survive for a long time period in vivo and differentiate into neuronal- and glial-like cells. These results suggest that hair fol icle stem cells can promote the recovery of spinal cord injury.

  2. 地中海贫血患者来源外周血及脐带血细胞诱导式多能干细胞的建系和造血分化%Establishment of the thalassemia patient-specific induced pluripotent stem cells from peripheral and cord blood ;cells and its hematopoietic differentiation

    Institute of Scientific and Technical Information of China (English)

    曾敏慧; 蒋满波; 艳飞; 彭澄; 张滨; 蔡柳洪

    2015-01-01

    Objective To investigate the construction and hematopoietic differentiation of induced pluripotent stem cells ( iPSCs) from thalassemia patients .Methods Cord blood from artificial labored fetus with HbH disease (α-thalassemia) and peripheral blood from a case of heterozygote of β-thalassemia (genotype IVS-II-654/CD17) were obtained.The iPSCs were re-programed from mononuclear cells separated from obtained cord blood and peripheral blood . Hematopoietic stem cell differentiation was induced by OP 9 cell co-culture.The pluripotent markers of iPSCs were detec-ted by immunofluorescence and alkaline phosphatase staining , while embryoid bodies ( EBs) and teratoma forming experi-ments were used to detect the pluripotency .Results Pluripotent biomarkers , including Oct4, SSEA4, tra-1-60 and tra-1-81, and alkaline phosphatase , were positive on iPSCs.EBs were formed by suspended culture .Three germ layer cells were found in the teratoma test .The results of flow cytometry showed that CD 34+cells was 4.46%and 8.71%from cord blood and peripheral sources , respectively, after co-cultured with OP9 cells.Conclusion Cord blood and periph-eral blood MNCs of patients with αorβthalassemia, can be reprogrammed into iPSCs , and differentiated into hematopoi-etic stem cells.%目的:探讨地中海贫血(地贫)患者特异诱导式多能干细胞系( iPSCs)细胞模型的建立及造血分化能力。方法采集HbH病引产胎儿(α地贫)的脐带血、双重杂合子β地贫输血患者(基因型为IVS-Ⅱ-654/CD17)外周血各1例,分离单核细胞后进行短期培养,核转染再程序化为iPSCs,检测iPSCs未分化状态和多能性标志物。 iPSCs与OP9细胞共培养向造血干细胞诱导分化,进行吉姆萨染色检查和流式细胞术检测造血干细胞的分化结果。结果地贫患者iPSCs表达干细胞多能性标志物Oct4、SSEA4、Tra-1-60、Tra-1-81,碱式磷酸酶染色阳性,悬浮培养可以形成类

  3. Breaking the Blood-Brain Barrier With Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain.

    Science.gov (United States)

    Tajiri, Naoki; Lee, Jea Young; Acosta, Sandra; Sanberg, Paul R; Borlongan, Cesar V

    2016-01-01

    Blood-brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague-Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke.

  4. Transplantation of erythropoietin gene-modified neural stem cells improves the repair of injured spinal cord

    Directory of Open Access Journals (Sweden)

    Min-fei Wu

    2015-01-01

    Full Text Available The protective effects of erythropoietin on spinal cord injury have not been well described. Here, the eukaryotic expression plasmid pcDNA3.1 human erythropoietin was transfected into rat neural stem cells cultured in vitro. A rat model of spinal cord injury was established using a free falling object. In the human erythropoietin-neural stem cells group, transfected neural stem cells were injected into the rat subarachnoid cavity, while the neural stem cells group was injected with non-transfected neural stem cells. Dulbecco′s modified Eagle′s medium/F12 medium was injected into the rats in the spinal cord injury group as a control. At 1-4 weeks post injury, the motor function in the rat lower limbs was best in the human erythropoietin-neural stem cells group, followed by the neural stem cells group, and lastly the spinal cord injury group. At 72 hours, compared with the spinal cord injury group, the apoptotic index and Caspase-3 gene and protein expressions were apparently decreased, and the bcl-2 gene and protein expressions were noticeably increased, in the tissues surrounding the injured region in the human erythropoietin-neural stem cells group. At 4 weeks, the cavities were clearly smaller and the motor and somatosensory evoked potential latencies were remarkably shorter in the human erythropoietin-neural stem cells group and neural stem cells group than those in the spinal cord injury group. These differences were particularly obvious in the human erythropoietin-neural stem cells group. More CM-Dil-positive cells and horseradish peroxidase-positive nerve fibers and larger amplitude motor and somatosensory evoked potentials were found in the human erythropoietin-neural stem cells group and neural stem cells group than in the spinal cord injury group. Again, these differences were particularly obvious in the human erythropoietin-neural stem cells group. These data indicate that transplantation of erythropoietin gene-modified neural stem

  5. Transplantation of erythropoietin gene-modified neural stem cells improves the repair of injured spinal cord.

    Science.gov (United States)

    Wu, Min-Fei; Zhang, Shu-Quan; Gu, Rui; Liu, Jia-Bei; Li, Ye; Zhu, Qing-San

    2015-09-01

    The protective effects of erythropoietin on spinal cord injury have not been well described. Here, the eukaryotic expression plasmid pcDNA3.1 human erythropoietin was transfected into rat neural stem cells cultured in vitro. A rat model of spinal cord injury was established using a free falling object. In the human erythropoietin-neural stem cells group, transfected neural stem cells were injected into the rat subarachnoid cavity, while the neural stem cells group was injected with non-transfected neural stem cells. Dulbecco's modified Eagle's medium/F12 medium was injected into the rats in the spinal cord injury group as a control. At 1-4 weeks post injury, the motor function in the rat lower limbs was best in the human erythropoietin-neural stem cells group, followed by the neural stem cells group, and lastly the spinal cord injury group. At 72 hours, compared with the spinal cord injury group, the apoptotic index and Caspase-3 gene and protein expressions were apparently decreased, and the bcl-2 gene and protein expressions were noticeably increased, in the tissues surrounding the injured region in the human erythropoietin-neural stem cells group. At 4 weeks, the cavities were clearly smaller and the motor and somatosensory evoked potential latencies were remarkably shorter in the human erythropoietin-neural stem cells group and neural stem cells group than those in the spinal cord injury group. These differences were particularly obvious in the human erythropoietin-neural stem cells group. More CM-Dil-positive cells and horseradish peroxidase-positive nerve fibers and larger amplitude motor and somatosensory evoked potentials were found in the human erythropoietin-neural stem cells group and neural stem cells group than in the spinal cord injury group. Again, these differences were particularly obvious in the human erythropoietin-neural stem cells group. These data indicate that transplantation of erythropoietin gene-modified neural stem cells into the

  6. Transplantation of erythropoietin gene-modiifed neural stem cells improves the repair of injured spinal cord

    Institute of Scientific and Technical Information of China (English)

    Min-fei Wu; Shu-quan Zhang; Rui Gu; Jia-bei Liu; Ye Li; Qing-san Zhu

    2015-01-01

    The protective effects of erythropoietin on spinal cord injury have not been well described. Here, the eukaryotic expression plasmid pcDNA3.1 human erythropoietin was transfected into rat neural stem cells culturedin vitro. A rat model of spinal cord injury was established using a free falling object. In the human erythropoietin-neural stem cells group, transfected neural stem cells were injected into the rat subarachnoid cavity, while the neural stem cells group was inject-ed with non-transfected neural stem cells. Dulbecco’s modified Eagle’s medium/F12 medium was injected into the rats in the spinal cord injury group as a control. At 1–4 weeks post injury, the motor function in the rat lower limbs was best in the human erythropoietin-neural stem cells group, followed by the neural stem cells group, and lastly the spinal cord injury group. At 72 hours, compared with the spinal cord injury group, the apoptotic index and Caspase-3 gene and protein expressions were apparently decreased, and the bcl-2 gene and protein expressions were noticeably increased, in the tissues surrounding the injured region in the human erythro-poietin-neural stem cells group. At 4 weeks, the cavities were clearly smaller and the motor and somatosensory evoked potential latencies were remarkably shorter in the human erythropoi-etin-neural stem cells group and neural stem cells group than those in the spinal cord injury group. These differences were particularly obvious in the human erythropoietin-neural stem cells group. More CM-Dil-positive cells and horseradish peroxidase-positive nerve fibers and larger amplitude motor and somatosensory evoked potentials were found in the human erythro-poietin-neural stem cells group and neural stem cells group than in the spinal cord injury group. Again, these differences were particularly obvious in the human erythropoietin-neural stem cells group. These data indicate that transplantation of erythropoietin gene-modified neural stem cells into the

  7. Cesarean section imprints cord blood immune cell distributions

    DEFF Research Database (Denmark)

    Thysen, Anna Hammerich; Larsen, Jeppe Madura; Rasmussen, Mette Annelie;

    2014-01-01

    Immune programming in early life may affect the risk of developing immune-related diseases later in life. Children born by cesarean section seem to be at higher risk of asthma, allergic rhinitis, and type-1 diabetes. We hypothesized that delivery by cesarean section may affect immune maturation...... in newborns. The objective of the study was to profile innate and adaptive immune cell subsets in cord blood of children born by cesarean section or natural birth....

  8. Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury.

    Science.gov (United States)

    Kumar, Hemant; Ropper, Alexander E; Lee, Soo-Hong; Han, Inbo

    2016-05-18

    The blood-spinal cord barrier (BSCB) is a specialized protective barrier that regulates the movement of molecules between blood vessels and the spinal cord parenchyma. Analogous to the blood-brain barrier (BBB), the BSCB plays a crucial role in maintaining the homeostasis and internal environmental stability of the central nervous system (CNS). After spinal cord injury (SCI), BSCB disruption leads to inflammatory cell invasion such as neutrophils and macrophages, contributing to permanent neurological disability. In this review, we focus on the major proteins mediating the BSCB disruption or BSCB repair after SCI. This review is composed of three parts. Section 1. SCI and the BSCB of the review describes critical events involved in the pathophysiology of SCI and their correlation with BSCB integrity/disruption. Section 2. Major proteins involved in BSCB disruption in SCI focuses on the actions of matrix metalloproteinases (MMPs), tumor necrosis factor alpha (TNF-α), heme oxygenase-1 (HO-1), angiopoietins (Angs), bradykinin, nitric oxide (NO), and endothelins (ETs) in BSCB disruption and repair. Section 3. Therapeutic approaches discusses the major therapeutic compounds utilized to date for the prevention of BSCB disruption in animal model of SCI through modulation of several proteins.

  9. Cord blood collection and banking from a population with highly diverse geographic origins increase HLA diversity in the registry and do not lower the proportion of validated cord blood units: experience of the Marseille Cord Blood Bank.

    Science.gov (United States)

    Bordoni, C; Magalon, J; Gilbertas, C; Gamerre, M; Le Coz, P; Berthomieu, M; Chabannon, C; Di Cristofaro, J; Picard, C

    2015-04-01

    Several Cord Blood (CB) Bank studies suggested that ethnicity impaired CB unit (CBU) qualification. The Bone Marrow Donors Worldwide registries present an over-representation of unrelated donors (UD) from Northwestern European descent. This raises the question of equality of access to hematopoietic stem cells transplant, especially in the Mediterranean zone, which has taken in many waves of immigration. The aim of our study is to address whether, in the Marseille CB Bank, CBU qualification rate is impaired by geographic origin. The study compared biological characteristics of 106 CBU disqualified for total nucleated cell (TNC) count (dCBU) and 136 qualified CBU in relation to registry enrichment and haplotype origin. A high proportion (>80%) of both dCBU and CBU had at least one non-European haplotype and enrich CB and UD registries to a higher extent than those with two European haplotypes (PBank inventories and to improve the representation of minorities.

  10. The therapeutic potential, challenges and future clinical directions of stem cells from the Wharton's jelly of the human umbilical cord.

    Science.gov (United States)

    Bongso, Ariff; Fong, Chui-Yee

    2013-04-01

    Mesenchymal stem cells (MSCs) from bone marrow, adult organs and fetuses face the disadvantages of invasive isolation, limited cell numbers and ethical constraints while embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) face the clinical hurdles of potential immunorejection and tumorigenesis respectively. These challenges have prompted interest in the study and evaluation of stem cells from birth-associated tissues. The umbilical cord (UC) has been the most popular. Hematopoietic stem cells (HSCs) harvested from cord blood have been successfully used for the treatment of hematopoietic diseases. Stem cell populations have also been reported in other compartments of the UC viz., amnion, subamnion, perivascular region, Wharton's jelly, umbilical blood vessel adventia and endothelium. Differences in stemness characteristics between compartments have been reported and hence derivation protocols using whole UC pieces containing all compartments yield mixed stem cell populations with varied characteristics. Stem cells derived directly from the uncontaminated Wharton's jelly (hWJSCs) appear to offer the best clinical utility because of their unique beneficial properties. They are non-controversial, can be harvested painlessly in abundance, proliferative, possess stemness properties that last several passages in vitro, multipotent, hypoimmunogenic and do not induce tumorigenesis even though they have some ESC markers. hWJSCs and its extracts (conditioned medium and lysate) also possess anti-cancer properties and support HSC expansion ex vivo. They are thus attractive autologous or allogeneic agents for the treatment of malignant and non-malignant hematopoietic and non-hematopoietic diseases. This review critically evaluates their therapeutic value, the challenges and future directions for their clinical application.

  11. Occurrence and transport of synthetic musks in paired maternal blood, umbilical cord blood, and breast milk.

    Science.gov (United States)

    Zhang, Xiaolan; Jing, Ye; Ma, Li; Zhou, Jing; Fang, Xiangming; Zhang, Xinyu; Yu, Yingxin

    2015-01-01

    Although early exposure to environmental pollutants may have important toxicological consequences, the mechanisms of transplacental transfer of synthetic musks are still not well understood. The objective of the present study was to learn the musk contaminations in three matrices, including maternal blood, umbilical cord blood, and breast milk; and investigate their placental transfer mechanisms. The concentrations of eight commonly used synthetic musks were measured in 42 paired samples (126 individual samples in total) of maternal serum, umbilical cord serum, and breast milk from Chinese women living in Shanghai. Musks were ubiquitously detected, especially galaxolide (HHCB) and musk xylene (MX). The total lipid-based concentrations were higher in umbilical cord sera (87.3ng/g), but lower in breast milk (35.2ng/g), compared with maternal serum concentrations (71.2ng/g). There were significant correlations between maternal serum concentrations of HHCBs (HHCB and HHCB-lactone) and umbilical cord serum concentrations, and between maternal serum concentrations and breast milk concentrations (Spearman's rho=0.338-0.597, pumbilical cord sera were >1. And the HHCB-lactone/HHCB ratio in maternal sera was higher compared with umbilical cord sera. Contamination levels were low compared with other regions and HHCBs were found to be the predominant constituents. No regional differences or age-related accumulations were observed. Our study suggests that prenatal exposure to HHCBs occurs and that transplacental transfer is the main route of exposure. Preferential accumulation in umbilical cord blood was observed. The results showed that transplacental transfer of HHCB did not correspond to passive diffusion since the transfer ratios were significantly different from 1. The transfer ratio for HHCB was also larger than that of HHCB-lactone, although HHCB has higher lipid solubility. Low fetal metabolism of HHCB was suggested by the HHCB-lactone/HHCB ratio in maternal and

  12. Contradictions of value: between use and exchange in cord blood bioeconomy.

    Science.gov (United States)

    Brown, Nik

    2013-01-01

    Umbilical cord blood (CB) has become established as an increasingly viable clinical alternative to bone marrow in the treatment of leukaemia leading to the construction of a global network of CB banks promoted through a moral ethos of gift. Additionally, some banks offer the opportunity to retain stem cells privately. CB is discursively presented as clinical 'waste', a 'by-product' of birthing. In this way CB units are made available to a global exchange-based bioeconomy. Crucially, CB collection has developed in parallel with several necessary obstetric practices, especially the immediate clamping of the cord following delivery, essential to high volume collection. However, this article strongly suggests the promotional basis of CB banking (such as by gift, waste or donation) is in tension with the growing preference of new parents to delay cord clamping. Based on focus groups with expectant parents, the promotion of CB banking can in fact be seen to feed into critical reflection on the value of CB for newborn infants, potentially reinvigorating a tradition of delayed umbilical cord clamping. Theoretically, these contradictory systems of valuing are conceptualised through recent literature on bioeconomy and Marx's writings on the contrasting tensions between use and exchange value. © 2012 The Author. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

  13. Neural Differentiation of Human Umbilical Cord Mesenchymal Stem Cells by Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Shirin FARIVAR*

    2015-01-01

    chick embryos. J Exp Zool A Comp Exp Biol 2004 Apr 1;301(4:280-9.Mitchell KE, Weiss ML. Matrix cells from Wharton’s jelly form neurons and glia. Stem Cells 2003;21(1:50-60.Marcus AJ, Woodbury D. Fetal stem cells from extra-embryonic tissues: do not discard. J Cell Mol Med 2008 Jun;12(3:730-42. doi: 10.1111/j.1582- 4934.2008.00221.x. Epub 2008 Jan 11.Miao Z, Jin J, Chen L, Zhu J, Huang W, Zhao J, Quian H, Zhang X. Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells. Cell Biol Int 2006 Sep;30(9:681-7. Epub 2006 Apr 22.In ‘tAnker PS, Scherjon SA, Kleijburg-van der Keur C, Noort WA, Claas FHJ, Willemze R, Fibbe WE, Kanhai HHH. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 2003;102(4:1548-49.Magatti M, De Munari S, Vertua E, Gibelli L, Wengler GS, Parolini O. Human amnion mesenchyme harbors cells with allogeneic T-cell suppression and stimulation capabilities. Stem Cells 2008 Jan;26(1:182-92. Epub 2007 Sep 27.Kang XQ, Zang WJ, Bao LJ, Li DL, Xu XL, Yu XJ. Differentiating characterization of human umbilical cord blood-derived mesenchymal stem cells in vitro. Cell Biol Int 2006 Jul;30(7:569-75. Epub 2006 Mar 6.Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006 May;24(5:1294-301. Epub 2006 Jan 12.Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, Krause U, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 2005 Nov;33(11:1402-16.Jackson JS, Golding JP, Chapon C, Jones WA, Bhakoo KK: Homing of stem cells to sites of inflammatory brain injury after intracerebral and intravenous administration: a longitudinal imaging study. Stem Cell Res Ther 2010 Jun 15;1(2:17. doi: 10.1186/scrt17.Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative

  14. Safety and efficacy of cord blood mononuclear cells and umbilical cord mesenchymal stem cells therapy for childhood autism%脐血单个核细胞和脐带间充质干细胞治疗儿童孤独症的安全性与有效性

    Institute of Scientific and Technical Information of China (English)

    刘敏; 罗朝霞; 安蕾; 吕涌涛; 郇英; 葛汝村; 张隽; 姜舒; 郭传琴; 胡祥; 陈兴旺

    2011-01-01

    背景:目前国内外尚没有治疗儿童孤独症的金标准,康复治疗效果不佳.目的:评价脐血单个核细胞和脐带间充质干细胞治疗儿童孤独症的临床安全性和有效性.方法:37例儿童孤独症患者非随机分为脐血组、混合组和对照组.脐血组应用脐血单个核细胞加康复训练治疗;混合组联合应用脐血单个核细胞和脐带间充质干细胞加康复训练治疗;对照组单纯行康复训练治疗.脐血组和混合组患者在干细胞治疗前和首次治疗后1,2,6个月分别行相关指标实验室检查,并观察有无不良反应发生.3组患者在治疗前和首次治疗后1,2,6个月分别行儿童孤独症评定量表(CARS)和异常行为量表(ABC)评估.结果与结论:脐血组和混合组患者在干细胞治疗前和首次治疗后1,2,6个月相关指标实验室检查未发现有意义异常变化,干细胞治疗后无严重不良反应发生;根据CARS和ABC评分,3组治疗均有效,其疗效比较:混合组优于脐血组,脐血组优于对照组.%BACKGROUND: There is no clear standard for curing autism, and the effect of rehabilitation treatment is not satisfied. OBJECTIVE: To evaluate the safety and efficacy of cord blood mononuclear cells (MNCs) and umbilical cord mesenchymal stem cells (MSCs) in treating autistic children.METHODS: Thirty-seven children with autism were divided into MNCs treatment (MNCs plus rehabilitation treatment), MNCs combined with MSCs treatment (MNCs combined with MSCs plus rehabilitation treatment) and control (rehabilitation treatment alone) groups. Related laboratory examinations were performed for each group before treatment, 1, 2 and 6 months after treatment to observe adverse effects. Childhood Autism Rating Scale and Aberrant Behavior Checklist were employed to assess the children of autism.RESULTS AND CONCLUSION: There was no statistical difference between MNCs treatment group and MNCs combined with MSCs treatment group in laboratory

  15. The High Yield Expansion and Megakaryocytic Differentiation of Human Umbilical Cord Blood CD133+ Cells

    Directory of Open Access Journals (Sweden)

    Mahin Nikougoftar Zarif

    2011-01-01

    Full Text Available Objective: Despite of many benefits, umbilical cord blood (UCB hematopoietic stem cell(HSC transplantation is associated with low number of stem cells and slow engraftment;in particular of platelets. So, expanded HSCs and co-transfusion of megakaryocyte (MKprogenitor cells can shorten this period. In this study, we evaluated the cytokine conditionsfor maximum expansion and MK differentiation of CD133+ HSCs.Materials and Methods: In this experimental study, The CD133+ cells were separatedfrom three cord blood samples by magnetic activated cell sorting (MACS method, expandedin different cytokine combinations for a week and differentiated in thrombopoietin(TPO for the second week. Differentiation was followed by the flow cytometry detectionof CD41 and CD61 surface markers. Colony forming unit (CFU assay and DNA analysiswere done for colonogenic capacity and ploidy assay.Results: CD133+ cells showed maximum expansion in the stem span medium with stemcell factor (SCF + FMS-like tyrosine kinase 3-ligand (Flt3-L + TPO but the maximum differentiationwas seen when CD133+ cells were expanded in stem span medium with SCF+ Interleukin 3 (IL-3 + TPO for the first and in TPO for the second week. Colony FormingUnit-MK (CFU-MK was formed in three sizes of colonies in the mega-cult medium. In theDNA analysis; 25.2 ± 6.7% of the cells had more than 2n DNA mass.Conclusion: Distinct differences in the MK progenitor cell count were observed when thecells were cultured in stem span medium with TPO, SCF, IL-3 and then the TPO in thesecond week. Such strategy could be applied for optimization of CD133+ cells expansionfollowed by MK differentiation.

  16. Umbilical Cord-Derived Mesenchymal Stem Cells Relieve Hindlimb Ischemia through Enhancing Angiogenesis in Tree Shrews

    Directory of Open Access Journals (Sweden)

    Cunping Yin

    2016-01-01

    Full Text Available Hindlimb ischemia is still a clinical problem with high morbidity and mortality. Patients suffer from consequent rest pain, ulcers, cool limbs, and even amputation. Angiogenesis is a promising target for the treatment of ischemic limbs, providing extra blood for the ischemic region. In the present study, we investigated the role of umbilical cord-derived mesenchymal stem cells (UC-MSCs in regulating angiogenesis and relieving hindlimb ischemia. UC-MSCs were isolated from the umbilical cord of tree shrews. Angiography results showed that UC-MSCs injection significantly promoted angiogenesis in tree shrews. Moreover, the ankle brachial index, transcutaneous oxygen pressure, blood perfusion, and capillary/muscle fiber ratio were all markedly increased by the application of UC-MSCs. In addition, the conditioned culture of human umbilical vein endothelial cells using medium collected from UC-MSCs showed higher expression of angiogenic markers and improved migration ability. In short, the isolated UC-MSCs notably contributed to restoring blood supply and alleviating the symptoms of limb ischemia through enhancing angiogenesis.

  17. Umbilical Cord-Derived Mesenchymal Stem Cells Relieve Hindlimb Ischemia through Enhancing Angiogenesis in Tree Shrews.

    Science.gov (United States)

    Yin, Cunping; Liang, Yuan; Zhang, Jian; Ruan, Guangping; Li, Zian; Pang, Rongqing; Pan, Xinghua

    2016-01-01

    Hindlimb ischemia is still a clinical problem with high morbidity and mortality. Patients suffer from consequent rest pain, ulcers, cool limbs, and even amputation. Angiogenesis is a promising target for the treatment of ischemic limbs, providing extra blood for the ischemic region. In the present study, we investigated the role of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in regulating angiogenesis and relieving hindlimb ischemia. UC-MSCs were isolated from the umbilical cord of tree shrews. Angiography results showed that UC-MSCs injection significantly promoted angiogenesis in tree shrews. Moreover, the ankle brachial index, transcutaneous oxygen pressure, blood perfusion, and capillary/muscle fiber ratio were all markedly increased by the application of UC-MSCs. In addition, the conditioned culture of human umbilical vein endothelial cells using medium collected from UC-MSCs showed higher expression of angiogenic markers and improved migration ability. In short, the isolated UC-MSCs notably contributed to restoring blood supply and alleviating the symptoms of limb ischemia through enhancing angiogenesis.

  18. Human umbilical cord-derived mesenchymal stem cells can secrete insulin in vitro and in vivo.

    Science.gov (United States)

    Boroujeni, Zahra Niki; Aleyasin, Ahmad

    2014-01-01

    Diabetes mellitus is characterized by autoimmune destruction of pancreatic beta cells, leading to decreased insulin production. Differentiation of mesenchymal stem cells (MSCs) into insulin-producing cells offers novel ways of diabetes treatment. MSCs can be isolated from the human umbilical cord tissue and differentiate into insulin-secreting cells. Human umbilical cord-derived stem cells (hUDSCs) were obtained after birth, selected by plastic adhesion, and characterized by flow cytometric analysis. hUDSCs were transduced with nonintegrated lentivirus harboring PDX1 (nonintegrated LV-PDX1) and was cultured in differentiation medium in 21 days. Pancreatic duodenum homeobox protein-1 (PDX1) is a transcription factor in pancreatic development. Significant expressions of PDX1, neurogenin3 (Ngn3), glucagon, glucose transporter2 (Glut2), and somatostatin were detected by quantitative RT-PCR (P insulin proteins were shown by immunocytochemistry analysis. Insulin secretion of hUDSCs(PDX1+) in the high-glucose medium was 1.8 μU/mL. They were used for treatment of diabetic rats and could decrease the blood glucose level from 400 mg/dL to a normal level in 4 days. In conclusion, our results demonstrated that hUDSCs are able to differentiate into insulin-producing cells by transduction with nonintegrated LV-PDX1. These hUDSCs(PDX1+) have the potential to be used as a viable resource in cell-based gene therapy of type 1 diabetes.

  19. 人脐带血干细胞移植对2型糖尿病家兔血清学的影响%Effection of human umbilical cord blood stem cell transplantation on serum of rabbits with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    丁海霞; 王富军; 刘贝; 史宁; 杜亚萍; 齐会卿; 丁娟

    2016-01-01

    目的::观察人脐带血干细胞( Human umbilical cord blood stem cells,HUCBSC)移植后2型糖尿病家兔血糖、胰岛素及二肽基肽酶Ⅳ( Dipeptidyl peptidase-Ⅳ,DPP-Ⅳ/CD26)的变化。方法:18只家兔随机分成正常对照组(6只,C组)和糖尿病造模组(12只),造模组制备2型糖尿病模型,其中6只经兔耳缘静脉输注给予免疫学表型为CD45+、CD34-的HUCBSC移植( A组),6只同法输注等量的PBS液作为对照( B组)。以上三组家兔均喂养观察4周,每天监测家兔血糖,每周测血胰岛素及DPP-Ⅳ/CD26的水平。结果:HUCBSC阳性标志物CD45表达率达100%,阴性标志物CD34表达率为3.5%。与非移植组相比,HUCBSC移植组家兔血糖和DPP-Ⅳ/CD26逐渐下降,胰岛素水平逐渐上升,差异均有统计学意义( P<0.01)。结论:HUCBSC呈圆形或椭圆形贴壁生长,免疫学表型为CD45+、CD34-。 HUCBSC移植可以明显降低家兔血糖、增加胰岛素分泌量、降低血DPP-Ⅳ/CD26的水平,从而为临床糖尿病及其并发症的治疗提供新的理论依据。%Objective:To observe the changes of blood glucose,insulin and dipeptidyl peptidase-Ⅳ(DPP-Ⅳ/CD26)on type 2 diabetes mellitus in rabbits after HUCBSC( human umbilical cord blood stem cells) transplantation. Methods:18 rabbits were randomly divided into normal control group (6 rats,Group C) and diabetic model group (12 rats). After preparation model of type 2 diabetes,and 6 rats of them were treated with HUCBSC ( CD45+,CD34-) transplantation by ear vein transfusion ( Group A) ,and 6 rats were treated with PBS(Group B). All three groups of rabbits were fed for 4 weeks,and the blood glucose was monitored every day,and the level of blood insulin and DPP-IV/CD26 were measured every week. Results:The negative expression rate of CD34 in HUCBSC was 96. 5%. The positive expression rate of CD45 in HUCBSC was 100%. Compared with non transplantation group,the blood glucose and DPP-IV/CD26 in the umbilical cord

  20. Effect of lycopene on the blood-spinal cord barrier after spinal cord injury in mice.

    Science.gov (United States)

    Zhang, Qian; Wang, Jianbo; Gu, Zhengsong; Zhang, Qing; Zheng, Hong

    2016-09-05

    The current study aimed to investigate the effect of lycopene on the blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) in a mouse model. Lycopene inhibited lipid peroxidation and oxidative DNA damage as a highly efficient antioxidant and free radical scavenger. Lycopene (4 mg/kg/d) was administrated immediately following SCI. The permeability of the BSCB and water content in the spinal cord tissue were evaluated. Additionally, levels of expression of tight junction proteins and heme oxygenase-1 (HO-1) were determined with Western blotting. An enzyme-linked immunosorbent assay analysis of spinal cord tissue homogenates was performed 48 h after SCI to evaluate the expression of inflammation-related cytokines. In addition, recovery of motor function was assessed 1 d, 2 d, 5 d, 10 d, and 15 d after SCI using the Basso Mouse Scale to score locomotion. Compared to the group with an untreated SCI, mice with an SCI treated with lycopene had significantly reduced spinal cord tissue water content and BSCB permeability. Furthermore, motor function of mice with an SCI was also greatly improved by lycopene administration. The expression of the proinflammatory factors TNF-α and NF-kB increased markedly 48 h after SCI, and their upregulation was significantly attenuated by lycopene treatment. The expression of molecules that protect tight junctions, zonula occluden-1 and claudin-5, was upregulated by lycopene treatment after SCI. Taken together, these results clearly indicate that lycopene attenuated SCI by promoting repair of the damaged BSCB, so lycopene is a novel and promising treatment for SCI in humans.

  1. Surfactant Protein D Levels in Umbilical Cord Blood and Capillary Blood of Premature Infants

    DEFF Research Database (Denmark)

    Dahl, Marianne; Holmskov, Uffe; Husby, Steffen

    2006-01-01

    of SP-D in capillary blood day 1 was 1,466 ng/mL (range 410-5,051 ng/mL), with lowest values in infants born with ROM and delivered vaginally. High SP-D levels in umbilical cord blood and capillary blood on day 1 were found to be more likely in infants in need for respiratory support or surfactant...

  2. Acetylcholine secretion by motor neuron-like cells from umbilical cord mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Xueyuan Liu; Dehua Li; Dong Jiang; Yan Fang

    2013-01-01

    Umbilical cord mesenchymal stem cel s were isolated by a double enzyme digestion method. The third passage of umbilical cord mesenchymal stem cel s was induced with heparin and/or basic fi-broblast growth factor. Results confirmed that cel morphology did not change after induction with basic fibroblast growth factor alone. However, neuronal morphology was visible, and microtu-bule-associated protein-2 expression and acetylcholine levels increased fol owing induction with heparin alone or heparin combined with basic fibroblast growth factor. Hb9 and choline acetyl-transferase expression was high fol owing inductive with heparin combined with basic fibroblast growth factor. Results indicate that the inductive effect of basic fibroblast growth factor alone was not obvious. Heparin combined with basic fibroblast growth factor noticeably promoted the differen-tiation of umbilical cord mesenchymal stem cel s into motor neuron-like cel s. Simultaneously, um-bilical cord mesenchymal stem cel s could secrete acetylcholine.

  3. Proteomic Profiling of Ex Vivo Expanded CD34-Positive Haematopoetic Cells Derived from Umbilical Cord Blood

    Directory of Open Access Journals (Sweden)

    Heiner Falkenberg

    2013-01-01

    Full Text Available Ex vivo expansion of haematopoetic cells by application of specific cytokines is one approach to overcome boundaries in cord blood transplantation due to limited numbers of haematopoetic stem cells. While many protocols describe an effective increase of total cell numbers and the amount of CD34-positive cells, it still remains unclear if and how the procedure actually affects the cells’ properties. In the presented publications, CD34-positive cells were isolated from cord blood and expanded for up to 7 days in media supplemented with stem cell factor (SCF, thrombopoietin (THPO, interleukin 6 (IL-6, and fms-related tyrosine kinase 3 ligand (FLT3lg. At days 3 and 7, expanded cells were harvested and analyzed by flow cytometry and quantitative proteomics. 2970 proteins were identified, whereof proteomic analysis showed 440 proteins significantly changed in abundance during ex vivo expansion. Despite the fact that haematopoetic cells still expressed CD34 on the surface after 3 days, major changes in regard to the protein profile were observed, while further expansion showed less effect on the proteome level. Enrichment analysis of biological processes clearly showed a proteomic change toward a protein biosynthesis phenotype already within the first three days of expression.

  4. Clinical study of human umbilical cord blood stem cell transplantation via peripheral vein in the treatment of decompensated cirrhosis%人脐血干细胞经外周静脉移植治疗失代偿期肝硬化的临床研究

    Institute of Scientific and Technical Information of China (English)

    张岁; 佟立新; 闫宝勇; 李全海; 贾蓓; 柳立平; 马文波; 张君

    2016-01-01

    目的 探讨人脐血干细胞经外周静脉移植治疗不同程度肝硬化患者的疗效及安全性.方法 失代偿期肝硬化患者65例,分为干细胞组34例,其中Child-Pugh A级13例、B级14例、C级7例,在常规保肝治疗的基础上给予脐血干细胞移植治疗;对照组31例,其中Child-Pugh A级11例、B级13例、C级7例,给予常规保肝治疗.于治疗后2、4、12及24周观察不同程度肝硬化患者肝功能和凝血功能变化,并观察临床症状改善以及不良反应发生情况.结果 (1)临床症状改善情况:Child-Pugh A、B级患者干细胞组临床症状较对照组明显改善.Child-Pugh C级患者2组临床症状改善程度差异无统计学意义.(2)肝功能和凝血功能改善情况:Child-Pugh A、B级患者干细胞组白蛋白(ALB)、凝血酶原活动度(PTA)治疗后2、4、12、24周均较治疗前升高,且干细胞组于12、24周均较对照组升高;干细胞组胆碱酯酶(CHE)治疗后4、12、24周均较治疗前升高,但与对照组比较差异无统计学意义;2组丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)比较差异均无统计学意义.干细胞组Child-Pugh C级患者治疗后ALT、AST、TBIL、ALB、CHE、PTA与治疗前及对照组比较差异均无统计学意义.(3)所有患者均未发生严重不良反应及并发症.结论 经外周静脉移植脐血干细胞治疗失代偿期肝硬化患者安全有效,Child-Pugh A、B级患者的疗效优于Child-Pugh C级患者.%Objective To investigate the effect and safety of human umbilical cord blood stem cell transplantation via peripheral vein in the treatment of different degrees of liver cirrhosis. Methods Sixty-five patients with liver cirrhosis were selected, and divided into stem cell group (n=34) and control group (n=31). Stem cell group included patients with different degrees of cirrhosis:13 with Child-Pugh A, 14 with Child-Pugh B and 7 with Child-Pugh C respectively, patients in stem cell group

  5. Effect of intracranial transplantation of CD34+ cells derived from human umbilical cord blood in rats with cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    LIU Hai-ying; ZHANG Qing-jun; LI Hong-jun; HAN Zhong-chao

    2006-01-01

    @@ As a source of transplantable stem cells, the CD34+ subpopulation in human umbilical cord blood (HUCB) has been used extensively to treat some hematopoietic system diseases. However,whether CD34+ cells hold the therapeutic potential to cerebral ischemia is unknown. The purpose of this study was to observe the recovery of neural function after transplantation of CD34+ cells derived from HUCB into ischemic cerebral tissue in rats.

  6. Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy

    Directory of Open Access Journals (Sweden)

    Irina Arutyunyan

    2016-01-01

    Full Text Available The paper presents current evidence on the properties of human umbilical cord-derived mesenchymal stem cells, including origin, proliferative potential, plasticity, stability of karyotype and phenotype, transcriptome, secretome, and immunomodulatory activity. A review of preclinical studies and clinical trials using this cell type is performed. Prospects for the use of mesenchymal stem cells, derived from the umbilical cord, in cell transplantation are associated with the need for specialized biobanking and transplant standardization criteria.

  7. Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy

    Science.gov (United States)

    2016-01-01

    The paper presents current evidence on the properties of human umbilical cord-derived mesenchymal stem cells, including origin, proliferative potential, plasticity, stability of karyotype and phenotype, transcriptome, secretome, and immunomodulatory activity. A review of preclinical studies and clinical trials using this cell type is performed. Prospects for the use of mesenchymal stem cells, derived from the umbilical cord, in cell transplantation are associated with the need for specialized biobanking and transplant standardization criteria. PMID:27651799

  8. Adult spinal cord ependymal layer: A promising pool of quiescent stem cells to treat spinal cord injury

    Directory of Open Access Journals (Sweden)

    Stavros eMalas

    2013-11-01

    Full Text Available Spinal cord injury is a major health burden and currently there is no effective medical intervention. Research performed over the last decade revealed that cells surrounding the central canal of the adult spinal cord and forming the ependymal layer acquire stem cell properties either in vitro or in response to injury. Following spinal cord injury activated ependymal cells generate progeny cells which migrate to the injury site but fail to produce the appropriate type of cells in sufficient number to limit the damage, rendering this physiological response mainly ineffective. Research is now focusing on the manipulation of ependymal cells to produce cells of the oligodendrocyte lineage which are primarily lost in such a situation leading to secondary neuronal degeneration. Thus, there is a need for a more focused approach to understand the molecular properties of adult ependymal cells in greater detail and develop effective strategies for guiding their response during spinal cord injury.

  9. A risk factor analysis of outcomes after unrelated cord blood transplantation for children with Wiskott-Aldrich syndrome

    Science.gov (United States)

    Shekhovtsova, Zhanna; Bonfim, Carmem; Ruggeri, Annalisa; Nichele, Samantha; Page, Kristin; AlSeraihy, Amal; Barriga, Francisco; de Toledo Codina, José Sánchez; Veys, Paul; Boelens, Jaap Jan; Mellgren, Karin; Bittencourt, Henrique; O’Brien, Tracey; Shaw, Peter J.; Chybicka, Alicja; Volt, Fernanda; Giannotti, Federica; Gluckman, Eliane; Kurtzberg, Joanne; Gennery, Andrew R.; Rocha, Vanderson

    2017-01-01

    Wiskott-Aldrich syndrome is a severe X-linked recessive immune deficiency disorder. A scoring system of Wiskott-Aldrich syndrome severity (0.5–5) distinguishes two phenotypes: X-linked thrombocytopenia and classic Wiskott-Aldrich syndrome. Hematopoietic cell transplantation is curative for Wiskott-Aldrich syndrome; however, the use of unrelated umbilical cord blood transplantation has seldom been described. We analyzed umbilical cord blood transplantation outcomes for 90 patients. The median age at umbilical cord blood transplantation was 1.5 years. Patients were classified according to clinical scores [2 (23%), 3 (30%), 4 (23%) and 5 (19%)]. Most patients underwent HLA-mismatched umbilical cord blood transplantation and myeloablative conditioning with anti-thymocyte globulin. The cumulative incidence of neutrophil recovery at day 60 was 89% and that of grade II–IV acute graft-versus-host disease at day 100 was 38%. The use of methotrexate for graft-versus-host disease prophylaxis delayed engraftment (P=0.02), but decreased acute graft-versus-host disease (P=0.03). At 5 years, overall survival and event-free survival rates were 75% and 70%, respectively. The estimated 5-year event-free survival rates were 83%, 73% and 55% for patients with a clinical score of 2, 4–5 and 3, respectively. In multivariate analysis, age <2 years at the time of the umbilical cord blood transplant and a clinical phenotype of X-linked thrombocytopenia were associated with improved event-free survival. Overall survival tended to be better in patients transplanted after 2007 (P=0.09). In conclusion, umbilical cord blood transplantation is a good alternative option for young children with Wiskott-Aldrich syndrome lacking an HLA identical stem cell donor. PMID:28255019

  10. Effects of human umbilical cord mesenchymal stem cells therapy on CD61,CD62P and CD54 in elderly patients with old myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    李侠

    2013-01-01

    Objective To study the effects of human umbilical cord mesenchymal stem cells (hUCM-SCs) therapy on peripheral blood CD61,CD62P and CD54 in elderly patients with old myocardial infarction.Methods From July2010 to August 2012,30 elderly patients with old myocardial infarction were randomly selected.Patients were

  11. Cord blood IgE. I. IgE screening in 2814 newborn children

    DEFF Research Database (Denmark)

    Hansen, L G; Høst, A; Halken, S;

    1992-01-01

    Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). 48.6% of the sera contained less IgE than the detection limit 0.1 kU/l. Cord blood IgE values greater than or equal to 0.5 kU/l were......E values in the autumn was found. No correlation between cord blood IgE and birth weight or gestational age was demonstrated. Only few newborns had cord blood IgA values greater than 0.014 g/l, calculated as geometric mean cord blood IgA + 2 SD among children with no detectable cord blood IgE, indicating...

  12. Blood gas values in clamped and unclamped umbilical cord at birth.

    Science.gov (United States)

    Di Tommaso, Mariarosaria; Seravalli, Viola; Martini, Irene; La Torre, Pasquale; Dani, Carlo

    2014-09-01

    To determine the reliability of the cord blood gas analysis on the unclamped cord compared to the standard technique of sampling on double clamped cord. Prospective observational study conducted on 46 singleton neonates vaginally delivered at term. Matched pairs of umbilical artery and vein blood samples were collected from unclamped cord within 90s after birth and from the same cord after clamping, with the clamping occurring immediately after the first blood collection. A blood gas analysis was performed on each collected sample. Arterial and venous blood samples were analyzed for pH, PO2, pCO2, SaO2, hemoglobin concentration (ctHb) and base excess (BE). The values were compared between the two groups (clamped vs unclamped) using a Wilcoxon test. No significant difference was found in pH, PO2, pCO2, SaO2 and ctHb values on arterial blood between unclamped and clamped cord. The only significant difference was related to BE (pblood, the values of pH, PO2, pCO2 were comparable between unclamped and clamped cord, while the values of SaO2, ctHb and BE were significantly different (pblood gas parameters and in the main venous blood gas parameters between unclamped and clamped cord. Sampling of cord blood for gas analysis may be performed on the unclamped cord right after birth without reducing the accuracy of the analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Lamotrigine in pregnancy - therapeutic drug monitoring in maternal blood, amniotic fluid, and cord blood.

    Science.gov (United States)

    Paulzen, Michael; Lammertz, Sarah E; Veselinovic, Tanja; Goecke, Tamme W; Hiemke, Christoph; Gründer, Gerhard

    2015-09-01

    This study is the first to measure and correlate lamotrigine concentrations in maternal blood, amniotic fluid, and umbilical cord blood and account for distribution of the drug between these three compartments. Concentrations of lamotrigine were measured in six mother-infant pairs at the time of delivery. Daily doses of lamotrigine ranged between 200 and 650 mg. Daily doses were correlated with maternal serum and umbilical cord blood concentrations, and serum levels were correlated with levels in amniotic fluid. Lamotrigine levels in serum correlated strongly with the lamotrigine levels in amniotic fluid (r=+0.986, Pamniotic fluid was in a range between 0.31 and 0.75 (mean 0.58, SD 0.17); the penetration ratio into the fetal circulation, calculated on the basis of umbilical cord blood levels, was found to be in a range between 0.48 and 1.27 (mean 0.81, SD 0.28). Lamotrigine concentrations in amniotic fluid provided evidence that maternally administered lamotrigine is accessible to the fetus in a manner not previously appreciated. Furthermore, the penetration ratio into umbilical cord blood calculated here is in line with the largest study carried out so far to explore transplacental transfer.

  14. Intracerebral transplantation of mesenchymal stem cells derived from human umbilical cord blood for improving the behavioural deficits in rats with Parkinson disease%人脐血间充质干细胞脑内移植改善帕金森病大鼠行为缺陷的研究

    Institute of Scientific and Technical Information of China (English)

    许予明; 邢莹; 杨红旗; 马杰; 孙玲

    2004-01-01

    BACKGROUND: Many researches have proved that cord blood cells can differentiate into neurons, and moreover, there are also reports regarding the successful application of cord blood in the treatments of cerebral apoplexy and other diseases of nervous system. However, it is still unknown whether cord blood stem cells can be used in the treatment of neurodegenerative diseases or not.OBJECTIVE: To investigate the feasibility and the mechanism of mesenchymal stem cells(MSCs) derived from human umbilical cord blood (HUCB) in the treatment of rats with Parkinson disease(PD).DESIGN: A randomized controlled trial.SETTING and MATERIALS: Eighteen healthy Sprague-Dawley (SD) rats of cleanness grade with a body mass from 220 g to 260 g were selected. Cord blood samples were obtained from the Department of Obstetrics and Gynecology of the Third Affiliated Hospital of Zhenzhou University. Each sample had 60 mL to 120 mL of cord blood.INTERVENTION: Lateral PD rat model induced by 6-hydroxydopamine was prepared. Rats were randomly divided into three groups: ① control group (n=6) . ② PBS group (n=6): injection of 10 μL PBS into the right striatum. ③ MSCs group( n = 6): injection of 3 × 106 MSCs( 10 μL) marked with BradU into the right striatum, apomorphine induced rotational behavior was tested after 4 weeks of transplantation, and immunohistochemistry assay was carried out to trace the survival of MSCs and the tyrosine hydroxylase (TH)-immucoreactive cells in the striatum as well.MAIN OUTCOME MEASURES: ① rotation rounds in rats of each group after transplantation. ② the results of immunohistochemistry.RESULTS: MSCs survived in the striatum. The rotational behavior induced by apomorphine in rats of MSCs group[ (212 ± 60) rounds/30 minutes] was significantly improved compared with that of control group[(340±30)rounds/minutes ] ( P < 0.05 ); However, the number of TH-positive cells in the right striatum had no statistical difference between MSCs and control group (P

  15. Cord blood 25(OH)-vitamin D deficiency and childhood asthma, allergy and eczema

    DEFF Research Database (Denmark)

    Chawes, Bo L; Bønnelykke, Klaus; Jensen, Pia F

    2014-01-01

    with respiratory infections or asthma. We saw no association between cord blood 25(OH)-Vitamin D level and lung function, sensitization, rhinitis or eczema. The effects were unaffected from adjusting for multiple lifestyle factors. CONCLUSION: Cord blood 25(OH)-Vitamin D deficiency associated with increased risk...... function and sensitization were performed repeatedly from birth. RESULTS: After adjusting for season of birth, deficient cord blood 25(OH)-Vitamin D level (

  16. Preterm Cord Blood Contains a Higher Proportion of Immature Hematopoietic Progenitors Compared to Term Samples.

    Directory of Open Access Journals (Sweden)

    Marina Podestà

    Full Text Available Cord blood contains high number of hematopoietic cells that after birth disappear. In this paper we have studied the functional properties of the umbilical cord blood progenitor cells collected from term and preterm neonates to establish whether quantitative and/or qualitative differences exist between the two groups.Our results indicate that the percentage of total CD34+ cells was significantly higher in preterm infants compared to full term: 0.61% (range 0.15-4.8 vs 0.3% (0.032-2.23 p = 0.0001 and in neonates <32 weeks of gestational age (GA compared to those ≥32 wks GA: 0.95% (range 0.18-4.8 and 0.36% (0.15-3.2 respectively p = 0.0025. The majority of CD34+ cells co-expressed CD71 antigen (p<0.05 preterm vs term and grew in vitro large BFU-E, mostly in the second generation. The subpopulations CD34+CD38- and CD34+CD45- resulted more represented in preterm samples compared to term, conversely, Side Population (SP did not show any difference between the two group. The absolute number of preterm colonies (CFCs/10microL resulted higher compared to term (p = 0.004 and these progenitors were able to grow until the third generation maintaining an higher proportion of CD34+ cells (p = 0.0017. The number of colony also inversely correlated with the gestational age (Pearson r = -0.3001 p<0.0168.We found no differences in the isolation and expansion capacity of Endothelial Colony Forming Cells (ECFCs from cord blood of term and preterm neonates: both groups grew in vitro large number of endothelial cells until the third generation and showed a transitional phenotype between mesenchymal stem cells and endothelial progenitors (CD73, CD31, CD34 and CD144The presence, in the cord blood of preterm babies, of high number of immature hematopoietic progenitors and endothelial/mesenchymal stem cells with high proliferative potential makes this tissue an important source of cells for developing new cells therapies.

  17. Neural stem cell transplantation in the repair of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Neural stem cells are a pronising candidate for neural transplantation aimed at neural cell replacement and repair of the damaged host central nervous system (CNS). Recent studies using neural stem cells have shown that implanted neural stem cells can effectively incorporate into the damaged CNS and differentiate into neurons, astrocytes, and oligodendrocytes. The recent explosion in the field of neural stem cell research has provided insight into the inductive factors influencing neural stem cell differentiation and may yield potential therapies for several neurological disorders, including spinal cord injury. In this review, we summarize recent studies involving neural stem cell biology in both rodents and humans. We also discuss unique advantages and possible mechanisms of using neural stem cell trans plantation in the repair of spinal cord injury.

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

    Directory of Open Access Journals (Sweden)

    Guang-ping Ruan

    2014-01-01

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

  19. Autoimmune Demyelinating Polyneuropathy as a Manifestation of Chronic Graft-versus-Host Disease after Adult Cord Blood Transplantation in a Patient with Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Fredrick Hogan

    2014-01-01

    Full Text Available Immune mediated demyelinating disease after allogeneic stem cell transplantation is a rare entity with unclear etiology. Acute inflammatory demyelinating polyneuropathy (AIDP has been reported after related and adult unrelated allogeneic stem cell transplantation but no such case has been reported after unrelated cord blood transplantation. We hereby present the first case of AIDP after double umbilical cord blood transplantation (DUCBT. A 55-year-old man with chronic lymphocytic leukemia (CLL received a cord blood transplant for relapsed refractory disease with high risk cytogenetics. On day 221, patient presented with skin rash, tingling in both lower extremites, and ascending paralysis that progressed rapidly over the course of 2 days. The workup resulted in a diagnosis of AIDP and administration of intravenous immunoglobulins plus steroids was initiated. Motor and sensory powers were fully recovered and his chronic GVHD was managed for several months with single agent sirolimus.

  20. Pregnancy hypertension and umbilical cord blood lead levels

    Energy Technology Data Exchange (ETDEWEB)

    Rabinowitz, M.; Bellinger, D.; Leviton, A. (Children' s Hospital, Boston, MA (USA)); Needleman, H. (Children' s Hospital, Pittsburgh, PA (USA)); Schoenbaum, S. (Harvard Community Health Plan, Brookline Village, MA (USA))

    Pregnancy hypertension, blood pressure during labor, and the umbilical cord blood lead concentration were assessed in 3,851 women for whom additional demographic, medical, and personal information was available. Lead levels correlated with both systolic and diastolic blood pressure during labor. The incidence of clinically defined pregnancy hypertension, nearly 11% overall, increased with lead level. A series of multivariate models of pregnancy hypertension and of systolic blood pressure as a function of maternal age, parity, hematocrit, ponderal index, race, season, and diabetes were improved by including lead as a predictor variable. These other risk factors are not affected by the lead term. The relative risk for pregnancy hypertension doubles when lead increases from 2 to 15 {mu}g/dl. The effect is statistically strong, with a magnitude of about 3 mm for a 10 {mu}g/dl range, about the same magnitude associated with diabetes. At these observed levels (mean blood lead = 6.0 {mu}g/dl, SD = 3.3, range 0 > 35), not currently recognized as overtly toxic, lead has a small but demonstrable association with pregnancy hypertension and blood pressure at the time of delivery, but not with pre-eclampsia nor toxemia. Although this association is not likely to influence the clinical management of hypertension, it indicates that lead at typical contemporary urban levels, does effect multiple physiological functions.

  1. TRAV and TRBV repertoire, clonality and the proliferative history of umbilical cord blood T-cells.

    Science.gov (United States)

    Li, Yangqiu; Chen, Shaohua; Yang, Lijian; Yin, Qingsong; Geng, Suxia; Wu, Xiuli; Schmidt, Christian A; Przybylski, Grzegorz K

    2007-11-01

    Umbilical cord blood (CB) has been used successfully as a source of hematopoietic stem cells for transplantation. But the distribution and clonality of T-cell receptor alpha variable region (TRAV) and T-cell receptor beta variable region (TRBV) subfamily T-cells, the naïve T-cells level and the diversity of thymic recent output function in CB has not been yet clearly defined. In order to characterize the repertoire of CB T-cells, the CDR3 of 29 TRAV and 24 TRBV subfamily genes were analyzed in T-cells from 12 cord blood samples, using RT-PCR and genescan technique. To determine the proliferative history of CB T-cells, quantitative analysis of deltaRec-psiJalpha signal joint T-cell receptor excision circles (sjTRECs) was performed in mononuclear cells, CD3+, CD4+ and CD8+ T-cells from 20 CB samples by real-time PCR. In addition the analysis of 23 TRBV-TRBD1 sjTRECs in 10 cases of CB CD4+ T-cells and CB CD8+ T-cells was performed by semi-nested PCR. We found a marked restriction of TRBV expression pattern in CBMCs compared to peripheral blood mononuclear cells (PBMC), which expressed all 24 TRBV genes. All PCR products of TRAV and TRBV subfamilies from CB, except for 3 cases, displayed polyclonal rearrangement pattern. The deltaRec-psiJalpha sjTRECs counts were significantly higher in CB, than in PB samples. Also the number of detectable TRBV sjTRECs was higher in CB than in peripheral blood. In conclusion, our results indicate polyclonal but restricted repertoire and a very short proliferative history of CB T-cells. The incomplete repertoire and naivety of CB T-cells might be the reason that CB hematopoietic stem cells transplant recipients are less likely to develop graft vs host disease.

  2. A comparative study of the protein C system in mother's blood, cord blood and amniotic fluid.

    OpenAIRE

    Ewa Zekanowska; Waldemar Uszyński; Mieczysław Uszyński; Jarosław Kuczyński; Marek Szymański

    2010-01-01

    Activated protein C (APC) is an important anticoagulant which plays a role in pathophysiology of pregnancy, e.g. in maintenance of the uteroplacental circulation and development of the fetus as well as in pathogenesis of preeclampsia. The study objective was to compare the levels of the respective components of the protein C system (protein C, PC; protein S, PS; thrombomodulin, TM) as well as thrombin activatable fibrinolysis inhibitor - TAFI in mother's blood, cord blood and amniotic fluid. ...

  3. Unrelated umbilical cord blood transplant for adult acute lymphoblastic leukemia in first and second complete remission: a comparison with allografts from adult unrelated donors

    Science.gov (United States)

    Marks, David I.; Woo, Kwang Ahn; Zhong, Xiaobo; Appelbaum, Frederick R.; Bachanova, Veronika; Barker, Juliet N.; Brunstein, Claudio G.; Gibson, John; Kebriaei, Partow; Lazarus, Hillard M.; Olsson, Richard; Perales, Miguel-Angel; Pidala, Joseph; Savani, Bipin; Rocha, Vanderson; Eapen, Mary

    2014-01-01

    Allogeneic hematopoietic cell transplantation has an established role in the treatment of adults with acute lymphoblastic leukemia whose survival when recipients of grafts from adult unrelated donors approaches that of recipients of grafts from sibling donors. Our aim was to determine the role of mismatched unrelated cord blood grafts in transplantation for 802 adults with acute lymphoblastic leukemia in first or second complete remission. Using Cox regression we compared outcomes after 116 mismatched single or double cord blood transplants, 546 peripheral blood progenitor cell transplants and 140 bone marrow transplants. The characteristics of the recipients and their diseases were similar except cord blood recipients were younger, more likely to be non-Caucasians and more likely to have a low white blood cell count at diagnosis. There were differences in donor-recipient human leukocyte antigen-match depending on the source of the graft. Most adult donor transplants were matched at the allele-level considering human leukocyte antigens-A, -B, -C and –DRB1. In contrast, most cord blood transplants were mismatched and considered antigen-level matching; 57% were mismatched at two loci and 29% at one locus whereas only 29% of adult donor transplants were mismatched at one locus and none at two loci. There were no differences in the 3-year probabilities of survival between recipients of cord blood (44%), matched adult donor (44%) and mismatched adult donor (43%) transplants. Cord blood transplants engrafted slower and were associated with less grade 2–4 acute but similar chronic graft-versus-host disease, relapse, and transplant-related mortality. The survival of cord blood graft recipients was similar to that of recipients of matched or mismatched unrelated adult donor grafts and so cord blood should be considered a valid alternative source of stem cells for adults with acute lymphoblastic leukemia in the absence of a matched unrelated adult donor. PMID:24056817

  4. Sangue de cordão umbilical para uso autólogo ou grupo de pacientes especiais The potential therapeutic use of cord blood in autologous transplants or in special patients: a review and update

    Directory of Open Access Journals (Sweden)

    Luis Eduardo Cruz

    2009-05-01

    Full Text Available O sangue de cordão umbilical e placentário (SCUP é uma rica fonte de células-tronco (CT hematopoéticas e é amplamente utilizado como substituto da medula óssea em casos de transplante. As células do SCUP possuem vantagens sobre as células da medula óssea (MO, principalmente por serem mais jovens e apresentarem maior taxa proliferativa. Além dos progenitores hematopoéticos, o sangue de cordão umbilical contém progenitores endoteliais e mesenquimais, sugerindo sua possível aplicação nos novos protocolos de terapia celular para diferentes tecidos. Na presente revisão, discutimos a importância do armazenamento do sangue de cordão umbilical autólogo e as pesquisas desenvolvidas para a sua aplicação em doenças degenerativas.Umbilical Cord Blood is a rich source of hematopoietic stem cells widely used as a substitute of bone marrow (BM in transplants. Cells from umbilical cord blood present advantages over BM cells, mainly as they are younger and a have higher proliferative rate. Besides hematopoietic stem cells, umbilical cord blood contains endothelial and mesenchymal progenitor cells, suggesting their possible application in cell therapy protocols for different tissues. In this paper, we discuss the importance of autologous umbilical cord blood storage and the research on stem cell transplantation for degenerative diseases.

  5. Good practices in collecting umbilical cord and placental blood.

    Science.gov (United States)

    Lopes, Lauren Auer; Bernardino, Elizabeth; Crozeta, Karla; Guimarães, Paulo Ricardo Bittencourt

    2016-08-18

    to identify the factors related to the quality of umbilical cord and placental blood specimens, and define best practices for their collection in a government bank of umbilical cord and placental blood. this was a descriptive study, quantitative approach, performed at a government umbilical cord and placental blood bank, in two steps: 1) verification of the obstetric, neonatal and operational factors, using a specific tool for gathering data as non-participant observers; 2) definition of best practices by grouping non-conformities observed before, during and after blood collection. The data was analyzed using descriptive statistics and the following statistical software: Statistica(r) and R(r). while there was a correlation with obstetrical and neonatal factors, there was a larger correlation with operational factors, resulting in the need to adjust the professional practices of the nursing staff and obstetrical team involved in collecting this type of blood. Based on these non-conformities we defined best practices for nurses before, during and after blood collection. the best practices defined in this study are an important management tool for the work of nurses in obtaining blood specimens of high cell quality. identificar fatores relacionados à qualidade das amostras do sangue de cordão umbilical e placentário e definir boas práticas para sua coleta em um banco público de sangue de cordão umbilical e placentário. pesquisa descritiva, abordagem quantitativa, realizada em um banco público de sangue de cordão umbilical e placentário, desenvolvida em duas etapas: 1) verificação dos fatores obstétricos, neonatais e operacionais, obtidos por coleta em instrumento próprio e observação não participante; 2) definição das boas práticas, por meio do agrupamento de não-conformidades observadas antes, durante e após a coleta do sangue. Os dados foram analisados por meio da estatística descritiva, utilizando-se dos softwares Statistica(r) e R(r). houve

  6. 脐血干细胞移植对失代偿期肝硬化肝功能及血流动力学的影响%Effect of liver volume and liver hemodynamics of human umbilical cord blood stem cell transplantation on decompen-sated cirrhosis

    Institute of Scientific and Technical Information of China (English)

    王可敬; 罗晓红; 孙厚坦; 王方; 包建涛

    2014-01-01

    Objective To observe the therapeutic effect of umbilical cord blood stem cells transplantation in the treat -ment of decompensated cirrhosis of the liver and the effects on liver hemodynamics .Methods 30 cases of patients with de-compensated liver cirrhosis as treatment group , underwent the proper hepatic artery allogeneic umbilical cord blood stem cell transplantation;chosen the data matched 20 cases of patients with decompensated cirrhosis who did not receive the injection of umbilical cord blood stem cells treatment as the control group .Liver function , coagulation function , hemodynamics of portal vein, B ultrasound contrast agent was compared between the 2 groups of patients .The time of the liver volume and other indi-cators, the clinical symptoms and adverse reaction were observed .Results The success rate of intrahepatic umbilical cord blood stem cell transplantation was 100%in the treatment group , no adverse reaction and complication were occurred. Com-pared with before treatment, after the treatment in the 2 groups, 3, 6 months of glutamate aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb) were improved ( P 0.05).Thromboplastin time (APTT) and prothrombin time (TT) after transplantation showed a decreasing trend , but with no significant difference before transplantation , the control group had no significant changes ( P >0.05).Compared with before treatment, 2 groups of portal vein diameter (DPV), splenic vein (DSV), portal vein flow velocity (PVX), splenic vein (SVV), portal venous blood flow (QPV), splenic vein blood flow (QSV) did not show statistically significant differences ( P >0.05).After treatment, 2 groups of liver volume were showing increasing trend, but no significant difference were found ( P >0.05).Compared with before treatment, umbilical cord blood stem cell transplantation, the treatment group contrast agent subsided significantly slow down ( P <0.05), compared with the control group, a statistically significant

  7. Repair of injured spinal cord using biomaterial scaffolds and stem cells.

    Science.gov (United States)

    Shrestha, Bikesh; Coykendall, Katherine; Li, Yongchao; Moon, Alex; Priyadarshani, Priyanka; Yao, Li

    2014-08-01

    The loss of neurons and degeneration of axons after spinal cord injury result in the loss of sensory and motor functions. A bridging biomaterial construct that allows the axons to grow through has been investigated for the repair of injured spinal cord. Due to the hostility of the microenvironment in the lesion, multiple conditions need to be fulfilled to achieve improved functional recovery. A scaffold has been applied to bridge the gap of the lesion as contact guidance for axonal growth and to act as a vehicle to deliver stem cells in order to modify the microenvironment. Stem cells may improve functional recovery of the injured spinal cord by providing trophic support or directly replacing neurons and their support cells. Neural stem cells and mesenchymal stem cells have been seeded into biomaterial scaffolds and investigated for spinal cord regeneration. Both natural and synthetic biomaterials have increased stem cell survival in vivo by providing the cells with a controlled microenvironment in which cell growth and differentiation are facilitated. This optimal multi‒disciplinary approach of combining biomaterials, stem cells, and biomolecules offers a promising treatment for the injured spinal cord.

  8. Visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury

    Directory of Open Access Journals (Sweden)

    Rui-ping Zhang

    2015-01-01

    Full Text Available An important factor in improving functional recovery from spinal cord injury using stem cells is maximizing the number of transplanted cells at the lesion site. Here, we established a contusion model of spinal cord injury by dropping a weight onto the spinal cord at T 7-8 . Superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells were transplanted into the injured spinal cord via the subarachnoid space. An outer magnetic field was used to successfully guide the labeled cells to the lesion site. Prussian blue staining showed that more bone marrow mesenchymal stem cells reached the lesion site in these rats than in those without magnetic guidance or superparamagnetic iron oxide labeling, and immunofluorescence revealed a greater number of complete axons at the lesion site. Moreover, the Basso, Beattie and Bresnahan (BBB locomotor rating scale scores were the highest in rats with superparamagnetic labeling and magnetic guidance. Our data confirm that superparamagnetic iron oxide nanoparticles effectively label bone marrow mesenchymal stem cells and impart sufficient magnetism to respond to the external magnetic field guides. More importantly, superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells can be dynamically and non-invasively tracked in vivo using magnetic resonance imaging. Superparamagnetic iron oxide labeling of bone marrow mesenchymal stem cells coupled with magnetic guidance offers a promising avenue for the clinical treatment of spinal cord injury.

  9. Delayed Umbilical Cord