Comparison of survival outcome between donor types or stem cell sources for childhood acute myeloid leukemia after allogenic hematopoietic stem cell transplantation: A multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology-oncology.

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Shim, Ye Jee; Lee, Jae Min; Kim, Heung Sik; Jung, Nani; Lim, Young Tak; Yang, Eu Jeen; Hah, Jeong Ok; Lee, Young-Ho; Chueh, Hee Won; Lim, Jae Young; Park, Eun Sil; Park, Jeong A; Park, Ji Kyoung; Park, Sang Kyu

2018-06-19

We compared transplant outcomes between donor types and stem cell sources for childhood acute myeloid leukemia (AML). The medical records of children with AML in the Yeungnam region of Korea from January 2000 to June 2017 were reviewed. In all, 76 children with AML (male-to-female ratio = 46:30) received allogenic hematopoietic stem cell transplantation (allo-HSCT). In total, 29 patients received HSCT from either a matched-related donor or a mismatched-related donor, 32 patients received an unrelated donor, and 15 patients received umbilical cord blood. In term of stem cell sources, bone marrow was used in 15 patients and peripheral blood in 46 patients. For all HSCT cases, the 5-year overall survival (OS) was 73.1% (95% CI: 62.7-83.5) and the 5-year event-free survival (EFS) was 66.1% (95% CI: 54.5-77.7). There was no statistical difference in 5-year OS according to the donor types or stem cell sources (P = .869 and P = .911). There was no statistical difference in 5-year EFS between donor types or stem cell sources (P = .526 and P = .478). For all HSCT cases, the 5-year relapse rate was 16.1% (95% CI: 7.3-24.9) and the 5-year non-relapse mortality (NRM) was 13.3% (95% CI: 5.1-21.5). There was no statistical difference in the 5-year relapse rate according to the donor types or stem cell sources (P = .971 and P = .965). There was no statistical difference in the 5-year NRM between donor types or stem cell sources (P = .461 and P = .470). © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Analysis of the results of allogeneic hematopoietic stem cell transplantation depending on HLA matching of the unrelated donor / recipient pair

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Ye. V. Kuzmich

2015-01-01

Full Text Available HLA matching of the donor / recipient pair is a major factor associated with the outcome of allogeneic stem cell transplantation. In the presentstudy we analyzed the risk of severe acute graft-versus-host disease, graft failure, 2.year overall survival of the patients after allogeneic stem cell transplantation depending on HLA matching of the unrelated donor / recipient pair.

Identification of a murine CD45-F4/80lo HSC-derived marrow endosteal cell associated with donor stem cell engraftment.

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Overholt, Kathleen M; Otsuru, Satoru; Olson, Timothy S; Guess, Adam J; Velazquez, Victoria M; Desbourdes, Laura; Dominici, Massimo; Horwitz, Edwin M

2017-12-26

Hematopoietic stem cells (HSCs) reside in specialized microenvironments within the marrow designated as stem cell niches, which function to support HSCs at homeostasis and promote HSC engraftment after radioablation. We previously identified marrow space remodeling after hematopoietic ablation, including osteoblast thickening, osteoblast proliferation, and megakaryocyte migration to the endosteum, which is critical for effective engraftment of donor HSCs. To further evaluate the impact of hematopoietic cells on marrow remodeling, we used a transgenic mouse model (CD45Cre/iDTR) to selectively deplete hematopoietic cells in situ. Depletion of hematopoietic cells immediately before radioablation and hematopoietic stem cell transplantation abrogated donor HSC engraftment and was associated with strikingly flattened endosteal osteoblasts with preserved osteoblast proliferation and megakaryocyte migration. Depletion of monocytes, macrophages, or megakaryocytes (the predominant hematopoietic cell populations that survive short-term after irradiation) did not lead to an alteration of osteoblast morphology, suggesting that a hematopoietic-derived cell outside these lineages regulates osteoblast morphologic adaptation after irradiation. Using 2 lineage-tracing strategies, we identified a novel CD45 - F4/80 lo HSC-derived cell that resides among osteoblasts along the endosteal marrow surface and, at least transiently, survives radioablation. This newly identified marrow cell may be an important regulator of HSC engraftment, possibly by influencing the shape and function of endosteal osteoblasts.

Donor characteristics and hematopoietic stem cell transplantation outcome: experience of a single center in Southern Brazil

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Alessandra Paz

2018-04-01

Full Text Available Background: Hematopoietic stem cell transplantation is a curative treatment for many patients with hematological disorders. Donor–recipient genetic disparity, especially involving the human leukocyte antigen system is a critical factor for transplant outcome. Objective: To evaluate retrospectively donor characteristics and correlations with the occurrence of acute and chronic graft-versus-host disease, disease-free survival and overall survival in a Brazilian population submitted to allogeneic hematopoietic stem cell transplantation between 1994 and 2012 in a single center. Results: Three hundred and forty-seven consecutive transplantations were included. Related transplants (81.2% were significantly more common than unrelated transplants (18.7%; donor and recipient median ages were 34 (range: 1–61 and 33 (range: 3–65 years respectively with donor HLAs being matched for 333 (95.9% patients. Donor gender, cytomegalovirus status and ABO incompatibility did not influence the five-year overall survival. In univariate analyses, overall survival was negatively influenced by the presence of acute graft-versus-host disease (33% vs. 47%, respectively; p-value = 0.04, unrelated transplant (41.5% vs. 50.9%, respectively; p-value = 0.045 and donors aged over 40 years (41% vs. 52%, respectively; p-value = 0.03. Older donors were associated with a higher rate of acute (52% vs. 65.8%; p-value = 0.03 and chronic graft-versus-host disease (60% vs. 43%, respectively; p-value = 0.015. In multivariate analyses, acute graft-versus-host disease [relative risk (RR: 1.8; 95% confidence interval (CI: 1.1–29; p-value = 0.008] and older donors (RR: 1.6; 95% CI 1.11–2.24; p-value = 0.013 were associated with higher transplant-related mortality. Conclusions: In transplant patients, to have a donor older than 40 years of age seems to significantly increase the incidence of acute and chronic graft-versus-host disease and transplant-related mortality

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

International Nuclear Information System (INIS)

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

1987-01-01

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

Having a sibling as donor: patients' experiences immediately before allogeneic hematopoietic stem cell transplantation.

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Kisch, Annika; Bolmsjö, Ingrid; Lenhoff, Stig; Bengtsson, Mariette

2014-08-01

Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential cure for a variety of diseases but is also associated with significant risks. With HSCT the donor is either a relative, most often a sibling, or an unrelated registry donor. The aim was to explore patients' experiences, immediately before transplantation, regarding having a sibling as donor. Ten adult patients with sibling donors were interviewed before admission for HSCT. The interviews were digitally recorded, transcribed verbatim and subjected to qualitative content analysis. The main theme Being in no man's land is a metaphor for the patients' complex situation with its mixture of emotions and thoughts prior to transplantation. The three subthemes Trust in the sibling donor, Concern about others and Loss of control cover the various experiences. The patient's experiences are influenced by their personal situation and the quality of the relationship with the sibling donor. While patients feel secure in having a sibling donor, they are dependent for their survival on the cell donation and feel responsible for the donor's safety during donation. These emotions intensify the patients' sense of dependency and loss of control. In caring for HSCT patients the nurses should be aware of the complexity of the patients' situation and keep in mind that having a sibling donor might imply extra pressure, including a sense of responsibility. Caring for both patients and sibling donors optimally is a challenge, which needs further improvement and exploration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Through the eyes of young sibling donors: the hematopoietic stem cell donation experience.

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D'Auria, Jennifer P; Fitzgerald, Tania M; Presler, Cammie M; Kasow, Kimberly A

2015-01-01

This qualitative study used a grounded theory approach to explore how pediatric sibling donors of a successful hematopoietic stem cell transplantation conceptualized their donation experiences. Saving my sister's (or brother's) life describes the central phenomenon identified by this purposive sample of 8 sibling donors. Five themes captured their memories: being the perfect match, stepping up, worrying about the outcome, the waiting process, and sharing a special bond. Further research surrounding changes in relational issues will provide insight into inter-sibling support and the developmental course of the sibling relationship into adulthood when intensified by a health crisis. Copyright © 2015 Elsevier Inc. All rights reserved.

Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen

DEFF Research Database (Denmark)

Rodrigues, Celso Arrais; Rocha, Vanderson; Dreger, Peter

2014-01-01

We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received...... an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97......%, respectively; Pblood than after matched unrelated donor, whereas no differences were observed in grade II-IV acute graft-versus-host disease (29% vs. 32%), non-relapse mortality (29% vs. 28...

Motivations, experiences, and perspectives of bone marrow and peripheral blood stem cell donors: thematic synthesis of qualitative studies.

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Garcia, Maria C; Chapman, Jeremy R; Shaw, Peter J; Gottlieb, David J; Ralph, Angelique; Craig, Jonathan C; Tong, Allison

2013-07-01

Hematopoietic stem cell (HSC) transplantation using bone marrow and peripheral blood stem cells is a lifesaving treatment for patients with leukemia or other blood disorders. However, donors face the risk of physical and psychosocial complications. We aimed to synthesize qualitative studies on the experiences and perspectives of HSC donors. We searched MEDLINE, Embase, PsycINFO, CINAHL, Google Scholar, and reference lists of relevant articles to November 13, 2012. Thematic synthesis was used to analyze the findings. Thirty studies involving 1552 donors were included. The decision to donate included themes of saving life, family loyalty, building a positive identity, religious conviction, fear of invasive procedures, and social pressure and obligation. Five themes about the donation experience were identified: mental preparedness (pervasive pain, intense disappointment over recipient death, exceeding expectations, and valuing positive recipient gains), burden of responsibility (striving to be a quality donor, unresolved guilt, and exacerbated grief), feeling neglected (medical dismissiveness and family inattention), strengthened relationships (stronger family ties, establishing blood bonds), and personal sense of achievement (satisfaction and pride, personal development, hero status, and social recognition). Although HSC donation was appreciated as an opportunity to save life, some donors felt anxious and unduly compelled to donate. HSC donors became emotionally invested and felt responsible for their recipient's outcomes and were profoundly grieved and disappointed if the transplantation was unsuccessful. To maximize donor satisfaction and mitigate the psychosocial risks for HSC donors, strategies to address the emotional challenges of anxiety, sense of coercion, guilt, and grief in donors are warranted. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Age Is Relative—Impact of Donor Age on Induced Pluripotent Stem Cell-Derived Cell Functionality

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Elisabeth Tamara Strässler

2018-01-01

Full Text Available Induced pluripotent stem cells (iPSCs avoid many of the restrictions that hamper the application of human embryonic stem cells: limited availability of source material due to legal restrictions in some countries, immunogenic rejection and ethical concerns. Also, the donor’s clinical phenotype is often known when working with iPSCs. Therefore, iPSCs seem ideal to tackle the two biggest tasks of regenerative medicine: degenerative diseases with genetic cause (e.g., Duchenne’s muscular dystrophy and organ replacement in age-related diseases (e.g., end-stage heart or renal failure, especially in combination with recently developed gene-editing tools. In the setting of autologous transplantation in elderly patients, donor age becomes a potentially relevant factor that needs to be assessed. Here, we review and critically discuss available data pertinent to the questions: How does donor age influence the reprogramming process and iPSC functionality? Would it even be possible to reprogram senescent somatic cells? How does donor age affect iPSC differentiation into specialised cells and their functionality? We also identify research needs, which might help resolve current unknowns. Until recently, most hallmarks of ageing were attributed to an accumulation of DNA damage over time, and it was thus expected that DNA damage from a somatic cell would accumulate in iPSCs and the cells derived from them. In line with this, a decreased lifespan of cloned organisms compared with the donor was also observed in early cloning experiments. Therefore, it was questioned for a time whether iPSC derived from an old individual’s somatic cells would suffer from early senescence and, thus, may not be a viable option either for disease modelling nor future clinical applications. Instead, typical signs of cellular ageing are reverted in the process of iPSC reprogramming, and iPSCs from older donors do not show diminished differentiation potential nor do i

Long-term human immune system reconstitution in non-obese diabetic (NOD)-Rag (-)-γ chain (-) (NRG) mice is similar but not identical to the original stem cell donor.

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Harris, D T; Badowski, M; Balamurugan, A; Yang, O O

2013-12-01

The murine immune system is not necessarily identical to it human counterpart, which has led to the construction of humanized mice. The current study analysed whether or not a human immune system contained within the non-obese diabetic (NOD)-Rag1(null) -γ chain(null) (NRG) mouse model was an accurate representation of the original stem cell donor and if multiple mice constructed from the same donor were similar to one another. To that end, lightly irradiated NRG mice were injected intrahepatically on day 1 of life with purified cord blood-derived CD34(+) stem and progenitor cells. Multiple mice were constructed from each cord blood donor. Mice were analysed quarterly for changes in the immune system, and followed for periods up to 12 months post-transplant. Mice from the same donor were compared directly with each other as well as with the original donor. Analyses were performed for immune reconstitution, including flow cytometry, T cell receptor (TCR) and B cell receptor (BCR) spectratyping. It was observed that NRG mice could be 'humanized' long-term using cord blood stem cells, and that animals constructed from the same cord blood donor were nearly identical to one another, but quite different from the original stem cell donor immune system. © 2013 British Society for Immunology.

[The contribution of persuasion social psychology to the retention of donors: the impact of labelling the previous donation].

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Callé, N; Plainfossé, C; Georget, P; Sénémeaud, C; Rasonglès, P

2011-12-01

The supply of blood cell products requires from the National French Blood Institute (Établissement Français du Sang - EFS) to rely upon regular blood donors. Contact with donors, tailored to individuals as much as possible, helps them to donate on a regular basis. Within the context of a research program conducted with the Psychology Department of the Université de Caen Basse-Normandie, persuasive theoretical models from social psychology have been tested. These models allow adapting messages according to the motivation of donors. The content is centred on the previous donation, differently labelled according to two types of labelling: functional labelling and social labelling. Functional labelling points out the efficiency of what "has been done" (the previous blood donation), whereas social labelling emphasizes the social value of the individual. Different types of mailing invitations have been sent to 1917 donors from the Normandy database, invited to three different blood collections. Every experimental letter worked better than the standard EFS letter (which was used as the "control" letter) in terms of effective blood donation after reception of the letter. Some of the letters are more efficient in motivating donors than other ones. The letters labelling the previous blood donation as functional (efficiency of the donation) appeared more efficient than those with social label (social value) in whichever motivation induced. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Crossing the Ts by case-story “Exploring moral distress in potential sibling stem cell donors"

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Kaltoft, Mette Kjer

Crossing the Ts by Exploring moral distress in potential sibling stem cell donors [1] Mette Kjer Kaltoft, Ph.d student, MPH, RN, Health Visitor University of Southern Denmark and Sydney School of Public Health Background: Catalysts aiming to reduce the burden of malignant disease by integrating...... off the benefits and harms specific to each stakeholder-context may increase live and posthumous donations without inflicting preventable harm. Reference: [1] Exploring moral distress in potential sibling stem cell donors, Nursing Ethics 20(2) 178-188, 2012 Begley A, Virtual University of Uganda......-type-test’) for enhanced decision quality and reduction of harm. Methods: A *case-story of siblings of a sick brother needing live donation is presented within an interactive model for prescriptive translation using a diagram and multi-criteria decision-analytic approach. Actual or projected results: You can see each...

Dengue Virus Transmission by Blood Stem Cell Donor after Travel to Sri Lanka; Germany, 2013

Centers for Disease Control (CDC) Podcasts

2014-09-22

Dr. Mike Miller reads an abridged version of the article, Dengue Virus Transmission by Blood Stem Cell Donor after Travel to Sri Lanka; Germany, 2013.  Created: 9/22/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 10/8/2014.

Modeling coverage gaps in haplotype frequencies via Bayesian inference to improve stem cell donor selection.

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Louzoun, Yoram; Alter, Idan; Gragert, Loren; Albrecht, Mark; Maiers, Martin

2018-05-01

Regardless of sampling depth, accurate genotype imputation is limited in regions of high polymorphism which often have a heavy-tailed haplotype frequency distribution. Many rare haplotypes are thus unobserved. Statistical methods to improve imputation by extending reference haplotype distributions using linkage disequilibrium patterns that relate allele and haplotype frequencies have not yet been explored. In the field of unrelated stem cell transplantation, imputation of highly polymorphic human leukocyte antigen (HLA) genes has an important application in identifying the best-matched stem cell donor when searching large registries totaling over 28,000,000 donors worldwide. Despite these large registry sizes, a significant proportion of searched patients present novel HLA haplotypes. Supporting this observation, HLA population genetic models have indicated that many extant HLA haplotypes remain unobserved. The absent haplotypes are a significant cause of error in haplotype matching. We have applied a Bayesian inference methodology for extending haplotype frequency distributions, using a model where new haplotypes are created by recombination of observed alleles. Applications of this joint probability model offer significant improvement in frequency distribution estimates over the best existing alternative methods, as we illustrate using five-locus HLA frequency data from the National Marrow Donor Program registry. Transplant matching algorithms and disease association studies involving phasing and imputation of rare variants may benefit from this statistical inference framework.

Alternative donor transplantation--"mixing and matching": the role of combined cord blood and haplo-identical donor transplantation (haplo-cord SCT) as a treatment strategy for patients lacking standard donors?

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Liu, Hongtao; van Besien, Koen

2015-03-01

In the past decade, haplo-cord stem cell transplantation (SCT) using myeloablative or reduced intensive conditioning regimens has been shown to result in reliable and fast engraftment of neutrophils and platelets comparable to HLA-matched donors and much faster than after cord stem cell transplant. Haplo-cord SCT also has a low incidence of early non-relapse mortality, low incidences of acute and chronic graft-vs-host disease (GVHD), and excellent graft-vs-leukemia (GVL) effects. Favorable long-term outcomes for high-risk patients with hematologic malignancies have been reported, including older patients. Haplo-cord SCT will likely overcome the limitations of cell dose during cord stem cell selection and might significantly expand the use of cord stem cell transplant in the adult population. The comparable survival outcomes of matched related donor (MRD), matched unrelated donor (MUD), and haplo-cord stem cell transplant strongly argue that haplo-cord SCT should be considered as effective alternative stem cell transplant for high-risk patients lacking standard donors. Further improvement in supportive care and incorporation of a better understanding of the human fetal immune development into the haplo-cord SCT are required to further improve this strategy.

Effectiveness of Visual Methods in Information Procedures for Stem Cell Recipients and Donors

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Çağla Sarıtürk

2017-12-01

Full Text Available Objective: Obtaining informed consent from hematopoietic stem cell recipients and donors is a critical step in the transplantation process. Anxiety may affect their understanding of the provided information. However, use of audiovisual methods may facilitate understanding. In this prospective randomized study, we investigated the effectiveness of using an audiovisual method of providing information to patients and donors in combination with the standard model. Materials and Methods: A 10-min informational animation was prepared for this purpose. In total, 82 participants were randomly assigned to two groups: group 1 received the additional audiovisual information and group 2 received standard information. A 20-item questionnaire was administered to participants at the end of the informational session. Results: A reliability test and factor analysis showed that the questionnaire was reliable and valid. For all participants, the mean overall satisfaction score was 184.8±19.8 (maximum possible score of 200. However, for satisfaction with information about written informed consent, group 1 scored significantly higher than group 2 (p=0.039. Satisfaction level was not affected by age, education level, or differences between the physicians conducting the informative session. Conclusion: This study shows that using audiovisual tools may contribute to a better understanding of the informed consent procedure and potential risks of stem cell transplantation.

Donor age and C1orf132/MIR29B2C determine age-related methylation signature of blood after allogeneic hematopoietic stem cell transplantation.

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Spólnicka, Magdalena; Piekarska, Renata Zbieć; Jaskuła, Emilia; Basak, Grzegorz W; Jacewicz, Renata; Pięta, Agnieszka; Makowska, Żanetta; Jedrzejczyk, Maciej; Wierzbowska, Agnieszka; Pluta, Agnieszka; Robak, Tadeusz; Berent, Jarosław; Branicki, Wojciech; Jędrzejczak, Wiesław; Lange, Andrzej; Płoski, Rafał

2016-01-01

Our recent study demonstrated that DNA methylation status in a set of CpGs located in ELOVL2, C1orf132, TRIM59, KLF14, and FHL2 can accurately predict calendar age in blood. In the present work, we used these markers to evaluate the effect of allogeneic hematopoietic stem cell transplantation (HSCT) on the age-related methylation signature of human blood. DNA methylation in 32 CpGs was investigated in 16 donor-recipient pairs using pyrosequencing. DNA was isolated from the whole blood collected from recipients 27-360 days (mean 126) after HSCT and from the donors shortly before the HSCT. It was found that in the recipients, the predicted age did not correlate with their calendar age but was correlated with the calendar age (r = 0.94, p = 4 × 10(-8)) and predicted age (r = 0.97, p = 5 × 10(-10)) of a respective donor. Despite this strong correlation, the predicted age of a recipient was consistently lower than the predicted age of a donor by 3.7 years (p = 7.8 × 10(-4)). This shift was caused by hypermethylation of the C1orf132 CpGs, for C1orf132 CpG_1. Intriguingly, the recipient-donor methylation difference correlated with calendar age of the donor (r = 0.76, p = 6 × 10(-4)). This finding could not trivially be explained by shifts of the major cellular factions of blood. We confirm the single previous report that after HSCT, the age of the donor is the major determinant of age-specific methylation signature in recipient's blood. A novel finding is the unique methylation dynamics of C1orf132 which encodes MIR29B2C implicated in the self-renewing of hematopoietic stem cells. This observation suggests that C1orf132 could influence graft function after HSCT.

Responses to recipient and donor B cells by genetically donor T cells from human haploidentical chimeras

International Nuclear Information System (INIS)

Schiff, S.; Sampson, H.; Buckley, R.

1986-01-01

Following administration of haploidentical stem cells to infants with severe combined immunodeficiency (SCID), mature T cells of donor karyotype appear later in the recipient without causing graft-versus-host disease. To investigate the effect of the host environment on the responsiveness of these genetically donor T cells, blood B and T lymphocytes from 6 SCID recipients, their parental donors and unrelated controls were purified by double SRBC rosetting. T cells were stimulated by irradiated B cells at a 1:1 ratio in 6 day cultures. Engrafted T cells of donor karyotype gave much smaller responses to irradiated genetically recipient B cells than did fresh donor T cells. Moreover, engrafted T cells of donor karyotype from two of the three SCIDs who are longest post-transplantation responded more vigorously (14,685 and 31,623 cpm) than fresh donor T cells (5141 and 22,709 cpm) to donor B cells. These data indicate that T lymphocytes which have matured from donor stem cells in the recipient microenvironment behave differently from those that have matured in the donor

Relapsed Diffuse Large B-Cell Lymphoma Treated by Reduced-Intensity Allogeneic Stem Cell Transplantation with Donor Lymphocyte Infusion

International Nuclear Information System (INIS)

Chudhry, Q.N.; Ahmed, P.; Ullah, K.; Satti, T.M.; Raza, S.; Mehmood, S.K.; Akram, M.; Ahmed, S.

2010-01-01

A 42 years old male with relapsed diffuse large B-cell lymphoma was given second-line chemotherapy followed by reduced intensity allogeneic stem cell transplantation from HLA matched brother. Twelve weeks post transplant, his disease relapsed evidenced by the appearance of lymphoma cells in the peripheral blood and declining donor chimerism. Donor lymphocyte infusion was given that induced complete lymphoma remission. The patient is well 3 years post transplant with his disease in complete remission. (author)

Molecular profile and cellular characterization of human bone marrow mesenchymal stem cells: donor influence on chondrogenesis.

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Cicione, Claudia; Díaz-Prado, Silvia; Muiños-López, Emma; Hermida-Gómez, Tamara; Blanco, Francisco J

2010-01-01

The use of autologous or allogenic stem cells has recently been suggested as an alternative therapeutic approach for treatment of cartilage defects. Bone marrow mesenchymal stem cells (BM-MSCs) are well-characterized multipotent cells that can differentiate into different cell types. Understanding the potential of these cells and the molecular mechanisms underlying their differentiation should lead to innovative protocols for clinical applications. The aim of this study was to evaluate the usefulness of surface antigen selection of BM-MSCs and to understand the mechanisms underlying their differentiation. MSCs were isolated from BM stroma and expanded. CD105+ subpopulation was isolated using a magnetic separator. We compared culture-expanded selected cells with non-selected cells. We analyzed the phenotypic profiles, the expression of the stem cell marker genes Nanog, Oct3/4, and Sox2 and the multi-lineage differentiation potential (adipogenic, osteogenic, and chondrogenic). The multi-lineage differentiation was confirmed using histochemistry, immunohistochemistry and/or real-time polymerase chain reaction (qPCR) techniques. The selected and non-selected cells displayed similar phenotypes and multi-lineage differentiation potentials. Analyzing each cell source individually, we could divide the six donors into two groups: one with a high percentage of CD29 (β1-integrin) expression (HL); one with a low percentage of CD29 (LL). These two groups had different chondrogenic capacities and different expression levels of the stem cell marker genes. This study showed that phenotypic profiles of donors were related to the chondrogenic potential of human BM-MSCs. The chondrogenic potential of donors was related to CD29 expression levels. The high expression of CD29 antigen seemed necessary for chondrogenic differentiation. Further investigation into the mechanisms responsible for these differences in BM-MSCs chondrogenesis is therefore warranted. Understanding the mechanisms

[Information booklet for related hematopoietic stem cell donors: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

Science.gov (United States)

Polomeni, Alice; Tardieu, Laure; Ainaoui, Malika; Andrianne, Christelle; Bancillon, Nelly; Chapel, Valerie; Chevallier, Nathalie; Evrard, Solène; Fournier, Isabelle; Gargallo, Guillaume; Godin, Sandrine; Issarni, Dominique; Le Bars, Laetitia; Renaud, Barbara; Yakoub-Agha, Ibrahim; Wallart, Anne; De Bentzmann, Natacha

2017-12-01

Providing information to living donors is first and foremost a legal obligation as well as an ethical one, not to mention necessary to health care provision. It's been shown that quality of information concerning the procedure's practical aspects, scheduling of clinical tests and examinations, withdrawing stem cells for the donation, post-donation symptoms, and support provided by healthcare teams, directly impacts the donor's quality of experience. Taking this into consideration our group decided it was essential to create an informational support for donors in the form of a booklet to be provided in different hematopoietic stem cell transplant centers across France. In September 2016 in Lille, France, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th allergenic hematopoietic stem cell transplantation clinical practices harmonization workshops. As part of these workshops, our group worked collectively to develop a basis of indispensable information to be included in the booklet and presented using clear and accessible language. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study.

Science.gov (United States)

Lee, Hyunah; Park, Jae Berm; Lee, Sanghoon; Baek, Soyoung; Kim, HyunSoo; Kim, Sung Joo

2013-04-11

Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow. MSCs were derived from negative HLA cross-match donors. Donor bone marrow was harvested 5 weeks prior to KT. At the time of transplantation, 1 x 106 cell/kg of donor MSC was directly injected into the bone marrow of the recipient's right iliac bone. Patients' clinical outcomes, presence of mixed chimerism by short tandem repeat polymerase chain reaction, analysis of plasma FoxP3 mRNA and cytokine level, and mixed lymphocyte reaction (MLR) were performed. Seven patients enrolled in this study and received donor MSC injections simultaneously with LDKT. The median age of recipients was 36 years (32 ~ 48). The number of HLA mismatches was 3 or less in 5 and more than 3 in 2. No local complications or adverse events such as hypersensitivity occurred during or after the injection of donor MSC. There was no graft failure, but the biopsy-proven acute rejections were observed in 3 recipients during the follow-up period controlled well with steroid pulse therapy (SPT). The last serum creatinine was a median of 1.23 mg/dL (0.83 ~ 2.07). Mixed chimerism was not detected in the peripheral blood of the recipients at 1 and 8 week of post-transplantation. Donor-specific lymphocyte or T cell proliferation and Treg priming responses were observed in some patients. Plasma level of IL-10, a known mediator of MSC-induced immune suppression, increased in the patients with Treg induction. Donor MSC injection into the iliac bone at the time of KT was feasible and safe. A possible correlation was observed between the induction of inhibitory

Current practices for screening, consent and care of related donors in France: Haematopoietic stem cell transplantation coordinator nurses' perceptions.

Science.gov (United States)

Polomeni, A; Bompoint, C; Gomez, A; Brissot, E; Ruggeri, A; Belhocine, R; Mohty, M

2017-11-01

Haematopoietic stem cell transplantation-coordinating nurses (HSCT-CNs) play an important role in informing related donors (RDs) and in organising human leucocyte antigen (HLA) tests, pre-donation workup and stem cells collection. Our pilot study aimed to explore French HSCT-CNs' perceptions of RD care issues. Twenty-nine French HSCT adult units were sent a questionnaire on the subject of donation procedures, HSCT-CNs' data and their professional experience of related donation issues. Twenty-two HSCT-CNs returned a completed questionnaire, and 90% of HSCT units were involved to some degree in both patient and donor care. Responses indicated that the provision of information to potential donors prior to HLA tests was insufficient, while donors were given a medical consultation only during the pre-donation workup. Questions were raised about the consent and voluntary status of RDs. None of the HSCT teams organised a post-donation consultation, while 57% provided follow-up by phone or via a questionnaire. Our results draw attention to the conflict of interest experienced by HSCT-CNs when caring simultaneously for patients and donors. The specific psychosocial difficulties associated with becoming an RD are also highlighted. French HSCT-CNs' perceptions of related donation reveal many ethical and clinical problems that have yet to be fully explored. Data on this topic remain scarce, and our pilot study may contribute to the current debate on the organisation of RD care. © 2016 John Wiley & Sons Ltd.

Parvovirus B19 in the Context of Hematopoietic Stem Cell Transplantation: Evaluating Cell Donors and Recipients

Science.gov (United States)

Gama, Bianca E.; Emmel, Vanessa E.; Oliveira-Silva, Michelle; Gutiyama, Luciana M.; Arcuri, Leonardo; Colares, Marta; de Cássia Tavares, Rita; Bouzas, Luis F.; Abdelhay, Eliana; Hassan, Rocio

2017-01-01

Background Parvovirus B19 (B19V) is a common human pathogen, member of the family Parvoviridae. Typically, B19V has been found to infect erythroid progenitors and cause hematological disorders, such as anemia and aplastic crisis. However, the persistence of genomic deoxyribonucleic acid (DNA) has been demonstrated in tonsils, liver, skin, brain, synovial, and testicular tissues as well as bone marrow, for both symptomatic and asymptomatic subjects. Although the molecular and cellular mechanisms of persistence remain undefined, it raises questions about potential virus transmissibility and its effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods With this aim, we retrospectively screened allogeneic stem cell donors from 173 patients admitted for allo-HSCT from January 2008 to May 2013 using a seminested polymerase chain reaction approach. Results We found 8 positive donor samples, yielding a 4.6% of parvovirus prevalence (95% confidence interval, 2.36-8.85). Pre- and post-HSCT samples (n = 51) from the 8 recipients of the positive donors were also investigated, and 1 case exhibited B19V DNA in the post-HSCT follow-up (D + 60). Direct DNA sequencing was performed to determine the genotype of isolates and classification, performed by phylogenetic reconstruction, showed a predominance of genotype 1a, whereas the rare genotype 3b was detected in 2 additional patients. By molecular cloning, different B19V 1a substrains polymorphisms were evidenced in the single case in which donor and its recipient were B19V+. Conclusions Our results suggest that HSCT allografts are not a main source for B19V transmission, pointing to potential events of reinfection or endogenous viral reactivation. PMID:29184906

Parvovirus B19 in the Context of Hematopoietic Stem Cell Transplantation: Evaluating Cell Donors and Recipients.

Science.gov (United States)

Gama, Bianca E; Emmel, Vanessa E; Oliveira-Silva, Michelle; Gutiyama, Luciana M; Arcuri, Leonardo; Colares, Marta; de Cássia Tavares, Rita; Bouzas, Luis F; Abdelhay, Eliana; Hassan, Rocio

2017-11-01

Parvovirus B19 (B19V) is a common human pathogen, member of the family Parvoviridae. Typically, B19V has been found to infect erythroid progenitors and cause hematological disorders, such as anemia and aplastic crisis. However, the persistence of genomic deoxyribonucleic acid (DNA) has been demonstrated in tonsils, liver, skin, brain, synovial, and testicular tissues as well as bone marrow, for both symptomatic and asymptomatic subjects. Although the molecular and cellular mechanisms of persistence remain undefined, it raises questions about potential virus transmissibility and its effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. With this aim, we retrospectively screened allogeneic stem cell donors from 173 patients admitted for allo-HSCT from January 2008 to May 2013 using a seminested polymerase chain reaction approach. We found 8 positive donor samples, yielding a 4.6% of parvovirus prevalence (95% confidence interval, 2.36-8.85). Pre- and post-HSCT samples (n = 51) from the 8 recipients of the positive donors were also investigated, and 1 case exhibited B19V DNA in the post-HSCT follow-up (D + 60). Direct DNA sequencing was performed to determine the genotype of isolates and classification, performed by phylogenetic reconstruction, showed a predominance of genotype 1a, whereas the rare genotype 3b was detected in 2 additional patients. By molecular cloning, different B19V 1a substrains polymorphisms were evidenced in the single case in which donor and its recipient were B19V+. Our results suggest that HSCT allografts are not a main source for B19V transmission, pointing to potential events of reinfection or endogenous viral reactivation.

Biosimilar G-CSF based mobilization of peripheral blood hematopoietic stem cells for autologous and allogeneic stem cell transplantation.

Science.gov (United States)

Schmitt, Michael; Publicover, Amy; Orchard, Kim H; Görlach, Matthias; Wang, Lei; Schmitt, Anita; Mani, Jiju; Tsirigotis, Panagiotis; Kuriakose, Reeba; Nagler, Arnon

2014-01-01

The use of granulocyte colony stimulating factor (G-CSF) biosimilars for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. However, the use of biosimilar G-CSF was approved by the European Medicines Agency (EMA) for all the registered indications of the originator G-CSF (Neupogen (®) ) including mobilization of stem cells. Here, we performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization at multiple centers using site-specific non-randomized regimens with a biosimilar G-CSF in the autologous and allogeneic setting. A total of 904 patients mostly with hematological malignancies as well as healthy donors underwent successful autologous or allogeneic stem cell mobilization, respectively, using a biosimilar G-CSF (520 with Ratiograstim®/Tevagrastim, 384 with Zarzio®). The indication for stem cell mobilization in hematology patients included 326 patients with multiple myeloma, 273 with Non-Hodgkin's lymphoma (NHL), 79 with Hodgkin's lymphoma (HL), and other disease. 156 sibling or volunteer unrelated donors were mobilized using biosimilar G-CSF. Mobilization resulted in good mobilization of CD34+ stem cells with side effects similar to originator G-CSF. Post transplantation engraftment did not significantly differ from results previously documented with the originator G-CSF. The side effects experienced by the patients or donors mobilized by biosimilar G-CSF were minimal and were comparable to those of originator G-CSF. In summary, the efficacy of biosimilar G-CSFs in terms of PBSC yield as well as their toxicity profile are equivalent to historical data with the reference G-CSF.

Blood donations from previously transfused or pregnant donors: a multicenter study to determine the frequency of alloexposure.

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Rios, Jorge A; Schlumpf, Karen S; Kakaiya, Ram M; Triulzi, Darrell J; Roback, John D; Kleinman, Steve H; Murphy, Edward L; Gottschall, Jerome L; Carey, Patricia M

2011-06-01

Transfusion-related acute lung injury (TRALI) mitigation strategies include the deferral of female donors from apheresis platelet (PLT) donations and the distribution of plasma for transfusion from male donors only. We studied the implications of these policies in terms of component loss at six blood centers in the United States. We collected data from allogeneic blood donors making whole blood and blood component donations during calendar years 2006 through 2008. We analyzed the distribution of donations in terms of the sex, transfusion and pregnancy histories, and blood type. A TRALI mitigation policy that would not allow plasma from female whole blood donors to be prepared into transfusable plasma components would result in nearly a 50% reduction in the units of whole blood available for plasma manufacturing and would decrease the number of type AB plasma units that could be made from whole blood donations by the same amount. Deferral of all female apheresis PLT donors, all female apheresis PLT donors with histories of prior pregnancies, or all female apheresis PLT donors with histories of prior pregnancies and positive screening test results for antibodies to human leukocyte antigens (HLAs) will result in a loss of 37.1, 22.5, and 5.4% of all apheresis PLT donations, respectively. A TRALI mitigation policy that only defers female apheresis PLT donors with previous pregnancies and HLAs would result in an approximately 5% decrease in the inventory of apheresis PLTs, but would eliminate a large proportion of components that are associated with TRALI. © 2010 American Association of Blood Banks.

Donor mesenchymal stem cells home to maternal wounds after transamniotic stem cell therapy (TRASCET) in a rodent model.

Science.gov (United States)

Graham, Christopher D; Shieh, Hester F; Brazzo, Joseph A; Zurakowski, David; Fauza, Dario O

2017-06-01

Transamniotic stem cell therapy (TRASCET) with amniotic fluid-derived MSCs (afMSCs) has emerged experimentally as a practical treatment strategy for congenital anomalies. In this study, we sought to determine whether afMSCs migrate to the mother following TRASCET. Pregnant rat dams were divided into three groups. Two groups received volume-matched injections into all amniotic cavities of either a suspension of afMSCs labeled with a luciferase reporter gene or the luciferase protein alone. In a third group, a suspension of labeled cells was aliquoted onto the serosal surface of the uterus. Maternal samples from the laparotomy scar (fascia and skin separately), bone marrow, and peripheral blood were procured, along with placenta and umbilical cord. Specimens were screened for luminescence via microplate luminometry. Luminescence was detected in 60% (9/15) of the fascial scars from the group receiving intraamniotic injection of afMSCs, but in none of the other groups (Pcells in the placenta and their presence in maternal fascia (Wald test=10.2; P=0.001). Amniotic mesenchymal stem cells migrate to maternal sites of injury after intraamniotic injection. Maternal homing of donor cells must be considered in the setting of transamniotic stem cell therapy. N/A (animal and laboratory study). Copyright © 2017 Elsevier Inc. All rights reserved.

Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient.

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Hayakawa, Kayoko; Takasaki, Tomohiko; Tsunemine, Hiroko; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Mawatari, Momoko; Fujiya, Yoshihiro; Yamamoto, Kei; Ohmagari, Norio; Kato, Yasuyuki

2015-08-01

The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hematopoietic Stem Cell Transplantation Using Preimplantation Genetic Diagnosis and Human Leukocyte Antigen Typing for Human Leukocyte Antigen-Matched Sibling Donor: A Turkish Multicenter Study.

Science.gov (United States)

Kurekci, Emin; Küpesiz, Alphan; Anak, Sema; Öztürk, Gülyüz; Gürsel, Orhan; Aksoylar, Serap; Ileri, Talia; Kuşkonmaz, Barış; Eker, İbrahim; Cetin, Mualla; Tezcan Karasu, Gülsün; Kaya, Zühre; Fışgın, Tunç; Ertem, Mehmet; Kansoy, Savaş; Yeşilipek, Mehmet Akif

2017-05-01

Preimplantation genetic diagnosis involves the diagnosis of a genetic disorder in embryos obtained through in vitro fertilization, selection of healthy embryos, and transfer of the embryos to the mother's uterus. Preimplantation genetic diagnosis has been used not only to avoid the risk of having an affected child, but it also offers, using HLA matching, preselection of potential HLA-genoidentical healthy donor progeny for an affected sibling who requires bone marrow transplantation. Here, we share the hematopoietic stem cell transplantation results of 52 patients with different benign and malign hematological or metabolic diseases or immunodeficiencies whose donors were siblings born with this technique in Turkey since 2008. The median age of the patients' at the time of the transplantation was 8 years (range, 3 to 16 years) and the median age of the donors was 2 years (range, .5 to 6 years). The most common indication for HSCT was thalassemia major (42 of all patients, 80%). The stem cell source in all of the transplantations was bone marrow. In 37 of the transplantations, umbilical cord blood of the same donor was also used. In 50 of the 52 patients, full engraftment was achieved with a mean of 4.6 × 10 6 CD 34 + cells per kg of recipient weight. Ninety-six percent of the patients have been cured through hematopoietic stem cell transplantation without any complication. Primary engraftment failure was seen in only 2 patients with thalassemia major. All of the donors and the patients are alive with good health status. Preimplantation genetic diagnosis with HLA matching offers a life-saving chance for patients who need transplantation but lack an HLA genoidentical donor. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Potential organ donor audit in Ireland.

LENUS (Irish Health Repository)

Hegarty, M

2010-11-01

As increasing demand for organs is a challenge for transplant services worldwide it is essential to audit the process of organ donation. To address this, a national audit of potential organ donors was undertaken across hospitals with Intensive Care Units (N = 36). Questionnaires were returned on all patients (n = 2073) who died in these units from 1\\/9\\/07-31\\/8\\/08; 200 (10%) of these patients were considered for Brain Stem Testing (BST), 158 patients (79%) were diagnosed Brain Stem Dead (BSD) and 138 patients (87%) became potential donors. Consent for donation was given by 92 (69%) next of kin and 90 potential donors (65%) became organ donors. There was no evidence of a large number of potential organ donors being missed. Recommendations included completion of BSTs on all appropriate patients, development of support on BST, referral of all BSD patients to the Organ Procurement Service; enhanced co-ordination within hospitals and sustained information\\/education campaigns.

Living donor liver transplantation from a donor previously treated with interferon for hepatitis C virus: a case report

Directory of Open Access Journals (Sweden)

Nakao Kazuhiko

2011-07-01

Full Text Available Abstract Introduction Selecting a marginal donor in liver transplantation (LT remains controversial but is necessary because of the small number of available donors. Case presentation A 46-year-old Japanese woman was a candidate to donate her liver to her brother, who had decompensated liver cirrhosis of unknown origin. Eight years before the donation, she had a mild liver dysfunction that was diagnosed as a hepatitis C virus (HCV infection (serotype 2. She had received anti-viral therapy with interferon α-2b three times weekly for 24 weeks and had a sustained viral response (SVR. A biopsy of her liver before the donation showed normal findings without any active hepatitis, and her serum was negative for HCV-RNA. Only 67 patients have undergone LT from a cadaveric donor in Japan. The family in this case decided to have living donor LT. A careful selection for the liver graft donation was made; however, since she was the only candidate, we approved her as a living donor. She was discharged nine days after the liver donation. Her liver function recovered immediately. A computed tomography scan showed sufficient liver regeneration one year later. Her brother also had good liver function after LT and had no HCV infection 48 months after surgery and no de novo malignancy. Neither of the siblings has developed an HCV infection. Conclusions A patient with SVR status after interferon therapy might be considered a candidate for living donor LT but only if there are no other possibilities of LT for the recipient. A careful follow-up of the donor after donation is needed. The recipient also must have a very close follow-up because it is difficult to predict what might happen to the graft with post-transplant immunosuppression.

Generation of human induced pluripotent stem cells from urinary cells of a healthy donor using a non-integration system.

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Uhm, Kyung-Ok; Jo, Eun Hee; Go, Gue Youn; Kim, So-Jung; Choi, Hye Young; Im, Young Sam; Ha, Hye-Yeong; Jung, Ji-Won; Koo, Soo Kyung

2017-05-01

Urinary cells can be an ideal source for generating hiPSCs and progenitors, as they are easily accessible, non-invasive, and universally available. We generated human induced pluripotent stem cells (hiPSCs) from the urinary cells of a healthy donor using a Sendai virus-based gene delivery method. The generated hiPSC line, KSCBi001-A, has a normal karyotype (46,XY). The pluripotency and capacity of multilineage differentiation were characterized by comparison with those of a human embryonic stem cell line. This cell line is registered and available from National Stem Cell Bank, Korea National Institute of Health. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Improved survival after transplantation of more donor plasmacytoid dendritic or naïve T cells from unrelated-donor marrow grafts: results from BMTCTN 0201.

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Waller, Edmund K; Logan, Brent R; Harris, Wayne A C; Devine, Steven M; Porter, David L; Mineishi, Shin; McCarty, John M; Gonzalez, Corina E; Spitzer, Thomas R; Krijanovski, Oleg I; Linenberger, Michael L; Woolfrey, Ann; Howard, Alan; Wu, Juan; Confer, Dennis L; Anasetti, Claudio

2014-08-01

To characterize relationships between specific immune cell subsets in bone marrow (BM) or granulocyte colony-stimulating factor-mobilized peripheral blood (PB) stem cells collected from unrelated donors and clinical outcomes of patients undergoing transplantation in BMTCTN 0201. Fresh aliquots of 161 BM and 147 PB stem-cell allografts from North American donors randomly assigned to donate BM or PB stem cells and numbers of transplanted cells were correlated with overall survival (OS), relapse, and graft-versus-host disease (GvHD). Patients with evaluable grafts were similar to all BMTCTN 0201 patients. The numbers of plasmacytoid dendritic cells (pDCs) and naïve T cells (Tns) in BM allografts were independently associated with OS in multivariable analyses including recipient and donor characteristics, such as human leukocyte antigen mismatch, age, and use of antithymocyte globulin. BM recipients of > median number of pDCs, naïve CD8(+) T cells (CD8Tns), or naïve CD4(+) T cells (CD4Tns) had better 3-year OS (pDCs, 56% v 35%; P = .025; CD8Tns, 56% v 37%; P = .012; CD4Tns, 55% v 37%; P = .009). Transplantation of more BM Tns was associated with less grade 3 to 4 acute GvHD but similar rates of relapse. Transplantation of more BM pDCs was associated with fewer deaths resulting from GvHD or from graft rejection. Analysis of PB grafts did not identify a donor cell subset significantly associated with OS, relapse, or GvHD. Donor immune cells in BM but not PB stem-cell grafts were associated with survival after unrelated-donor allogeneic hematopoietic stem-cell transplantation. The biologic activity of donor immune cells in allogeneic transplantation varied between graft sources. Donor grafts with more BM-derived Tns and pDCs favorably regulated post-transplantation immunity in allogeneic hematopoietic stem-cell transplantation. © 2014 by American Society of Clinical Oncology.

Systematic donor blood qualification by flow cytometry would have been able to avoid CLL-type MBL transmission after unrelated hematopoietic stem cell transplantation.

Science.gov (United States)

Ferrand, Christophe; Garnache-Ottou, Francine; Collonge-Rame, Marie Agnès; Larosa, Fabrice; Blanc, Michel; Behar, Catherine; Giannoli, Catherine; Garnier, Frédérico; Tiberghien, Pierre; Deconinck, Eric; Rohrlich, Pierre Simon

2012-03-01

The current screening for eligibility of unrelated volunteer marrow donors comprises a complete clinical check-up, a blood CBC and serum protein immunoelectrophoresis. This allows to eliminate acute leukemias, myeloproliferative and myelodysplastic disorders, myelomas and MGUS. To date, the risk of transmission of chronic lymphocytic leukemia (CLL) disease is only evaluated by the clinical evaluation and CBC. We report here the case of a CLL-type MBL disease occurring in a 12-year-old boy after unrelated BMT. Deep biological investigations, as Immunophenotyping, cytogenetic and molecular biology allow us to determine the donor origin of the CLL clone. In 2010, 14.2% donor (105/737) for unrelated hematopoietic stem cell transplantation were over 45y. It is currently estimated (USA) that 1 in 210 men and women will be diagnosed with CLL during their lifetime. Given the long asymptomatic phase of CLL, this raises the case for a detection strategy analog to that used for MGUS and myeloma through serum protein electrophoresis. This case-report, to our knowledge, of a CLL-type MBL unrelated donor-to-recipient transmission through BMT raises ethical and practical questions, such as the proper information about disease transmission risk. The cost-effectiveness of a systematic peripheral blood Immunophenotyping in donors elder than 40y at time of stem cell donation should be evaluated. © 2012 John Wiley & Sons A/S.

Granulocyte-colony stimulating factor for hematopoietic stem cell donation from healthy female donors during pregnancy and lactation: what do we know?

Science.gov (United States)

Pessach, Ilias; Shimoni, Avichai; Nagler, Arnon

2013-01-01

BACKGROUND Hematopoietic growth factors (HGFs) are mostly used as supportive measures to reduce infectious complications associated with neutropenia. Over the past decade, the use of HGFs became a common method for mobilizing human CD34+ stem cells, either for autologous or allogeneic transplantation. However, since their introduction the long-term safety of the procedure has become a major focus of discussion and research. Most information refers to healthy normal donors and data concerning pregnant and lactating women are scarce. The clinical question, which is the core of this review, is whether stem cell donation, preceded by administration of granulocyte-colony stimulating factor (G-CSF) for mobilization, is a safe procedure for pregnant donors. METHODS Literature searches were performed in Pubmed for English language articles published before the end of May 2012, focusing on G-CSF administration during pregnancy, lactation and hematopoietic stem cell donation. Searches included animal and human studies. RESULTS Data from animals (n = 15 studies) and women (n = 46 studies) indicate that G-CSF crosses the placenta, stimulates fetal granulopoiesis, improves neonatal survival mostly for very immature infants, promotes trophoblast growth and placental metabolism and has an anti-abortive role. Granulocyte macrophage-CSF is a key cytokine in the maternal immune tolerance towards the implanted embryo and exerts protective long-term programming effects to preimplantation embryos. The available data suggest that probably CSFs should not be administered during the time of most active organogenesis (first trimester), except perhaps for the first week during which implantation takes place. Provided CSF is administered during the second and third trimesters, it appears to be safe, and pregnant women receiving the CSF treatment can become hematopoietic stem cell donors. There are also risks related to the anesthesia, which is required for the bone marrow aspiration. During

Working with previously anonymous gamete donors and donor-conceived adults: recent practice experiences of running the DNA-based voluntary information exchange and contact register, UK DonorLink.

Science.gov (United States)

Crawshaw, Marilyn; Gunter, Christine; Tidy, Christine; Atherton, Freda

2013-03-01

This article describes recent practice experiences with donor conceived adults, donors, non-donor-conceived adult children of donors using the voluntary DNA-based register, UK DonorLink. It highlights additional complexities faced when using DNA rather than paper records for searching, in particular from the risk of false positives, low chances of success and potential inclusion of biological parents' DNA. Professionals' experiences in supporting those being "linked" suggest challenges as well as rewards. Registration carries the potential to be therapeutic for donor-conceived adults and donors and to enhance their political awareness regardless of links being made. Registrants value both peer and professional support, providing the latter can respond flexibly and be delivered by staff experienced in intermediary work. Given that the majority of those affected by donor conception internationally come from anonymous donation systems, these findings are highly pertinent and argue the need for political and moral debate about such service provision.

The implication of follicular lymphoma patients receiving allogeneic stem cell transplantation from donors carrying t(14;18)-positive cells.

Science.gov (United States)

McGregor, D K; Keever-Taylor, C A; Bredeson, C; Schur, B; Vesole, D H; Logan, B; Chang, C-C

2005-06-01

We performed real-time quantitative polymerase chain reaction (RQ-PCR) in peripheral blood (PB) and/or bone marrow (BM) samples collected pre- and post transplant from 23 recipient-donor pairs receiving allogeneic stem cell transplantation (allo-SCT) for follicular lymphoma (FL). Of 23 donors, 11 had a PB and/or BM sample positive for t(14;18) (BCL2/IGH fusion) at low levels (donors with (n=11) and those without (n=12) detectable t(14:18) cells were similar in age, sex, and disease status pretransplant. No differences in the incidence of graft-versus-host-disease (GVHD), delayed engraftment, relapse rate, disease-free survival and overall survival were identified between the groups. Two recipients without detectable t(14;18) cells pre-transplant showed detectable t(14;18) cells at 2 and 11 years after receiving grafts from donors with t(14:18) cells. Neither patient developed FL 1.5 and 2 years after the emergence of t(14;18) cells. Although the sample size is relatively small, our findings suggest that individuals carrying t(14;18) cells may not be excluded as donors given the lack of an association of t(14;18) detected in donors with adverse clinical outcome. It may be necessary to screen for the donor's t(14;18) status before using t(14;18) for monitoring minimal residual disease by RQ-PCR to exclude the possibility of confounding donor's t(14;18) clone.

In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation

Directory of Open Access Journals (Sweden)

Max eJameson-Lee

2014-11-01

Full Text Available Donor T cell mediated graft versus host effects (GVH may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA presented by the HLA molecules in each donor-recipient pair undergoing stem cell transplantation (SCT. Whole exome sequencing has previously demonstrated a large number of nonsynonymous single nucleotide polymorphisms (SNP present in HLA-matched recipients of SCT donors (GVH direction. The nucleotide sequence flanking each of these SNPs was obtained and the amino acid sequence determined. All the possible nonameric-peptides incorporating the variant amino acid resulting from these SNPs were interrogated in-silico for their likelihood to be presented by the HLA class I molecules using the Immune Epitope Database stabilized matrix method (SMM and NetMHCpan algorithms. The SMM algorithm predicted that a median of 18,396 peptides weakly bound HLA class I molecules in individual SCT recipients, and 2,254 peptides displayed strong binding. A similar library of presented peptides was identified when the data was interrogated using the NetMHCpan algorithm. The bioinformatic algorithm presented here demonstrates that there may be a high level of mHA variation in HLA-matched individuals, constituting an HLA-specific alloreactivity potential.

Evolution of human cytomegalovirus-seronegative donor/-seropositive recipient high-risk combination frequency in allogeneic hematopoietic stem cell transplantations at Institute of Hematology and Blood Transfusion during 1995-2014.

Science.gov (United States)

Nemeckova, S; Sroller, V; Stastna-Markova, M

2016-04-01

Human cytomegalovirus (HCMV) establishes lifelong latent infection that can result in severe life-threatening disease in immunosuppressed patients after hematopoietic stem cell transplantation (HSCT). An HCMV-seropositive transplant recipient who receives a graft from a seronegative donor (R+/D-) is at high risk of recurrent HCMV reactivation. To assess the incidence of R+/D- combination, we retrospectively evaluated HCMV-seronegative donors for 746 allogeneic HSCT treatments carried out at our center during 1995-2014. In our cohort, 20% HCMV-seronegative HSCT recipients, 21% HCMV-seronegative related graft donors, and 52% HCMV-seronegative unrelated graft donors were included. Analyses of the HCMV serostatus of hematopoietic stem cell donors during 2 consecutive calendar periods (1995-2005 and 2006-2014) showed a significant increase in the proportion of seronegative donors (odds ratio [OR] = 1.947). In addition, the number of HSCT treatments using an unrelated donor increased (OR = 2.376). Finally, the use of grafts from countries with a very low HCMV prevalence increased. This increase in HCMV seronegativity in unrelated donors and the increased proportion of unrelated donors were responsible for the increased occurrence of the high-risk combination R+/D- (OR = 1.680). If the reduction in the rate of HCMV-seropositive graft donors continues, an increased frequency of HCMV reactivation events in our transplant recipients can be expected, because of the increasing occurrence of the high-risk R+/D- combination. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transplantation and differentiation of donor cells in the cloned pigs

International Nuclear Information System (INIS)

Shimada, Arata; Tomii, Ryo; Kano, Koichiro; Nagashima, Hiroshi

2006-01-01

The application of nuclear transfer technology is an interesting approach to investigate stem and progenitor cell transplantation therapy. If stem cells are used as a nuclear donor, donor cells can engraft into cloned animals without histocompatible problems. However, it is still uncertain whether donor cells can engraft to cloned animal and differentiate in vivo. To address this problem, we transplanted donor cells to dermal tissues of cloned pigs developed by using preadipocytes as donor cells. Preadipocytes are adipocytic progenitor which can differentiate to mature adipocytes in vitro. We showed that the donor preadipocytes were successfully transplanted into the cloned pigs without immune rejection and they differentiated into mature adipocytes in vivo 3 weeks after transplantation. In contrast, allogenic control preadipocytes, which can differentiate in vitro, did not differentiate in vivo. These results indicate that donor progenitor cells can differentiate in cloned animal

Gnom 3 as a Donor for Ultra Short- Stem Trait of Winter Rye

Directory of Open Access Journals (Sweden)

В. В. Скорик

2011-05-01

Full Text Available The article reflects the progress of genetic decrease of Rye F 3k- 10029/ Saratovske (Саратовське 4 height by means of the shortest stem plants selection during the period from 1974 to 2010. 37 years selection of the shortest- stern genotypes decreased the plants height from 119.33 cm to 22.57cm. Targeted selection into minus direction decreased the plants height in 5,29 times on the background of the dominant HI expression. In average, the height of plants in the course of 27 breeding cycles were decreasing by 2.69 cm, but that was not going gradually. A new donor Gnom 3 had been created for ultra short-stem trait of the Winter Rye, with the marking of alleles HI-3HI-3. Relative influence on the minus selection efficiency has been established by height of plants for the selection differential (38% and coefficient of inheritance in narrow sense (14,56%. Realized efficiency of selection in decrease of winter rye height in 72,08% of cases corresponded to predicted hit ration of the breeding. Analyzes of genetic and statistical parameters and correlation clusters of 11 utilitarian average characteristics of ultra short- stem rye Gnom 3 for the period of 1974 to 2010 has been performed.

Egg donation for stem cell research: ideas of surplus and deficit in Australian IVF patients' and reproductive donors' accounts.

Science.gov (United States)

Waldby, Catherine; Carroll, Katherine

2012-05-01

We report on a study undertaken with an Australian in vitro fertilisation (IVF) clinic to understand IVF patients' and reproductive donors' perceptions of oocyte (egg) donation for stem cell research. Such perspectives are particularly valuable because IVF patients form a major recruitment group for oocyte donation for research, and because patients and donors have direct experience of the medical procedures involved. Similar studies of oocyte donation have been carried out elsewhere in the world, but to date very little social science research has been published that reports on donation for research, as distinct from donation for reproduction. Our respondents expressed a distinct unwillingness to donate viable oocytes for stem cell research. In our analysis we consider a number of factors that explain this unwillingness. These include the labour of oocyte production, the inscrutability of oocytes (the lack of a test to identify degrees of fertility) and the extent to which the oocytes' fertility sets the parameters for all downstream reproductive possibilities. We draw on the science studies literature on affordances to make sense of the social intractability of oocytes, and compare them with the respondents' much greater willingness to donate frozen embryos for human embryonic stem cells research. © 2011 The Authors. Sociology of Health & Illness © 2011 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

Scotblood 2007: Tackling local and global issues in transfusion medicine - donor recruitment, effective use of blood, stem cell plasticity, and vCJD.

Science.gov (United States)

Bessos, Hagop; Fraser, Robin; Seghatchian, Jerard

2008-02-01

This commentary briefly highlights some of the local and the global contemporary issues affecting transfusion medicine worldwide. The main areas of focus addressed this year were: donor recruitment, stem cell plasticity, the effective use of blood, and vCJD.

Evaluation of the Procleix Ultrio Elite Assay and the Panther-System for Individual NAT Screening of Blood, Hematopoietic Stem Cell, Tissue and Organ Donors.

Science.gov (United States)

Heim, Albert

2016-05-01

The performance of the multiplex Procleix Ultrio Elite assay as individual donor nucleic acid test (ID-NAT) for the detection of HIV-1, HIV-2, HCV, and HBV was evaluated in a retrospective, single center study. ID-NAT results of 21,181 blood donors, 984 tissue donors, 293 hematopoietic stem cell donors and 4 organ donors were reviewed in synopsis with results of serological screening and additional discriminatory and repetitive NAT in case of positive donors. Specificity of the initial Procleix Ultrio Elite assay was 99.98% and after discriminatory testing 100.00%. Initially invalid results were observed in 75 of 21,181 blood donors (0.35%) but 16 of 984 tissue donors (1.62%, p donors. All these had valid negative ID-NAT results after repeated testing or testing of 1:5 diluted specimens in case of tissue donors. Occult hepatitis B (defined here as HBV DNAemia without HBsAg detection) was demonstrated by ID-NAT in two anti-HBc-positive tissue donors and suspected in two other tissue donors, where a definite diagnosis was not achieved due to the insufficient sample volumes available. The Procleix Ultrio Elite assay proved to be specific, robust and rapid. Therefore, routine ID-NAT may also be feasible for organ and granulocyte donors.

Donor versus no-donor comparison of newly diagnosed myeloma patients included in the HOVON-50 multiple myeloma study

NARCIS (Netherlands)

Lokhorst, Henk M.; van der Holt, Bronno; Cornelissen, Jan J.; Kersten, Marie-José; van Oers, Marinus; Raymakers, Reinier; Minnema, Monique C.; Zweegman, Sonja; Janssen, Jeroen J.; Zijlmans, Mark; Bos, Gerard; Schaap, Nicolaas; Wittebol, Shulamiet; de Weerdt, Okke; Ammerlaan, Rianne; Sonneveld, Pieter

2012-01-01

To prospectively evaluate allogeneic stem cell transplantation (allo-SCT) for myeloma as part of first-line therapy, a donor versus no-donor analysis was performed of patients treated in the HOVON-50 study, a study that was originally designed to examine thalidomide combined with intensive therapy.

Alternative allogeneic donor sources for transplantation for childhood diseases: unrelated cord blood and haploidentical family donors.

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Cairo, Mitchell S; Rocha, Vanderson; Gluckman, Eliane; Hale, Gregory; Wagner, John

2008-01-01

Allogeneic stem cell transplantation has been demonstrated to be curative in a wide variety of pediatric malignant and nonmalignant diseases, and can be traced back over 50 years ago to the original report of Thomas et al. HLA matched sibling donors have been the gold standard for pediatric recipients requiring allogeneic donors for both nonmalignant and malignant conditions. However, only 25% of potential pediatric recipients possesses an HLA-matched sibling donor, and the frequency is even less in those with genetic nonmalignant conditions because of genetically affected other siblings within the family. Therefore, 75% to 90% of potential pediatric recipients require alternative allogeneic donor cells for treatment of their underlying conditions. Potential alternative allogeneic donor sources include unrelated cord blood donors, unrelated adult donors, and haploidentical family donors. In this article we review the experience of both unrelated cord blood donor and haploidentical family donor transplants in selected pediatric malignant and nonmalignant conditions.

Acute toxicities of unrelated bone marrow versus peripheral blood stem cell donation: results of a prospective trial from the National Marrow Donor Program.

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Pulsipher, Michael A; Chitphakdithai, Pintip; Logan, Brent R; Shaw, Bronwen E; Wingard, John R; Lazarus, Hillard M; Waller, Edmund K; Seftel, Matthew; Stroncek, David F; Lopez, Angela M; Maharaj, Dipnarine; Hematti, Peiman; O'Donnell, Paul V; Loren, Alison W; Leitman, Susan F; Anderlini, Paolo; Goldstein, Steven C; Levine, John E; Navarro, Willis H; Miller, John P; Confer, Dennis L

2013-01-03

Although peripheral blood stem cells (PBSCs) have replaced bone marrow (BM) as the most common unrelated donor progenitor cell product collected, a direct comparison of concurrent PBSC versus BM donation experiences has not been performed. We report a prospective study of 2726 BM and 6768 PBSC donors who underwent collection from 2004 to 2009. Pain and toxicities were assessed at baseline, during G-CSF administration, on the day of collection, within 48 hours of donation, and weekly until full recovery. Peak levels of pain and toxicities did not differ between the 2 donation processes for most donors. Among obese donors, PBSC donors were at increased risk of grade 2 to 4 pain as well as grade 2 to 4 toxicities during the pericollection period. In contrast, BM donors were more likely to experience grade 2 to 4 toxicities at 1 week and pain at 1 week and 1 month after the procedure. BM donors experienced slower recovery, with 3% still not fully recovered at 24 weeks, whereas 100% of PBSC donors had recovered. Other factors associated with toxicity included obesity, increasing age, and female sex. In summary, this study provides extensive detail regarding individualized risk patterns of PBSC versus BM donation toxicity, suggesting donor profiles that can be targeted with interventions to minimize toxicity.

Generation of human induced pluripotent stem cells from a Bombay individual: Moving towards 'universal-donor' red blood cells

International Nuclear Information System (INIS)

Seifinejad, Ali; Taei, Adeleh; Totonchi, Mehdi; Vazirinasab, Hamed; Hassani, Seideh Nafiseh; Aghdami, Nasser; Shahbazi, Ebrahim; Yazdi, Reza Salman; Salekdeh, Ghasem Hosseini; Baharvand, Hossein

2010-01-01

Bombay phenotype is one of the rare phenotypes in the ABO blood group system that fails to express ABH antigens on red blood cells. Nonsense or missense mutations in fucosyltransfrase1 (FUT1) and fucosyltransfrase2 (FUT2) genes are known to create this phenotype. This blood group is compatible with all other blood groups as a donor, as it does not express the H antigen on the red blood cells. In this study, we describe the establishment of human induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of a Bombay blood-type individual by the ectopic expression of established transcription factors Klf4, Oct4, Sox2, and c-Myc. Sequence analyses of fibroblasts and iPSCs revealed a nonsense mutation 826C to T (276 Gln to Ter) in the FUT1 gene and a missense mutation 739G to A (247 Gly to Ser) in the FUT2 gene in the Bombay phenotype under study. The established iPSCs resemble human embryonic stem cells in morphology, passaging, surface and pluripotency markers, normal karyotype, gene expression, DNA methylation of critical pluripotency genes, and in-vitro differentiation. The directed differentiation of the iPSCs into hematopoietic lineage cells displayed increased expression of the hematopoietic lineage markers such as CD34, CD133, RUNX1, KDR, α-globulin, and γ-globulin. Such specific stem cells provide an unprecedented opportunity to produce a universal blood group donor, in-vitro, thus enabling cellular replacement therapies, once the safety issue is resolved.

Evaluation of the Procleix Ultrio Elite Assay and the Panther-System for Individual NAT Screening of Blood, Hematopoietic Stem Cell, Tissue and Organ Donors

Science.gov (United States)

Heim, Albert

2016-01-01

Summary Background The performance of the multiplex Procleix Ultrio Elite assay as individual donor nucleic acid test (ID-NAT) for the detection of HIV-1, HIV-2, HCV, and HBV was evaluated in a retrospective, single center study. Methods ID-NAT results of 21,181 blood donors, 984 tissue donors, 293 hematopoietic stem cell donors and 4 organ donors were reviewed in synopsis with results of serological screening and additional discriminatory and repetitive NAT in case of positive donors. Results Specificity of the initial Procleix Ultrio Elite assay was 99.98% and after discriminatory testing 100.00%. Initially invalid results were observed in 75 of 21,181 blood donors (0.35%) but 16 of 984 tissue donors (1.62%, p donors. All these had valid negative ID-NAT results after repeated testing or testing of 1:5 diluted specimens in case of tissue donors. Occult hepatitis B (defined here as HBV DNAemia without HBsAg detection) was demonstrated by ID-NAT in two anti-HBc-positive tissue donors and suspected in two other tissue donors, where a definite diagnosis was not achieved due to the insufficient sample volumes available. Conclusion The Procleix Ultrio Elite assay proved to be specific, robust and rapid. Therefore, routine ID-NAT may also be feasible for organ and granulocyte donors. PMID:27403089

[Information and consent forms for hematopoietic stem cell transplantation donors and recipients: Guidelines from the Franchophone society of bone marrow transplantation and cellular therapy (SFGM-TC)].

Science.gov (United States)

Bruno, Bénédicte; Thibert, Jean-Baptiste; Bancillon, Nelly; Desbos, Anna; Fawaz, Abir; Fournier, Isabelle; Genty, Carole; Issarni, Dominique; Leveille, Sandrine; Premel, Christelle; Polomeni, Alice; Renault, Myriam; Tarillon, Sylvie; Wallart, Anne; Yakoub-Agha, Ibrahim; Bordessoule, Dominique

2016-11-01

Within the context of the SFGM-TC's 6th workshop series on the harmonization of clinical practices, our workshop proposes a standardization of the informed consent process for hematopoietic stem cell donors and recipients leading up to an autologous or allogenic transplantation. All informed consent was for bone marrow or peripheral stem cell donors, and mononuclear/lymphocyte donors according to usual procedures. The informed consent for autologous and allogenic related or unrelated adults and pediatric transplantation patients have been included. A first step has been conducted for collecting in advance the informed consent forms used routinely in all francophone transplantation centers. In a second step, a comprehensive version has been re-written by a multidisciplinary team. For the purposes of understanding the risks and advantages, language has been carefully considered and streamlined. In the third step, texts were sent to stem cell transplantation experts, experts at the French biomedical agency (agence de la biomédecine [ABM]), law specialists, members of the ethical committee of the French society of hematology and several transplant recipients to be edited and proofread. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Recovery of Unrelated Donors of Peripheral Blood Stem Cells versus Recovery of Unrelated Donors of Bone Marrow: A Prespecified Analysis from the Phase III Blood and Marrow Transplant Clinical Trials Network Protocol 0201.

Science.gov (United States)

Burns, Linda J; Logan, Brent R; Chitphakdithai, Pintip; Miller, John P; Drexler, Rebecca; Spellman, Stephen; Switzer, Galen E; Wingard, John R; Anasetti, Claudio; Confer, Dennis L

2016-06-01

We report a comparison of time to recovery, side effects, and change in blood counts from baseline to after donation from unrelated donors who participated in the Blood and Marrow Transplant Clinical Trials Network phase III randomized, multicenter trial (0201) in which donor-recipient pairs were randomized to either peripheral blood stem cell (PBSC) or bone marrow (BM) donation. Of the entire cohort, 262 donated PBSC and 264 donated BM; 372 (71%) donors were from domestic and 154 (29%) were from international centers (145 German and 9 Canadian). PBSC donors recovered in less time, with a median time to recovery of 1 week compared with 2.3 weeks for BM donors. The number of donors reporting full recovery was significantly greater for donors of PBSC than of BM at 1, 2, and 3 weeks and 3 months after donation. Multivariate analysis showed that PBSC donors were more likely to recover at any time after donation compared with BM donors (hazard ratio, 2.08; 95% confidence interval [CI], 1.73 to 2.50; P donor and donation in more recent years. Donors of BM were more likely to report grades 2 to 4 skeletal pain, body symptoms, and fatigue at 1 week after donation. In logistic regression analysis of domestic donors only in which toxicities at peri-collection time points (day 5 filgrastim for PBSC donors and day 2 after collection of BM donors) could be analyzed, no variable was significantly associated with grades 2 to 4 skeletal pain, including product donated (BM versus PBSC; odds ratio, 1.13; 95% CI, .74 to 1.74; P = .556). Blood counts were affected by product donated, with greater mean change from baseline to after donation for white blood cells, neutrophils, mononuclear cells, and platelets in PBSC donors whereas BM donors experienced a greater mean change in hemoglobin. This analysis provided an enhanced understanding of donor events as product donated was independent of physician bias or donor preference. Copyright © 2016 The American Society for Blood and

[A comparative study of unrelated donor and matched-sibling donor allogeneic hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia].

Science.gov (United States)

Zhou, J; Fu, Y W; Liang, L J; Wang, Q; Han, L J; Zu, Y L; Zhang, Yanli; Zhu, X H; Yu, F K; Fang, B J; Wei, X D; Song, Y P

2016-12-01

Objective: To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT) for children and adolescents with severe aplastic anemia (SAA). Methods: Clinical data of 34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015. According to the source of donor, the patients were divided into matched sibling donor allo-HSCT group (MSD group) and unrelated donor group (URD group). The clinical outcome of SAA children and adolescents receiving URD allo-HSCT was assessed, and patients in MSD allo-HSCT group were enrolled as control at the same period. Results: The rate of hematopoietic reconstitution, the time of neutrophil and platelet engraftment, incidence of chimerism and graft rejection between two groups were not statistically different.The incidence of acute graft-versus-host disease (GVHD) in URD group was significantly higher than that in MSD group [42.9%(6/14) vs 10.5%(2/19), P =0.047]. The incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD in URD were higher than those in MSD group [21.4%(3/14) vs 5.3%(1/19), P =0.288; 35.7%(5/14) vs 5.3%(1/19), P =0.062, respectively], yet without significant difference between two groups. Other transplant-related complications including pulmonary complications, hemorrhagic cystitis, incidence of EBV and CMV reactivation and venous occlusive disease were comparable with two regimens. Estimated 5-years overall survival (OS) rate and disease free survival (DFS) rate were not statistically significant between URD group and MSD group [(84.4±6.6)% vs (89.4±7.1)%, (82.5±5.4)% vs (82.1±4.3)%; P =0.766, P =0.884, respectively]. Conclusions: By multivariate analysis, the outcome of URD allo-HSCT in SAA children and adolescent is similar to MSD allo-HSCT. It could be an alternative option as the first-line treatment for SAA children and adolescents without HLA matched sibling donors.

Human umbilical cord derived mesenchymal stem cells promote interleukin-17 production from human peripheral blood mononuclear cells of healthy donors and systemic lupus erythematosus patients.

Science.gov (United States)

Ren, S; Hu, J; Chen, Y; Yuan, T; Hu, H; Li, S

2016-03-01

Inflammation instigated by interleukin (IL)-17-producing cells is central to the development and pathogenesis of several human autoimmune diseases and animal models of autoimmunity. The expansion of IL-17-producing cells from healthy donors is reportedly promoted by mesenchymal stem cells derived from fetal bone marrow. In the present study, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were examined for their effects on lymphocytes from healthy donors and from patients with systemic lupus erythematosus (SLE). Significantly higher levels of IL-17 were produced when CD4(+) T cells from healthy donors were co-cultured with hUC-MSCs than those that were cultured alone. Blocking experiments identified that this effect might be mediated partially through prostaglandin E2 (PGE2 ) and IL-1β, without IL-23 involvement. We then co-cultured hUC-MSCs with human CD4(+) T cells from systemic lupus erythematosus patients. Ex-vivo inductions of IL-17 by hUC-MSCs in stimulated lymphocytes were significantly higher in SLE patients than in healthy donors. This effect was not observed for IL-23. Taken together, our results represent that hUC-MSCs can promote the IL-17 production from CD4(+) T cells in both healthy donor and SLE patients. PGE2 and IL-1β might also be partially involved in the promotive effect of hUC-MSCs. © 2015 British Society for Immunology.

A comparison between allogeneic stem cell transplantation from unmanipulated haploidentical and unrelated donors in acute leukemia

Directory of Open Access Journals (Sweden)

Simona Piemontese

2017-01-01

Full Text Available Abstract Background In the absence of a HLA-matched related or matched unrelated donor, allogeneic stem cell transplantation (allo-SCT from mismatched unrelated donors or haploidentical donors are potential alternatives for patients with acute leukemia with an indication to allo-SCT. The objective of this study was to compare the outcome of allo-SCT from T cell-replete haploidentical (Haplo versus matched (MUD 10/10 or mismatched unrelated donor at a single HLA-locus (MMUD 9/10 for patients with acute leukemia in remission. Methods Two hundred sixty-five adult patients with de novo acute leukemia in first or second remission that received a Haplo-SCT between January 2007 and December 2013 were compared with 2490 patients receiving a MUD 10/10 and 813 receiving a MMUD 9/10. Propensity score weighted analysis was conducted in order to control for disease risk imbalances between the groups. Results The weighted 3-year non-relapse mortality and relapse incidence were 29 and 30% for Haplo, 21 and 29% for MUD 10/10, and 29 and 25% for MMUD 9/10, respectively. The weighted 3-year leukemia-free survival (LFS and overall survival (OS were 41 and 46% for Haplo, 50 and 56% for MUD 10/10, and 46 and 48% for MMUD 9/10, respectively. Using weighted Cox model, both LFS and OS were significantly higher in transplants from MUD 10/10 compared from those in Haplo but not different between transplants from MMUD 9/10 and Haplo. The type of donor was not significantly associated with neither acute nor chronic graft-versus-host disease. Conclusions Patients with acute leukemia in remission have better outcomes if transplanted from a MUD 10/10. We did not find any significant difference in outcome between transplants from MMUD 9/10 and Haplo, suggesting that both can be equally used in the absence of a 10/10 MUD. Key point 1 Better outcomes using fully (10/10 matched unrelated donor for allo-SCT in acute leukemia in remission. Key point 2 Similar outcomes after allo

Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation.

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Ljungman, Per; Brand, Ronald; Hoek, Jennifer; de la Camara, Rafael; Cordonnier, Catherine; Einsele, Hermann; Styczynski, Jan; Ward, Katherine N; Cesaro, Simone

2014-08-15

The use of a cytomegalovirus (CMV)-seronegative donor for a CMV-seronegative allogeneic hematopoietic stem cell transplant (HSCT) recipient is generally accepted. However, the importance of donor serostatus in CMV-seropositive patients is controversial. A total of 49 542 HSCT patients, 29 349 seropositive and 20 193 seronegative, were identified from the European Group for Blood and Marrow Transplantation database. Cox multivariate models were fitted to estimate the effect of donor CMV serological status on outcome. Seronegative patients receiving seropositive unrelated-donor grafts had decreased overall survival (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21; P donors, whereas no difference was seen in patients receiving HLA-matched sibling grafts. Seropositive patients receiving grafts from seropositive unrelated donors had improved overall survival (HR, 0.92; 95% CI, .86-.98; P donors, if they had received myeloablative conditioning. This effect was absent when they received reduced-intensity conditioning. No effect was seen in patients grafted from HLA-identical sibling donors. The same association was found if the study was limited to patients receiving transplants from the year 2000 onward. We confirm the negative impact on overall survival if a CMV-seropositive unrelated donor is selected for a CMV-seronegative patient. For a CMV-seropositive patient, our data support selecting a CMV-seropositive donor if the patient receives a myeloablative conditioning regimen. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cost-effective master cell bank validation of multiple clinical-grade human pluripotent stem cell lines from a single donor.

Science.gov (United States)

Devito, Liani; Petrova, Anastasia; Miere, Cristian; Codognotto, Stefano; Blakely, Nicola; Lovatt, Archie; Ogilvie, Caroline; Khalaf, Yacoub; Ilic, Dusko

2014-10-01

Standardization guidelines for human pluripotent stem cells are still very broadly defined, despite ongoing clinical trials in the U.S., U.K., and Japan. The requirements for validation of human embryonic (hESCs) and induced pluripotent stem cells (iPSCs) in general follow the regulations for other clinically compliant biologics already in place but without addressing key differences between cell types or final products. In order to realize the full potential of stem cell therapy, validation criteria, methodology, and, most importantly, strategy, should address the shortfalls and efficiency of current approaches; without this, hESC- and, especially, iPSC-based therapy will not be able to compete with other technologies in a cost-efficient way. We addressed the protocols for testing cell lines for human viral pathogens and propose a novel strategy that would significantly reduce costs. It is highly unlikely that the multiple cell lines derived in parallel from a tissue sample taken from one donor would have different profiles of endogenous viral pathogens; we therefore argue that samples from the Master Cell Banks of sibling lines could be safely pooled for validation. We illustrate this approach with tiered validation of two sibling clinical-grade hESC lines, KCL033 and KCL034 (stage 1, sterility; stage 2, specific human pathogens; and stage 3, nonspecific human pathogens). The results of all tests were negative. This cost-effective strategy could also be applied for validation of Master Cell Banks of multiple clinical-grade iPSC lines derived from a single donor. ©AlphaMed Press.

Stem Cell Transplant

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... Graft-versus-host disease: A potential risk when stem cells come from donors If you receive a transplant ... medications and blood products into your body. Collecting stem cells for transplant If a transplant using your own ...

Peripheral blood stem cell collection for allogeneic hematopoietic stem cell transplantation: Practical implications after 200 consequent transplants.

Science.gov (United States)

Goren Sahin, Deniz; Arat, Mutlu

2017-12-01

Proper stem cell mobilization is one of the most important steps in hematopoietic stem cell transplantation (HSCT). The aim of this paper is to share our 6 years' experience and provide practical clinical approaches particularly for stem cell mobilization and collection within the series of more than 200 successive allogeneic HSCT at our transplant center. Two hundred and seven consecutive patients who underwent allogeneic peripheral blood stem cell transplantation were included in this study. Age, sex, weight, complete blood counts, CD34 + cell counts, total collected amount of CD34 + cells, CD34 + cells per 10l processed, mobilization failure and adverse events were reviewed. Median age was 40.2±12.9 (21-68) years and 46.4±13.4 (17-67) years for donors and patients, respectively. The number of donors who had undergone adequate CD34 + cell harvesting and completed the procedure on the fourth day was 67 (32.8% of all patients). Only 12 patients required cell apheresis both on day 5 and 6. Apheresis was completed on day 4 and/or day 5 in 94.2% of all our donors. There was no significant association between CD34 + stem cell volume and age, gender and weight values of donors. Mobilization failure was not seen in our series. G-CSF is highly effective in 1/3 of the donors on the 4th day in order to collect enough number of stem cells. We propose that peripheral stem cell collection might start on day 4th of G-CSF treatment for avoiding G-CSF related side effects and complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

PREDICTIVE VALUE OF CD34+ CELLS IN BLOOD OF PATIENT/DONOR BEFORE HEMATOPOIETIC STEM CELLS COLLECTION BY LEUKAPHERESIS

Directory of Open Access Journals (Sweden)

Dragoslav Domanovič

2004-12-01

Full Text Available Background. In the study we tried to define a predictive value of the circulating CD34+ cells in patients/ donors blood for estimation of the hematopoietic stem cells (HSC collection efficacy determine the optimal time to initiate the collection by leukapheresis procedure.Methods. We retrospectively analyzed 75 collections of HSC using the Amicus cell separator in 39 patients and 15 donors. Circulating CD34+cell counts in patients/donors were compared to the achieved CD34+ cell yields to determine its predictive value for the collection of a targeted yield of > 2 × 106 CD34+ cells/kg body weight of patient.Results. The results of cell counts confirmed that mobilization regimens were successful and HSC collections efficient. High correlation coefficient (r = 0.82 between the number of circulating CD34+ cells before collection and CD34+ cell yield/kg of patient’s body weight was statistically significant (p < 0.05. With ROC analysis we determined the cut-off value 42 × 106/l CD34+ cell counts in the blood of patients/donors before collection that had a positive predictive value 87% and a negative predictive value 91.6%.Conclusions. Analysis showed that the number of circulating CD34+ cells before the procedure express a very high predictive value and can be used for determining the optimal time to initiate collection of HSC by leukapheresis.

Stem cell collection in unmanipulated HLA-haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised blood and bone marrow for patients with haematologic malignancies: the impact of donor characteristics and procedural settings.

Science.gov (United States)

Zhang, C; Chen, X-H; Zhang, X; Gao, L; Gao, L; Kong, P-Y; Peng, X-G; Sun, A-H; Gong, Y; Zeng, D-F; Wang, Q-Y

2010-06-01

Unmanipulated haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilised bone marrow (G-BM) has been developed as an alternative transplantation strategy for patients with haematologic malignancies. However, little information is available about the factors predicting the outcome of peripheral blood stem cell (PBSC) collection and bone marrow (BM) harvest in this transplantation. The effects of donor characteristics and procedure factors on CD34(+) cell yield were investigated. A total of 104 related healthy donors received granulocyte-colony stimulating factor (G-CSF) followed by PBSC collection and BM harvest. Male donors had significantly higher yields compared with female donors. In multiple regression analysis for peripheral blood collection, age and flow rate were negatively correlated with cell yield, whereas body mass index, pre-aphaeresis white blood cell (WBC) and circulating immature cell (CIC) counts were positively correlated with cell yields. For BM harvest, age was negatively correlated with cell yields, whereas pre-BM collection CIC counts were positively correlated with cell yield. All donors achieved the final product of >or=6 x10(6) kg(-1) recipient body weight. This transplantation strategy has been shown to be a feasible approach with acceptable outcomes in stem cell collection for patients who received HLA-haploidentical/mismatched transplantation with combined G-PBSCs and G-BM. In donors with multiple high-risk characteristics for poor aphaeresis CD34(+) cell yield, BM was an alternative source.

Recovery of Unrelated Donors of Peripheral Blood Stem Cells versus Bone Marrow: A Prespecified Analysis from the Phase III BMT CTN Protocol 0201

Science.gov (United States)

Burns, Linda J.; Logan, Brent R.; Chitphakdithai, Pintip; Miller, John P.; Drexler, Rebecca; Spellman, Stephen; Switzer, Galen E.; Wingard, John R.; Anasetti, Claudio; Confer, Dennis L.

2016-01-01

We report a comparison of time to recovery, side effects, and change in blood counts from baseline to post-donation of unrelated donors who participated in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) phase III randomized, multicenter trial (0201) in which donor/recipient pairs were randomized to either peripheral blood stem cell (PBSC) or bone marrow (BM) donation. Of the entire cohort, 262 donated PBSC and 264 donated BM; 372 (71%) donors were from domestic and 154 (29%) from international centers (145 German and 9 Canadian). PBSC donors recovered in less time with a median time to recovery of 1 week compared to 2.3 weeks for BM donors. The number of donors reporting full recovery was significantly greater for donors of PBSC than of BM at 1, 2, and 3 weeks and 3 months post-donation. Multivariate analysis showed that PBSC donors were more likely to recover at any time post donation compared to BM donors (HR 2.08 [95% CI 1.73–2.50], pdonor and donation in more recent years. Donors of BM were more likely to report grade 2–4 skeletal pain, body symptoms and fatigue at 1 week post donation. In logistic regression analysis of domestic donors only in which toxicities at peri-collection time points (day 5 filgrastim for PBSC donors and day 2 post-collection of BM donors) could be analyzed, no variable was significantly associated with grade 2–4 skeletal pain, including product donated (BM vs PBSC, OR 1.13 [95% CI 0.74–1.74], p=0.556). Blood counts were impacted by product donated, with mean change from baseline to post-donation being greater for white blood cells, neutrophils, mononuclear cells and platelets in PBSC donors whereas BM donors experienced a greater mean change in hemoglobin. This analysis provided an enhanced understanding of donor events as product donated was independent of physician bias or donor preference. PMID:27013014

Donating Peripheral Blood Stem Cells

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... Print this page My Cart Donating peripheral blood stem cells Peripheral blood stem cell (PBSC) donation is a nonsurgical procedure to collect ... Donating bone marrow Donor experiences videos Peripheral blood stem cell (PBSC) donation is one of two methods of ...

Myeloid Conditioning with c-kit-Targeted CAR-T Cells Enables Donor Stem Cell Engraftment.

Science.gov (United States)

Arai, Yasuyuki; Choi, Uimook; Corsino, Cristina I; Koontz, Sherry M; Tajima, Masaki; Sweeney, Colin L; Black, Mary A; Feldman, Steven A; Dinauer, Mary C; Malech, Harry L

2018-05-02

We report a novel approach to bone marrow (BM) conditioning using c-kit-targeted chimeric antigen receptor T (c-kit CAR-T) cells in mice. Previous reports using anti-c-kit or anti-CD45 antibody linked to a toxin such as saporin have been promising. We developed a distinctly different approach using c-kit CAR-T cells. Initial studies demonstrated in vitro killing of hematopoietic stem cells by c-kit CAR-T cells but poor expansion in vivo and poor migration of CAR-T cells into BM. Pre-treatment of recipient mice with low-dose cyclophosphamide (125 mg/kg) together with CXCR4 transduction in the CAR-T cells enhanced trafficking to and expansion in BM (c-kit + population (9.0%-0.1%). Because congenic Thy1.1 CAR-T cells were used in the Thy1.2-recipient mice, anti-Thy1.1 antibody could be used to deplete CAR-T cells in vivo before donor BM transplant. This achieved 20%-40% multilineage engraftment. We applied this conditioning to achieve an average of 28% correction of chronic granulomatous disease mice by wild-type BM transplant. Our findings provide a proof of concept that c-kit CAR-T cells can achieve effective BM conditioning without chemo-/radiotherapy. Our work also demonstrates that co-expression of a trafficking receptor can enhance targeting of CAR-T cells to a designated tissue. Published by Elsevier Inc.

Generating pluripotent stem cells: Differential epigenetic changes during cellular reprogramming

OpenAIRE

Tobin, Stacey C.; Kim, Kitai

2012-01-01

Pluripotent stem cells hold enomous potential for therapuetic applications in tissue replacement therapy. Reprogramming somatic cells from a patient donor to generate pluripotent stem cells involves both ethical concerns inherent in the use of embryonic and oocyte-derived stem cells, as well as issues of histocompatibility. Among the various pluripotent stem cells, induced pluripotent stem cells (iPSC)—derived by ectopic expression of four reprogramming factors in donor somatic cells—are supe...

Generation of human induced pluripotent stem cells from a Bombay individual: Moving towards 'universal-donor' red blood cells

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Seifinejad, Ali; Taei, Adeleh [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Totonchi, Mehdi; Vazirinasab, Hamed [Department of Genetics, Royan Institute for Reproductive Biomedicine, ACECR, Tehran (Iran, Islamic Republic of); Hassani, Seideh Nafiseh [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Aghdami, Nasser [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Department of Regenerative Biomedicine, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Shahbazi, Ebrahim [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Yazdi, Reza Salman [Department of Genetics, Royan Institute for Reproductive Biomedicine, ACECR, Tehran (Iran, Islamic Republic of); Salekdeh, Ghasem Hosseini, E-mail: Salekdeh@royaninstitute.org [Department of Molecular Systems Biology, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Department of Systems Biology, Agricultural Biotechnology Research Institute of Iran, Karaj (Iran, Islamic Republic of); Baharvand, Hossein, E-mail: Baharvand@royaninstitute.org [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Department of Regenerative Biomedicine, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Department of Developmental Biology, University of Science and Culture, ACECR, Tehran (Iran, Islamic Republic of)

2010-01-01

Bombay phenotype is one of the rare phenotypes in the ABO blood group system that fails to express ABH antigens on red blood cells. Nonsense or missense mutations in fucosyltransfrase1 (FUT1) and fucosyltransfrase2 (FUT2) genes are known to create this phenotype. This blood group is compatible with all other blood groups as a donor, as it does not express the H antigen on the red blood cells. In this study, we describe the establishment of human induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of a Bombay blood-type individual by the ectopic expression of established transcription factors Klf4, Oct4, Sox2, and c-Myc. Sequence analyses of fibroblasts and iPSCs revealed a nonsense mutation 826C to T (276 Gln to Ter) in the FUT1 gene and a missense mutation 739G to A (247 Gly to Ser) in the FUT2 gene in the Bombay phenotype under study. The established iPSCs resemble human embryonic stem cells in morphology, passaging, surface and pluripotency markers, normal karyotype, gene expression, DNA methylation of critical pluripotency genes, and in-vitro differentiation. The directed differentiation of the iPSCs into hematopoietic lineage cells displayed increased expression of the hematopoietic lineage markers such as CD34, CD133, RUNX1, KDR, {alpha}-globulin, and {gamma}-globulin. Such specific stem cells provide an unprecedented opportunity to produce a universal blood group donor, in-vitro, thus enabling cellular replacement therapies, once the safety issue is resolved.

Umbilical Cord-Derived Mesenchymal Stem Cells for Hematopoietic Stem Cell Transplantation

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Yu-Hua Chao

2012-01-01

Full Text Available Hematopoietic stem cell transplantation (HSCT is becoming an effective therapeutic modality for a variety of diseases. Mesenchymal stem cells (MSCs can be used to enhance hematopoietic engraftment, accelerate lymphocyte recovery, reduce the risk of graft failure, prevent and treat graft-versus-host disease, and repair tissue damage in patients receiving HSCT. Till now, most MSCs for human clinical application have been derived from bone marrow. However, acquiring bone-marrow-derived MSCs involves an invasive procedure. Umbilical cord is rich with MSCs. Compared to bone-marrow-derived MSCs, umbilical cord-derived MSCs (UCMSCs are easier to obtain without harm to the donor and can proliferate faster. No severe adverse effects were noted in our previous clinical application of UCMSCs in HSCT. Accordingly, application of UCMSCs in humans appears to be feasible and safe. Further studies are warranted.

Liver fibrosis alleviation after co-transplantation of hematopoietic stem cells with mesenchymal stem cells in patients with thalassemia major.

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Ghavamzadeh, Ardeshir; Sotoudeh, Masoud; Hashemi Taheri, Amir Pejman; Alimoghaddam, Kamran; Pashaiefar, Hossein; Jalili, Mahdi; Shahi, Farhad; Jahani, Mohammad; Yaghmaie, Marjan

2018-02-01

The aims of this study are to determine the replacement rate of damaged hepatocytes by donor-derived cells in sex-mismatched recipient patients with thalassemia major and to determine whether co-transplantation of mesenchymal stem cells and hematopoietic stem cells (HSCs) can alleviate liver fibrosis. Ten sex-mismatched donor-recipient pairs who received co-transplantation of HSCs with mesenchymal stem cells were included in our study. Liver biopsy was performed before transplantation. Two other liver biopsies were performed between 2 and 5 years after transplantation. The specimens were studied for the presence of donor-derived epithelial cells or hepatocytes using fluorescence in situ hybridization by X- and Y-centromeric probes and immunohistochemical staining for pancytokeratin, CD45, and a hepatocyte-specific antigen. All sex-mismatched tissue samples demonstrated donor-derived hepatocyte independent of donor gender. XY-positive epithelial cells or hepatocytes accounted for 11 to 25% of the cells in histologic sections of female recipients in the first follow-up. It rose to 47-95% in the second follow-up. Although not statistically significant, four out of ten patients showed signs of improvement in liver fibrosis. Our results showed that co-transplantation of HSC with mesenchymal stem cells increases the rate of replacement of recipient hepatocytes by donor-derived cells and may improve liver fibrosis.

Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

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Eolia Brissot

2017-06-01

Full Text Available Abstract Background Primary refractory acute myeloid leukemia (PRF-AML is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML. Methods The current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660 versus unrelated donors (n = 381, for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results HSCT provide patients with PRF-AML a 2-year leukemia-free survival and overall survival of about 25 and 30%, respectively. In multivariate analysis, two predictive factors, cytogenetics and time from diagnosis to transplant, were associated with lower leukemia-free survival, whereas Karnofsky performance status at transplant ≥90% was associated with better leukemia-free survival (LFS. Concerning relapse incidence, cytogenetics and time from diagnosis to transplant were associated with increased relapse. Reduced intensity conditioning regimen was the only factor associated with lower non-relapse mortality. Conclusions HSCT was able to rescue about one quarter of the patients with PRF-AML. The donor type did not have any impact on PRF patients’ outcomes. In contrast, time to transplant was a major prognostic factor for LFS. For patients with PRF-AML who do not have a matched sibling donor, HSCT from an

Reduced reactivation from dormancy but maintained lineage choice of human mesenchymal stem cells with donor age.

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Verena Dexheimer

Full Text Available UNLABELLED: Mesenchymal stem cells (MSC are promising for cell-based regeneration therapies but up to date it is still controversial whether their function is maintained throughout ageing. Aim of this study was to address whether frequency, activation in vitro, replicative function, and in vitro lineage choice of MSC is maintained throughout ageing to answer the question whether MSC-based regeneration strategies should be restricted to younger individuals. MSC from bone marrow aspirates of 28 donors (5-80 years were characterized regarding colony-forming unit-fibroblast (CFU-F numbers, single cell cloning efficiency (SSCE, osteogenic, adipogenic and chondrogenic differentiation capacity in vitro. Alkaline phosphatase (ALP activity, mineralization, Oil Red O content, proteoglycan- and collagen type II deposition were quantified. While CFU-F frequency was maintained, SSCE and early proliferation rate decreased significantly with advanced donor age. MSC with higher proliferation rate before start of induction showed stronger osteogenic, adipogenic and chondrogenic differentiation. MSC with high osteogenic capacity underwent better chondrogenesis and showed a trend to better adipogenesis. Lineage choice was, however, unaltered with age. CONCLUSION: Ageing influenced activation from dormancy and replicative function of MSC in a way that it may be more demanding to mobilize MSC to fast cell growth at advanced age. Since fast proliferation came along with high multilineage capacity, the proliferation status of expanded MSC rather than donor age may provide an argument to restrict MSC-based therapies to certain individuals.

Generation of human induced pluripotent stem cells from urinary cells of a healthy donor using a non-integration system

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Uhm, Kyung-Ok; Jo, Eun Hee; Go, Gue Youn; Kim, So-Jung; Choi, Hye Young; Im, Young Sam; Ha, Hye-Yeong; Jung, Ji-Won; Koo, Soo Kyung

2017-01-01

Urinary cells can be an ideal source for generating hiPSCs and progenitors, as they are easily accessible, non-invasive, and universally available. We generated human induced pluripotent stem cells (hiPSCs) from the urinary cells of a healthy donor using a Sendai virus-based gene delivery method. The generated hiPSC line, KSCBi001-A, has a normal karyotype (46,XY). The pluripotency and capacity of multilineage differentiation were characterized by comparison with those of a human embryonic st...

Nuclear Nox4 Role in Stemness Power of Human Amniotic Fluid Stem Cells

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Tullia Maraldi

2015-01-01

Full Text Available Human amniotic fluid stem cells (AFSC are an attractive source for cell therapy due to their multilineage differentiation potential and accessibility advantages. However the clinical application of human stem cells largely depends on their capacity to expand in vitro, since there is an extensive donor-to-donor heterogeneity. Reactive oxygen species (ROS and cellular oxidative stress are involved in many physiological and pathophysiological processes of stem cells, including pluripotency, proliferation, differentiation, and stress resistance. The mode of action of ROS is also dependent on the localization of their target molecules. Thus, the modifications induced by ROS can be separated depending on the cellular compartments they affect. NAD(PH oxidase family, particularly Nox4, has been known to produce ROS in the nucleus. In the present study we show that Nox4 nuclear expression (nNox4 depends on the donor and it correlates with the expression of transcription factors involved in stemness regulation, such as Oct4, SSEA-4, and Sox2. Moreover nNox4 is linked with the nuclear localization of redox sensitive transcription factors, as Nrf2 and NF-κB, and with the differentiation potential. Taken together, these results suggest that nNox4 regulation may have important effects in stem cell capability through modulation of transcription factors and DNA damage.

Improved survival of acute lymphoblastic leukemia patients of HLA-A3/11 absent for donor KIR3DL2 after non-T-cell depleted HLA-identical sibling hematopoietic stem cells transplantation

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farhad shahsavar

2011-08-01

Conclusion: These data indicate that the absence of HLA class I ligand in the recipient for donor-inhibitory KIR can be a prognostic factor for transplantation outcomes in non-T-cell depleted HLA-identical sibling hematopoietic stem-cell transplantation and that the lack of HLA-A3/11 for donor KIR3DL2 can contribute to improved survival for patients with ALL.

Multilineage potential and proteomic profiling of human dental stem cells derived from a single donor

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Patil, Rajreddy; Kumar, B. Mohana; Lee, Won-Jae; Jeon, Ryoung-Hoon; Jang, Si-Jung; Lee, Yeon-Mi; Park, Bong-Wook; Byun, June-Ho; Ahn, Chun-Seob; Kim, Jae-Won; Rho, Gyu-Jin

2014-01-01

Dental tissues provide an alternative autologous source of mesenchymal stem cells (MSCs) for regenerative medicine. In this study, we isolated human dental MSCs of follicle, pulp and papilla tissue from a single donor tooth after impacted third molar extraction by excluding the individual differences. We then compared the morphology, proliferation rate, expression of MSC-specific and pluripotency markers, and in vitro differentiation ability into osteoblasts, adipocytes, chondrocytes and functional hepatocyte-like cells (HLCs). Finally, we analyzed the protein expression profiles of undifferentiated dental MSCs using 2DE coupled with MALDI-TOF-MS. Three types of dental MSCs largely shared similar morphology, proliferation potential, expression of surface markers and pluripotent transcription factors, and differentiation ability into osteoblasts, adipocytes, and chondrocytes. Upon hepatogenic induction, all MSCs were transdifferentiated into functional HLCs, and acquired hepatocyte functions by showing their ability for glycogen storage and urea production. Based on the proteome profiling results, we identified nineteen proteins either found commonly or differentially expressed among the three types of dental MSCs. In conclusion, three kinds of dental MSCs from a single donor tooth possessed largely similar cellular properties and multilineage potential. Further, these dental MSCs had similar proteomic profiles, suggesting their interchangeable applications for basic research and call therapy. - Highlights: • Isolated and characterized three types of human dental MSCs from a single donor. • MSCs of dental follicle, pulp and papilla had largely similar biological properties. • All MSCs were capable of transdifferentiating into functional hepatocyte-like cells. • 2DE proteomics with MALDI-TOF/MS identified 19 proteins in three types of MSCs. • Similar proteomic profiles suggest interchangeable applications of dental MSCs

Multilineage potential and proteomic profiling of human dental stem cells derived from a single donor

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Patil, Rajreddy; Kumar, B. Mohana; Lee, Won-Jae; Jeon, Ryoung-Hoon; Jang, Si-Jung; Lee, Yeon-Mi [Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Park, Bong-Wook; Byun, June-Ho [Department of Oral and Maxillofacial Surgery, School of Medicine and Institute of Health Science, Gyeongsang National University, Jinju 660-702 (Korea, Republic of); Ahn, Chun-Seob; Kim, Jae-Won [Department of Microbiology, Division of Life Sciences, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Rho, Gyu-Jin, E-mail: jinrho@gnu.ac.kr [Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Research Institute of Life Sciences, Gyeongsang National University, Jinju 660-701 (Korea, Republic of)

2014-01-01

Dental tissues provide an alternative autologous source of mesenchymal stem cells (MSCs) for regenerative medicine. In this study, we isolated human dental MSCs of follicle, pulp and papilla tissue from a single donor tooth after impacted third molar extraction by excluding the individual differences. We then compared the morphology, proliferation rate, expression of MSC-specific and pluripotency markers, and in vitro differentiation ability into osteoblasts, adipocytes, chondrocytes and functional hepatocyte-like cells (HLCs). Finally, we analyzed the protein expression profiles of undifferentiated dental MSCs using 2DE coupled with MALDI-TOF-MS. Three types of dental MSCs largely shared similar morphology, proliferation potential, expression of surface markers and pluripotent transcription factors, and differentiation ability into osteoblasts, adipocytes, and chondrocytes. Upon hepatogenic induction, all MSCs were transdifferentiated into functional HLCs, and acquired hepatocyte functions by showing their ability for glycogen storage and urea production. Based on the proteome profiling results, we identified nineteen proteins either found commonly or differentially expressed among the three types of dental MSCs. In conclusion, three kinds of dental MSCs from a single donor tooth possessed largely similar cellular properties and multilineage potential. Further, these dental MSCs had similar proteomic profiles, suggesting their interchangeable applications for basic research and call therapy. - Highlights: • Isolated and characterized three types of human dental MSCs from a single donor. • MSCs of dental follicle, pulp and papilla had largely similar biological properties. • All MSCs were capable of transdifferentiating into functional hepatocyte-like cells. • 2DE proteomics with MALDI-TOF/MS identified 19 proteins in three types of MSCs. • Similar proteomic profiles suggest interchangeable applications of dental MSCs.

Total body irradiation in hematopoietic stem cell transplantation

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Fundagul Andic

2014-06-01

Full Text Available Total body irradiation is used in conjunction with chemotherapy as a conditioning regimen in the treatment of many disease such as leukemia, myelodysplastic syndrome, aplastic anemia, multiple myeloma and lymphoma prior to the hematopoetic stem cell transplantation. The main purposes of the hematopoetic stem cell transplantation are eradication of the recipient bone marrow and any residual cancer cells, creation of space in the receipient bone marrow for donor hematopoetic stem cells, and immunosuppression to prevent rejection of donor stem cells in the case of an allotransplant. [Archives Medical Review Journal 2014; 23(3.000: 398-410

Blood-Forming Stem Cell Transplants

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... 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 ...

Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment

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Brend Ray-Sea Hsu

2017-01-01

Full Text Available The aim of this study was to investigate whether tolerance-induced protection of islets in the renal subcapsular space can also prevent subcutaneous allogeneic islets from being rejected. We used bone marrow stem cells from C57BL/6 (H2b mice to construct donor chimerism in conditioned diabetic BALB/c (H2d mice and investigated the effect of donor chimerism on engraftment and survival of subcutaneously transplanted allogeneic islets in streptozotocin-induced diabetic mice. We also studied the anti-inflammatory effect of mesenchymal stem cell on islet engraftment. Full but not low-grade or no donor chimerism was associated with successful engraftment of allogeneic islets and restoration of normoglycemia in the treated diabetic mice. The temporary hyperglycemia was 11 ± 1 versus 19 ± 5 days (p<0.05 for the mice with full donor chimerism with transplanted islets in the renal subcapsular space versus the subcutaneous space, respectively. Cotransplantation of mesenchymal stem cell did not enhance alloislet engraftment. Full multilineage donor chimerism was associated with a higher transient expansion of CD11b+ and Gr-1+ myeloid progenitor cells and effector memory CD4 and CD8 T cells. In conclusion, full donor chimerism protected both renal subcapsular and subcutaneous allogeneic islets in this rodent transplantation model.

GVHD (Graft-Versus-Host Disease): A Guide for Patients and Families After Stem Cell Transplant

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... Disease): A guide for patients and families after stem cell transplant The immune system is the body's tool ... and attacking them. When you receive a donor's stem cells (the “graft”), the stem cells recreate the donor's ...

Haematopoietic transplants combining a single unrelated cord blood unit and mobilized haematopoietic stem cells from an adult HLA-mismatched third party donor. Comparable results to transplants from HLA-identical related donors in adults with acute leukaemia and myelodysplastic syndromes.

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Sebrango, Ana; Vicuña, Isabel; de Laiglesia, Almudena; Millán, Isabel; Bautista, Guiomar; Martín-Donaire, Trinidad; Regidor, Carmen; Cabrera, Rafael; Fernandez, Manuel N

2010-06-01

We describe results of the strategy, developed by our group, of co-infusion of mobilized haematopoietic stem cells as a support for single-unit unrelated cord blood transplant (dual CB/TPD-MHSC transplants) for treatment of haematological malignancies in adults, and a comparative analysis of results obtained using this strategy and transplants performed with mobilized haematopoietic stem cells from related HLA-identical donors (RTD) for treatment of adults with acute leukaemia and myelodysplastic syndromes. Our data show that the dual CB/TPD-MHSC transplant strategy results in periods of post-transplant neutropenia, final rates of full donor chimerism and transplant-related mortality rates comparable to those of the RTD. Final survival outcomes are comparable in adults transplanted because of acute leukaemia, with different incidences of the complications that most influence these: a higher incidence of infections related to late recovery of protective immunity dependent on T cell functions, and a lower incidence of serious acute graft-versus-host disease and relapses. Recent advances in cord blood transplant techniques allow allogeneic haematopoietic stem cell transplantation (HSCT) to be a viable option for almost every patient who may benefit from this therapeutic approach. Development of innovative strategies to improve the post-transplant recovery of T cells function is currently the main challenge to further improving the possibilities of unrelated cord blood transplantation. Copyright © 2010 Elsevier Ltd. All rights reserved.

Reduced-intensity conditioning for alternative donor hematopoietic stem cell transplantation in patients with dyskeratosis congenita.

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Nishio, Nobuhiro; Takahashi, Yoshiyuki; Ohashi, Haruhiko; Doisaki, Sayoko; Muramatsu, Hideki; Hama, Asahito; Shimada, Akira; Yagasaki, Hiroshi; Kojima, Seiji

2011-03-01

DC is an inherited bone marrow failure syndrome mainly characterized by nail dystrophy, abnormal skin pigmentation, and oral leukoplakia. Bone marrow failure is the most common cause of death in patients with DC. Because previous results of HSCT with a myeloablative regimen were disappointing, we used a reduced-intensity conditioning regimen for two patients with classic DC, and one patient with cryptic DC who harbored the TERT mutation. Graft sources included two mismatched-related bone marrow (BM) donors and one unrelated BM donor. Successful engraftment was achieved with few regimen-related toxicities in all patients. They were alive 10, 66, and 72 months after transplantation, respectively. Long-term follow-up is crucial to determine the late effects of our conditioning regimen. © 2010 John Wiley & Sons A/S.

Isolation of highly suppressive CD25+FoxP3+ T regulatory cells from G-CSF-mobilized donors with retention of cytotoxic anti-viral CTLs: application for multi-functional immunotherapy post stem cell transplantation.

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Edward R Samuel

Full Text Available Previous studies have demonstrated the effective control of cytomegalovirus (CMV infections post haematopoietic stem cell transplant through the adoptive transfer of donor derived CMV-specific T cells (CMV-T. Strategies for manufacturing CMV immunotherapies has involved a second leukapheresis or blood draw from the donor, which in the unrelated donor setting is not always possible. We have investigated the feasibility of using an aliquot of the original G-CSF-mobilized graft as a starting material for manufacture of CMV-T and examined the activation marker CD25 as a targeted approach for identification and isolation following CMVpp65 peptide stimulation. CD25+ cells isolated from G-CSF-mobilized apheresis revealed a significant increase in the proportion of FoxP3 expression when compared with conventional non-mobilized CD25+ cells and showed a superior suppressive capacity in a T cell proliferation assay, demonstrating the emergence of a population of Tregs not present in non-mobilized apheresis collections. The expansion of CD25+ CMV-T in short-term culture resulted in a mixed population of CD4+ and CD8+ T cells with CMV-specificity that secreted cytotoxic effector molecules and lysed CMVpp65 peptide-loaded phytohaemagglutinin-stimulated blasts. Furthermore CD25 expanded cells retained their suppressive capacity but did not maintain FoxP3 expression or secrete IL-10. In summary our data indicates that CD25 enrichment post CMV stimulation in G-CSF-mobilized PBMCs results in the simultaneous generation of both a functional population of anti-viral T cells and Tregs thus illustrating a potential single therapeutic strategy for the treatment of both GvHD and CMV reactivation following allogeneic haematopoietic stem cell transplantation. The use of G-CSF-mobilized cells as a starting material for cell therapy manufacture represents a feasible approach to alleviating the many problems incurred with successive donations and procurement of cells from

Human decellularized bone scaffolds from aged donors show improved osteoinductive capacity compared to young donor bone.

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Christopher A Smith

Full Text Available To improve the safe use of allograft bone, decellularization techniques may be utilized to produce acellular scaffolds. Such scaffolds should retain their innate biological and biomechanical capacity and support mesenchymal stem cell (MSC osteogenic differentiation. However, as allograft bone is derived from a wide age-range, this study aimed to determine whether donor age impacts on the ability an osteoinductive, acellular scaffold produced from human bone to promote the osteogenic differentiation of bone marrow MSCs (BM-MSC. BM-MSCs from young and old donors were seeded on acellular bone cubes from young and old donors undergoing osteoarthritis related hip surgery. All combinations resulted in increased osteogenic gene expression, and alkaline phosphatase (ALP enzyme activity, however BM-MSCs cultured on old donor bone displayed the largest increases. BM-MSCs cultured in old donor bone conditioned media also displayed higher osteogenic gene expression and ALP activity than those exposed to young donor bone conditioned media. ELISA and Luminex analysis of conditioned media demonstrated similar levels of bioactive factors between age groups; however, IGF binding protein 1 (IGFBP1 concentration was significantly higher in young donor samples. Additionally, structural analysis of old donor bone indicated an increased porosity compared to young donor bone. These results demonstrate the ability of a decellularized scaffold produced from young and old donors to support osteogenic differentiation of cells from young and old donors. Significantly, the older donor bone produced greater osteogenic differentiation which may be related to reduced IGFBP1 bioavailability and increased porosity, potentially explaining the excellent clinical results seen with the use of allograft from aged donors.

Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia

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Bo Cai

2016-11-01

Full Text Available Abstract Background Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. Case presentation We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC following induction chemotherapy. Undetectable minimal residual disease by flow cytometry was achieved, and full donor cell engraftment was established. The transient release of cytokines and mild fever were detected. Significantly elevated serum lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic transaminase were observed from days 14 to 18, all of which were reversible after immunosuppressive therapy. Conclusions Our preliminary results suggest that co-infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may induce full donor engraftment in relapsed and refractory ALL including elderly patients, but complications related to donor cell infusions should still be cautioned. Trial registration Allogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT02799550

The Core of Sibling Stem Cell Donation - A Grounded Theory Study.

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Kisch, Annika M; Forsberg, Anna

2017-01-01

There is a lack of theoretical framework supporting stem cell transplant nurses in their assessment, judgment and caring interventions of sibling stem cell donors. The purpose of this study was to explore sibling stem cell donors' main concerns and how they deal with them before and after donation. Ten healthy sibling donors, 5 men and 5 women, with a median age of 54 years were included in this study when they were due to donate stem cells to a brother or sister. Data were collected prospectively on three occasions (before the donation and three and twelve months after it) through in-depth interviews, which were recorded and transcribed verbatim for analysis by the Grounded Theory method according to Charmaz. This study describes the efforts of the ten donors to fulfil their duty as a sibling by doing what they considered necessary in order to help. Their efforts were summarised in a process wherein the grounded theory generated three main categories; Prepare, Promote and Preserve. A clear path of transition leading to fulfilment is evident, starting before the donation and continuing for one year afterwards. Being a sibling stem cell donor means doing what you have to do to fulfil your duty and if possible, saving the life of a seriously ill brother or sister. The relationship between the siblings is strengthened by the donation process. Sibling stem cell donation appears to be about fulfilment and the theoretical framework may support clinicians in their evaluation and support of donors.

Two subpopulations of stem cells for T cell lineage

International Nuclear Information System (INIS)

Katsura, Y.; Amagai, T.; Kina, T.; Sado, T.; Nishikawa, S.

1985-01-01

An assay system for the stem cell that colonizes the thymus and differentiates into T cells was developed, and by using this assay system the existence of two subpopulations of stem cells for T cell lineage was clarified. Part-body-shielded and 900-R-irradiated C57BL/6 (H-2b, Thy-1.2) recipient mice, which do not require the transfer of pluripotent stem cells for their survival, were transferred with cells from B10 X Thy-1.1 (H-2b, Thy-1.1) donor mice. The reconstitution of the recipient's thymus lymphocytes was accomplished by stem cells in the donor cells and those spared in the shielded portion of the recipient that competitively colonize the thymus. Thus, the stem cell activity of donor cells can be evaluated by determining the proportion of donor-type (Thy-1.1+) cells in the recipient's thymus. Bone marrow cells were the most potent source of stem cells. By contrast, when the stem cell activity was compared between spleen and bone marrow cells of whole-body-irradiated (800 R) C57BL/6 mice reconstituted with B10 X Thy-1.1 bone marrow cells by assaying in part-body-shielded and irradiated C57BL/6 mice, the activity of these two organs showed quite a different time course of development. The results strongly suggest that the stem cells for T cell lineage in the bone marrow comprise at least two subpopulations, spleen-seeking and bone marrow-seeking cells

Donor Satellite Cell Engraftment is Significantly Augmented When the Host Niche is Preserved and Endogenous Satellite Cells are Incapacitated

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Boldrin, Luisa; Neal, Alice; Zammit, Peter S; Muntoni, Francesco; Morgan, Jennifer E

2012-01-01

Stem cell transplantation is already in clinical practice for certain genetic diseases and is a promising therapy for dystrophic muscle. We used the mdx mouse model of Duchenne muscular dystrophy to investigate the effect of the host satellite cell niche on the contribution of donor muscle stem cells (satellite cells) to muscle regeneration. We found that incapacitation of the host satellite cells and preservation of the muscle niche promote donor satellite cell contribution to muscle regeneration and functional reconstitution of the satellite cell compartment. But, if the host niche is not promptly refilled, or is filled by competent host satellite cells, it becomes nonfunctional and donor engraftment is negligible. Application of this regimen to aged host muscles also promotes efficient regeneration from aged donor satellite cells. In contrast, if the niche is destroyed, yet host satellite cells remain proliferation-competent, donor-derived engraftment is trivial. Thus preservation of the satellite cell niche, concomitant with functional impairment of the majority of satellite cells within dystrophic human muscles, may improve the efficiency of stem cell therapy. Stem Cells2012;30:1971–1984 PMID:22730231

Unrelated haematopoietic stem cell transplantation in Taiwan and beyond.

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Yang, K L; Chang, C Y; Lin, S; Shyr, M H; Lin, P Y

2009-06-01

Since its inception in October 1993, the world-renowned Buddhist Tzu Chi Marrow Donor Registry has facilitated more than 1800 cases of stem cell donations for patients in 27 countries to date. Under the auspices of the Buddhist Tzu Chi Stem Cells Center (BTCSCC), the Registry (> 310,000 donors) offers, on average, one case of stem cell donation every day to national or international transplantation community. The accomplishment of the Registry stems from the philosophy and spirit of giving without reward that was inspired by its founder Dharma Master Cheng Yen, the Samaritan devotions of selfless voluntary stem cell donors and the efforts from a dedicated network of volunteer workers. Demographically speaking, slightly less than one third of the donations are provided to domestic patients and the rest to mainland China and countries in Asia, North America, Europe, Middle East, Oceania, and South Africa. While most of the patients belong to the Oriental ethnic group, a few of the patients are non-Oriental. In addition to the Registry, a non-profit umbilical cord blood (UCB) bank is operating since 2002 to provide a complimentary role for patients unable to identify appropriate bone marrow stem cell donors in the Registry in time. To date, with an inventory of over 12,000 units of UCB cryopreserved in the Tzu Chi Cord Blood Bank, 47 units have been employed in 37 cases of transplantation for both paediatric and adult patients domestically and internationally. The fact that Buddhist Tzu Chi Marrow Donor Registry and Cord Blood Bank are established and operating without governmental financial support is unique and special. To facilitate haematopoietic stem cells to its domestic patients experiencing financial burdens, the BTCSCC offers financial aids to the underprivileged for their medical relief. This humanitarian approach and compassion is definitely a role model for many countries in the world.

HLA-Matched Sibling versus Unrelated versus Haploidentical Related Donor Allogeneic Hematopoietic Stem Cell Transplantation for Patients Aged Over 60 Years with Acute Myeloid Leukemia: A Single-Center Donor Comparison.

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Devillier, Raynier; Legrand, Faezeh; Rey, Jérôme; Castagna, Luca; Fürst, Sabine; Granata, Angela; Charbonnier, Aude; Harbi, Samia; d'Incan, Evelyne; Pagliardini, Thomas; Faucher, Catherine; Lemarie, Claude; Saillard, Colombe; Calmels, Boris; Mohty, Bilal; Maisano, Valerio; Weiller, Pierre-Jean; Chabannon, Christian; Vey, Norbert; Blaise, Didier

2018-02-12

Haploidentical related donor (HRD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) was developed as a valid option for the treatment of acute myeloid leukemia (AML) in the absence of a matched donor. However, many investigators are reluctant to consider the use of this alternative in elderly patients, anticipating high morbidity. Here, we report a single-center comparison of HRD versus matched sibling donor (MSD) and unrelated donor (UD) allo-HSCT for patients with AML aged ≥60 years. Ninety-four patients (MSD: n = 31; UD: n = 30; HRD: n = 33) were analyzed. The median age was 65 (range, 60 to 73) years. We observed a higher cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) after UD allo-HSCT (MSD versus UD versus HRD: 3% versus 33% versus 6%, respectively; P = .006). Two-year cumulative incidence of moderate or severe chronic GVHD was 17%, 27%, and 16% in the MSD, UD, and HRD groups, respectively (P = .487). No difference was observed in the 2-year cumulative incidence of relapse or nonrelapse mortality (NRM) (relapse: MSD versus UD versus HRD: 32% versus 25% versus 25%, respectively; P = .411; NRM: MSD versus UD versus HRD: 19% versus 27% versus 24%, respectively; P = .709). At 2 years, progression-free survival, overall survival, and GVHD- and relapse-free survival were 48%, 50%, and 39%, respectively, in the MSD group; 48%, 51%, and 23%, respectively, in the UD group; and 50%, 52%, and 32%, respectively, in the HRD group, without statistically significant differences between the groups. We conclude that HRD allo-HSCT is highly feasible and no less efficient than MSD or UD allo-HSCT in patients with AML aged ≥60 years. Thus, the absence of a HLA-identical donor should not limit the consideration of allo-HSCT for the treatment of AML. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Factors Influencing Hematopoietic Stem Cell Donation Intention in Hong Kong: A Web-Based Survey.

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Kwok, Janette; Leung, Eva; Wong, William; Leung, Kate; Lee, Cheuk Kwong; Lam, Wendy; Ip, Patrick

2015-10-08

Hematopoietic stem cell transplantation (HSCT) has become increasingly common for treatment of severe hematological disorders. However, the number of compatible hematopoietic stem cell (HSC) donors is usually limited. Expanding donor pool size would enhance matching success by increasing donor frequency and introducing allelic diversity within the registry. Identifying factors that affect public willingness towards HSC donation allows better strategic recruitment planning to facilitate donor pool expansion. Previous studies in white populations showed knowledge, family attitude, trust towards the healthcare system, fear, self-identity, and social identity are important factors related to HSC donation intention. However, given the differences in cultural and society values that exist across different regions, in particular between the East and West, whether these factors influence HSC donation willingness in Hong Kong remained to be determined. The objective of this study was to identify factors associated with HSC donation motivation in Hong Kong. A large-scale, cross-sectional, observational study involving 3479 local participants. There is a positive correlation of HSC donation intention with younger age (18-32, OR: 1.80, p≤0·001) and higher education (OR: 1·47, p≤0.001). Better HSCT knowledge is also related to greater HSC donation intention (OR: 2.55, p£0.001). Our data suggests HSCT education could help to improve donor recruitment and that more resources should be allocated for public education.

Donor-Cell Origin High-Risk Myelodysplastic Syndrome Synchronous with an Intracranial Meningioma-Like Tumor, 8 Years after Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia

Directory of Open Access Journals (Sweden)

G. Brás

2017-01-01

Full Text Available Secondary neoplasias are well known consequences of radiotherapy or chemotherapy for a primary cancer. In this report, we describe two rare secondary neoplasias occurring in the same patient: a meningioma-like intracranial tumor and high-risk myelodysplastic syndrome (MDS of donor-cells origin, both diagnosed simultaneously, 8 years after an allogeneic hematopoietic stem cell transplantation (allo-HSCT for chronic lymphocytic leukemia (CLL. Due to an engraftment failure during the first allo-HSCT of a matched related donor for CLL treatment, the salvage treatment was a second allo-HSCT. At the moment of meningioma-like tumor diagnosis, the patient was pancytopenic due to high-risk MDS, so it was decided to postpone a surgical intervention until hematological improvement. For the high-risk MDS of donor-cells origin the chosen treatment was induction with intensive chemotherapy. Due to refractory disease, the patient was treated with 5-azacitidine and donor-lymphocytes infusion with no response and, finally, a third allo-HSCT of a matched unrelated donor was performed. The patient died 6 months after the third allo-HSCT, in cytogenetic remission but without hematological recovery, due to an intracranial hemorrhage with origin in the meningioma-like tumor.

The osteogenic response of undifferentiated human mesenchymal stem cells (hMSCs) to mechanical strain is inversely related to body mass index of the donor.

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Friedl, Gerald; Windhager, Reinhard; Schmidt, Helena; Aigner, Reingard

2009-08-01

While the importance of physical factors in the maintenance and regeneration of bone tissue has been recognized for many years and the mechano-sensitivity of bone cells is well established, there is increasing evidence that body fat constitutes an independent risk factor for complications in bone fracture healing and aseptic loosening of implants. Although mechanical causes have been widely suggested, we hypothesized that the osteogenic mechano-response of human mesenchymal stem cells (hMSCs) may be altered in obese patients. We determined the phenotypic and genotypic response of undifferentiated hMSCs of 10 donors to cyclic tensile strain (CTS) under controlled in vitro conditions and analyzed the potential relationship relevant to the donor's anthropomorphometric and biochemical parameters related to donor's fat and bone metabolism. The osteogenic marker genes were all statistically significantly upregulated by CTS, which was accompanied by a significant increase in cell-based ALP activity. Linear correlation analysis revealed that there was a significant correlation between phenotypic CTS response and the body mass index of the donor (r = -0.91, p < 0.001) and phenotypic CTS response was also significantly related to leptin levels (r = -0.68) and estradiol levels (r = 0.67) within the bone marrow microenvironment of the donor. Such an upstream imprinting process mediated by factors tightly related to the donor's fat metabolism, which hampers the mechanosensitivity of hMSCs in obese patients, may be of pathogenetic relevance for the complications associated with obesity that are seen in orthopedic surgery.

Characterization of hemopoietic stem cell chimerism in antibody-facilitated bone marrow chimeras

International Nuclear Information System (INIS)

Francescutti, L.H.; Gambel, P.; Wegmann, T.G.

1985-01-01

The authors have previously described a model for bone marrow transplantation that involves preparation of the host with monoclonal antibody against class I or class II antigens instead of irradiation or cytotoxic drugs. This allows engraftment and subsequent repopulation of the host by donor tissue. They have previously reported on chimerism in the peripheral blood of P1----(P1 X P2)F1 animals. In this report, the authors describe the examination of the bone marrow and spleen stem cell chimerism of these antibody-facilitated (AF) chimeras, by determining, with an isozyme assay, the phenotype of methylcellulose colonies grown from stem cells. They have found a correlation between peripheral blood chimerism and the stem cell constitution of both spleen and bone marrow. The peripheral blood chimerism also correlates with the level of chimerism in macrophages derived from peritoneal exudate cells. These findings indicate that assaying the peripheral blood of such chimeras provides an excellent indication of the degree of chimerism at the stem cell level and stands in sharp contrast to the level of chimerism in certain lymphoid compartments

In vitro regeneration of kidney from pluripotent stem cells

Energy Technology Data Exchange (ETDEWEB)

Osafune, Kenji, E-mail: osafu@cira.kyoto-u.ac.jp [Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan); JST Yamanaka iPS Cell Special Project, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan)

2010-10-01

Although renal transplantation has proved a successful treatment for the patients with end-stage renal failure, the therapy is hampered by the problem of serious shortage of donor organs. Regenerative medicine using stem cells, including cell transplantation therapy, needs to be developed to solve the problem. We previously identified the multipotent progenitor cells in the embryonic mouse kidney that can give rise to several kinds of epithelial cells found in adult kidney, such as glomerular podocytes and renal tubular epithelia. Establishing the method to generate the progenitors from human pluripotent stem cells that have the capacity to indefinitely proliferate in vitro is required for the development of kidney regeneration strategy. We review the current status of the research on the differentiation of pluripotent stem cells into renal lineages and describe cues to promote this research field.

In vitro regeneration of kidney from pluripotent stem cells

International Nuclear Information System (INIS)

Osafune, Kenji

2010-01-01

Although renal transplantation has proved a successful treatment for the patients with end-stage renal failure, the therapy is hampered by the problem of serious shortage of donor organs. Regenerative medicine using stem cells, including cell transplantation therapy, needs to be developed to solve the problem. We previously identified the multipotent progenitor cells in the embryonic mouse kidney that can give rise to several kinds of epithelial cells found in adult kidney, such as glomerular podocytes and renal tubular epithelia. Establishing the method to generate the progenitors from human pluripotent stem cells that have the capacity to indefinitely proliferate in vitro is required for the development of kidney regeneration strategy. We review the current status of the research on the differentiation of pluripotent stem cells into renal lineages and describe cues to promote this research field.

Limiting dilution analysis of the stem cells for T cell lineage

International Nuclear Information System (INIS)

Katsura, Y.; Kina, T.; Amagai, T.; Tsubata, T.; Hirayoshi, K.; Takaoki, Y.; Sado, T.; Nishikawa, S.I.

1986-01-01

Stem cell activities of bone marrow, spleen, thymus, and fetal liver cells for T cell lineage were studied comparatively by transferring the cells from these organs through i.v. or intrathymus (i.t.) route into right leg- and tail-shielded (L-T-shielded) and 900 R-irradiated recipient mice, which were able to survive without supplying hemopoietic stem cells. Cells from B10.Thy-1.1 (H-2b, Thy-1.1) mice were serially diluted and were transferred into L-T-shielded and irradiated C57BL/6 (H-2b, Thy-1.2) mice, and 21 days later the thymus cells of recipient mice were assayed for Thy-1.1+ cells by flow cytofluorometry. The percentage of recipient mice possessing donor-type T cells was plotted against the number of cells transferred, and the stem cell activity in each cell source was expressed as the 50% positive value, the number of donor cells required for generating donor-type T cells in the thymuses of 50% of recipient mice. In i.v. transfer experiments, the activity of bone marrow cells was similar to that of fetal liver cells, and about 100 times and nearly 1000 times higher than those of spleen cells and thymus cells, respectively. In i.t. transfer experiments, the number of cells required for generating donor-type T cells was much lower than that in i.v. transfer experiments, although the ratio in 50% positive values between i.v. and i.t. transfers differed among cell sources. In i.t. transfers, the 50% positive value of bone marrow cells was five times, 400 times, and 500 times higher than that of fetal liver cells, spleen cells, and thymus cells, respectively. Our previous finding that stem cells are enriched in the spleens of mice which were whole body-irradiated and marrow-reconstituted 7 days earlier was confirmed also by the present limiting dilution assay carried out in i.v. as well as i.t. transfers

Irreversible barrier to the reprogramming of donor cells in cloning with mouse embryos and embryonic stem cells.

Science.gov (United States)

Ono, Yukiko; Kono, Tomohiro

2006-08-01

Somatic cloning does not always result in ontogeny in mammals, and development is often associated with various abnormalities and embryo loss with a high frequency. This is considered to be due to aberrant gene expression resulting from epigenetic reprogramming errors. However, a fundamental question in this context is whether the developmental abnormalities reported to date are specific to somatic cloning. The aim of this study was to determine the stage of nuclear differentiation during development that leads to developmental abnormalities associated with embryo cloning. In order to address this issue, we reconstructed cloned embryos using four- and eight-cell embryos, morula embryos, inner cell mass (ICM) cells, and embryonic stem cells as donor nuclei and determined the occurrence of abnormalities such as developmental arrest and placentomegaly, which are common characteristics of all mouse somatic cell clones. The present analysis revealed that an acute decline in the full-term developmental competence of cloned embryos occurred with the use of four- and eight-cell donor nuclei (22.7% vs. 1.8%) in cases of standard embryo cloning and with morula and ICM donor nuclei (11.4% vs. 6.6%) in serial nuclear transfer. Histological observation showed abnormal differentiation and proliferation of trophoblastic giant cells in the placentae of cloned concepti derived from four-cell to ICM cell donor nuclei. Enlargement of placenta along with excessive proliferation of the spongiotrophoblast layer and glycogen cells was observed in the clones derived from morula embryos and ICM cells. These results revealed that irreversible epigenetic events had already started to occur at the four-cell stage. In addition, the expression of genes involved in placentomegaly is regulated at the blastocyst stage by irreversible epigenetic events, and it could not be reprogrammed by the fusion of nuclei with unfertilized oocytes. Hence, developmental abnormalities such as placentomegaly as

Limbal Stem Cell Deficiency and Treatment with Stem Cell Transplantation.

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Barut Selver, Özlem; Yağcı, Ayşe; Eğrilmez, Sait; Gürdal, Mehmet; Palamar, Melis; Çavuşoğlu, Türker; Ateş, Utku; Veral, Ali; Güven, Çağrı; Wolosin, Jose Mario

2017-10-01

The cornea is the outermost tissue of the eye and it must be transparent for the maintenance of good visual function. The superficial epithelium of the cornea, which is renewed continuously by corneal stem cells, plays a critical role in the permanence of this transparency. These stem cells are localized at the cornea-conjunctival transition zone, referred to as the limbus. When this zone is affected/destroyed, limbal stem cell deficiency ensues. Loss of limbal stem cell function allows colonization of the corneal surface by conjunctival epithelium. Over 6 million people worldwide are affected by corneal blindness, and limbal stem cell deficiency is one of the main causes. Fortunately, it is becoming possible to recover vision by autologous transplantation of limbal cells obtained from the contralateral eye in unilateral cases. Due to the potential risks to the donor eye, only a small amount of tissue can be obtained, in which only 1-2% of the limbal epithelial cells are actually limbal stem cells. Vigorous attempts are being made to expand limbal stem cells in culture to preserve or even enrich the stem cell population. Ex vivo expanded limbal stem cell treatment in limbal stem cell deficiency was first reported in 1997. In the 20 years since, various protocols have been developed for the cultivation of limbal epithelial cells. It is still not clear which method promotes effective stem cell viability and this remains a subject of ongoing research. The most preferred technique for limbal cell culture is the explant culture model. In this approach, a small donor eye limbal biopsy is placed as an explant onto a biocompatible substrate (preferably human amniotic membrane) for expansion. The outgrowth (cultivated limbal epithelial cells) is then surgically transferred to the recipient eye. Due to changing regulations concerning cell-based therapy, the implementation of cultivated limbal epithelial transplantation in accordance with Good Laboratory Practice using

Evaluation of the efficacy and safety of original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) in CD34(+) peripheral hematopoietic stem cell mobilization procedures for allogeneic hematopoietic stem cell transplant donors.

Science.gov (United States)

Sivgin, Serdar; Karakus, Esen; Keklik, Muzaffer; Zararsiz, Gokmen; Solmaz, Musa; Kaynar, Leylagul; Eser, Bulent; Cetin, Mustafa; Unal, Ali

2016-06-01

In this study, we aimed to compare the potency of different G-CSF agents including original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34(+) cell mobilization in patients that underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). The data of 243 donors for alloHSCT recipients diagnosed with mostly acute leukemia and myelodsyplastic syndromes (MDS) were analyzed, retrospectively. Data for stem cell mobilization have been recorded from patients' files. Donors who received Filgrastim (Neupogen®, Group I), biosimilar Filgrastim (Leucostim®, Group II) and Lenograstim (Granocyte®, Group III) were analyzed for total CD34(+) cell count at the end of mobilization procedures. A total of 243 donors and patients for alloHSCT were analyzed retrospectively. The diagnosis of the patients were; acute myeloid leukemia (AML) (110 patients, 45.2%), acute lymphoid leukemia (ALL) (61 patients, 25.1%), aplastic anemia (AA) (38 patients, 15.6%), lymphomas (14 patients, 5.7%) and others (20 patients, 8.4%). The median number of total collected PB CD34(+) cells (×10(6)/kg) was 7.12 (min-max: 5.38-7.90) in the Neupogen® group, 7.27 (min-max: 6.79-7.55) in the Leucostim® group and 7.15 (min-max: 5.34-7.58) in the Granocyte® group. There was no statistically significant difference among groups in terms of total collected PB CD34(+) cells (p = 0.919). The median doses of G-CSF agents (µg/kg/day) in PBSC collection in Neupogen® group was; 11.00 (10.00-12.00) in Leucostim® group10.35 (min-max: 10.00-11.10) and in Granocyte® group11.00 (min-max: 10.00-11.00). There was no statistical significance among groups (p = 0.215). Biosimilar filgrastim (Leucostim®) was found comparable to original Filgrastim (Neupogen®) and Lenograstim (Granocyte®) for PBSC mobilization in donors of the patients that underwent alloHSCT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transient hemolysis due to anti-D and anti-A1 produced by engrafted donor's lymphocytes after allogeneic unmanipulated haploidentical hematopoietic stem cell transplantation.

Science.gov (United States)

Bailén, Rebeca; Kwon, Mi; Pérez-Corral, Ana María; Pascual, Cristina; Buño, Ismael; Balsalobre, Pascual; Serrano, David; Gayoso, Jorge; Díez-Martín, José Luis; Anguita, Javier

2017-10-01

Development of de novo alloantibodies against recipient's red blood cell (RBC) antigens by engrafted donor's lymphocytes is a known phenomenon in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). This situation is usually clinically insignificant. We report a case of early clinically relevant hemolytic anemia in a blood group A 1 D+ patient, due to a limited production of anti-D and anti-A 1 produced by nonpreviously sensitized newly engrafted donor's immune system. A 31-year-old Caucasian woman, blood group A 1 , D+, with Hodgkin's lymphoma, received an unmanipulated haploidentical allogeneic peripheral blood HSCT after a nonmyeloablative conditioning regimen. Donor blood group was A 2 B, D-. The patient had an uneventful course until Day +34, when she developed clinically significant hemolytic anemia with a positive direct antiglobulin test. Anti-D and anti-A 1 produced by the donor-engrafted lymphocytes were detected both in serum and in eluate. The hemolysis produced an accelerated group change, turning the patient's ABO group into A 2 B 2 weeks after the detection of the alloantibodies. As the residual patient's RBCs progressively disappeared, anti-D and anti-A 1 production decreased and were not detected in serum by Day +41. This case illustrates that de novo alloantibody production against ABO and D antigens by the newly engrafted donor's lymphocytes can occasionally cause clinically significant anemia. To our knowledge, this is the first case reported of clinically significant hemolytic anemia due to a transient anti-D anti-A 1 alloimmunization after T-cell-repleted haploidentical HSCT. © 2017 AABB.

The Core of Sibling Stem Cell Donation – A Grounded Theory Study

Science.gov (United States)

Kisch, Annika M; Forsberg, Anna

2017-01-01

Background: There is a lack of theoretical framework supporting stem cell transplant nurses in their assessment, judgment and caring interventions of sibling stem cell donors. Objective: The purpose of this study was to explore sibling stem cell donors’ main concerns and how they deal with them before and after donation. Method: Ten healthy sibling donors, 5 men and 5 women, with a median age of 54 years were included in this study when they were due to donate stem cells to a brother or sister. Data were collected prospectively on three occasions (before the donation and three and twelve months after it) through in-depth interviews, which were recorded and transcribed verbatim for analysis by the Grounded Theory method according to Charmaz. Results: This study describes the efforts of the ten donors to fulfil their duty as a sibling by doing what they considered necessary in order to help. Their efforts were summarised in a process wherein the grounded theory generated three main categories; Prepare, Promote and Preserve. A clear path of transition leading to fulfilment is evident, starting before the donation and continuing for one year afterwards. Conclusions: Being a sibling stem cell donor means doing what you have to do to fulfil your duty and if possible, saving the life of a seriously ill brother or sister. The relationship between the siblings is strengthened by the donation process. Sibling stem cell donation appears to be about fulfilment and the theoretical framework may support clinicians in their evaluation and support of donors. PMID:28839511

Controversies in hybrid banking: attitudes of Swiss public umbilical cord blood donors toward private and public banking.

Science.gov (United States)

Manegold, Gwendolin; Meyer-Monard, Sandrine; Tichelli, André; Granado, Christina; Hösli, Irene; Troeger, Carolyn

2011-07-01

Umbilical cord blood (UCB) stored in public inventories has become an alternative stem cell source for allogeneic stem cell transplantation. The potential use of autologous UCB from private banks is a matter of debate. In the face of the limited resources of public inventories, a discussion on "hybrid" public and private UCB banking has evolved. We aimed to explore the attitudes of the donating parents toward public and private UCB banking. A standardized, anonymous questionnaire was sent to the most recent 621 public UCB donors including items regarding satisfaction with recruitment process, the need for a second consent before release of the UCB unit for stem cell transplantation, and the donors' views on public and private UCB banking. Furthermore, we asked about their views on UCB research. Of the questionnaires, 48% were returned, and 16% were lost due to mail contact. Of our donors, 95% would donate to the public bank again. As much as 35% of them were convinced that public banking was useful. Whereas 27% had never heard about private UCB banking, 34% discussed both options. Nearly 70% of donors opted for public banking due to altruism and the high costs of private banking. Of our public UCB donors, 81% stated that they did not need a re-consent before UCB release for stem cell transplantation. In case of sample rejection, 53.5% wanted to know details about the particular research project. A total of 9% would not consent. Almost all donors would choose public banking again due to altruism and the high costs of private banking. Shortly after donation, mail contact with former UCB donors was difficult. This might be a relevant issue in any sequential hybrid banking.

Turnover of circulating hematopoietic stem cells

Energy Technology Data Exchange (ETDEWEB)

Dorie, M J; Maloney, M A; Patt, H M

1979-10-01

Short-term parabiosis of male and female CBA/CaJ mice was used to investigate the turnover of circulating hematopoietic stem cells. The change and subsequent disappearance of donor stem cells were monitored by spleen colony assay and chromosome analysis of individual colonies. The results revealed an exponential disappearance of pluripotent stem cells from blood with a characteristic half time of 1.7 h. Blood-borne stem cells were shown to be equilibrated with a subpopulation of marrow stem cells exhibiting a disappearance half time of 9.5 h. Splenectomy did not change the apparent rate of stem cell removal from the blood.

Iron deficiency among blood donors

DEFF Research Database (Denmark)

Rigas, A S; Pedersen, O B; Magnussen, K

2017-01-01

Blood components collected from blood donors are an invaluable part of modern-day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation...... and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood...... donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark...

A perspective on the selection of unrelated donors and cord blood units for transplantation

Science.gov (United States)

Spellman, Stephen R.; Eapen, Mary; Logan, Brent R.; Mueller, Carlheinz; Rubinstein, Pablo; Setterholm, Michelle I.; Woolfrey, Ann E.; Confer, Dennis L.; Hurley, Carolyn K.

2012-01-01

Selection of a suitable graft for allogeneic hematopoietic stem cell transplantation involves consideration of both donor and recipient characteristics. Of primary importance is sufficient donor-recipient HLA matching to ensure engraftment and acceptable rates of GVHD. In this Perspective, the National Marrow Donor Program and the Center for International Blood and Marrow Transplant Research provide guidelines, based on large studies correlating graft characteristics with clinical transplantation outcomes, on appropriate typing strategies and matching criteria for unrelated adult donor and cord blood graft selection. PMID:22596257

Human mesenchymal stem cells suppress donor CD4(+) T cell proliferation and reduce pathology in a humanized mouse model of acute graft-versus-host disease.

Science.gov (United States)

Tobin, L M; Healy, M E; English, K; Mahon, B P

2013-05-01

Acute graft-versus-host disease (aGVHD) is a life-threatening complication following allogeneic haematopoietic stem cell transplantation (HSCT), occurring in up to 30-50% of patients who receive human leucocyte antigen (HLA)-matched sibling transplants. Current therapies for steroid refractory aGVHD are limited, with the prognosis of patients suboptimal. Mesenchymal stem or stromal cells (MSC), a heterogeneous cell population present in many tissues, display potent immunomodulatory abilities. Autologous and allogeneic ex-vivo expanded human MSC have been utilized to treat aGVHD with promising results, but the mechanisms of therapeutic action remain unclear. Here a robust humanized mouse model of aGVHD based on delivery of human peripheral blood mononuclear cells (PBMC) to non-obese diabetic (NOD)-severe combined immunodeficient (SCID) interleukin (IL)-2rγ(null) (NSG) mice was developed that allowed the exploration of the role of MSC in cell therapy. MSC therapy resulted in the reduction of liver and gut pathology and significantly increased survival. Protection was dependent upon the timing of MSC therapy, with conventional MSC proving effective only after delayed administration. In contrast, interferon (IFN)-γ-stimulated MSC were effective when delivered with PBMC. The beneficial effect of MSC therapy in this model was not due to the inhibition of donor PBMC chimerism, as CD45(+) and T cells engrafted successfully in this model. MSC therapy did not induce donor T cell anergy, FoxP3(+) T regulatory cells or cause PBMC apoptosis in this model; however, it was associated with the direct inhibition of donor CD4(+) T cell proliferation and reduction of human tumour necrosis factor-α in serum. © 2012 British Society for Immunology.

Higher refusal rates for organ donation among older potential donors in the Netherlands: impact of the donor register and relatives.

NARCIS (Netherlands)

Leiden, H.A. van; Jansen, N.E.; Haase-Kromwijk, B.J.; Hoitsma, A.J.

2010-01-01

BACKGROUND: The availability of donor organs is considerably reduced by relatives refusing donation after death. There is no previous large-scale evaluation of the influence of the Donor Register (DR) consultation and the potential donor's age on this refusal in The Netherlands. METHODS: This study

ALLOGENEIC STEM CELL TRANSPLANTATION FOR ADULT PATIENTS WITH ACUTE LEUKEMIA – 14 YEARS EXPERIENCE

Directory of Open Access Journals (Sweden)

Jože Pretnar

2004-12-01

Full Text Available Background. This study was designed to evaluate the impact of various prognostic factors on long-term survival and event free survival after allogeneic hematopoietic stem cell transplantation for patients with acute leukemia.Methods and patients. Between years 1989 and 2002 44 patients with acute leukemia (30 with AML and 14 with ALL were transplanted. Survival curves using the Kaplan-Meier method were calculated for patients transplanted with two different sources of stem cells – bone marrow and peripheral blood and separately for patients with female donor.Results. Estimated 10 years survival for AML is 43% and 64% for ALL patients which is not statistically different. There are no significant differences in outcome regarding source of stem cells and in donors’ gender.Conclusions. To conclude, our results show that neither source of stem cells nor donor’s gender has impact on the long-term survival after hematopoietic stem cell transplantation. As published previously patients transplanted beyond the first remission have significantly worse outcome.

Generation, characterization and potential therapeutic applications of mature and functional hepatocytes from stem cells.

Science.gov (United States)

Zhang, Zhenzhen; Liu, Jianfang; Liu, Yang; Li, Zheng; Gao, Wei-Qiang; He, Zuping

2013-02-01

Liver cancer is the sixth most common tumor in the world and the majority of patients with this disease usually die within 1 year. The effective treatment for end-stage liver disease (also known as liver failure), including liver cancer or cirrhosis, is liver transplantation. However, there is a severe shortage of liver donors worldwide, which is the major handicap for the treatment of patients with liver failure. Scarcity of liver donors underscores the urgent need of using stem cell therapy to the end-stage liver disease. Notably, hepatocytes have recently been generated from hepatic and extra-hepatic stem cells. We have obtained mature and functional hepatocytes from rat hepatic stem cells. Here, we review the advancements on hepatic differentiation from various stem cells, including hepatic stem cells, embryonic stem cells, the induced pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, and probably spermatogonial stem cells. The advantages, disadvantages, and concerns on differentiation of these stem cells into hepatic cells are highlighted. We further address the methodologies, phenotypes, and functional characterization on the differentiation of numerous stem cells into hepatic cells. Differentiation of stem cells into mature and functional hepatocytes, especially from an extra-hepatic stem cell source, would circumvent the scarcity of liver donors and human hepatocytes, and most importantly it would offer an ideal and promising source of hepatocytes for cell therapy and tissue engineering in treating liver disease. Copyright © 2012 Wiley Periodicals, Inc.

Pushing the boundaries in liver graft utilisation in transplantation: Case report of a donor with previous bile duct injury repair.

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Sultana, Asma; Powell, James J; Oniscu, Gabriel C

2017-01-01

Liver transplantation is a recognised treatment for extensive bile duct injuries with secondary biliary cirrhosis or recurring sepsis. However, there have been no reports of successful liver transplantation from a donor who sustained a previous bile duct injury. Here we discuss the case of a liver transplant from a 51-year-old brain dead donor who had suffered a Strasberg E1 bile duct injury and had undergone a Roux-en-Y hepaticojejunostomy 24 years prior to donation. The liver was successfully recovered and transplanted into a 56-year-old male recipient with end stage liver disease consequent to alpha 1 antitrypsin deficiency. The graft continues to function well 36 months post-transplant, with normal liver function tests and imaging revealing a patent hepaticojejunostomy. The potential associated vascular injuries should be identified during bench preparation whilst the management of biliary reconstruction at the time of transplant should follow the principles of biliary reconstruction in cases with biliary injuries, extending the hilar opening into the left duct. This case highlights the successful utilisation of a post bile duct injury repair liver, employing an experienced procurement team and careful bench assessment and reconstruction. Copyright © 2017. Published by Elsevier Ltd.

The role of donor characteristics and post-granulocyte colony-stimulating factor white blood cell counts in predicting the adverse events and yields of stem cell mobilization.

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Chen, Shu-Huey; Yang, Shang-Hsien; Chu, Sung-Chao; Su, Yu-Chieh; Chang, Chu-Yu; Chiu, Ya-Wen; Kao, Ruey-Ho; Li, Dian-Kun; Yang, Kuo-Liang; Wang, Tso-Fu

2011-05-01

Granulocyte colony-stimulating factor (G-CSF) is now widely used for stem cell mobilization. We evaluated the role of post-G-CSF white blood cell (WBC) counts and donor factors in predicting adverse events and yields associated with mobilization. WBC counts were determined at baseline, after the third and the fifth dose of G-CSF in 476 healthy donors. Donors with WBC ≥ 50 × 10(3)/μL post the third dose of G-CSF experienced more fatigue, myalgia/arthralgia, and chills, but final post-G-CSF CD34(+) cell counts were similar. Although the final CD34(+) cell count was higher in donors with WBC ≥ 50 × 10(3)/μL post the fifth G-CSF, the incidence of side effects was similar. Females more frequently experienced headache, nausea/anorexia, vomiting, fever, and lower final CD34(+) cell count than did males. Donors with body mass index (BMI) ≥ 25 showed higher incidences of sweat and insomnia as well as higher final CD34(+) cell counts. Donor receiving G-CSF ≥ 10 μg/kg tended to experience bone pain, headache and chills more frequently. Multivariate analysis indicated that female gender is an independent factor predictive of the occurrence of most side effects, except for ECOG > 1 and chills. Higher BMI was also an independent predictor for fatigue, myalgia/arthralgia, and sweat. Higher G-CSF dose was associated with bone pain, while the WBC count post the third G-CSF was associated with fatigue only. In addition, one donor in the study period did not complete the mobilization due to suspected anaphylactoid reaction. Observation for 1 h after the first injection of G-CSF is required to prevent complications from unpredictable side effects.

Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study.

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Cruz, Conrad Russell Y; Micklethwaite, Kenneth P; Savoldo, Barbara; Ramos, Carlos A; Lam, Sharon; Ku, Stephanie; Diouf, Oumar; Liu, Enli; Barrett, A John; Ito, Sawa; Shpall, Elizabeth J; Krance, Robert A; Kamble, Rammurti T; Carrum, George; Hosing, Chitra M; Gee, Adrian P; Mei, Zhuyong; Grilley, Bambi J; Heslop, Helen E; Rooney, Cliona M; Brenner, Malcolm K; Bollard, Catherine M; Dotti, Gianpietro

2013-10-24

Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity. We treated 8 patients with allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in blood and up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR-VST persistence, whereas 2 patients who received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control.

Use of G-CSF-stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review.

Science.gov (United States)

Chang, Ying-Jun; Huang, Xiao-Jun

2011-01-01

In recent years, several researchers have unraveled the previously unrecognized effects of granulocyte colony-stimulating factor (G-CSF) on hematopoiesis and the immune cell functions of bone marrow in healthy donors. In human leukocyte antigen-matched or haploidentical transplant settings, available data have established the safety of using G-CSF-stimulated bone marrow grafts, as well as the ability of this source to produce rapid and sustained engraftment. Interestingly, G-CSF-primed bone marrow transplants could capture the advantages of blood stem cell transplants, without the increased risk of chronic graft-versus-host disease that is associated with blood stem cell transplants. This review summarizes the growing body of evidence that supports the use of G-CSF-stimulated bone marrow grafts as an alternative stem cell source in allogeneic hematopoietic stem cell transplantation. © 2010 John Wiley & Sons A/S.

The use of cytokine-stimulated healthy donors in allogeneic stem cell transplantation.

Science.gov (United States)

Cesaro, Simone; Marson, Piero; Gazzola, Maria Vittoria; De Silvestro, Giustina; Destro, Roberta; Pillon, Marta; Calore, Elisabetta; Messina, Chiara; Zanesco, Luigi

2002-08-01

Treatment of healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows the mobilization and peripheralization into circulating blood of an adequate number of CD34+ cells that can then be collected by leukapheresis (PBSC). This procedure avoids the invasiveness of bone marrow harvest and the risks related to general anesthesia. The main adverse effects of rhG-CSF are: bone pain, 84%, headache, 54%, fatigue, 31%, and nausea, 13%, which are usually scored by the donors as moderate to severe, resolving within 2-3 days after discontinuation of the cytokine. Analgesics, mainly acetaminophen, are sufficient to control the pain. Less than 5% of the donors experience non-cardiac chest pain, a local reaction at the injection site, insomnia, dizziness or a low-grade fever. Discontinuation of the PBSC procedure because of adverse effects of rhG-CSF or leukapheresis is rarely necessary (0.5%) but this good tolerability can be hampered by the need, in 5-20% of cases, for an adequate venous access that requires insertion of a central or venous catheter. There are no absolute contraindications to the stimulation of healthy donors with rhG-CSF but the description of cases of non-traumatic splenic rupture, iritis, cardiac ischemia, and gouty arthritis suggests that further precautionary restrictions are advisable when deciding eligibility for PBSC collection. The main advantages for patients receiving an allogeneic PBSC transplant are the faster hematologic and immunologic recovery and the potential for a greater efficacy in advanced disease by lowering the transplant-related mortality. One of the major concerns regarding the use of rhG-CSF in unrelated healthy donors is the uncertainty about its possible role in triggering malignancy, in particular myelodysplastic syndrome and acute myeloid leukemia. There are no studies with an adequate sample size and follow-up that can answer this question but two recent retrospective studies reported that in

Laparoscopic donor nephrectomy increases the supply of living donor kidneys: a center-specific microeconomic analysis.

Science.gov (United States)

Kuo, P C; Johnson, L B

2000-05-27

A tenet of microeconomics is that new technology will shift the supply curve to the right. Laparoscopic donor nephrectomy (LDN) is a new technique for removal of living donor kidneys. Centers performing this procedure have noted an increased number of patients presenting for donor evaluation. This has not been previously studied. The records of all LDN performed from May 1998 to February 1999 were reviewed. The following variables were examined: sex, age, related vs. unrelated donation, estimated blood loss, i.v. analgesia, length of stay, and time out of work. Donors undergoing traditional open donor nephrectomy during January 1997 to May 1998 served as the control group. A composite cost index was constructed. LDN significantly decreased length of stay, pain, and time out of work; the supply function shifted to the right. Telephone interviews revealed that 47% donated solely because of the LDN procedure. LDN increases the supply of living donor kidneys.

Infusion of Sibling Marrow in a Patient with Purine Nucleoside Phosphorylase Deficiency Leads to Split Mixed Donor Chimerism and Normal Immunity

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Laura Yeates

2017-06-01

Full Text Available Purine nucleoside phosphorylase (PNP deficiency, a rare autosomal recessive metabolic disease causes combined immunodeficiency and developmental delay, hypotonia, and spasticity. Patients present with recurrent infections associated with T-lymphocytopenia, characteristically presenting later than patients with classical severe combined immunodeficiency (SCID. PNP, with adenosine deaminase (ADA, is part of the purine salvage pathway. The only curative therapy is hematopoietic stem cell transplantation. Myeloablative conditioning is recommended to prevent rejection caused by residual immune function. However, HLA-identical sibling stem cell infusions in ADA-SCID result in some donor stem cell engraftment and long-term thymopoiesis. We report a patient with PNP deficiency, who received HLA-identical sibling marrow without chemotherapy because of disseminated cytomegalovirus (CMV infection. The patient presented at 14 months of age following recurrent infections, from early infancy, with persistent irritability, developmental delay, and hypotonia. She had neutropenia, pan-lymphocytopenia, and hypogammaglobulinemia with low plasma urate and erythrocyte PNP activity. Diagnosis was confirmed with a homozygous mutation in PNP. The patient was viremic with CMV detected in blood and CSF by PCR. Dual antiviral therapy improved the clinical condition and reduced the viral load. In view of the disseminated CMV infection, the decision was made to infuse stem cells without any pre-conditioning chemotherapy. She received a matched sibling donor unconditioned stem cell infusion at 16 months of age. The post-transplant course was uneventful. Blood PCR became negative for CMV. Global hypotonia persisted, although with significant improvement in irritability. At 4 years of age and 29 months post-transplant, the patient demonstrated normal T-lymphocyte and natural killer cell numbers. Recent thymic emigrants represented 12% of the total T

Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.

Science.gov (United States)

Shah, Sandeep N; Gelderman, Monique P; Lewis, Emily M A; Farrel, John; Wood, Francine; Strader, Michael Brad; Alayash, Abdu I; Vostal, Jaroslav G

2016-01-01

Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs) is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs) is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle) under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.

Directory of Open Access Journals (Sweden)

Sandeep N Shah

Full Text Available Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

Human skeletal muscle-derived stem cells retain stem cell properties after expansion in myosphere culture

International Nuclear Information System (INIS)

Wei, Yan; Li, Yuan; Chen, Chao; Stoelzel, Katharina; Kaufmann, Andreas M.; Albers, Andreas E.

2011-01-01

Human skeletal muscle contains an accessible adult stem-cell compartment in which differentiated myofibers are maintained and replaced by a self-renewing stem cell pool. Previously, studies using mouse models have established a critical role for resident stem cells in skeletal muscle, but little is known about this paradigm in human muscle. Here, we report the reproducible isolation of a population of cells from human skeletal muscle that is able to proliferate for extended periods of time as floating clusters of rounded cells, termed 'myospheres' or myosphere-derived progenitor cells (MDPCs). The phenotypic characteristics and functional properties of these cells were determined using reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry and immunocytochemistry. Our results showed that these cells are clonogenic, express skeletal progenitor cell markers Pax7, ALDH1, Myod, and Desmin and the stem cell markers Nanog, Sox2, and Oct3/4 significantly elevated over controls. They could be maintained proliferatively active in vitro for more than 20 weeks and passaged at least 18 times, despite an average donor-age of 63 years. Individual clones (4.2%) derived from single cells were successfully expanded showing clonogenic potential and sustained proliferation of a subpopulation in the myospheres. Myosphere-derived cells were capable of spontaneous differentiation into myotubes in differentiation media and into other mesodermal cell lineages in induction media. We demonstrate here that direct culture and expansion of stem cells from human skeletal muscle is straightforward and reproducible with the appropriate technique. These cells may provide a viable resource of adult stem cells for future therapies of disease affecting skeletal muscle or mesenchymal lineage derived cell types.

Pluripotent stem cells with normal or reduced self renewal survive lethal irradiation

International Nuclear Information System (INIS)

Brecher, G.; Neben, S.; Yee, M.; Bullis, J.; Cronkite, E.P.

1988-01-01

Transfusion with 10,000 or 20,000 marrow cells resulted in 30+ days survival of 15%-50% of mice exposed to an Ld90 or LD100 or radiation. The use of congenic mice with alloenzyme markers permitted the identification of host and donor cells in the peripheral blood of transfused animals. Donor cells were present initially in all hosts. Between 55% and 92% of the animals became 100% host type by 12-24 weeks after transfusion in three separate experiments. To explore whether the temporary repopulation by donor cells was due to short-lived stem cells, the marrows of several primary hosts were transfused into secondary, lethally irradiated hosts. Some of the retransplanted primary donor and host cells persisted only temporarily. It is suggested that some of the donor stem cells in both the primary and secondary hosts had an intrinsically shortened life span

Syntheses of donor-acceptor-functionalized dihydroazulenes

DEFF Research Database (Denmark)

Broman, Søren Lindbæk; Jevric, Martyn; Bond, Andrew

2014-01-01

The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has been of interest for use in molecular electronics and advanced materials. The switching between the two isomers has previously been found to depend strongly on the presence of donor and acceptor groups. The fine-tuning of opt......The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has been of interest for use in molecular electronics and advanced materials. The switching between the two isomers has previously been found to depend strongly on the presence of donor and acceptor groups. The fine...

CMV infection after transplant from cord blood compared to other alternative donors: the importance of donor-negative CMV serostatus.

Science.gov (United States)

Mikulska, Małgorzata; Raiola, Anna Maria; Bruzzi, Paolo; Varaldo, Riccardo; Annunziata, Silvana; Lamparelli, Teresa; Frassoni, Francesco; Tedone, Elisabetta; Galano, Barbara; Bacigalupo, Andrea; Viscoli, Claudio

2012-01-01

Cytomegalovirus (CMV) infection and disease are important complications after hematopoietic stem cell transplant, particularly after transplant from alternative donors. Allogeneic cord blood transplantation (CBT) is being increasingly used, but immune recovery may be delayed. The aim of this study was to compare CMV infection in CBT with transplants from unrelated or mismatched related donors, from now on defined as alternative donors. A total of 165 consecutive transplants were divided in 2 groups: (1) alternative donors transplants (n = 85) and (2) CBT recipients (n = 80). Donor and recipient (D/R) CMV serostatus were recorded. The incidence of CMV infection, its severity, timing, and outcome were compared. Median follow-up was 257 days (1-1328). CMV infection was monitored by CMV antigenemia and expressed as CMV Ag positive cell/2 × 10(5) polymorphonuclear blood cells. There was a trend toward a higher cumulative incidence of CMV infection among CBT than alternative donor transplant recipients (64% vs 51%, P = .12). The median time to CMV reactivation was 35 days, and was comparable in the 2 groups (P = .8). The maximum number of CMV-positive cells was similar in the 2 groups (11 versus 16, P = .2). The time interval between the first and the last positive CMV antigenemia was almost 4 times longer in CBT compared with alternative donor transplants (109 vs 29 days, respectively, P = .008). The incidence of late CMV infection was also higher in CBT (62% vs 24%, P donor transplants, whereas no difference in mortality was observed. The duration and incidence of late CMV infection were similar when D-/R+ CBT were compared with D-/R+ alternative donor transplants. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Daunorubicin, Cytarabine, and Cladribine Regimen Plus Radiotherapy and Donor Lymphocyte Infusion for Extramedullary Relapse of Acute Myeloid Leukemia after Hematopoietic Stem Cell Transplantation

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Marco Sanna

2013-01-01

Full Text Available Myeloid sarcoma is a rare tumor consisting of myeloid blasts that involve anatomic sites outside the bone marrow. Fatal prognosis is inevitable in patients with extramedullary relapse after hematopoietic stem cell transplantation (HSCT, and no standard treatments are available yet. We report the first case of extramedullary relapse after HSCT treated with a combination of daunorubicin, cytarabine, and cladribine (DAC regimen plus radiotherapy and donor lymphocyte infusion (DLI. This treatment induced a new and durable remission in our patient. The favorable toxicity profile and the reduced cost make this combination worthy of further investigations.

Differentiation of hepatocytes from induced pluripotent stem cells derived from human hair follicle mesenchymal stem cells.

Science.gov (United States)

Shi, Xu; Lv, Shuang; He, Xia; Liu, Xiaomei; Sun, Meiyu; Li, Meiying; Chi, Guangfan; Li, Yulin

2016-10-01

Due to the limitations of organ donors and immune rejection in severe liver diseases, stem cell-based therapy presents a promising application for tissue repair and regeneration. As a novel cell source, mesenchymal stem cells separated from human hair follicles (HF-MSCs) are convenient to obtain and have no age limit. To date, the differentiation of HF-MSCs into hepatocytes has not been reported. In this study, we explored whether HF-MSCs and HF-MSC-derived-induced pluripotent stem cells (HF-iPS) could differentiate into hepatocytes in vitro. Flow cytometry, Oil Red O stain and Alizarin Red stain were used to identify the characteristics of HF-MSCs. The expression of liver-specific gene was detected by immunofluorescence and Quantitative Polymerase Chain Reaction. Periodic Acid-Schiff stain, Indocyanine Green stain and Low-Density Lipoprotein stain were performed to evaluate the functions of induced hepatocyte-like cells (HLCs). HF-MSCs were unable to differentiate into HLCs using previously reported procedures for MSCs from other tissues. However, HF-iPS efficiently induced the generation of HLCs that expressed hepatocyte markers and drug metabolism-related genes. HF-iPS can be used as novel and alternative cellular tools for inducing hepatocytes in vitro, simultaneously benefiting from utilizing HF-MSCs as a noninvasive and convenient cell source for reprogramming.

Allogeneic split-skin grafting in stem cell transplanted patients

DEFF Research Database (Denmark)

Olsen, Jan Kyrre Berg; Vindeløv, Lars; Schmidt, G.

2008-01-01

donor chimaerism will not recognise skin from the stem cell donor as foreign. Due to advances in haematology, the number of BMT patients and their long-term survival is expected to increase. cGvHD, predisposing to skin problems and ulcerations, complicates up to 70% of cases of BMT. In BMT patients...

Publishing SNP genotypes of human embryonic stem cell lines: policy statement of the International Stem Cell Forum Ethics Working Party.

Science.gov (United States)

Knoppers, Bartha M; Isasi, Rosario; Benvenisty, Nissim; Kim, Ock-Joo; Lomax, Geoffrey; Morris, Clive; Murray, Thomas H; Lee, Eng Hin; Perry, Margery; Richardson, Genevra; Sipp, Douglas; Tanner, Klaus; Wahlström, Jan; de Wert, Guido; Zeng, Fanyi

2011-09-01

Novel methods and associated tools permitting individual identification in publicly accessible SNP databases have become a debatable issue. There is growing concern that current technical and ethical safeguards to protect the identities of donors could be insufficient. In the context of human embryonic stem cell research, there are no studies focusing on the probability that an hESC line donor could be identified by analyzing published SNP profiles and associated genotypic and phenotypic information. We present the International Stem Cell Forum (ISCF) Ethics Working Party's Policy Statement on "Publishing SNP Genotypes of Human Embryonic Stem Cell Lines (hESC)". The Statement prospectively addresses issues surrounding the publication of genotypic data and associated annotations of hESC lines in open access databases. It proposes a balanced approach between the goals of open science and data sharing with the respect for fundamental bioethical principles (autonomy, privacy, beneficence, justice and research merit and integrity).

Reprogramming LCLs to iPSCs Results in Recovery of Donor-Specific Gene Expression Signature.

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Samantha M Thomas

2015-05-01

Full Text Available Renewable in vitro cell cultures, such as lymphoblastoid cell lines (LCLs, have facilitated studies that contributed to our understanding of genetic influence on human traits. However, the degree to which cell lines faithfully maintain differences in donor-specific phenotypes is still debated. We have previously reported that standard cell line maintenance practice results in a loss of donor-specific gene expression signatures in LCLs. An alternative to the LCL model is the induced pluripotent stem cell (iPSC system, which carries the potential to model tissue-specific physiology through the use of differentiation protocols. Still, existing LCL banks represent an important source of starting material for iPSC generation, and it is possible that the disruptions in gene regulation associated with long-term LCL maintenance could persist through the reprogramming process. To address this concern, we studied the effect of reprogramming mature LCL cultures from six unrelated donors to iPSCs on the ensuing gene expression patterns within and between individuals. We show that the reprogramming process results in a recovery of donor-specific gene regulatory signatures, increasing the number of genes with a detectable donor effect by an order of magnitude. The proportion of variation in gene expression statistically attributed to donor increases from 6.9% in LCLs to 24.5% in iPSCs (P < 10-15. Since environmental contributions are unlikely to be a source of individual variation in our system of highly passaged cultured cell lines, our observations suggest that the effect of genotype on gene regulation is more pronounced in iPSCs than in LCLs. Our findings indicate that iPSCs can be a powerful model system for studies of phenotypic variation across individuals in general, and the genetic association with variation in gene regulation in particular. We further conclude that LCLs are an appropriate starting material for iPSC generation.

Discovery of the rare HLA-B*39:77 allele in an unrelated Taiwanese bone marrow stem cell donor using the sequence-based typing method.

Science.gov (United States)

Yang, K L; Lee, S K; Lin, P Y

2013-08-01

We detected a rare HLA-B locus allele, B*39:77, in a Taiwanese unrelated marrow stem cell donor in our routine HLA sequence-based typing (SBT) exercise for a possible haematopoietic stem cell donation. In exons 2, 3 and 4, the DNA sequence of B*39:77 is identical to the sequence of B*39:01:01:01 except one nucleotide at nucleotide position 733 (G->A) in exon 4. The nucleotide variation caused one amino acid alteration at residue 221 (Gly->Ser). B*39:77 was probably derived from a nucleotide substitution event involving B*39:01:01:01. The probable HLA-A, -B, -C, -DRB1 and -DQB1 haplotype in association with B*39:77 may be deduced as A*02:01-B*39:77-C*07:02-DRB1*08:03-DQB1*06:01. Our discovery of B*39:77 in Taiwanese adds further polymorphism of B*39 variants in Taiwanese population. © 2013 John Wiley & Sons Ltd.

Stimulation and inhibition of erythropoiesis in donors and hematopoietic effect in irradiated recipient

Energy Technology Data Exchange (ETDEWEB)

Ninkov, V; Piletic, O; Stepanovic, D [Institut za Nuklearne Nauke Boris Kidric, Vinca (Yugoslavia); Belgrade Univ. (Yugoslavia). Inst. of Histology)

1976-03-01

Regeneration dynamics in bone marrow and spleen was studied in rats after irradiation of 800 R and transfusion of bone marrow cells from donors treated in different ways. Priority of the microenvironment of the recipient or of the information obtained in cell donors with respect to further hematopoietic cell differentiation was studied in irradiated recipients. Rats irradiated with 800 R were used as recipients in the experiments. The donors of marrow cells were the rats with stimulated or inhibited erythropoiesis. Stimulation of erythropoiesis was induced by bleeding and experimental polycythemia was provoked by packed erythrocytes. According to our results, it can be concluded that the processes of postirradiation hematopoiesis after transplantation of the bone marrow cells depend on the number and proliferative state of both donors and recipient stem cells, and microenvironment, not excluding the information introduced with the donor cell transplant.

Analyzing actual risk in malaria-deferred donors through selective serologic testing.

Science.gov (United States)

Nguyen, Megan L; Goff, Tami; Gibble, Joan; Steele, Whitney R; Leiby, David A

2013-08-01

Approximately 150,000 US blood donors are deferred annually for travel to malaria-endemic areas. However, the majority do not travel to the high-risk areas of Africa associated with transfusion-transmitted malaria (TTM) but visit low-risk areas such as Mexico. This study tests for Plasmodium infection among malaria-deferred donors, particularly those visiting Mexico. Blood donors deferred for malaria risk (travel, residence, or previous infection) provided blood samples and completed a questionnaire. Plasma was tested for Plasmodium antibodies by enzyme immunoassay (EIA); repeat-reactive (RR) samples were considered positive and tested by real-time polymerase chain reaction (PCR). Accepted donors provided background testing data. During 2005 to 2011, a total of 5610 malaria-deferred donors were tested by EIA, including 5412 travel deferrals. Overall, 88 (1.6%) were EIA RR; none were PCR positive. Forty-nine (55.7%) RR donors previously had malaria irrespective of deferral category, including 34 deferred for travel. Among 1121 travelers to Mexico, 90% visited Quintana Roo (no or very low risk), but just 2.2% visited Oaxaca/Chiapas (moderate or high risk). Only two Mexican travelers tested RR; both previously had malaria not acquired in Mexico. Travel to Mexico represents a large percentage of US donors deferred for malaria risk; however, these donors primarily visit no- or very-low-risk areas. No malaria cases acquired in Mexico were identified thereby supporting previous risk estimates. Consideration should be given to allowing blood donations from U.S. donors who travel to Quintana Roo and other low-risk areas in Mexico. A more effective approach to preventing TTM would be to defer all donors with a history of malaria, even if remote. © 2012 American Association of Blood Banks.

Cord Blood Stem Cell Procurement in Minority Donors

National Research Council Canada - National Science Library

Ratanatharathorn, Voravit

2008-01-01

... of building minority CBU inventory. This final annual report is to give the report of the transplantation outcomes of African/American CBU recipients compared with other racial groups. This analysis is limited to those patients who have received an allogeneic cord blood stem cell transplantation at Karmanos Cancer Center.

Cell culture density affects the stemness gene expression of adipose tissue-derived mesenchymal stem cells.

Science.gov (United States)

Kim, Dae Seong; Lee, Myoung Woo; Lee, Tae-Hee; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

2017-03-01

The results of clinical trials using mesenchymal stem cells (MSCs) are controversial due to the heterogeneity of human MSCs and differences in culture conditions. In this regard, it is important to identify gene expression patterns according to culture conditions, and to determine how the cells are expanded and when they should be clinically used. In the current study, stemness gene expression was investigated in adipose tissue-derived MSCs (AT-MSCs) harvested following culture at different densities. AT-MSCs were plated at a density of 200 or 5,000 cells/cm 2 . After 7 days of culture, stemness gene expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The proliferation rate of AT-MSCs harvested at a low density (~50% confluent) was higher than that of AT-MSCs harvested at a high density (~90% confluent). Although there were differences in the expression levels of stemness gene, such as octamer-binding transcription factor 4, nanog homeobox ( Nanog ), SRY-box 2, Kruppel like factor 4, v-myc avian myelocytomatosis viral oncogene homolog ( c-Myc ), and lin-28 homolog A, in the AT-MSCs obtained from different donors, RT-qPCR analysis demonstrated differential gene expression patterns according to the cell culture density. Expression levels of stemness genes, particularly Nanog and c-Myc , were upregulated in AT-MSCs harvested at a low density (~50% confluent) in comparison to AT-MSCs from the same donor harvested at a high density (~90% confluent). These results imply that culture conditions, such as the cell density at harvesting, modulate the stemness gene expression and proliferation of MSCs.

Donor cell differentiation, reprogramming, and cloning efficiency: elusive or illusive correlation?

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Oback, B; Wells, D N

2007-05-01

Compared to other assisted reproductive technologies, mammalian nuclear transfer (NT) cloning is inefficient in generating viable offspring. It has been postulated that nuclear reprogramming and cloning efficiency can be increased by choosing less differentiated cell types as nuclear donors. This hypothesis is mainly supported by comparative mouse cloning experiments using early blastomeres, embryonic stem (ES) cells, and terminally differentiated somatic donor cells. We have re-evaluated these comparisons, taking into account different NT procedures, the use of donor cells from different genetic backgrounds, sex, cell cycle stages, and the lack of robust statistical significance when post-blastocyst development is compared. We argue that while the reprogrammability of early blastomeres appears to be much higher than that of somatic cells, it has so far not been conclusively determined whether differentiation status affects cloning efficiency within somatic donor cell lineages. Copyright (c) 2006 Wiley-Liss, Inc.

Molecular and environmental cues in cardiac differentiation of mesenchymal stem cells

NARCIS (Netherlands)

Ramkisoensing, Arti Anushka

2014-01-01

In this thesis molecular and environmental cues in cardiac differentiation of mesenchymal stem cells were investigated. The main conclusions were that the cardiac differentiation potential of human mesenchymal stem cells negatively correlates with donor age. This in its own shows a negative

Posttransplantation Disseminated Coccidioidomycosis Acquired from Donor Lungs

OpenAIRE

Miller, Melissa B.; Hendren, Ryan; Gilligan, Peter H.

2004-01-01

A North Carolinian developed fatal coccidioidomycosis immediately after bilateral lung transplantation. The donor had previously traveled to Mexico, and the recipient had no travel history to an area where Coccidioides immitis is endemic. Immunosuppresive therapy of the transplant recipient likely reactivated latent Coccidioides infection in the donor lungs, leading to posttransplant coccidioidomycosis.

Donor-Dependent and Other Nondefined Factors Have Greater Influence on the Hepatic Phenotype Than the Starting Cell Type in Induced Pluripotent Stem Cell Derived Hepatocyte-Like Cells.

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Heslop, James A; Kia, Richard; Pridgeon, Christopher S; Sison-Young, Rowena L; Liloglou, Triantafillos; Elmasry, Mohamed; Fenwick, Stephen W; Mills, John S; Kitteringham, Neil R; Goldring, Chris E; Park, Bong K

2017-05-01

Drug-induced liver injury is the greatest cause of post-marketing drug withdrawal; therefore, substantial resources are directed toward triaging potentially dangerous new compounds at all stages of drug development. One of the major factors preventing effective screening of new compounds is the lack of a predictive in vitro model of hepatotoxicity. Primary human hepatocytes offer a metabolically relevant model for which the molecular initiating events of hepatotoxicity can be examined; however, these cells vary greatly between donors and dedifferentiate rapidly in culture. Induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) offer a reproducible, physiologically relevant and genotypically normal model cell; however, current differentiation protocols produce HLCs with a relatively immature phenotype. During the reprogramming of somatic cells, the epigenome undergoes dramatic changes; however, this "resetting" is a gradual process, resulting in an altered differentiation propensity, skewed toward the lineage of origin, particularly in early passage cultures. We, therefore, performed a comparison of human hepatocyte- and dermal fibroblast-derived iPSCs, assessing the impact of epigenetic memory at all stages of HLC differentiation. These results provide the first isogenic assessment of the starting cell type in human iPSC-derived HLCs. Despite a trend toward improvement in hepatic phenotype in albumin secretion and gene expression, few significant differences in hepatic differentiation capacity were found between hepatocyte and fibroblast-derived iPSCs. We conclude that the donor and inter-clonal differences have a greater influence on the hepatocyte phenotypic maturity than the starting cell type. Therefore, it is not necessary to use human hepatocytes for generating iPSC-derived HLCs. Stem Cells Translational Medicine 2017;6:1321-1331. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of Alpha

Analysis of the motivation for hematopoietic stem cell donation.

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Aurelio, M T; Aniasi, A; Haworth, S E; Colombo, M B; Dimonopoli, T; Mocellin, M C; Poli, F; Torelli, R; Crespiatico, L; Serafini, M; Scalamogna, M

2011-05-01

The Italian Bone Marrow Donor Register is the institutional organization for management of unrelated hematopoietic stem cell donors. The law requires only a donor's clinical history, but not a psychosocial profile for registration. We have studied the donor's motivation for enlistment on the donor registry and the medical staff's need for this information to interact correctly with the donor. For this purpose we distributed a questionnaire to new donors at the 20 centers in the Lombardy Region over a period of 1 year. The analysis of the responses revealed a prevalence of extrinsic motivations that would not ensure continued registration for donation. Therefore, it is necessary that the donor be well informed and better educated about all aspects of donation, in order to produce a shift to an intrinsic motivation. This objective can be facilitated via professional training of health workers in communication. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model

DEFF Research Database (Denmark)

Rasmussen, Jeppe; Frøbert, Ole; Holst-Hansen, Claus

2014-01-01

Background: Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal...... myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully...... grown non-immunecompromised rat model. Methods: Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were...

Hematopoietic Stem Cell Transplantation and History

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Atila Tanyeli

2014-02-01

Full Text Available Attemps to employ marrow stem cell for therapeutic purpose began in 1940’s. Marrow transplantation might be of use not only in irradiation protection, but also with therapeutic aim to marrow aplasia, leukemia and other diseases. The use and defining tissue antigens in humans were crucial to the improving of transplantation. The administration of methotrexate for GVHD improved the long term survival. Conditioning regimens for myeloablation designed according to diseases. Cord blood and peripheral blood stem cells were used for transplantion after 1980’s. Cord blood and bone marrow stem cell banks established to find HLA matched donor.

Hematopoietic Stem Cell Transplantation in Thalassemia and Sickle Cell Anemia

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Lucarelli, Guido; Isgrò, Antonella; Sodani, Pietro; Gaziev, Javid

2012-01-01

The globally widespread single-gene disorders β-thalassemia and sickle cell anemia (SCA) can only be cured by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT treatment of thalassemia has substantially improved over the last two decades, with advancements in preventive strategies, control of transplant-related complications, and preparative regimens. A risk class–based transplantation approach results in disease-free survival probabilities of 90%, 84%, and 78% for class 1, 2, and 3 thalassemia patients, respectively. Because of disease advancement, adult thalassemia patients have a higher risk for transplant-related toxicity and a 65% cure rate. Patients without matched donors could benefit from haploidentical mother-to-child transplantation. There is a high cure rate for children with SCA who receive HSCT following myeloablative conditioning protocols. Novel non-myeloablative transplantation protocols could make HSCT available to adult SCA patients who were previously excluded from allogeneic stem cell transplantation. PMID:22553502

Megakaryocytes promote murine osteoblastic HSC niche expansion and stem cell engraftment after radioablative conditioning.

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Olson, Timothy S; Caselli, Anna; Otsuru, Satoru; Hofmann, Ted J; Williams, Richard; Paolucci, Paolo; Dominici, Massimo; Horwitz, Edwin M

2013-06-27

Successful hematopoietic stem cell (HSC) transplantation requires donor HSC engraftment within specialized bone marrow microenvironments known as HSC niches. We have previously reported a profound remodeling of the endosteal osteoblastic HSC niche after total body irradiation (TBI), defined as relocalization of surviving megakaryocytes to the niche site and marked expansion of endosteal osteoblasts. We now demonstrate that host megakaryocytes function critically in expansion of the endosteal niche after preparative radioablation and in the engraftment of donor HSC. We show that TBI-induced migration of megakaryocytes to the endosteal niche depends on thrombopoietin signaling through the c-MPL receptor on megakaryocytes, as well as CD41 integrin-mediated adhesion. Moreover, niche osteoblast proliferation post-TBI required megakaryocyte-secreted platelet-derived growth factor-BB. Furthermore, blockade of c-MPL-dependent megakaryocyte migration and function after TBI resulted in a significant decrease in donor HSC engraftment in primary and competitive secondary transplantation assays. Finally, we administered thrombopoietin to mice beginning 5 days before marrow radioablation and ending 24 hours before transplant to enhance megakaryocyte function post-TBI, and found that this strategy significantly enhanced donor HSC engraftment, providing a rationale for improving hematopoietic recovery and perhaps overall outcome after clinical HSC transplantation.

Reduced intensity conditioning, combined transplantation of haploidentical hematopoietic stem cells and mesenchymal stem cells in patients with severe aplastic anemia.

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Xiao-Hong Li

Full Text Available We examined if transplantation of combined haploidentical hematopoietic stem cells (HSC and mesenchymal stem cells (MSC affected graft failure and graft-versus-host disease (GVHD in patients with severe aplastic anemia (SAA. Patients with SAA-I (N = 17 received haploidentical HSCT plus MSC infusion. Stem cell grafts used a combination of granulocyte colony-stimulating factor (G-CSF-primed bone marrow and G-CSF-mobilized peripheral blood stem cells of haploidentical donors and the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs, respectively. Reduced intensity conditioning consisted of fludarabine (30 mg/m2·d+cyclosphamide (500 mg/m2·d+anti-human thymocyte IgG. Transplant recipients also received cyclosporin A, mycophenolatemofetil, and CD25 monoclonal antibody. A total of 16 patients achieved hematopoietic reconstitution. The median mononuclear cell and CD34 count was 9.3×10(8/kg and 4.5×10(6/kg. Median time to ANC was >0.5×10(9/L and PLT count >20×10(9/L were 12 and 14 days, respectively. Grade III-IV acute GVHD was seen in 23.5% of the cases, while moderate and severe chronic GVHD were seen in 14.2% of the cases. The 3-month and 6-month survival rates for all patients were 88.2% and 76.5%, respectively; mean survival time was 56.5 months. Combined transplantation of haploidentical HSCs and MSCs on SAA without an HLA-identical sibling donor was safe, effectively reduced the incidence of severe GVHD, and improved patient survival.

Xenotransplantation: A Potential Solution to the Critical Organ Donor Shortage

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K Howe Sim

1999-01-01

Full Text Available The success of allotransplantation as a treatment for end-stage organ failure has resulted in the need for an increasing number of organ donors. Attempts to meet this need include the use of organs from living related and unrelated donors, financial or other incentives for the donor family, and even the reuse of transplanted organs. Despite these initiatives, the supply of organs for transplantation still falls far short of the demand, as evidenced by longer waiting times for transplantation and decreasing transplantation rates. Even if Canada were able to increase its organ donor rate to that of Spain (40 to 50/million, where organ donation is governed by ‘presumed consent’ legislation, this would not alleviate the problem of donor shortage. Interest in xenotransplantation stems from the need to overcome this increasingly severe shortage of human organs. Indeed, some argue that xenotransplantation is the only potential way of addressing this shortage. As immunological barriers to xenotransplantation are better understood, those hurdles are being addressed through genetic engineering of donor animals and the development of new drug therapies. However, before xenotransplantation can be fully implemented, both the scientific/medical communities and the general public must seriously consider and attempt to resolve the many complex ethical, social and economic issues that it presents.

In vitro analysis of equine, bone marrow-derived mesenchymal stem cells demonstrates differences within age- and gender-matched horses.

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Carter-Arnold, J L; Neilsen, N L; Amelse, L L; Odoi, A; Dhar, M S

2014-09-01

Stem cell therapies are used routinely in equine practice. Most published reports characterise stem cells derived from younger horses; however, middle-aged horses are often in athletic performance, and experience degenerative medical conditions. Thus, mesenchymal stem cells (MSCs) from this group should be investigated. To describe differences in in vitro adherence, proliferation and potential for differentiation of equine bone marrow-derived MSCs (equine BMMSCs) harvested from middle-aged (10-13 years old) female donors. Descriptive study of stem cell characteristics. Equine BMMSCs from 6 horses were cultured in vitro and evaluated for viability, proliferation, osteogenesis, chondrogenesis, adipogenesis, cluster-of-differentiation markers and gene expression. Equine BMMSCs from all 6 donors demonstrated fibroblastic, cellular morphology, adherence to plastic and expression of cluster-of-differentiation markers. They varied in their rate of proliferation and trilineage differentiation. The equine BMMSCs of one of 6 donors demonstrated a higher rate of proliferation, enhanced ability for cell passaging and a more robust in vitro differentiation. Comparatively, equine BMMSCs from 2 donors demonstrated a lower rate of proliferation and lack of osteogenic and chondrogenic differentiation. The results of this study confirm that donor-to-donor variation in equine BMMSCs exists and this variation can be documented using in vitro assays. Subjective assessment suggests that the rate of proliferation tends to correlate with differentiation potential. © 2013 EVJ Ltd.

Recruitment of feces donors among blood donors

DEFF Research Database (Denmark)

Dahl Jørgensen, Simon Mark; Erikstrup, Christian; Dinh, Khoa Manh

2018-01-01

As the use of fecal microbiota transplantation (FMT) has gained momentum, an increasing need for continuous access to healthy feces donors has developed. Blood donors constitute a healthy subset of the general population and may serve as an appropriate group for recruitment. In this study, we...... investigated the suitability of blood donors as feces donors. In a prospective cohort study, we recruited blood donors onsite at a public Danish blood bank. Following their consent, the blood donors underwent a stepwise screening process: First, blood donors completed an electronic pre-screening questionnaire...... to rule out predisposing risk factors. Second, eligible blood donors had blood and fecal samples examined. Of 155 blood donors asked to participate, 137 (88%) completed the electronic pre-screening questionnaire, 16 declined, and 2 were excluded. Of the 137 donors who completed the questionnaire, 79 (58...

Efficient CRISPR/Cas9-Mediated Versatile, Predictable, and Donor-Free Gene Knockout in Human Pluripotent Stem Cells.

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Liu, Zhongliang; Hui, Yi; Shi, Lei; Chen, Zhenyu; Xu, Xiangjie; Chi, Liankai; Fan, Beibei; Fang, Yujiang; Liu, Yang; Ma, Lin; Wang, Yiran; Xiao, Lei; Zhang, Quanbin; Jin, Guohua; Liu, Ling; Zhang, Xiaoqing

2016-09-13

Loss-of-function studies in human pluripotent stem cells (hPSCs) require efficient methodologies for lesion of genes of interest. Here, we introduce a donor-free paired gRNA-guided CRISPR/Cas9 knockout strategy (paired-KO) for efficient and rapid gene ablation in hPSCs. Through paired-KO, we succeeded in targeting all genes of interest with high biallelic targeting efficiencies. More importantly, during paired-KO, the cleaved DNA was repaired mostly through direct end joining without insertions/deletions (precise ligation), and thus makes the lesion product predictable. The paired-KO remained highly efficient for one-step targeting of multiple genes and was also efficient for targeting of microRNA, while for long non-coding RNA over 8 kb, cleavage of a short fragment of the core promoter region was sufficient to eradicate downstream gene transcription. This work suggests that the paired-KO strategy is a simple and robust system for loss-of-function studies for both coding and non-coding genes in hPSCs. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Facts about Stem Cells and Importance of Them

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Masumeh Saeidi

2014-05-01

Full Text Available Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis to produce more stem cells. They are found in multicellular organisms. In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cells—ectoderm, endoderm and mesoderm (see induced pluripotent stem cells—but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues. There are three accessible sources of autologous adult stem cells in humans: Bone marrow, which requires extraction by harvesting, that is, drilling into bone (typically the femur or iliac crest, Adipose tissue (lipid cells, which requires extraction by liposuction, and Blood, which requires extraction through apheresis, wherein blood is drawn from the donor (similar to a blood donation, and passed through a machine that extracts the stem cells and returns other portions of the blood to the donor. Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures. Adult stem cells are frequently used in medical therapies, for example in bone marrow transplantation. Stem cells can now be artificially grown and transformed (differentiated into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. Embryonic cell lines and autologous embryonic stem cells generated through Somatic-cell nuclear transfer or dedifferentiation

Complementarity of SOMAscan to LC-MS/MS and RNA-seq for quantitative profiling of human embryonic and mesenchymal stem cells.

Science.gov (United States)

Billing, Anja M; Ben Hamidane, Hisham; Bhagwat, Aditya M; Cotton, Richard J; Dib, Shaima S; Kumar, Pankaj; Hayat, Shahina; Goswami, Neha; Suhre, Karsten; Rafii, Arash; Graumann, Johannes

2017-01-06

Dynamic range limitations are challenging to proteomics, particularly in clinical samples. Affinity proteomics partially overcomes this, yet suffers from dependence on reagent quality. SOMAscan, an aptamer-based platform for over 1000 proteins, avoids that issue using nucleic acid binders. Targets include low expressed proteins not easily accessible by other approaches. Here we report on the potential of SOMAscan for the study of differently sourced mesenchymal stem cells (MSC) in comparison to LC-MS/MS and RNA sequencing. While targeting fewer analytes, SOMAscan displays high precision and dynamic range coverage, allowing quantification of proteins not measured by the other platforms. Expression between cell types (ESC and MSC) was compared across techniques and uncovered the expected large differences. Sourcing was investigated by comparing subtypes: bone marrow-derived, standard in clinical studies, and ESC-derived MSC, thought to hold similar potential but devoid of inter-donor variability and proliferating faster in vitro. We confirmed subtype-equivalency, as well as vesicle and extracellular matrix related processes in MSC. In contrast, the proliferative nature of ESC was captured less by SOMAscan, where nuclear proteins are underrepresented. The complementary of SOMAscan allowed the comprehensive exploration of CD markers and signaling molecules, not readily accessible otherwise and offering unprecedented potential in subtype characterization. Mesenchymal stem cells (MSC) represent promising stem cell-derived therapeutics as indicated by their application in >500 clinical trials currently registered with the NIH. Tissue-derived MSC require invasive harvesting and imply donor-to-donor differences, to which embryonic stem cell (ESC)-derived MSC may provide an alternative and thus warrant thorough characterization. In continuation of our previous study where we compared in depth embryonic stem cells (ESC) and MSC from two sources (bone marrow and ESC

Allogeneic Stem Cell Transplantation: A Historical and Scientific Overview.

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Singh, Anurag K; McGuirk, Joseph P

2016-11-15

The field of hematopoietic stem cell transplant (HSCT) has made ground-breaking progress in the treatment of many malignant and nonmalignant conditions. It has also pioneered the concepts of stem cell therapy and immunotherapy as a tool against cancer. The success of transplant for hematologic malignancies derives both from the ability to treat patients with intensive chemoradiotherapy and from potent graft-versus-leukemia (GVL) effects mediated by donor immunity. Additionally, HSCT has been a curative therapy for several nonmalignant hematologic disorders through the provision of donor-derived hematopoiesis and immunity. Preclinical and clinical research in the field has contributed to an advanced understanding of histocompatibility, graft-versus-host disease (GVHD), GVL effect, and immune reconstitution after transplant. Improved donor selection, tailored conditioning regimens, and better supportive care have helped reduce transplant-related morbidity and mortality and expanded access. The development of unrelated donor registries and increased utilization of cord blood and partially matched related donor transplants have ensured a donor for essentially everyone who needs a transplant. However, significant barriers still remain in the form of disease relapse, GVHD infectious complications, and regimen-related toxicities. Recent developments in the field of cellular therapy are expected to further improve the efficacy of transplant. In this review, we discuss the current science of HSCT from a historical perspective, highlighting major discoveries. We also speculate on future directions in this field. Cancer Res; 76(22); 6445-51. ©2016 AACR. ©2016 American Association for Cancer Research.

CRISPR-Mediated Integration of Large Gene Cassettes Using AAV Donor Vectors

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Rasmus O. Bak

2017-07-01

Full Text Available The CRISPR/Cas9 system has recently been shown to facilitate high levels of precise genome editing using adeno-associated viral (AAV vectors to serve as donor template DNA during homologous recombination (HR. However, the maximum AAV packaging capacity of ∼4.5 kb limits the donor size. Here, we overcome this constraint by showing that two co-transduced AAV vectors can serve as donors during consecutive HR events for the integration of large transgenes. Importantly, the method involves a single-step procedure applicable to primary cells with relevance to therapeutic genome editing. We use the methodology in primary human T cells and CD34+ hematopoietic stem and progenitor cells to site-specifically integrate an expression cassette that, as a single donor vector, would otherwise amount to a total of 6.5 kb. This approach now provides an efficient way to integrate large transgene cassettes into the genomes of primary human cells using HR-mediated genome editing with AAV vectors.

Successful haploidentical donor hematopoietic stem cell transplant and restoration of STAT3 function in an adolescent with autosomal dominant hyper-IgE syndrome.

Science.gov (United States)

Patel, N C; Gallagher, J L; Torgerson, T R; Gilman, A L

2015-07-01

Autosomal dominant hyper-IgE syndrome (AD-HIES), caused by mutations in Signal Transducer and Activator of Transcription 3 (STAT3) is associated with defective STAT3 signaling and Th17 differentiation and recurrent bacterial and fungal infections. Most patients suffer significant morbidity and premature mortality. Hematopoietic stem cell transplantation (HSCT) has been reported in a small number of cases, with mixed outcomes. We report successful haploidentical donor HSCT in a patient with AD-HIES. Evaluation of lymphocyte subsets, STAT3 signaling, and Th17 cells was performed pre- and post-HSCT. A 14-year old female with AD-HIES developed recurrent methicillin-resistant Staphylococcus aureus (MRSA) abscesses. Immunologic analysis showed elevated IgE (4331 kU/L), absent Th17 cells, and markedly decreased STAT3 phosphorylation in cytokine stimulated peripheral blood mononuclear cells. She had breakthrough abscesses despite clindamycin and trimethoprim-sulfamethoxazole prophylaxis, and developed steroid refractory autoimmune hemolytic anemia. She underwent T-cell depleted haploidentical HSCT from her father following reduced intensity conditioning. She developed one MRSA hand abscess after transplant. Twenty-four months post transplant, she had complete donor chimerism (>95 % donor), normal absolute T cell numbers, and a normal percentage of Th17 cells. IgE was normal at 25 kU/L. She remains well 42 months after transplantation off all antibacterial prophylaxis. Haploidentical HSCT led to successful bone marrow engraftment, normalization of STAT3 signaling in hematopoietic cells, normalization of IgE, and restoration of immune function in this patient with AD-HIES.

Development of an encapsulated stem cell-based therapy for diabetes.

Science.gov (United States)

Tomei, Alice Anna; Villa, Chiara; Ricordi, Camillo

2015-01-01

Islet transplantation can treat the most severe cases of type 1 diabetes but it currently requires deceased donor pancreata as an islet source and chronic immunosuppression to prevent rejection and recurrence of autoimmunity. Stem cell-derived insulin-producing cells may address the shortage of organ donors, whereas cell encapsulation may reduce or eliminate the requirement for immunosuppression, minimizing the risks associated with the islet transplantation procedure, and potentially prolonging graft survival. This review focuses on the design principles for immunoisolation devices and on stem cell differentiation into insulin-producing cell products. The reader will gain understanding of the different types of immunoisolation devices and the key parameters that affect the outcome of the encapsulated graft. Progresses in stem cell differentiation towards mature endocrine islet cells, including the most recent clinical trials and the challenges associated with the application of immunoisolation devices designed for primary islets to stem-cell products, are also discussed. Recent advancements in the field of stem cell-derived islet cell products and immunoisolation strategies hold great promise for type 1 diabetes. However, a combination product including both cells and an immunoisolation strategy still needs to be optimized and tested for safety and efficacy.

Incidence and dynamics of active cytomegalovirus infection in allogeneic stem cell transplant patients according to single nucleotide polymorphisms in donor and recipient CCR5, MCP-1, IL-10, and TLR9 genes.

Science.gov (United States)

Corrales, Isabel; Giménez, Estela; Solano, Carlos; Amat, Paula; de la Cámara, Rafael; Nieto, José; Garcia-Noblejas, Ana; Navarro, David

2015-02-01

Single nucleotide polymorphisms (SNPs) in genes involved in the activation or regulation of innate and adaptive immune responses may modulate the susceptibility to and the natural history of certain chronic viral infections. The current study aimed to investigate whether donor and recipient SNPs in the chemokine receptor 5 (rs1800023), monocyte chemoattractant protein 1 (rs13900), interleukin-10 (rs1878672), and Toll-like receptor 9 (rs352140) genes would exert any influence on the rate of incidence and features of CMV DNAemia in the allogeneic stem cell transplantation setting. This was a retrospective observational multicenter study. The cohort consisted of 102 non-consecutive allogeneic stem cell transplant recipients. SNP genotyping was performed by allele-specific real-time PCR. CMV surveillance was performed by the pp65 antigenemia assay/and or by real-time PCR. Seventy-three patients developed CMV DNAemia within the first 100 days after transplantation (71.5%). Neither donor nor recipient SNPs were associated significantly with the rate of incidence of active CMV infection, nor with the need for pre-emptive antiviral therapy. Both the duration of CMV DNAemia and the plasma CMV DNA peak load during episodes were significantly higher in patients harboring the donor (but not the recipient) chemokine receptor 5 A/A genotype, than in their A/G and G/G counterparts (P = 0.022 and P = 0.045, respectively). The data reported suggest that SNPs in chemokine receptor 5 may influence the dynamics of CMV infection in the Allo-SCT setting. © 2014 Wiley Periodicals, Inc.

Role of HLA in Hematopoietic Stem Cell Transplantation

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Meerim Park

2012-01-01

Full Text Available The selection of hematopoietic stem cell transplantation (HSCT donors includes a rigorous assessment of the availability and human leukocyte antigen (HLA match status of donors. HLA plays a critical role in HSCT, but its involvement in HSCT is constantly in flux because of changing technologies and variations in clinical transplantation results. The increased availability of HSCT through the use of HLA-mismatched related and unrelated donors is feasible with a more complete understanding of permissible HLA mismatches and the role of killer-cell immunoglobulin-like receptor (KIR genes in HSCT. The influence of nongenetic factors on the tolerability of HLA mismatching has recently become evident, demonstrating a need for the integration of both genetic and nongenetic variables in donor selection.

Stem Cell Banking for Regenerative and Personalized Medicine

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David T. Harris

2014-02-01

Full Text Available Regenerative medicine, tissue engineering and gene therapy offer the opportunity to treat and cure many of today’s intractable afflictions. These approaches to personalized medicine often utilize stem cells to accomplish these goals. However, stem cells can be negatively affected by donor variables such as age and health status at the time of collection, compromising their efficacy. Stem cell banking offers the opportunity to cryogenically preserve stem cells at their most potent state for later use in these applications. Practical stem cell sources include bone marrow, umbilical cord blood and tissue, and adipose tissue. Each of these sources contains stem cells that can be obtained from most individuals, without too much difficulty and in an economical fashion. This review will discuss the advantages and disadvantages of each stem cell source, factors to be considered when contemplating banking each stem cell source, the methodology required to bank each stem cell source, and finally, current and future clinical uses of each stem cell source.

Stem Cell Banking for Regenerative and Personalized Medicine

Science.gov (United States)

Harris, David T.

2014-01-01

Regenerative medicine, tissue engineering and gene therapy offer the opportunity to treat and cure many of today’s intractable afflictions. These approaches to personalized medicine often utilize stem cells to accomplish these goals. However, stem cells can be negatively affected by donor variables such as age and health status at the time of collection, compromising their efficacy. Stem cell banking offers the opportunity to cryogenically preserve stem cells at their most potent state for later use in these applications. Practical stem cell sources include bone marrow, umbilical cord blood and tissue, and adipose tissue. Each of these sources contains stem cells that can be obtained from most individuals, without too much difficulty and in an economical fashion. This review will discuss the advantages and disadvantages of each stem cell source, factors to be considered when contemplating banking each stem cell source, the methodology required to bank each stem cell source, and finally, current and future clinical uses of each stem cell source. PMID:28548060

Hematopoietic stem cell transplantation in children with leukemia: a single institution experience with respect to donors.

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Baek, Hee Jo; Kook, Hoon; Han, Dong Kyun; Hwang, Tai Ju

2011-12-01

Aim of this study was to compare the outcomes of transplantation by donor source and to help select the best alternative donor in children with leukemia. Donor sources included matched related donor (MRD, n = 35), allele-matched unrelated donor (M-UD, n = 10) or -mismatched (MM)-UD (n = 13) or unrelated umbilical cord blood (UCB, n = 11). UCB group had a significantly higher incidence of grade II-IV acute graft versus host disease (MRD, 11.8%; M-UD, 30.0%; MM-UD, 15.4%, UCB, 54.4%, P = 0.004) but there was no difference in incidence of chronic graft versus host disease between 4 groups. The 5-yr leukemia-free survival (LFS) was 76.7%, 60.0%, 69.2%, and 45.5%, respectively (P = 0.128). MRD group showed higher LFS rate than UCB group (P = 0.022). However, LFS of M-UD and MM-UD together (65.2%) was not different from that of MRD group (76.7%, P = 0.325), or from that of UCB (45.5%, P = 0.190). The relapse incidence at 5 yr was 17.1%, 20.0%, 15.4%, and 0%, respectively (P = 0.460). The 100-day treatment-related mortality was 2.9%, 20.0%, 7.7%, and 36.4%, respectively (P = 0.011). Despite the limitations of small number of patients, unrelated donor transplants including even allele-mismatched ones, seem to be as effective in children with leukemia lacking suitable relative donors. Also, UCB transplant may serve as another possible option in urgent transplants.

Biological Significance of the Suppression of Oxidative Phosphorylation in Induced Pluripotent Stem Cells

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Cheng Zhang

2017-11-01

Full Text Available We discovered that induced pluripotent stem cell (iPSC clones generated from aged tissue donors (A-iPSCs fail to suppress oxidative phosphorylation. Compared to embryonic stem cells (ESCs and iPSCs generated from young donors (Y-iPSCs, A-iPSCs show poor expression of the pluripotent stem cell-specific glucose transporter 3 (GLUT3 and impaired glucose uptake, making them unable to support the high glucose demands of glycolysis. Persistent oxidative phosphorylation in A-iPSCs generates higher levels of reactive oxygen species (ROS, which leads to excessive elevation of glutathione (a ROS-scavenging metabolite and a blunted DNA damage response. These phenotypes were recapitulated in Y-iPSCs by inhibiting pyruvate dehydrogenase kinase (PDK or supplying citrate to activate oxidative phosphorylation. In addition, oxidative phosphorylation in A-iPSC clones depletes citrate, a nuclear source of acetyl group donors for histone acetylation; this consequently alters histone acetylation status. Expression of GLUT3 in A-iPSCs recovers the metabolic defect, DNA damage response, and histone acetylation status.

Risk of Exposure to Zika Virus and Impact on Cord Blood Banking and Adult Unrelated Donors in Hematopoietic Cell Transplantation: The Canadian Blood Services Experience.

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Adams, Zachary; Morris, Gail; Campbell, Todd; Mostert, Karen; Dibdin, Nicholas; Fearon, Margaret; Elmoazzen, Heidi; Mercer, Dena; Young, Kimberly; Allan, David

2018-04-01

Zika virus has emerged as a potential threat to the Canadian blood supply system. Stem cell donors within Canadian Blood Services' Cord Blood Bank (CBB) and OneMatch Stem Cell and Marrow Network (OM) now undergo screening measures designed to reduce the risk of Zika virus transmission. The impact these screening measures have on cord blood and unrelated adult stem cell donations is currently unknown. Among 146 donor workups initiated by OM between July 2016 and May 2017, 102 were completed and 44 workups were canceled. There were 17 potential donors (11.6%) with a risk of Zika virus exposure identified by the donor questionnaire (13 completed, 4 canceled workups). None of the workups involved a donor diagnosed with confirmed Zika virus within the past 6 months. Only 1 of the 44 canceled workups (and only 1 of 4 cases with a risk of Zika transmission) was canceled because of the risk of Zika transmission, and a backup donor was selected. Canadian Blood Services' CBB identified 25 of 875 cord blood units (2.9%) from women who donated their infants' cord blood and underwent screening that otherwise met the initial cell number thresholds for banking and had at least 1 risk factor for exposure to Zika virus. No women were diagnosed with Zika virus at any point of their pregnancy. All 25 units were discarded. Unrelated donors at OM have a higher incidence of a risk of exposure to Zika virus compared with cord blood donors. Only rarely did transplant centers cancel donor workups due to potential Zika virus exposure. The impact of screening for Zika virus exposure risk on cord blood banking was minor. Continued vigilance and surveillance is recommended. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Desensitization for solid organ and hematopoietic stem cell transplantation.

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Zachary, Andrea A; Leffell, Mary S

2014-03-01

Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft. © 2014 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

stem cell research: applications in haematological conditions

African Journals Online (AJOL)

Dr. E. P. Gharoro

chemotherapy and radiation. This has allowed HSCT to be conducted in older patients without the need for hospitalization. STEM CELL COLLECTION. Types of Donors. There are two major types of bone marrow transplantation namely;. Autologous and Allogenic transplantations. Autologous: Bone marrow transplantation.

Trends in organ donor management: 2002 to 2012.

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Callahan, Devon S; Kim, Dennis; Bricker, Scott; Neville, Angela; Putnam, Brant; Smith, Jennifer; Bongard, Frederic; Plurad, David

2014-10-01

Refinements in donor management have resulted in increased numbers and quality of grafts after neurologic death. We hypothesize that the increased use of hormone replacement therapy (HRT) has been accompanied by improved outcomes over time. Using the Organ Procurement and Transplant Network donor database, all brain-dead donors procured from July 1, 2001 to June 30, 2012 were studied. Hormone replacement therapy was identified by an infusion of thyroid hormone. An expanded criteria donor was defined as age 60 years or older. Incidence of HRT administration and number of donors and organs recovered were calculated. Using the Organ Procurement and Transplant Network thoracic recipient database transplant list, wait times were examined. There were 74,180 brain-dead donors studied. Hormone replacement therapy use increased substantially from 25.6% to 72.3% of donors. However, mean number of organs procured per donor remained static (3.51 to 3.50; p = 0.083), and the rate of high-yield donors decreased (46.4% to 43.1%; p donors decreased (42.1% to 33.9%; p donors (22.1% to 26%). Despite this, there has been an increase in the raw number of donors (20,558 to 24,308; p organs (5,857 to 6,945; p organs per traumatic brain injury donor (4.02 to 4.12; p = 0.002) and a decrease in days on the waiting list (462.2 to 170.4 days; p donors has been accompanied by increased organ availability overall. Potential mechanisms might include successful conversion of previously unacceptable donors and improved recovery in certain subsets of donors. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Proliferative capacity of murine hematopoietic stem cells

International Nuclear Information System (INIS)

Hellman, S.; Botnick, L.E.; Hannon, E.C.; Vigneulle, R.M.

1978-01-01

The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferatively quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cells progress in the continuum in one direction and such progression is not reversible

Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

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Nagwa El-Badri

2013-01-01

Full Text Available Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy is a promising alternative for islet transplantation in type 2 diabetic patients who fail to control hyperglycemia even with insulin injection. Autologous stem cell transplantation may provide the best outcome for those patients, since autologous cells are readily available and do not entail prolonged hospital stays or sustained immunotoxic therapy. Among autologous adult stem cells, mesenchymal stem cells (MSCs therapy has been applied with varying degrees of success in both animal models and in clinical trials. This review will focus on the advantages of MSCs over other types of stem cells and the possible mechanisms by which MSCs transplant restores normoglycemia in type 2 diabetic patients. Sources of MSCs including autologous cells from diabetic patients and the use of various differentiation protocols in relation to best transplant outcome will be discussed.

Hematopoietic stem cell transplantation from unrelated donors in children with DOCK8 deficiency.

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Uygun, Dilara Fatma K; Uygun, Vedat; Reisli, İsmail; Keleş, Sevgi; Özen, Ahmet; Yılmaz, Mustafa; Sayar, Esra H; Daloğlu, Hayriye; Öztürkmen, Seda I; Çakı, Suar; Karasu, Gülsün T; Yeşilipek, Akif

2017-11-01

DIDS is a unique form of combined immune deficiency characterized by an unusual susceptibility to cutaneous viral infections, severe allergies with eosinophilia and elevated immunoglobulin E titers, autoimmunity, and cancer. HSCT is considered the standard of care for this deadly disease. We have retrospectively analyzed the outcome of allogeneic HSCT from unrelated donors in patients with DIDS. Data from four patients, with five transplants, are presented. All patients received transplants from unrelated donors' BM, except for one patient who received a cord blood transplant. The conditioning regimens were based on myeloablative protocols for BM derived transplants; a NM regimen was pursued for the patient who received a cord blood transplant, which resulted in graft rejection. Although recurrent pneumonia and skin infections resolved immediately after transplantation, all patients subsequently developed human herpesvirus infection, including cutaneous herpetic lesions, cytomegalovirus reactivation, and zona zoster, which could be attributed to the use of ATG. Despite the presence of serious morbidities prior to transplantation, all patients recovered successfully. DIDS can be successfully treated with allogeneic HSCT from unrelated donors following a myeloablative conditioning regimen, with a reasonable safety profile. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Safety and immune regulatory properties of canine induced pluripotent stem cell-derived mesenchymal stem cells.

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Chow, Lyndah; Johnson, Valerie; Regan, Dan; Wheat, William; Webb, Saiphone; Koch, Peter; Dow, Steven

2017-12-01

Mesenchymal stem cells (MSCs) exhibit broad immune modulatory activity in vivo and can suppress T cell proliferation and dendritic cell activation in vitro. Currently, most MSC for clinical usage are derived from younger donors, due to ease of procurement and to the superior immune modulatory activity. However, the use of MSC from multiple unrelated donors makes it difficult to standardize study results and compare outcomes between different clinical trials. One solution is the use of MSC derived from induced pluripotent stem cells (iPSC); as iPSC-derived MSC have nearly unlimited proliferative potential and exhibit in vitro phenotypic stability. Given the value of dogs as a spontaneous disease model for pre-clinical evaluation of stem cell therapeutics, we investigated the functional properties of canine iPSC-derived MSC (iMSC), including immune modulatory properties and potential for teratoma formation. We found that canine iMSC downregulated expression of pluripotency genes and appeared morphologically similar to conventional MSC. Importantly, iMSC retained a stable phenotype after multiple passages, did not form teratomas in immune deficient mice, and did not induce tumor formation in dogs following systemic injection. We concluded therefore that iMSC were phenotypically stable, immunologically potent, safe with respect to tumor formation, and represented an important new source of cells for therapeutic modulation of inflammatory disorders. Copyright © 2017. Published by Elsevier B.V.

Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

OpenAIRE

El-Badri, Nagwa; Ghoneim, Mohamed A.

2013-01-01

Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy...

Outcomes of peripheral blood stem cell transplantation patients from HLA-mismatched unrelated donor with antithymocyte globulin (ATG)-Thymoglobulin versus ATG-Fresenius: a single-center study.

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Huang, Wenrong; Zhao, Xiaoli; Tian, Yamin; Cao, Tingting; Li, Yanfen; Liu, Zhanxiang; Jing, Yu; Wang, Shuhong; Gao, Chunji; Yu, Li

2015-02-01

Although antithymocyte globulin (ATG) had been widely used in hematopoietic stem cell transplantation from unrelated donor due to its ability to prevent acute and chronic graft-versus-host disease (GVHD), the comparative efficacy and safety of ATG-Thymoglobulin (ATG-T) and ATG-Fresenius (ATG-F) in patients undergoing HLA-mismatched allogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) has not been evaluated. Retrospective analysis of patients who underwent HLA-mismatched UR-PBSCT between January 2003 and December 2013 and received pre-transplant ATG-T at a total dose of 10 mg/kg or ATG-F at a total dose of 20 mg/kg was performed. Patients who received ATG-T (n = 23) or ATG-F (n = 28) had similar baseline demographic, disease, and transplant characteristics. There were no significant between-groups differences in the probability of acute GVHD (P = 0.721) and chronic GVHD (P = 0.439). ATG-F was associated with nonsignificant trends toward higher disease-free survival at 3-year follow-up compared with ATG-T (45.7 ± 11.1 vs 61.3 ± 9.7 %, respectively, P = 0.07). A significantly greater proportion of ATG-T patients experienced high fever than ATG-F patients (P < 0.01) during ATG infusion. There was no difference in the rate of infection between the two treatment groups. There were less adverse effects comparing ATG-F with ATG-T. ATG-T at a total dose of 10 mg/kg and ATG-F at a total dose of 20 mg/kg had a similar clinical outcome in the setting of HLA-mismatched UR-PBSCT.

Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody Mediated Rejection After Vascularized Composite Allotransplantation

Science.gov (United States)

2017-10-01

Award Number: W81XWH-16-1-0664 TITLE: Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody-Mediated Rejection after...Annual 3. DATES COVERED 15 Sep 2016 – 14 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Autologous Hematopoietic Stem Cell Transplantation to...sensitization, autologous hematopoietic stem cell transplantation, antibody mediated rejection, donor specific antibodies 16. SECURITY CLASSIFICATION OF

Prevention of lethal murine graft versus host disease by treatment of donor cells with L-leucyl-L-leucine methyl ester

International Nuclear Information System (INIS)

Charley, M.; Thiele, D.L.; Bennett, M.; Lipsky, P.E.

1986-01-01

Graft vs. host disease (GVHD) remains one of the main problems associated with bone marrow transplantation. The current studies were undertaken to determine whether treatment of the donor inoculum with the anticytotoxic cell compound L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) would alter the development of GVHD in a murine model. Irradiated recipient mice transplanted with a mixture of control bone marrow and spleen cells from naive semiallogeneic donors died rapidly from GVHD, whereas the recipients of cells incubated with 250 microM Leu-Leu-OMe all survived. In addition, Leu-Leu-OMe treatment of cells obtained from donors immunized against host alloantigens resulted in significantly prolonged survival. Phenotypic characterization of spleen cells from the various groups of mice that had received Leu-Leu-OMe-treated cells and survived consistently revealed the donor phenotype. Treatment of marrow cells with 250 microM Leu-Leu-OMe appeared to have no adverse effects on stem cell function. Erythropoiesis was undiminished, as assayed by splenic 5-iodo-2'-deoxyuridine- 125 I uptake. Moreover, granulocytic and megakaryocytic regeneration were histologically equivalent in the spleens of recipients of control or Leu-Leu-OMe-treated cells. Treatment of the donor inoculum with Leu-Leu-OMe thus prevents GVHD in this murine strain combination with no apparent stem cell toxicity

Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin.

Science.gov (United States)

Dorn, Isabel; Klich, Katharina; Arauzo-Bravo, Marcos J; Radstaak, Martina; Santourlidis, Simeon; Ghanjati, Foued; Radke, Teja F; Psathaki, Olympia E; Hargus, Gunnar; Kramer, Jan; Einhaus, Martin; Kim, Jeong Beom; Kögler, Gesine; Wernet, Peter; Schöler, Hans R; Schlenke, Peter; Zaehres, Holm

2015-01-01

Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential. Copyright© Ferrata Storti Foundation.

Accumulation of GC donor splice signals in mammals

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Koonin Eugene V

2008-07-01

Full Text Available Abstract The GT dinucleotide in the first two intron positions is the most conserved element of the U2 donor splice signals. However, in a small fraction of donor sites, GT is replaced by GC. A substantial enrichment of GC in donor sites of alternatively spliced genes has been observed previously in human, nematode and Arabidopsis, suggesting that GC signals are important for regulation of alternative splicing. We used parsimony analysis to reconstruct evolution of donor splice sites and inferred 298 GT > GC conversion events compared to 40 GC > GT conversion events in primate and rodent genomes. Thus, there was substantive accumulation of GC donor splice sites during the evolution of mammals. Accumulation of GC sites might have been driven by selection for alternative splicing. Reviewers This article was reviewed by Jerzy Jurka and Anton Nekrutenko. For the full reviews, please go to the Reviewers' Reports section.

Hematopoietic stem cell transplantation in sickle cell disease: patient selection and special considerations

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Bhatia M

2015-07-01

Full Text Available Monica Bhatia,1 Sujit Sheth21Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Medical Center, 2Division of Pediatric Hematology and Oncology, Weill Cornell Medical College, New York, NY, USAAbstract: Hematopoietic stem cell transplantation remains the only curative treatment currently in use for patients with sickle cell disease (SCD. The first successful hematopoietic stem cell transplantation was performed in 1984. To date, approximately 1,200 transplants have been reported. Given the high prevalence of this disorder in Africa, and its emergence in the developed world through immigration, this number is relatively small. There are many reasons for this; primary among them are the availability of a donor, the risks associated with this complex procedure, and the cost and availability of resources in the developing world. Of these, it is fair to say that the risks associated with the procedure have steadily decreased to the point where, if currently performed in a center with experience using a matched sibling donor, overall survival is close to 100% and event-free survival is over 90%. While there is little controversy around offering hematopoietic stem cell transplantation to symptomatic SCD patients with a matched sibling donor, there is much debate surrounding the use of this modality in “less severe” patients. An overview of the current state of our understanding of the pathology and treatment of SCD is important to show that our current strategy is not having the desired impact on survival of homozygous SCD patients, and should be changed to significantly impact the small proportion of these patients who have matched siblings and could be cured, especially those without overt clinical manifestations. Both patient families and providers must be made to understand the progressive nature of SCD, and should be encouraged to screen full siblings of patients with homozygous SCD for their potential to

Donor Outcomes in Living Donor Liver Transplantation-Analysis of 275 Donors From a Single Centre in India.

Science.gov (United States)

Narasimhan, Gomathy; Safwan, Mohamed; Kota, Venugopal; Reddy, Mettu S; Bharathan, Anand; Dabora, Abderrhaim; Kaliamoorthy, Ilankumaran; Kanagavelu, Rathnavel G; Srinivasan, Vijaya; Rela, Mohamed

2016-06-01

Live donor liver transplantation is the predominant form of liver transplantation in India and in most Asian countries. Donor outcome reports are an important source of information to be shared with prospective donors at the time of informed consent. This is the first donor outcome series from India. Analysis of donor characteristics and morbidity of 275 live donors from a single large volume center is documented. Two hundred seventy-five patients donated from November 2009 to October 2014, 144 were women and 131 were men, 180 donated to adults and 95 donated to children. Right lobe donors were majority at 62.2% followed by left lateral segment 28%. Two thirds of the live donors did not have any morbidity; 114 complications were encountered in 85 patients. The complications were graded as per Clavien 5 tier grading and major morbidity (grade III b, grade IV grade V) was 4.36%. Postoperative biliary complication was seen in 3 donors. This large single-center study is the first donor outcome report from India, and the results are comparable to other published donor series. Documentation and regular audit of donor outcomes is important to help improve the safety of donor hepatectomy and to provide a database for informed consent of prospective donors.

Stem cells of umbilical blood cord – therapeutic use

Directory of Open Access Journals (Sweden)

Beata Bielec

2015-07-01

Full Text Available For many years, the transplantation of hematopoietic stem cells has been used to treat some diseases of the hematopoietic system. For a very long time, only bone marrow was used as a source of hematopoietic stem cells for this method of treatment. However, to comply with allogeneic bone marrow transplantation, an antigenically compatible donor is necessary. Transplantations from unrelated donors are associated with increased risk of a graft-versus-host reaction, transplant rejection and, consequently, increased mortality. Many years ago, it was found that umbilical cord blood as well as bone marrow and peripheral blood contains hematopoietic stem cells and mesenchymal cells able to differentiate into different cell types and that the umbilical cord blood can be a source of stem cells for transplantation. Following this discovery, numerous attempts were made for its potential use in the treatment of hematologic diseases, metabolic diseases as well as regenerative medicine. Umbilical cord blood stem cells exhibit intermediate characteristics between embryonic and adult stem cells. They are distinguished from the latter by telomere length, telomerase activity, and lower risk of accumulation of DNA mutations or chromosomal aberrations. The only transplantation limitation appears to be the amount of cord blood collected, which on average is sufficient for transplantation in a 40-50 kg child. Collection of cord blood is a simple, short-lasting treatment, not causing any danger for a newborn or the mother. Umbilical cord blood is obtained during labor, and then frozen and stored at cord blood banks all over the world.

Cryopreservation of adult unrelated donor products in hematopoietic cell transplantation: the OneMatch experience and systematic review of the literature.

Science.gov (United States)

Aziz, Joseph; Morris, Gail; Rizk, Mina; Shorr, Risa; Mercer, Dena; Young, Kimberly; Allan, David

2017-11-01

The frequency of cryopreserving blood stem or progenitor products from unrelated donors is not known and the underlying reasons are poorly documented. Greater insight is needed to develop policies on cryopreservation that balance donor safety with patient needs. Cryopreservation requests between January 1, 2014, and May 31, 2016, at the OneMatch Stem Cell and Marrow Network at Canadian Blood Services were reviewed and a systematic review of the literature was performed. Thirty products of 719 (4.2%) unrelated donor collections facilitated by OneMatch were cryopreserved. Patient-related reasons were most common and included the need to delay transplant for continued antimicrobial treatment (six patients), patient too deconditioned to proceed with scheduled transplant (five patients), and/or need for more treatment for relapsed disease (three patients). Donor-related issues leading to cryopreservation requests were less common (five cases), mainly due to lack of donor availability after attempting to reschedule. Cryopreservation of a product that was never infused occurred infrequently (two cases, 7%). In our systematic review of the literature, 993 cases were identified in 32 published reports. Both patient-related and donor-related reasons were cited but not specifically reported, precluding quantitative insight regarding the relative frequency of causes. The impact of cryopreservation on hematopoietic engraftment appears negligible when compared to controls in a subset of studies; however, reporting of outcomes was inconsistent. Future studies with standard outcome measures are needed to clarify the impact of cryopreservation on engraftment and other transplant outcomes. International guidelines that consider the ethical framework surrounding requests for donor product cryopreservation are needed. © 2017 AABB.

Hematopoietic stem cell transplantation from non-sibling matched family donors for patients with thalassemia major in Jordan.

Science.gov (United States)

Hussein, Ayad Ahmed; Al-Zaben, Abdulhadi; Khattab, Eman; Haroun, Anas; Frangoul, Haydar

2016-02-01

There are limited data on the outcome of patients with thalassemia receiving HSCT from non-sibling matched family donors. Of the 341 patients with thalassemia major that underwent donor search at our center from January 2003 to December 2011, 236 (69.2%) had fully matched family donor of which 28 patients (8.2%) had non-sibling matched family donors identified. We report on seven patients with a median age of eight yr (4-21) who underwent myeloablative (n = 4) or RIC (n = 3) HSCT. The median age of the donors was 33 yr (4-47), three were parents, two first cousins, one paternal uncle, and one paternal aunt. All patients achieved primary neutrophil and platelet engraftment at a median of 18 (13-20) and 16 days (11-20), respectively. One patient developed grade II acute GVHD, and two patients developed limited chronic GVHD. One patient experienced secondary GF requiring a second transplant. At a median follow-up of 69 months (7-110), all patients are alive and thalassemia free. Our data emphasize the need for extended family HLA typing for patients with thalassemia major in regions where there is high rate of consanguinity. Transplant from non-sibling matched family donor can result in excellent outcome. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nonmyeloablative and reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation: a clinical review.

Science.gov (United States)

Pollack, Seth M; O'Connor, Thomas P; Hashash, Jana; Tabbara, Imad A

2009-12-01

Allogeneic hematopoietic stem cell transplantation provides many patients, with hematological and malignant diseases, hope of remission and in some cases cure. Because the toxicities of this approach are severe, its use has been limited to younger healthier patients. Nonmyeloablative and reduced intensity conditioning regimens depend more on donor cellular immune effects and less on the cytotoxic effects of the conditioning regimen to eradicate the underlying disease. This approach is based on the induction of host tolerance to donor cells followed by the administration of scheduled donor T-lymphocytes infusions. Accumulated clinical data have been encouraging, and prospective studies are underway to compare this approach to conventional myeloablative allogeneic stem cell transplantation with regard to outcome, durability of responses, effects on the immune system, and the consequences of late complications such as chronic graft-versus-host disease.

Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

Science.gov (United States)

Akita, Sadanori; Akino, Kozo; Hirano, Akiyoshi; Ohtsuru, Akira; Yamashita, Shunichi

2010-01-01

Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years. PMID:21151652

Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

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Sadanori Akita

2010-01-01

Full Text Available Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years.

Banking Umbilical Cord Blood (UCB) Stem Cells: Awareness, Attitude and Expectations of Potential Donors from One of the Largest Potential Repository (India).

Science.gov (United States)

Pandey, Deeksha; Kaur, Simar; Kamath, Asha

2016-01-01

The concept of Umbilical Cord blood (UCB) stem cells is emerging as a non-invasive, efficacious alternative source of hematopoietic stem cells to treat a variety of blood and bone marrow diseases, blood cancers, metabolic disorders and immune deficiencies. Aim of the present study was to determine the level of awareness about banking UCB among pregnant women in India. We also assessed patient perception for banking of UCB and explored the patient expectations of banking UCB in future. This is the first study to assess current attitudes, in a sample population of potential donors from one of the largest potential UCB repository (India). Obtaining this information may help optimize recruitment efforts and improve patient education. Present explorative questionnaire based survey included 254 pregnant women in the final analysis. We established only 26.5% pregnant women in our study population knew what exactly is meant by UCB. A large proportion (55.1%) was undecided on whether they want to bank UCB or not. Women were more aware of the more advertised private cord blood banking compared to public banking. More than half of the pregnant women expected their obstetrician to inform them regarding UCB. One-third of the women in our population had undue expectations from banking of the UCB. Obstetricians should play a more active role in explaining the patients regarding pros and cons of UCB banking.

Banking Umbilical Cord Blood (UCB Stem Cells: Awareness, Attitude and Expectations of Potential Donors from One of the Largest Potential Repository (India.

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Deeksha Pandey

Full Text Available The concept of Umbilical Cord blood (UCB stem cells is emerging as a non-invasive, efficacious alternative source of hematopoietic stem cells to treat a variety of blood and bone marrow diseases, blood cancers, metabolic disorders and immune deficiencies. Aim of the present study was to determine the level of awareness about banking UCB among pregnant women in India. We also assessed patient perception for banking of UCB and explored the patient expectations of banking UCB in future. This is the first study to assess current attitudes, in a sample population of potential donors from one of the largest potential UCB repository (India. Obtaining this information may help optimize recruitment efforts and improve patient education.Present explorative questionnaire based survey included 254 pregnant women in the final analysis.We established only 26.5% pregnant women in our study population knew what exactly is meant by UCB. A large proportion (55.1% was undecided on whether they want to bank UCB or not. Women were more aware of the more advertised private cord blood banking compared to public banking. More than half of the pregnant women expected their obstetrician to inform them regarding UCB. One-third of the women in our population had undue expectations from banking of the UCB.Obstetricians should play a more active role in explaining the patients regarding pros and cons of UCB banking.

Mesenchymal stem cell therapy for immune-modulation: the donor, the recipient, and the drugs in-between.

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Nemeth, Krisztian

2014-09-01

Adoptive transfer of cultured bone marrow stromal cells (mesenchymal stem cells also known as MSCs) is a promising new way to aid tissue regeneration and treat a wide variety of diseases where regulation of inflammatory responses is derailed. Although significant advances have been made in the field, pinpointing important mechanistic details about how MSCs function in vitro and in vivo, there are still many unanswered questions that need to be addressed before welcoming MSCs in the therapeutic arsenal of immune mediated diseases. In this viewpoint, we highlight and discuss a few factors that we believe are critical in terms of therapeutic success employing cultured MSCs. Selecting the right donor population, choosing the best culture conditions and picking the patient population that is most likely to give a favourable therapeutic response is just as important as considering interactions between MSCs and the combination of drugs in the recipient's body. Given the complexity of MSC-host interactions, it is also imperative to develop screening tools that account for as many variables as possible and predict precisely the in vivo response rates before MSCs enter the body. To achieve this, a multidisciplinary approach is required with comprehensive knowledge of basic MSC biology, immunology, pharmacology and good clinical practice. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects Of Hypoxia in Long-Term In Vitro Expansion of Human Bone Marrow Derived Mesenchymal Stem Cells.

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Pezzi, Annelise; Amorin, Bruna; Laureano, Álvaro; Valim, Vanessa; Dahmer, Alice; Zambonato, Bruna; Sehn, Filipe; Wilke, Ianaê; Bruschi, Lia; Silva, Maria Aparecida Lima da; Filippi-Chiela, Eduardo; Silla, Lucia

2017-10-01

Mesenchymal stem cells (MSC) are considered multipotent stromal, non-hematopoietic cells with properties of self-renovation and differentiation. Optimal conditions for culture of MSC have been under investigation. The oxygen tension used for cultivation has been studied and appears to play an important role in biological behavior of mesenchymal cells. The aim is characterize MSC in hypoxia and normoxia conditions comparing their morphological and functional characteristics. Bone marrow-derived mesenchymal stem cells obtained from 15 healthy donors and cultured. MSC obtained from each donor were separated into two cultivation conditions normoxia (21% O 2 ) and hypoxia (three donors at 1%, three donors at 2%, five donors at 3%, and four donors at 4% O 2 ) up to second passage. MSC were evaluated for proliferation, differentiation, immunophenotyping, size and cell complexity, oxidative stress, mitochondrial activity, and autophagy. Culture conditions applied did not seem to affect immunophenotypic features and cellular plasticity. However, cells subjected to hypoxia showed smaller size and greater cellular complexity, besides lower proliferation (P cells cultured in low O 2 tension had lower mitochondrial activity (P Cell. Biochem. 118: 3072-3079, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Stem cell-based approach in diabetes and pancreatic cancer management

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Yi-Zhou Jiang

2017-01-01

Full Text Available Stem cell-mediated therapy is a promising strategy for treating pancreatic diseases such as Type-1 diabetes (T1D and pancreatic cancers. Although islet transplantation has been reported to be an effective diabetes therapy, its worldwide application is extremely limited due to the shortage of donor islets and immune rejection problems. Stem cell-based approach for islet neogenesis in vivo could provide a promising alternative source of islets for treating diabetes. On the other hand, targeting the cancer stem cells could be very effective for the treatment of pancreatic cancers. In this review, we focused on the present progress in the field of adult pancreatic stem cells, stem cell-mediated strategies for treating T1D, and pancreatic cancer stem cells, while discussing of the possible challenges involved in them.

Application of MultiStem® allogeneic cells for immunomodulatory therapy: clinical progress and pre-clinical challenges in prophylaxis for graft vs host disease

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Bart eVaes

2012-11-01

Full Text Available The last decade has seen much progress in adjunctive cell therapy for immune disorders. Both corporate and institutional Phase III studies have been run using mesenchymal stromal cells (MSC for treatment of Graft vs Host Disease (GvHD, and product approval has been achieved for treatment of pediatric GvHD in Canada and New Zealand (Prochymal®; Osiris Therapeutics. This effectiveness has prompted the prophylactic use of adherent stem cells at the time of allogeneic hematopoietic stem cell transplantation (HSCT to prevent occurrence of GvHD and possibly provide stromal support for hematopoietic recovery. The MultiStem® product is an adult adherent stem cell product derived from bone marrow which has significant clinical exposure. MultiStem cells are currently in phase II clinical studies for treatment of ischemic stroke and ulcerative colitis, with Phase I studies completed in acute myocardial infarction and for GvHD prophylaxis in allogeneic HSCT, demonstrating that MultiStem administration was well tolerated while the incidence and severity of GvHD was reduced. In advancing this clinical approach, it is important to recognize that alternate models exist based on clinical manufacturing strategies. Corporate sponsors exploit the universal donor properties of adherent stem cells and manufacture at large scale, with many products obtained from one or limited donors and used across many patients. In Europe, institutional sponsors often produce allogeneic product in a patient designated context. For this approach, disposable bioreactors producing <10 products per donor in a closed system manner are very well suited. In this review, the use of adherent stem cells for GvHD prophylaxis is summarized and the suitability of disposable bioreactors for MultiStem production is presented, with an emphasis on quality control parameters, which are critical with a multiple donor approach for manufacturing.

Dynamical system modeling to simulate donor T cell response to whole exome sequencing-derived recipient peptides: Understanding randomness in alloreactivity incidence following stem cell transplantation.

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Vishal Koparde

Full Text Available Quantitative relationship between the magnitude of variation in minor histocompatibility antigens (mHA and graft versus host disease (GVHD pathophysiology in stem cell transplant (SCT donor-recipient pairs (DRP is not established. In order to elucidate this relationship, whole exome sequencing (WES was performed on 27 HLA matched related (MRD, & 50 unrelated donors (URD, to identify nonsynonymous single nucleotide polymorphisms (SNPs. An average 2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p<0.01; resulting peptide antigens that may be presented on HLA class I molecules in each DRP were derived in silico (NetMHCpan ver2.0 and the tissue expression of proteins these were derived from determined (GTex. MRD DRP had an average 3,670 HLA-binding-alloreactive peptides, putative mHA (pmHA with an IC50 of <500 nM, and URD, had 5,386 (p<0.01. To simulate an alloreactive donor cytotoxic T cell response, the array of pmHA in each patient was considered as an operator matrix modifying a hypothetical cytotoxic T cell clonal vector matrix; each responding T cell clone's proliferation was determined by the logistic equation of growth, accounting for HLA binding affinity and tissue expression of each alloreactive peptide. The resulting simulated organ-specific alloreactive T cell clonal growth revealed marked variability, with the T cell count differences spanning orders of magnitude between different DRP. Despite an estimated, uniform set of constants used in the model for all DRP, and a heterogeneously treated group of patients, higher total and organ-specific T cell counts were associated with cumulative incidence of moderate to severe GVHD in recipients. In conclusion, exome wide sequence differences and the variable alloreactive peptide binding to HLA in each DRP yields a large range of possible alloreactive donor T cell responses. Our findings also help understand the apparent randomness observed in the development of alloimmune responses.

Application of hollow cylindrical wheat stem for electromembrane extraction of thorium in water samples

DEFF Research Database (Denmark)

Khajeh, Mostafa; Pedersen-Bjergaard, Stig; Barkhordar, Afsaneh

2015-01-01

-octanol and 5%v/v Di-(2-ethylhexyl) phosphate (DEHP) immobilized in the pores of a porous stem, and into an acceptor phase solution present inside the lumen of the stem. The pH of donor and acceptor phases, extraction time, voltage, and stirring speed were optimized. At the optimum conditions...

Pediatric transplantation using hearts refused on the basis of donor quality.

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Bailey, Leonard L; Razzouk, Anees J; Hasaniya, Nahidh W; Chinnock, Richard E

2009-06-01

There is always more demand than supply of organs in pediatric heart transplantation. Yet, potential donor organs are regularly declined for a variety of reasons, among them donor organ quality as determined by United Network for Organ Sharing (UNOS) refusal code 830 or its equivalent. For the study group institutional and UNOS databases (July 2000 to December 2008) were reviewed to examine outcomes of pediatric heart transplantation using donor hearts that had been previously refused one or more times because of organ quality. Variation between outcomes of this cohort and recipients who received primarily offered heart grafts in a single institution was analyzed. In 29 recipients, transplantation or retransplantation was with heart grafts previously declined on the basis of quality. Recovery distances (p actuarial survival was 74% +/- 10.5%. At the present time, 24 of the 29 recipients (83%) are alive. These results do not vary statistically from those experienced by 84 recipients of 86 primarily offered donor organs during the same time. Despite longer distance recovery (ie, longer graft cold ischemic times), outcomes of pediatric heart transplantation using donor heart grafts refused on the basis of organ quality are highly competitive. Pediatric donor hearts should seldom be declined on the basis of organ quality (UNOS code 830).

Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration.

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Jones, Brendan A; Pei, Ming

2012-08-01

Articular cartilage is difficult to heal once injury or disease occurs. Autologous chondrocyte transplantation is a biological treatment with good prognosis, but donor site morbidity and limited cell source are disadvantages. Currently, mesenchymal stem cells (MSCs) are a promising approach for cartilage regeneration. Despite there being various sources, the best candidate for cartilage regeneration is the one with the greatest chondrogenic potential and the least hypertrophic differentiation. These properties are able to insure that the regenerated tissue is hyaline cartilage of high quality. This review article will summarize relevant literature to justify synovium-derived stem cells (SDSCs) as a tissue-specific stem cell for chondrogenesis by comparing synovium and cartilage with respect to anatomical location and functional structure, comparing the growth characterization and chondrogenic capacity of SDSCs and MSCs, evaluating the application of SDSCs in regenerative medicine and diseases, and discussing potential future directions.

A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells

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Siddaraju V. Boregowda

2016-02-01

Full Text Available In addition to their stem/progenitor properties, mesenchymal stem cells (MSCs also exhibit potent effector (angiogenic, antiinflammatory, immuno-modulatory functions that are largely paracrine in nature. It is widely believed that effector functions underlie most of the therapeutic potential of MSCs and are independent of their stem/progenitor properties. Here we demonstrate that stem/progenitor and effector functions are coordinately regulated at the cellular level by the transcription factor Twist1 and specified within populations according to a hierarchical model. We further show that manipulation of Twist1 levels by genetic approaches or by exposure to widely used culture supplements including fibroblast growth factor 2 (Ffg2 and interferon gamma (IFN-gamma alters MSC efficacy in cell-based and in vivo assays in a predictable manner. Thus, by mechanistically linking stem/progenitor and effector functions our studies provide a unifying framework in the form of an MSC hierarchy that models the functional complexity of populations. Using this framework, we developed a CLinical Indications Prediction (CLIP scale that predicts how donor-to-donor heterogeneity and culture conditions impact the therapeutic efficacy of MSC populations for different disease indications.

Interaction between adipose tissue-derived mesenchymal stem cells and regulatory T-cells

OpenAIRE

Engela, Anja; Baan, Carla; Peeters, Anna; Weimar, Willem; Hoogduijn, Martin

2013-01-01

textabstractMesenchymal stem cells (MSCs) exhibit immunosuppressive capabilities, which have evoked interest in their application as cell therapy in transplant patients. So far it has been unclear whether allogeneic MSCs and host regulatory T-cells (Tregs) functionally influence each other. We investigated the interaction between both cell types using perirenal adipose tissue-derived MSCs (ASCs) from kidney donors and Tregs from blood bank donors or kidney recipients 6 months after transplant...

Grafting of a Single Donor Myofibre Promotes Hypertrophy in Dystrophic Mouse Muscle

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Boldrin, Luisa; Morgan, Jennifer E.

2013-01-01

Skeletal muscle has a remarkable capability of regeneration following injury. Satellite cells, the principal muscle stem cells, are responsible for this process. However, this regenerative capacity is reduced in muscular dystrophies or in old age: in both these situations, there is a net loss of muscle fibres. Promoting skeletal muscle muscle hypertrophy could therefore have potential applications for treating muscular dystrophies or sarcopenia. Here, we observed that muscles of dystrophic mdx nude host mice that had been acutely injured by myotoxin and grafted with a single myofibre derived from a normal donor mouse exhibited increased muscle area. Transplantation experiments revealed that the hypertrophic effect is mediated by the grafted fibre and does not require either an imposed injury to the host muscle, or the contribution of donor cells to the host muscle. These results suggest the presence of a crucial cross-talk between the donor fibre and the host muscle environment. PMID:23349935

MicroRNA Levels as Prognostic Markers for the Differentiation Potential of Human Mesenchymal Stromal Cell Donors

NARCIS (Netherlands)

Georgi, Nicole; Taipaleenmaeki, H.; Raiss, C.C.; Groen, N.; Portalska, K.K.; van Blitterswijk, Clemens; de Boer, Jan; Post, Janine Nicole; van Wijnen, A.; Karperien, Hermanus Bernardus Johannes

2015-01-01

The ability of human mesenchymal stromal/stem cells (hMSCs) to differentiate into various mesenchymal cell lineages makes them a promising cell source for the use in tissue repair strategies. Because the differentiation potential of hMSCs differs between donors, it is necessary to establish

Ureaplasma Transmitted From Donor Lungs Is Pathogenic After Lung Transplantation.

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Fernandez, Ramiro; Ratliff, Amy; Crabb, Donna; Waites, Ken B; Bharat, Ankit

2017-02-01

Hyperammonemia is a highly fatal syndrome in lung recipients that is usually refractory to medical therapy. We recently reported that infection by a Mollicute, Ureaplasma, is causative for hyperammonemia and can be successfully treated with antimicrobial agents. However, it remains unknown whether the pathogenic strain of Ureaplasma is donor or recipient derived. Here we provide evidence that donor-derived Ureaplasma infection can be pathogenic. As such, we uncover a previously unknown lethal donor-derived opportunistic infection in lung recipients. Given the high mortality associated with hyperammonemia, strategies for routine donor screening or prophylaxis should be further evaluated in prospective studies. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Gene Transfer Properties and Structural Modeling of Human Stem Cell-derived AAV

OpenAIRE

Smith, Laura J; Ul-Hasan, Taihra; Carvaines, Sarah K; Van Vliet, Kim; Yang, Ethel; Wong, Kamehameha K; Agbandje-McKenna, Mavis; Chatterjee, Saswati

2014-01-01

Adeno-associated virus (AAV) vectors are proving to be remarkably successful for in vivo gene delivery. Based upon reports of abundant AAV in the human marrow, we tested CD34+ hematopoietic stem cells for the presence of natural AAV. Here, we report for the first time, the presence of novel AAV variants in healthy CD34+ human peripheral blood stem cells. The majority of healthy peripheral blood stem cell donors were found to harbor AAV in their CD34+ cells. Every AAV isolated from CD34+ cells...

What Unrelated Hematopoietic Stem Cell Transplantation in Thalassemia Taught us about Transplant Immunogenetics

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La Nasa, Giorgio; Vacca, Adriana; Littera, Roberto; Piras, Eugenia; Orru, Sandro; Greco, Marianna; Carcassi, Carlo; Caocci, Giovanni

2016-01-01

Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT) continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cord blood banks has significantly increased the odds of finding a suitable HLA matched donor. Stringent immunogenetic criteria for donor selection have made it possible to achieve overall survival (OS) and thalassemia-free survival (TFS) rates comparable to those of sibling transplants. However, acute and chronic graft-versus-host disease (GVHD) remains the most important complication in unrelated HSCT in thalassemia, leading to significant rates of morbidity and mortality for a chronic non-malignant disease. A careful immunogenetic assessment of donors and recipients makes it possible to individualize appropriate strategies for its prevention and management. This review provides an overview of recent insights about immunogenetic factors involved in GVHD, which seem to have a potential role in the outcome of transplantation for thalassemia. PMID:27872728

WHAT UNRELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THALASSEMIA TAUGHT US ABOUT TRANSPLANT IMMUNOGENETICS.

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Giorgio La Nasa

2016-10-01

Full Text Available Abstract Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cordon blood banks has significantly increased the odds of finding a suitable HLA matched donor. Stringent immunogenetic criteria for donor selection have made it possible to achieve overall survival (OS and thalassemia-free survival (TFS rates comparable to those of sibling transplants. However, acute and chronic graft-versus-host disease (GVHD remains the most important complication in unrelated HSCT in thalassemia, leading to considerable rates of morbidity and mortality for a chronic non-malignant disease. A careful immunogenetic assessment of donors and recipients makes it possible to individuate appropriate strategies for its prevention and management. This review provides an overview on recent insights about immunogenetic factors involved in GVHD, which seem to have a potential role in the outcome of transplantation for thalassemia.

Hematopoietic Stem Cell Transplantation Activity and Trends at a Pediatric Transplantation Center in Turkey During 1998-2008

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Volkan Hazar

2012-06-01

Full Text Available OBJECTIVE: The aim of this study was to document hematopoietic stem cell transplantation (HSCT activity and trends at our treatment center. METHODS: Data collected over a 10-year period were retrospectively analyzed, concentrating primarily on types of HSCT, transplant-related mortality (TRM, stem cell sources, indications for HSCT, and causes of death following HSCT. RESULTS: In total, 222 allogeneic (allo-HSCT (87.4% and 32 autologous (auto-HSCT (12.6% procedures were performed between 1998 and 2008. Stem cells obtained from unrelated donors were used in 22.6% (50/222 of the allo- HSCTs. Cord blood was the source of hematopoietic stem cells (HSC in 12.2% of all transplants. The most common indication for allo-HSCT was hemoglobinopathy (43.2%, versus neuroblastoma (53.1% for auto-HSCT. The TRM rate 1 year post transplantation was 18.3% ± 2.5% for all transplants, but differed according to transplantation type (23.5% ± 7.9% for auto-HSCT and 17.5% ± 2.6% for allo-HSCT. The most common cause of death 1 year post HSCT was infection (35.9%. CONCLUSION: The TRM rate in the patients that underwent allo-HSCT was similar to that which has been previously reported; however, the TRM rate in the patients that underwent auto-HSCT was higher than previously reported in developed countries. The selection of these patients to be transplanted must be made attentively.

Human finger-prick induced pluripotent stem cells facilitate the development of stem cell banking.

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Tan, Hong-Kee; Toh, Cheng-Xu Delon; Ma, Dongrui; Yang, Binxia; Liu, Tong Ming; Lu, Jun; Wong, Chee-Wai; Tan, Tze-Kai; Li, Hu; Syn, Christopher; Tan, Eng-Lee; Lim, Bing; Lim, Yoon-Pin; Cook, Stuart A; Loh, Yuin-Han

2014-05-01

Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients can be a good model for studying human diseases and for future therapeutic regenerative medicine. Current initiatives to establish human iPSC (hiPSC) banking face challenges in recruiting large numbers of donors with diverse diseased, genetic, and phenotypic representations. In this study, we describe the efficient derivation of transgene-free hiPSCs from human finger-prick blood. Finger-prick sample collection can be performed on a "do-it-yourself" basis by donors and sent to the hiPSC facility for reprogramming. We show that single-drop volumes of finger-prick samples are sufficient for performing cellular reprogramming, DNA sequencing, and blood serotyping in parallel. Our novel strategy has the potential to facilitate the development of large-scale hiPSC banking worldwide.

Differentiation of hematopoietic stem cells in irradiated mouse thymic lobes. Kinetics and phenotype of progeny

International Nuclear Information System (INIS)

Spangrude, G.J.; Scollay, R.

1990-01-01

To define cell populations which participate in the very early stages of T cell development in the mouse thymus, we enriched hematopoietic stem cells from mouse bone marrow and injected them into thymic lobes of irradiated Ly-5 congenic recipients. The progeny of the stem cells were identified and their phenotypes were determined by two-color flow cytometry for the expression of various cell surface differentiation Ag during the course of their subsequent intrathymic development. The majority of the differentiation which occurred in the first 10 days after intrathymic cell transfer was myeloid in nature; hence, this study demonstrates that the irradiated thymus is not strictly selective for T cell development. Further, the maximum rate of T cell development was observed after intrathymic injection of 200 stem cells. Donor-derived cells which did not express Ag characteristic of the myeloid lineage could be detected and their phenotypes could be determined by flow cytometry as early as 7 days after intrathymic injection. At this time, the cells were still very similar phenotypically to the bone marrow hematopoietic stem cells. Exceptions to this were the expression of stem cell Ag 2 and a decrease in the level of MHC class I Ag expression. After 9 days, the donor-derived cells expressed high levels of the Thy-1 Ag and proceeded to change in cell surface phenotype as differentiation continued. These cell phenotypes are described for the time frame ending 18 days after injection, when most donor-derived cells were phenotypically small CD4+ CD8+ (double-positive) thymocytes

Robotic-Assisted Live Donor Ileal Segmentectomy for Intestinal Transplantation

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Guosheng Wu, MD, PhD

2017-10-01

Full Text Available Background. Every effort should be made to optimize surgical techniques and to minimize potential morbidity rates associated with live donor operations. Advances in a minimally invasive approach by robotic surgery to donor nephrectomy have raised the possibility of applying this technique to live donor bowel resections for intestinal transplantation. Methods. We report the first 5 consecutive cases of a robotic-assisted live donor ileal segmentectomy. We describe the technical aspects of the procedure, discuss the rationale for considering this option, and evaluate potential advantages of this approach. Results. We found that this new approach is associated with less postoperative discomfort, a shorter hospital length of stay, and a faster recovery of bowel function compared to our previous open surgery. Conclusions. Our initial experience suggests that robotic surgery is a safe and feasible procedure for live donor ileal resection for intestinal transplantation and is a useful alternative to conventional open surgery.

In utero hematopoietic stem cell transfer: current status and future strategies.

Science.gov (United States)

Surbek, D V; Gratwohl, A; Holzgreve, W

1999-07-01

Successful prenatal treatment of severe immunodeficiencies by allogeneic hematopoietic stem cell transplantation in utero has been reported. Though other diseases like hemoglobinopathies or storage diseases are potentially amenable to this novel therapeutic approach, no success has yet been achieved in recipients without severe immunodeficiency. Graft rejection by the developing fetus and/or lack of selective, competitive advantage of donor versus host stem cells preventing stable engraftment seem to be the major obstacles. Several strategies to overcome these hurdles are being explored in preclinical settings, including timing and repeated dosing of stem cell administration to the fetus, ex vivo modification of the transplant, using different fetal compartments as targets for early stem cell transfer, or inducing microchimerism for postnatal transplantation from the same donor. In addition, the exact definition of the basic concept of early fetal immunologic naivete and the understanding of the molecular basics of migration and homing in fetal hematopoiesis system seem mandatory for a successful approach. Gene therapy using ex vivo transduced autologous cord blood cells or direct gene targeting in utero are other potential means to correct hematopoietic and immunologic single gene disorders in utero, though this approach is still away from the stage of clinical trials.

Effect of donor STAT4 polymorphism rs7574865 on clinical outcomes of pediatric acute leukemia patients after hematopoietic stem cell transplant.

Science.gov (United States)

Wun, Cheng Mun; Piao, Zhe; Hong, Kyung Taek; Choi, Jung Yoon; Hong, Che Ry; Park, June Dong; Park, Kyung Duk; Shin, Hee Young; Kang, Hyoung Jin

2017-02-01

STAT4 polymorphism, rs7574865 is linked to various autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Its T minor allele is associated with higher STAT4 mRNA and protein expression, indicating a stronger skewed immune response than the norm. Although widely studied in autoimmune disease patients and the general population, its effect on immunocompromised subjects is still unknown. Especially in situations, i.e. post-hematopoietic stem cell transplantation (post-HSCT), where control of the immune response is crucial. Hence, this study investigates if the presence of the T minor allele in donors would affect immunological response and clinical outcomes post-HSCT. Samples from 161 pediatric patients who underwent allogeneic HSCT for acute leukemia and showed complete chimerism by donor cells were obtained. Six clinical outcomes were investigated; hepatic veno-occlusive disease, acute graft-vs-host disease, chronic graft-vs-host disease, cytomegalovirus (CMV) infection, relapse and overall survival. The TT genotype was found to be significant in the occurrence of CMV infection (P=0.049), showing higher incidence of CMV infection compared to the others. Multivariate analysis confirmed that association of the TT genotype is independent from other variables in CMV infection occurrence (P=0.010). This is the first study on STAT4 polymorphism rs7574865 in allogeneic HSCT as well as immunocompromised patients. As the TT genotype is associated with autoimmune diseases, our results seem at a paradox with current evidence hinting at a different role of STAT4 in normal circumstances versus immunocompromised patients. Further investigation is needed to elicit the reason behind this and discover novel applications for better post-transplant outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

Are drowned donors marginal donors? A single pediatric center experience.

Science.gov (United States)

Kumm, Kayla R; Galván, N Thao N; Koohmaraie, Sarah; Rana, Abbas; Kueht, Michael; Baugh, Katherine; Hao, Liu; Yoeli, Dor; Cotton, Ronald; O'Mahony, Christine A; Goss, John A

2017-09-01

Drowning, a common cause of death in the pediatric population, is a potentially large donor pool for OLT. Anecdotally, transplant centers have deemed these organs high risk over concerns for infection and graft dysfunction. We theorized drowned donor liver allografts do not portend worse outcomes and therefore should not be excluded from the donation pool. We reviewed our single-center experience of pediatric OLTs between 1988 and 2015 and identified 33 drowned donor recipients. These OLTs were matched 1:2 to head trauma donor OLTs from our center. A chart review assessed postoperative peak AST and ALT, incidence of HAT, graft and recipient survival. Recipient survival at one year between patients with drowned donor vs head trauma donor allografts was not statistically significant (94% vs 97%, P=.63). HAT incidence was 6.1% in the drowned donor group vs 7.6% in the control group (P=.78). Mean postoperative peak AST and ALT was 683 U/L and 450 U/L for drowned donors vs 1119 U/L and 828 U/L in the matched cohort. These results suggest drowned donor liver allografts do not portend worse outcomes in comparison with those procured from head trauma donors. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Modular femoral component for conversion of previous hip surgery in total hip arthroplasty.

Science.gov (United States)

Goldstein, Wayne M; Branson, Jill J

2005-09-01

The conversion of previous hip surgery to total hip arthroplasty creates a durable construct that is anatomically accurate. Most femoral components with either cemented or cementless design have a fixed tapered proximal shape. The proximal femoral anatomy is changed due to previous hip surgery for fixation of an intertrochanteric hip fracture, proximal femoral osteotomy, or a fibular allograft for avascular necrosis. The modular S-ROM (DePuy Orthopaedics Inc., Warsaw, Ind) hip stem accommodates these issues and independently prepares the proximal and distal portion of the femur. In preparation and implantation, the S-ROM hip stem creates less hoop stresses on potentially fragile stress risers from screws and thin bone. The S-ROM hip stem also prepares a previously distorted anatomy by milling through cortical bone that can occlude the femoral medullar canals and recreate proper femoral anteversion and reduces the risk of intraoperative or postoperative periprosthetic fracture due to the flexible titanium-slotted stem. The S-ROM femoral stem is recommended for challenging total hip reconstructions.

Generation and Characterization of Erythroid Cells from Human Embryonic Stem Cells and Induced Pluripotent Stem Cells: An Overview

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Kai-Hsin Chang

2011-01-01

Full Text Available Because of the imbalance in the supply and demand of red blood cells (RBCs, especially for alloimmunized patients or patients with rare blood phenotypes, extensive research has been done to generate therapeutic quantities of mature RBCs from hematopoietic stem cells of various sources, such as bone marrow, peripheral blood, and cord blood. Since human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs can be maintained indefinitely in vitro, they represent potentially inexhaustible sources of donor-free RBCs. In contrast to other ex vivo stem-cell-derived cellular therapeutics, tumorigenesis is not a concern, as RBCs can be irradiated without marked adverse effects on in vivo function. Here, we provide a comprehensive review of the recent publications relevant to the generation and characterization of hESC- and iPSC-derived erythroid cells and discuss challenges to be met before the eventual realization of clinical usage of these cells.

Imaging evaluation of potential donors in living-donor liver transplantation

International Nuclear Information System (INIS)

Low, G.; Wiebe, E.; Walji, A.H.; Bigam, D.L.

2008-01-01

Liver transplants, originally obtained from deceased donors, can now be harvested from living donors as well. This technique, called living-donor liver transplantation (LDLT), provides an effective alternative means of liver transplantation and is a method of expanding the donor pool in light of the demand and supply imbalance for organ transplants. Imaging plays an important role in LDLT programmes by providing robust evaluation of potential donors to ensure that only anatomically suitable donors with no significant co-existing pathology are selected and that crucial information that allows detailed preoperative planning is available. Imaging evaluation helps to improve the outcome of LDLT for both donors and recipients, by improving the chances of graft survival and reducing the postoperative complication rate. In this review, we describe the history of LDLT and discuss in detail the application of imaging in donor assessment with emphasis on use of modern computed tomography (CT) and magnetic resonance imaging (MRI) techniques

Glucosamine derived DISAL donors for stereoselective glycosylations under neutral conditions

DEFF Research Database (Denmark)

Grathe, S.; Thygesen, M.B.; Larsen, K.

2005-01-01

DISAL (methyl 3,5-dinitrosa/icylate) D-glcosyl, D-galactosyl, D-mannosyl, and L-quinovosyl donors have previously provided the efficient glycosylation of a range of substrates under either strictly neutral, mildly basic, or very mildly Lewis acidic (LiClO4) conditions. Herein we report the synthe......DISAL (methyl 3,5-dinitrosa/icylate) D-glcosyl, D-galactosyl, D-mannosyl, and L-quinovosyl donors have previously provided the efficient glycosylation of a range of substrates under either strictly neutral, mildly basic, or very mildly Lewis acidic (LiClO4) conditions. Herein we report...... the synthesis of new glucosamine DISAL donors, carrying N-TCP, -Troc, or -TFAc protecting groups, and their use in beta-(1,2-trans) selective glycosylations, primarily in NMP in the absence of any added Lewis acids, or in CH3NO2 with LiClO4. Finally, precise microwave heating proved effective in promoting...

Gamete donation: parents' experiences of searching for their child's donor siblings and donor.

Science.gov (United States)

Freeman, T; Jadva, V; Kramer, W; Golombok, S

2009-03-01

This study investigates the new phenomenon of parents of donor offspring searching for and contacting their child's 'donor siblings' (i.e. donor offspring conceived by the same donor) and donor. Online questionnaires were completed by 791 parents (39% lone-mother, 35% lesbian-couple, 21% heterosexual-couple, 5% non-specified) recruited via the Donor Sibling Registry; a US-based international registry that facilitates contact between donor conception families who share the same donor. Data were collected on parents' reasons for searching for their child's donor siblings and/or donor, the outcome of these searches and parents' and their child's experiences of any resulting contact. Parents' principal motivation for searching for their child's donor siblings was curiosity and for their donor, enhancing their child's sense of identity. Some parents had discovered large numbers of donor siblings (maximum = 55). Most parents reported positive experiences of contacting and meeting their child's donor siblings and donor. This study highlights that having access to information about a child's donor origins is important for some parents and has potentially positive consequences. These findings have wider implications because the removal of donor anonymity in the UK and elsewhere means that increasing numbers of donor offspring are likely to seek contact with their donor relations in the future.

Biodegradable Polymers and Stem Cells for Bioprinting.

Science.gov (United States)

Lei, Meijuan; Wang, Xiaohong

2016-04-29

It is imperative to develop organ manufacturing technologies based on the high organ failure mortality and serious donor shortage problems. As an emerging and promising technology, bioprinting has attracted more and more attention with its super precision, easy reproduction, fast manipulation and advantages in many hot research areas, such as tissue engineering, organ manufacturing, and drug screening. Basically, bioprinting technology consists of inkjet bioprinting, laser-based bioprinting and extrusion-based bioprinting techniques. Biodegradable polymers and stem cells are common printing inks. In the printed constructs, biodegradable polymers are usually used as support scaffolds, while stem cells can be engaged to differentiate into different cell/tissue types. The integration of biodegradable polymers and stem cells with the bioprinting techniques has provided huge opportunities for modern science and technologies, including tissue repair, organ transplantation and energy metabolism.

Effect of Induced Pluripotent Stem Cell Technology in Blood Banking

Science.gov (United States)

Focosi, Daniele

2016-01-01

Summary Population aging has imposed cost-effective alternatives to blood donations. Artificial blood is still at the preliminary stages of development, and the need for viable cells seems unsurmountable. Because large numbers of viable cells must be promptly available for clinical use, stem cell technologies, expansion, and banking represent ideal tools to ensure a regular supply. Provided key donors can be identified, induced pluripotent stem cell (iPSC) technology could pave the way to a new era in transfusion medicine, just as it is already doing in many other fields of medicine. The present review summarizes the current state of research on iPSC technology in the field of blood banking, highlighting hurdles, and promises. Significance The aging population in Western countries is causing a progressive reduction of blood donors and a constant increase of blood recipients. Because blood is the main therapeutic option to treat acute hemorrhage, cost-effective alternatives to blood donations are being actively investigated. The enormous replication capability of induced pluripotent stem cells and their promising results in many other fields of medicine could be an apt solution to produce the large numbers of viable cells required in transfusion and usher in a new era in transfusion medicine. The present report describes the potentiality, technological hurdles, and promises of induced pluripotent stem cells to generate red blood cells by redifferentiation. PMID:26819256

Infectivity of blood products from donors with occult hepatitis B virus infection

DEFF Research Database (Denmark)

Allain, Jean-Pierre; Mihaljevic, Ivanka; Gonzalez-Fraile, Maria Isabel

2013-01-01

BACKGROUND: Occult hepatitis B virus (HBV) infection (OBI) is identified in 1:1000 to 1:50,000 European blood donations. This study intended to determine the infectivity of blood products from OBI donors. STUDY DESIGN AND METHODS: Recipients of previous donations from OBI donors were investigated...... blood cells [RBCs], p Donor and recipient strains sequence homology of at least 99% confirmed transfusion-transmitted infection in 10 cases and excluded it in one case. CONCLUSION: Blood...... through lookback (systematic retrieval of recipients) or traceback (triggered by clinical cases). Serologic and genomic studies were undertaken on consenting donors and recipients. Multiple variables potentially affecting infectivity were examined. RESULTS: A total of 45 of 105 (42.9%) donor...

Adult dual kidney transplantations obtained from marginal donors: two case reports.

Science.gov (United States)

Kim, Y H; Jung, J H; Song, K B; Chung, Y S; Park, J B; Cho, Y M; Jang, H J; Kim, S-C; Han, D J

2012-01-01

Organ shortage has led us to use grafts from expanded criteria donors (ECD). Dual kidney transplantation (DKT) using organs from an ECD, which are not acceptable for single kidney transplantation (KT), may overcome the insufficient functioning nephron mass. We performed DKTs in two recipients, the first DKT to be reported from Korea. In case 1, the donor was a 36-year-old man with hypertension. The cause of his brain death was intracranial hemorrhage. He had no known underlying renal disease; his serum creatinine level was 4.2 mg/dL. Despite the relatively young age of the donor, a biopsy revealed mild interstitial fibrosis and tubular atrophy with moderate arteriolar narrowing. The recipient's postoperative course was uneventful over the 69-month follow-up; her last serum creatinine was 1.3 mg/dL. In case 2, the 80-year-old male donor with a history of hypertension had a normal creatinine. The donor biopsy revealed mild glomerular sclerosis, tubular atrophy, and interstitial fibrosis with moderate arteriolar narrowing. The recipient had undergone a previous KT 14 years previously on the right side of the abdomen, but had resumed dialysis 2 years previously due to chronic allograft nephropathy. There was no delayed graft function. At month 4 posttransplantation, lymphoceles were treated by fenestration. At 6-month follow-up, her creatinine was 1.0 mg/dL. In our experience with these two cases, DKT with ECD kidney grafts seemed to be a successful strategy to avoid poor graft outcomes and overcome the donor organ shortage. Further studies including histological criteria for DKT, should be performed to determine the safest means to utilize ECD grafts. Copyright © 2012. Published by Elsevier Inc.

Stem Cell Treatment for Type 1 Diabetes

Directory of Open Access Journals (Sweden)

Ming eLi

2014-03-01

Full Text Available Type 1 diabetes mellitus (T1DM is a common chronic disease in children, characterized by a loss of  cells, which results in defects in insulin secretion and hyperglycemia. Chronic hyperglycemia causes diabetic complications, including diabetic nephropathy, neuropathy and retinopathy. Curative therapies mainly include diet and insulin administration. Although hyperglycemia can be improved by insulin administration, exogenous insulin injection cannot successfully mimic the insulin secretion from normal  cells, which keeps blood glucose levels within the normal range all the time. Islet and pancreas transplantation achieves better glucose control, but there is a lack of organ donors. Cell based therapies have also been attempted to treat T1DM. Stem cells such as embryonic stem cells, induced pluripotent stem cells and tissue stem cells (TSCs such as bone marrow-, adipose tissue- and cord blood-derived stem cells, have been shown to generate insulin-producing cells. In this review, we summarize the most-recently available information about T1DM and the use of TSCs to treat T1DM.

Associations of health status with subsequent blood donor behavior-An alternative perspective on the Healthy Donor Effect from Donor InSight

NARCIS (Netherlands)

van den Hurk, Katja; Zalpuri, Saurabh; Prinsze, Femmeke J.; Merz, Eva-Maria; de Kort, Wim L. A. M.

2017-01-01

In donor health research, the 'Healthy Donor Effect' (HDE) often biases study results and hampers their interpretation. This refers to the fact that donors are a selected 'healthier' subset of a population due to both donor selection procedures and self-selection. Donors with long versus short donor

Inactivation of hemopoietic stem cells by lymphocytes as related to genotype of interacting cells

Energy Technology Data Exchange (ETDEWEB)

Petrov, R V; Seslavina, L S; Panteleev, E I; Egorova, O S

1975-05-01

Inoculation of a mixture of bone marrow cells with allogeneic lymphocytes into irradiated mice of inbred strains or into F/sub 1/ hybrids results in the depression of bone marrow cell proliferation in the spleen of the recipient: the effect of inactivation of nonsyngeneic stem cells. The inactivation of stem cells by allogeneic lymphocytes can be detected in all tested combinations of mice strains - donors of lymphocytes and bone marrow cells and mice - recipients but the degree of inactivation differs and depends on the genotype of cell donors rather than on the genotype of the recipient. Lymphocytes of some mice strains (haplotypes H-2sup(k) and H-2sup(a)) are more active killers of bone marrow cells as compared with lymphocytes of other strains (hyplotypes H-2sup(b) and H-2sup(d)). Probably, the degree of stem cells inactivation by lymphocytes depends on the differences of their histocompatibility in H-2 system.

Megakaryocytes promote murine osteoblastic HSC niche expansion and stem cell engraftment after radioablative conditioning

OpenAIRE

Olson, Timothy S.; Caselli, Anna; Otsuru, Satoru; Hofmann, Ted J.; Williams, Richard; Paolucci, Paolo; Dominici, Massimo; Horwitz, Edwin M.

2013-01-01

After radioablative conditioning, host megakaryocytes promote endosteal HSC niche expansion and donor stem cell engraftment.Thrombopoietin administration before radiation and bone marrow transplant enhances megakaryocyte promotion of HSC engraftment.

Stem Cells and Liver Disease | Akhter | Internet Journal of Medical ...

African Journals Online (AJOL)

Liver transplantation is the primary treatment for various end-stage hepatic diseases but is hindered by the lack of donor organs, complications associated with rejection and immunosuppression. An increasingly unbridgeable gap exists between the supply and demand of transplantable organs. Hence stem cell research ...

Donor transplant programme

International Nuclear Information System (INIS)

Abu Bakar Sulaiman

1999-01-01

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

Generation of retinal pigmented epithelium from iPSCs derived from the conjunctiva of donors with and without age related macular degeneration.

Directory of Open Access Journals (Sweden)

Zhouhui Geng

Full Text Available Fidelity in pluripotent stem cell differentiation protocols is necessary for the therapeutic and commercial use of cells derived from embryonic and induced pluripotent stem cells. Recent advances in stem cell technology, especially the widespread availability of a range of chemically defined media, substrates and differentiation components, now allow the design and implementation of fully defined derivation and differentiation protocols intended for replication across multiple research and manufacturing locations. In this report we present an application of these criteria to the generation of retinal pigmented epithelium from iPSCs derived from the conjunctiva of donors with and without age related macular degeneration. Primary conjunctival cells from human donors aged 70-85 years were reprogrammed to derive multiple iPSC lines that were differentiated into functional RPE using a rapid and defined differentiation protocol. The combination of defined iPSC derivation and culture with a defined RPE differentiation protocol, reproducibly generated functional RPE from each donor without requiring protocol adjustments for each individual. This successful validation of a standardized, iPSC derivation and RPE differentiation process demonstrates a practical approach for applications requiring the cost-effective generation of RPE from multiple individuals such as drug testing, population studies or for therapies requiring patient-specific RPE derivations. In addition, conjunctival cells are identified as a practical source of somatic cells for deriving iPSCs from elderly individuals.

Iron Administration before Stem Cell Harvest Enables MR Imaging Tracking after Transplantation

OpenAIRE

Khurana, Aman; Chapelin, Fanny; Beck, Graham; Lenkov, Olga D.; Donig, Jessica; Nejadnik, Hossein; Messing, Solomon; Derugin, Nikita; Chan, Ray Chun-Fai; Gaur, Amitabh; Sennino, Barbara; McDonald, Donald M.; Kempen, Paul J.; Tikhomirov, Grigory A.; Rao, Jianghong

2013-01-01

Transplanted mesenchymal stem cells (MSCs) could be detected and tracked with MR imaging, if the donor is treated with an intravenous injection of the Food and Drug Administration–approved iron supplement ferumoxytol prior to MSC harvesting.

In Vitro and In Vivo Hepatic Differentiation of Adult Somatic Stem Cells and Extraembryonic Stem Cells for Treating End Stage Liver Diseases

Directory of Open Access Journals (Sweden)

Chenxia Hu

2015-01-01

Full Text Available The shortage of liver donors is a major handicap that prevents most patients from receiving liver transplantation and places them on a waiting list for donated liver tissue. Then, primary hepatocyte transplantation and bioartificial livers have emerged as two alternative treatments for these often fatal diseases. However, another problem has emerged. Functional hepatocytes for liver regeneration are in short supply, and they will dedifferentiate immediately in vitro after they are isolated from liver tissue. Alternative stem-cell-based therapeutic strategies, including hepatic stem cells (HSCs, embryonic stem cells (ESCs, induced pluripotent stem cells (iPSCs, and mesenchymal stem cells (MSCs, are more promising, and more attention has been devoted to these approaches because of the high potency and proliferation ability of the cells. This review will focus on the general characteristics and the progress in hepatic differentiation of adult somatic stem cells and extraembryonic stem cells in vitro and in vivo for the treatment of end stage liver diseases. The hepatic differentiation of stem cells would offer an ideal and promising source for cell therapy and tissue engineering for treating liver diseases.

Organ Donation Registration and Decision-Making Among Current Blood Donors in the Netherlands

NARCIS (Netherlands)

Merz, Eva-Maria; van den Hurk, Katja; de Kort, Wim L. A. M.

2017-01-01

Introduction: In the Netherlands, there is a constant shortage in donor organs, resulting in long waiting lists. The decision to register as organ donor is associated with several demographic, cultural, and personal factors. Previous research on attitudes and motivations toward blood and organ

Conformational dynamics of semiflexibly bridged electron donor-acceptor systems comprising long aliphatic tails

NARCIS (Netherlands)

Bleisteiner, B.; Marian, T.; Schneider, S.; Brouwer, A.M.; Verhoeven, J.W.

2001-01-01

In continuation of our previous work on the conformational dynamics (harpooning mechanism) of semiflexibly bridged electron donor-acceptor systems we have studied a derivative with two long aliphatic chains tethered to the donor and acceptor moieties, respectively. The fitting of the time- and

Follow up Evaluation of Air Force Blood Donors Screening Positive for Chagas Disease

Science.gov (United States)

2017-10-05

59 MDW/SGVU SUBJECT: Professional Presentation Approval 31 JULY2017 Your paper, entitled Follow-up Evaluation of Air Force Blood Donors Screening...PUBLISHED OR PRESENTED: Follow-up Evaluation of Air Force Blood Donors Screening Positive for Chagas Disease 7. FUNDING RECEIVED FOR THIS STUDY? 0...PREVIOUS EDITIONS ARE OBSOLETE 50. DATE Page 3 of 3 Pages Follow-up Evaluation of Air Force Blood Donors Screening Positive for Chagas Disease

A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy

OpenAIRE

Guillaume Spielmann; Catherine M. Bollard; Hawley Kunz; Patrick J. Hanley; Richard J. Simpson

2016-01-01

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exer...

Challenges in unrelated hematopoietic stem cell transplantation. Access | Donor search and selection | Outcome

NARCIS (Netherlands)

Jöris, Monique Maria

2013-01-01

The studies described in this thesis are aimed at improving the whole spectrum of unrelated HSCT in order to help as many patients in need of HSCT as possible. It covers three different but related topics; from access to HSCT to optimizing donor search and selection of acceptable mismatches to

Impact of Donor Epstein-Barr Virus Serostatus on the Incidence of Graft-Versus-Host Disease in Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation: A Study From the Acute Leukemia and Infectious Diseases Working Parties of the European Society for Blood and Marrow Transplantation.

Science.gov (United States)

Styczynski, Jan; Tridello, Gloria; Gil, Lidia; Ljungman, Per; Hoek, Jennifer; Iacobelli, Simona; Ward, Katherine N; Cordonnier, Catherine; Einsele, Hermann; Socie, Gerard; Milpied, Noel; Veelken, Hendrik; Chevallier, Patrice; Yakoub-Agha, Ibrahim; Maertens, Johan; Blaise, Didier; Cornelissen, Jan; Michallet, Mauricette; Daguindau, Etienne; Petersen, Eefke; Passweg, Jakob; Greinix, Hildegard; Duarte, Rafael F; Kröger, Nicolaus; Dreger, Peter; Mohty, Mohamad; Nagler, Arnon; Cesaro, Simone

2016-07-01

We investigated the effect of Epstein-Barr virus (EBV) serostatus on the overall outcome of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The study included 11,364 patients who underwent allogeneic peripheral-blood or bone marrow transplantation for acute leukemia between 1997 and 2012. We analyzed the impact of donor and recipient EBV serologic status on overall survival, relapse-free survival, relapse incidence, nonrelapse mortality, and incidence of graft-versus-host disease (GVHD) after allo-HSCT. Patients receiving grafts from EBV-seropositive donors had the same overall survival as patients who received grafts from EBV-seronegative donors (hazard ratio [HR], 1.05; 95% CI, 0.97 to 1.12; P = .23). Seropositive donors also had no influence on relapse-free survival (HR, 1.04; 95% CI, 0.97 to 1.11; P = 0.31), relapse incidence (HR, 1.03; 95% CI, 0.94 to 1.12; P = .58), and nonrelapse mortality (HR, 1.05; 95% CI, 0.94 to 1.17; P = .37). However, in univariate analysis, recipients receiving grafts from seropositive donors had a higher risk of chronic GVHD than those with seronegative donors (40.8% v 31.0%, respectively; P donors, the HR for chronic GVHD was 1.30 (95% CI, 1.06 to 1.59; P = .039). In seropositive patients with seropositive donors, the HR was 1.24 (95% CI, 1.07 to 1.45; P = .016) for acute GVHD and 1.43 (95% CI, 1.23 to 1.67; P donors did not have an increased risk of GVHD. Our data suggest that donor EBV status significantly influences development of acute and chronic GVHD after allo-HSCT. © 2016 by American Society of Clinical Oncology.

Omentin-1 effects on mesenchymal stem cells: proliferation, apoptosis, and angiogenesis in vitro

OpenAIRE

Yin, Li; Huang, Dan; Liu, Xinxin; Wang, Yongshun; Liu, Jingjin; Liu, Fang; Yu, Bo

2017-01-01

Background Mesenchymal stem cells (MSCs) are emerging as an extremely promising therapeutic agent for tissue repair. However, limitations exist such as the low numbers of MSCs obtained from donors, and the poor survival and function of donor cells. Omentin-1, a new fat depot-specific secretory adipokine, exerts proproliferation, prosurvival, and proangiogenic functions in certain cells via an Akt-dependent mechanism; however, little is known about the influence of omentin-1 on MSCs. Methods M...

Control of charge transfer by conformational and electronic effects: Donor-donor and donor-acceptor phenyl pyrroles

International Nuclear Information System (INIS)

Neubauer, Antje; Bendig, Juergen; Rettig, Wolfgang

2009-01-01

Derivatives of N-pyrrolobenzene with a para-donor and a para-acceptor substituent on the benzene ring are compared. It is shown that by a suitable increase of the donor strength of the pyrrolo group, CT fluorescence can be achieved even for donor-donor-substituted benzenes. The ICT emission for sterically hindered compounds is more forbidden than that of unhindered phenyl pyrroles. This suggests conformational effects which induce a narrower twist angle distribution around a perpendicular minimum in the excited state.

Risk Factors for Hepatitis C Virus Infection among Blood Donors in Georgia

International Nuclear Information System (INIS)

Zaller, Nickolas; Nelson, Kenrad E.; Aladashvili, Malvina; Badridze, Nino; Rio, Carlos del; Tsertsvadze, Tengiz

2004-01-01

Background: Growing awareness about the importance of blood safety for controlling the transmission of hepatitis C virus (HCV) has helped to decrease the spread of this virus in many settings. This study was conducted in order to evaluate potential risk factors for HCV infection among blood donors in Georgia. Methods: The study population consisted of 553 blood donors in three major Georgian cities; Tbilisi, the capital city and Batumi and Poti, naval port cities. Risk factors were examined using a behavior questionnaire. All blood samples were initially tested using 3rd generation anti-HCV enzyme-linked immunosorbent assays and confirmed using recombinant immunoblot assays and nucleic acid testing. Results: Forty-three blood donors, 7.8%, were confirmed HCV positive. Significant risk factors included: drug injection ever (OR: 42; 95% CI: 3.2-550.7); history of hepatitis (OR: 25.9; 95% CI: 4.6-145.5); history of a previous surgical procedure (OR: 148.4; 95% CI: 26.9-817.4); blood transfusion (OR: 25.9; 95% CI: 3.2-210.9). Conclusions: This study found a very high prevalence of HCV among blood donors in Georgia. The main risk factor for HCV infection in this population of blood donors was previous contact with contaminated blood or blood products. Reliable screening of donors and their blood is critical for controlling the further spread of HCV in Georgia

Impact of pretransplant donor and recipient cytomegalovirus serostatus on outcome for multiple myeloma patients undergoing reduced intensity conditioning allogeneic stem cell transplantation.

Science.gov (United States)

El-Cheikh, Jean; Devillier, Raynier; Crocchiolo, Roberto; Fürst, Sabine; Calmels, Boris; Faucher, Catherine; Stoppa, Anne Marie; Granata, Angela; Castagna, Luca; Ladaique, Patrick; Lemarie, Claude; Bouabdallah, Reda; Zandotti, Christine; Merlin, Michele; Berger, Pierre; Chabannon, Christian; Blaise, Didier

2013-01-01

Scope of the study was to investigate the impact of pre-transplant CMV serostatus of the donor and/or recipient on the outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-SCT) for Multiple Myeloma (MM). To our knowledge no data are available in the literature about this issue. We retrospectively followed 99 consecutive patients who underwent reduced-intensity conditioning (RIC) Allo-SCT for MM in our cancer center at Marseille between January 2000 and January 2012. Based upon CMV serostatus, patients were classified as low risk (donor [D]-/recipient [R] -) 17 patients (17.1%), intermediate risk (D+/R) 14 patients (14.1%), or high risk - either (D-/R+) 31 patients (31.3%) or (D+/R+), 37 patients (37.3%). Cumulative incidence of CMV reactivation was 39% with a median time of 61 days (26-318). Three patients (3%) developed CMV disease. Two factors were associated with CMV reactivation: CMV serostatus group (low: 0% vs. intermediate: 29% vs. high: 50%; p=0.001) and the presence of grade II-IV acute GvHD (Hazard Ratio: HR=2.1 [1.1-3.9]). Thirty-six of the 39 patients (92%) with CMV reactivation did not present positive detection of CMV after a 21-day median duration preemptive treatment with ganciclovir. Cumulative incidence of day 100 grade II-IV acute GvHD, 1-year chronic GvHD and day 100 transplantation related mortality (TRM) were 37%, 36% and 9%, respectively. CMV reactivation and serostatus were not associated with increased GvHD and TRM or short survival. Only the presence of acute GvHD as a time dependent variable was significantly associated with increased TRM (p=0.005). Two-year overall and progression free survival were 56% and 34%, respectively. Donor and recipient CMV serostatus and acute GvHD are independent factors for increased CMV reactivation in high-risk MM patients undergoing RIC Allo-SCT. However, we did not find any influence of CMV reactivation on post transplantation outcome. CMV monitoring and pre

IMPACT OF PRETRANSPLANT DONOR AND RECIPIENT CYTOMEGALOVIRUS SEROSTATUS ON OUTCOME FOR MULTIPLE MYELOMA PATIENTS UNDERGOING REDUCED INTENSITY CONDITIONING ALLOGENEIC STEM CELL TRANSPLANTATION.

Directory of Open Access Journals (Sweden)

Jean Elcheikh

2013-04-01

Full Text Available To investigate the impact of pre-transplant CMV serostatus of donor or recipient on outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-SCT for Multiple Myeloma (MM. To our knowledge no data are available in the literature about this issue. We retrospectively followed 99 consecutive patients who underwent reduced-intensity conditioning (RIC Allo-SCT for MM in our cancer centre at Marseille between January 2000 and January 2012. Based upon CMV serostatus, patients were classified as low risk (donor [D]-/recipient [R]- 17 patients (17.1%, intermediate risk (D+/R 14 patients (14.1%, or high risk – either (D-/R+ 31 patients (31.3% or (D+/R+, 37 patients (37.3%. Cumulative incidence of CMV reactivation was 39% with a median time of 61 days (26–318. Three patients (3% developed CMV disease. Two factors were associated with CMV reactivation: CMV serostatus group (low: 0% vs intermediate: 29% vs high: 50%; p=0.001 and the presence of grade II–IV acute GvHD (Hazard Ratio: HR=2.1 [1.1–3.9]. Thirty-six of the 39 patients (92% with CMV reactivation did not present positive detection of CMV after a 21-day median duration preemptive treatment with ganciclovir. Cumulative incidence of day 100 grade II–IV acute GvHD, 1-year chronic GvHD and day 100 transplantation related mortality (TRM were 37%, 36% and 9%, respectively. CMV reactivation and serostatus were not associated with increased GvHD and TRM or short survival. Only the presence of acute GvHD as a time dependent variable was significantly associated with increased TRM (p=0.005. Two-year overall and progression free survival were 56% and 34%, respectively. Donor and recipient CMV serostatus and acute GvHD are independent factors for increased CMV reactivation in high-risk MM patients undergoing RIC Allo-SCT. However, we did not find any influence of CMV reactivation on post transplantation outcome. CMV monitoring and pre-emptive treatment strategy could in

Experiences of offspring searching for and contacting their donor siblings and donor.

Science.gov (United States)

Jadva, Vasanti; Freeman, Tabitha; Kramer, Wendy; Golombok, Susan

2010-04-01

This study investigates a new phenomenon whereby individuals conceived by donor insemination are searching for and contacting their donor and/or 'donor siblings' (i.e. donor offspring conceived by the same donor who are their genetic half siblings). On-line questionnaires were completed by members of the Donor Sibling Registry (DSR), a US-based registry that facilitates contact between donor conception families who share the same donor. Of the 165 donor offspring who completed the survey, 15% were searching for their donor siblings, 13% were searching for their donor, and 64% were searching for both. Differences were found according to family type and age of disclosure. Fewer offspring from heterosexual couple families had told their father about their search when compared with offspring from lesbian couple families who had told their co-parent. Offspring who had found out about their conception after age 18 were more likely to be searching for medical reasons, whereas those who had found out before age 18 tended to be searching out of curiosity. Some offspring had discovered large numbers of half siblings (maximum=13). The majority of offspring who had found their donor relations reported positive experiences and remained in regular contact with them. Copyright (c) 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Stem and Progenitor Cell-Based Therapy of the Central Nervous System

DEFF Research Database (Denmark)

Goldman, Steven A.

2016-01-01

A variety of neurological disorders are attractive targets for stem and progenitor cell-based therapy. Yet many conditions are not, whether by virtue of an inhospitable disease environment, poorly understood pathophysiology, or poor alignment of donor cell capabilities with patient needs. Moreove...

Stem Cell Microencapsulation for Phenotypic Control, Bioprocessing, and Transplantation

Science.gov (United States)

Wilson, Jenna L.

2014-01-01

Cell microencapsulation has been utilized for decades as a means to shield cells from the external environment while simultaneously permitting transport of oxygen, nutrients, and secretory molecules. In designing cell therapies, donor primary cells are often difficult to obtain and expand to appropriate numbers, rendering stem cells an attractive alternative due to their capacities for self-renewal, differentiation, and trophic factor secretion. Microencapsulation of stem cells offers several benefits, namely the creation of a defined microenvironment which can be designed to modulate stem cell phenotype, protection from hydrodynamic forces and prevention of agglomeration during expansion in suspension bioreactors, and a means to transplant cells behind a semi-permeable barrier, allowing for molecular secretion while avoiding immune reaction. This review will provide an overview of relevant microencapsulation processes and characterization in the context of maintaining stem cell potency, directing differentiation, investigating scalable production methods, and transplanting stem cells for clinically relevant disorders. PMID:23239279

Biodegradable Polymers and Stem Cells for Bioprinting

Directory of Open Access Journals (Sweden)

Meijuan Lei

2016-04-01

Full Text Available It is imperative to develop organ manufacturing technologies based on the high organ failure mortality and serious donor shortage problems. As an emerging and promising technology, bioprinting has attracted more and more attention with its super precision, easy reproduction, fast manipulation and advantages in many hot research areas, such as tissue engineering, organ manufacturing, and drug screening. Basically, bioprinting technology consists of inkjet bioprinting, laser-based bioprinting and extrusion-based bioprinting techniques. Biodegradable polymers and stem cells are common printing inks. In the printed constructs, biodegradable polymers are usually used as support scaffolds, while stem cells can be engaged to differentiate into different cell/tissue types. The integration of biodegradable polymers and stem cells with the bioprinting techniques has provided huge opportunities for modern science and technologies, including tissue repair, organ transplantation and energy metabolism.

Evaluation of hollow fiber culture for large-scale production of mouse embryonic stem cell-derived hematopoietic stem cells.

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Nakano, Yu; Iwanaga, Shinya; Mizumoto, Hiroshi; Kajiwara, Toshihisa

2018-03-03

Hematopoietic stem cells (HSCs) have the ability to differentiate into all types of blood cells and can be transplanted to treat blood disorders. However, it is difficult to obtain HSCs in large quantities because of the shortage of donors. Recent efforts have focused on acquiring HSCs by differentiation of pluripotent stem cells. As a conventional differentiation method of pluripotent stem cells, the formation of embryoid bodies (EBs) is often employed. However, the size of EBs is limited by depletion of oxygen and nutrients, which prevents them from being efficient for the production of HSCs. In this study, we developed a large-scale hematopoietic differentiation approach for mouse embryonic stem (ES) cells by applying a hollow fiber (HF)/organoid culture method. Cylindrical organoids, which had the potential for further spontaneous differentiation, were established inside of hollow fibers. Using this method, we improved the proliferation rate of mouse ES cells to produce an increased HSC population and achieved around a 40-fold higher production volume of HSCs in HF culture than in conventional EB culture. Therefore, the HF/organoid culture method may be a new mass culture method to acquire pluripotent stem cell-derived HSCs.

Peripheral blood hematopoietic stem cells for transplantation of hematological diseases from related, haploidentical donors after reduced-intensity conditioning.

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Raj, Kavita; Pagliuca, Antonio; Bradstock, Kenneth; Noriega, Victor; Potter, Victoria; Streetly, Matthew; McLornan, Donal; Kazmi, Majid; Marsh, Judith; Kwan, John; Huang, Gillian; Getzendaner, Lisa; Lee, Stephanie; Guthrie, Katherine A; Mufti, Ghulam J; O'Donnell, Paul

2014-06-01

In a multicenter collaboration, we carried out T cell-replete, peripheral blood stem cell (PBSC) transplantations from related, HLA-haploidentical donors with reduced-intensity conditioning (RIC) and post-transplantation cyclophosphamide (Cy) as graft-versus-host disease (GVHD) prophylaxis in 55 patients with high-risk hematologic disorders. Patients received 2 doses of Cy 50 mg/kg i.v. on days 3 and 4 after infusion of PBSC (mean, 6.4 × 10(6)/kg CD34(+) cells; mean, 2.0 × 10(8)/kg CD3(+) cells). The median times to neutrophil (500/μL) and platelet (>20,000/μL) recovery were 17 and 21 days respectively. All but 2 of the patients achieved full engraftment. The 1-year cumulative incidences of grade II and grade III acute GVHD were 53% and 8%, respectively. There were no cases of grade IV GVHD. The 2-year cumulative incidence of chronic GHVD was 18%. With a median follow-up of 509 days, overall survival and event-free survival at 2 years were 48% and 51%, respectively. The 2-year cumulative incidences of nonrelapse mortality and relapse were 23% and 28%, respectively. Our results suggest that PBSC can be substituted safely and effectively for bone marrow as the graft source for haploidentical transplantation after RIC. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Biological characteristics of human menstrual blood-derived endometrial stem cells.

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Liu, Yanli; Niu, Rongcheng; Yang, Fen; Yan, Yan; Liang, Shengying; Sun, Yuliang; Shen, Ping; Lin, Juntang

2018-03-01

Successful isolation of human endometrial stem cells from menstrual blood, namely menstrual blood-derived endometrial stem cells (MenSCs), has provided enticing alternative seed cells for stem cell-based therapy. MenSCs are enriched in the self-regenerative tissue, endometrium, which shed along the periodic menstrual blood and thus their acquisition involves no physical invasiveness. However, the impact of the storage duration of menstrual blood prior to stem cell isolation, the age of the donor, the number of passages on the self-renewing of MenSCs, the paracrine production of biological factors in MenSCs and expression of adhesion molecules on MenSCs remain elusive. In this study, we confirmed that MenSCs reside in shedding endometrium, and documented that up to 3 days of storage at 4°C has little impact on MenSCs, while the age of the donor and the number of passages are negatively associated with proliferation capacity of MenSCs. Moreover, we found that MenSCs were actually immune-privileged and projected no risk of tumour formation. Also, we documented a lung- and liver-dominated, spleen- and kidney-involved organic distribution profile of MenSC 3 days after intravenous transfer into mice. At last, we suggested that MenSCs may have potentially therapeutic effects on diseases through paracrine effect and immunomodulation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually.

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Passweg, J R; Baldomero, H; Bader, P; Bonini, C; Cesaro, S; Dreger, P; Duarte, R F; Dufour, C; Kuball, J; Farge-Bancel, D; Gennery, A; Kröger, N; Lanza, F; Nagler, A; Sureda, A; Mohty, M

2016-06-01

A record number of 40 829 hematopoietic stem cell transplantation (HSCT) in 36 469 patients (15 765 allogeneic (43%), 20 704 autologous (57%)) were reported by 656 centers in 47 countries to the 2014 survey. Trends include: continued growth in transplant activity, more so in Eastern European countries than in the west; a continued increase in the use of haploidentical family donors (by 25%) and slower growth for unrelated donor HSCT. The use of cord blood as a stem cell source has decreased again in 2014. Main indications for HSCT were leukemias: 11 853 (33%; 96% allogeneic); lymphoid neoplasias; 20 802 (57%; 11% allogeneic); solid tumors; 1458 (4%; 3% allogeneic) and non-malignant disorders; 2203 (6%; 88% allogeneic). Changes in transplant activity include more allogeneic HSCT for AML in CR1, myeloproliferative neoplasm (MPN) and aplastic anemia and decreasing use in CLL; and more autologous HSCT for plasma cell disorders and in particular for amyloidosis. In addition, data on numbers of teams doing alternative donor transplants, allogeneic after autologous HSCT, autologous cord blood transplants are presented.

Report of the International Stem Cell Banking Initiative Workshop Activity: Current Hurdles and Progress in Seed-Stock Banking of Human Pluripotent Stem Cells.

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Kim, Jung-Hyun; Kurtz, Andreas; Yuan, Bao-Zhu; Zeng, Fanyi; Lomax, Geoff; Loring, Jeanne F; Crook, Jeremy; Ju, Ji Hyeon; Clarke, Laura; Inamdar, Maneesha S; Pera, Martin; Firpo, Meri T; Sheldon, Michael; Rahman, Nafees; O'Shea, Orla; Pranke, Patricia; Zhou, Qi; Isasi, Rosario; Rungsiwiwut, Ruttachuk; Kawamata, Shin; Oh, Steve; Ludwig, Tenneille; Masui, Tohru; Novak, Thomas J; Takahashi, Tsuneo; Fujibuchi, Wataru; Koo, Soo Kyung; Stacey, Glyn N

2017-11-01

This article summarizes the recent activity of the International Stem Cell Banking Initiative (ISCBI) held at the California Institute for Regenerative Medicine (CIRM) in California (June 26, 2016) and the Korean National Institutes for Health in Korea (October 19-20, 2016). Through the workshops, ISCBI is endeavoring to support a new paradigm for human medicine using pluripotent stem cells (hPSC) for cell therapies. Priority considerations for ISCBI include ensuring the safety and efficacy of a final cell therapy product and quality assured source materials, such as stem cells and primary donor cells. To these ends, ISCBI aims to promote global harmonization on quality and safety control of stem cells for research and the development of starting materials for cell therapies, with regular workshops involving hPSC banking centers, biologists, and regulatory bodies. Here, we provide a brief overview of two such recent activities, with summaries of key issues raised. Stem Cells Translational Medicine 2017;6:1956-1962. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Human mesenchymal stem cells in rodent whole-embryo culture are reprogrammed to contribute to kidney tissues

OpenAIRE

Yokoo, Takashi; Ohashi, Toya; Shen, Jin Song; Sakurai, Ken; Miyazaki, Yoichi; Utsunomiya, Yasunori; Takahashi, Masanori; Terada, Yoshio; Eto, Yoshikatsu; Kawamura, Tetsuya; Osumi, Noriko; Hosoya, Tatsuo

2005-01-01

The use of stem cells has enabled the successful generation of simple organs. However, anatomically complicated organs such as the kidney have proven more refractory to stem-cell-based regenerative techniques. Given the limits of allogenic organ transplantation, an ultimate therapeutic solution is to establish self-organs from autologous stem cells and transplant them as syngrafts back into donor patients. To this end, we have striven to establish an in vitro organ factory to build up complex...

Relapsing tumefactive lesion in an adult with medulloblastoma previously treated with chemoradiotherapy and stem cell transplant.

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Mahta, Ali; Qu, Yan; Nastic, Denis; Sundstrom, Maria; Kim, Ryan Y; Saria, Marlon; Santagata, Sandro; Kesari, Santosh

2012-04-01

Herein, we present an adult case of medulloblastoma who received chemotherapy, radiation therapy and stem cell transplantation, and underwent multiple surgical resections for what were thought to be recurrences; however pathology confirmed a diagnosis of relapsing tumefactive lesions. This phenomenon seems to be a consequence of stem cell transplantation rather than a simple radiation treatment effect.

Donor, dad, or…? Young adults with lesbian parents' experiences with known donors.

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Goldberg, Abbie E; Allen, Katherine R

2013-06-01

In this exploratory qualitative study of 11 young adults, ages 19-29 years, we examine how young people who were raised by lesbian parents make meaning out of and construct their relationships with known donors. In-depth interviews were conducted to examine how participants defined their family composition, how they perceived the role of their donors in their lives, and how they negotiated their relationships with their donors. Findings indicate that mothers typically chose known donors who were family friends, that the majority of participants always knew who their donors were, and that their contact with donors ranged from minimal to involved. Further, participants perceived their donors in one of three ways: as strictly donors and not members of their family; as extended family members but not as parents; and as fathers. The more limited role of donors in participants' construction of family relationships sheds light on how children raised in lesbian, gay, and bisexual families are contributing to the redefinition and reconstruction of complex kinship arrangements. Our findings hold implications for clinicians who work with lesbian-mother families, and suggest that young adulthood is an important developmental phase during which interest in and contact with the donor may shift, warranting a transfer of responsibility from mother to offspring in terms of managing the donor-child relationship. © FPI, Inc.

In-vitro chondrogenic potential of synovial stem cells and chondrocytes allocated for autologous chondrocyte implantation

DEFF Research Database (Denmark)

Kubosch, Eva Johanna; Heidt, Emanuel; Niemeyer, Philipp

2017-01-01

Purpose: The use of passaged chondrocytes is the current standard for autologous chondrocyte implantation (ACI). De-differentiation due to amplification and donor site morbidity are known drawbacks highlighting the need for alternative cell sources. Methods: Via clinically validated flow cytometry...... analysis, we compared the expression of human stem cell and cartilage markers (collagen type 2 (Col2), aggrecan (ACAN), CD44) of chondrocytes (CHDR), passaged chondrocytes for ACI (CellGenix™), bone marrow derived mesenchymal stem cells (BMSC), and synovial derived stem cells (SDSC). Results: Primary...

Femoral Component Revision with Use of Impaction Bone-Grafting and a Cemented Polished Stem: A Concise Follow-up, at Fifteen to Twenty Years, of a Previous Report*

NARCIS (Netherlands)

Te Stroet, M.A.; Gardeniers, J.W.M.; Verdonschot, N.J.; Rijnen, W.H.C.; Slooff, T.J.J.H.; Schreurs, B.W.

2012-01-01

We previously reported our results for thirty-three consecutive femoral component revisions with impaction bone-grafting, performed with the X-change femoral revision system and a cemented polished Exeter stem, at a minimum of eight years of follow-up. The present updated study shows the results

Laparoscopic donor nephrectomy

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Gupta Nitin

2005-01-01

Full Text Available Of the various options for patients with end stage renal disease, kidney transplantation is the treatment of choice for a suitable patient. The kidney for transplantation is retrieved from either a cadaver or a live donor. Living donor nephrectomy has been developed as a method to address the shortfall in cadaveric kidneys available for transplantation. Laparoscopic living donor nephrectomy (LLDN, by reducing postoperative pain, shortening convalescence, and improving the cosmetic outcome of the donor nephrectomy, has shown the potential to increase the number of living kidney donations further by removing some of the disincentives inherent to donation itself. The technique of LLDN has undergone evolution at different transplant centers and many modifications have been done to improve donor safety and recipient outcome. Virtually all donors eligible for an open surgical procedure may also undergo the laparoscopic operation. Various earlier contraindications to LDN, such as right donor kidney, multiple vessels, anomalous vasculature and obesity have been overcome with increasing experience. Laparoscopic live donor nephrectomy can be done transperitoneally or retroperitoneally on either side. The approach is most commonly transperitoneal, which allows adequate working space and easy dissection. A review of literature and our experience with regards to standard approach and the modifications is presented including a cost saving model for the developing countries. An assessment has been made, of the impact of LDN on the outcome of donor and the recipient.

Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: perspectives from stem cell biology and molecular medicine.

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Wu, Ling; Cai, Xiaoxiao; Zhang, Shu; Karperien, Marcel; Lin, Yunfeng

2013-05-01

Adipose-derived stem cells (ASCs) have been discovered for more than a decade. Due to the large numbers of cells that can be harvested with relatively little donor morbidity, they are considered to be an attractive alternative to bone marrow derived mesenchymal stem cells. Consequently, isolation and differentiation of ASCs draw great attention in the research of tissue engineering and regenerative medicine. Cartilage defects cause big therapeutic problems because of their low self-repair capacity. Application of ASCs in cartilage regeneration gives hope to treat cartilage defects with autologous stem cells. In recent years, a lot of studies have been performed to test the possibility of using ASCs to re-construct damaged cartilage tissue. In this article, we have reviewed the most up-to-date articles utilizing ASCs for cartilage regeneration in basic and translational research. Our topic covers differentiation of adipose tissue derived mesenchymal stem cells into chondrocytes, increased cartilage formation by co-culture of ASCs with chondrocytes and enhancing chondrogenic differentiation of ASCs by gene manipulation. Copyright © 2012 Wiley Periodicals, Inc.

Pre- and postnatal transplantation of fetal mesenchymal stem cells in osteogenesis imperfecta: a two-center experience.

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Götherström, Cecilia; Westgren, Magnus; Shaw, S W Steven; Aström, Eva; Biswas, Arijit; Byers, Peter H; Mattar, Citra N Z; Graham, Gail E; Taslimi, Jahan; Ewald, Uwe; Fisk, Nicholas M; Yeoh, Allen E J; Lin, Ju-Li; Cheng, Po-Jen; Choolani, Mahesh; Le Blanc, Katarina; Chan, Jerry K Y

2014-02-01

Osteogenesis imperfecta (OI) can be recognized prenatally with ultrasound. Transplantation of mesenchymal stem cells (MSCs) has the potential to ameliorate skeletal damage. We report the clinical course of two patients with OI who received prenatal human fetal MSC (hfMSC) transplantation and postnatal boosting with same-donor MSCs. We have previously reported on prenatal transplantation for OI type III. This patient was retransplanted with 2.8 × 10(6) same-donor MSCs per kilogram at 8 years of age, resulting in low-level engraftment in bone and improved linear growth, mobility, and fracture incidence. An infant with an identical mutation who did not receive MSC therapy succumbed at 5 months despite postnatal bisphosphonate therapy. A second fetus with OI type IV was also transplanted with 30 × 10(6) hfMSCs per kilogram at 31 weeks of gestation and did not suffer any new fractures for the remainder of the pregnancy or during infancy. The patient followed her normal growth velocity until 13 months of age, at which time longitudinal length plateaued. A postnatal infusion of 10 × 10(6) MSCs per kilogram from the same donor was performed at 19 months of age, resulting in resumption of her growth trajectory. Neither patient demonstrated alloreactivity toward the donor hfMSCs or manifested any evidence of toxicities after transplantation. Our findings suggest that prenatal transplantation of allogeneic hfMSCs in OI appears safe and is of likely clinical benefit and that retransplantation with same-donor cells is feasible. However, the limited experience to date means that it is not possible to be conclusive and that further studies are required.

Tacrolimus and mycophenolate mofetil after nonmyeloablative matched-sibling donor allogeneic stem-cell transplantations conditioned with fludarabine and low-dose total body irradiation.

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Nieto, Yago; Patton, Nigel; Hawkins, Timothy; Spearing, Ruth; Bearman, Scott I; Jones, Roy B; Shpall, Elizabeth J; Rabinovitch, Rachel; Zeng, Chan; Barón, Anna; McSweeney, Peter A

2006-02-01

We evaluated tacrolimus/mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after a nonmyeloablative stem cell transplantation (NST) from a matched sibling donor (MSD). Thirty-two patients (median age, 57 years) with advanced hematologic malignancies, who were poor candidates for a conventional myeloablative transplantation, received fludarabine (30 mg/m(2), day -4 to day -2), total-body irradiation (TBI) (200 cGy, day 0), infusion of donor peripheral blood progenitor cells (day 0), oral tacrolimus 0.06 mg/kg twice daily (from day 3), and oral MMF at 15 mg/kg twice daily (days 0-+27). Tacrolimus was tapered from day +100 to day +180 in those patients with indolent malignancies (n = 25), and from day +35 to day +56 in those with aggressive tumors (n = 7). Regimen toxicities and myelosuppression were mild, allowing 75% of patients to have entirely outpatient transplantations. One patient (3%) experienced a nonfatal graft rejection. Rates of grades II-IV and III-IV acute GVHD were 15.6% and 3%, respectively. Acute GVHD was diagnosed at median day +78 (range, days +31-+84). Extensive chronic GVHD was observed in 10 of 24 evaluable patients (41.6%) at a median onset of day +198 (range, days +128-+277), either spontaneously (n = 5) or elicited after tumor progression (n = 5). Five patients experienced transplantation-related mortality (TRM) (15.6%) from either acute GVHD-related multiorgan failure (MOF) (n = 3) or infectious complications (n = 2). At median follow-up of 19 months (range, 2-41 months), the overall survival, progression-free survival, and disease-free survival rates are 62.5%, 50%, and 40%, respectively. In conclusion, the use of tacrolimus/MMF after MSD NST is associated with encouraging rates of GVHD control.

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.

In vivo stem cell function of interleukin-3-induced blast cells

International Nuclear Information System (INIS)

Tsunoda, J.; Okada, S.; Suda, J.; Nagayoshi, K.; Nakauchi, H.; Hatake, K.; Miura, Y.; Suda, T.

1991-01-01

The treatment of mice with high doses of 5-fluorouracil (5-FU) results in an enrichment of primitive hematopoietic progenitors. Using this procedure, the authors obtained a new class of murine hematopoietic colonies that had very high secondary plating efficiencies in vitro and could differentiate into not only myeloid cells but also into lymphoid lineage cells. The phenotypes of interleukin-3 (IL-3) induced blast colony cells were Thy-1-positive and lineage-marker-negative. They examined whether these blast colony cells contained primitive hematopoietic stem cells in vivo and could reconstitute hematopoietic tissues in lethally irradiated mice. Blast colony cells could generate macroscopic visible spleen colonies on days 8 and 12, and 5 x 10(3) blast cells were sufficient to protect them from lethally irradiation. It was shown that 6 or 8 weeks after transplantation of 5 x 10(3) blast cells, donor male cells were detected in the spleen and thymus of the female recipients but not in the bone marrow by Southern blot analysis using Y-encoded DNA probe. After 10 weeks, bone marrow cells were partially repopulated from donor cells. In a congenic mouse system, donor-derived cells (Ly5.2) were detected in the thymus and spleen 6 weeks after transplantation. Fluorescence-activated cell sorter analyses showed that B cells and macrophages developed from donor cells in the spleen. In the thymus, donor-derived cells were found in CD4, CD8 double-positive, single-positive, and double-negative populations. Reconstitution of bone marrow was delayed and myeloid and lymphoid cells were detected 10 weeks after transplantation. These results indicate that IL-3-induced blast cells contain the primitive hematopoietic stem cells capable of reconstituting hematopoietic organs in lethally irradiated mice

New York State's landmark policies on oversight and compensation for egg donation to stem cell research.

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Roxland, Beth E

2012-05-01

In 2009, New York became the first US state to implement a policy permitting researchers to use public funds to reimburse women who donate oocytes directly and solely to stem cell research, not only for the woman's out-of-pocket expenses, but also for the time, burden and discomfort associated with the donation process. The debate about the propriety of such compensation was recently renewed with the publication of a stem cell study in which women were provided with compensation for donating their eggs. This article explores the scientific and ethical rationales that led to New York's decision to allow donor compensation. The multifaceted deliberation process and comprehensive policies may serve as a model for other states and countries considering the issue of oocyte donor compensation.

Marginal kidney donor

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Ganesh Gopalakrishnan

2007-01-01

Full Text Available Renal transplantation is the treatment of choice for a medically eligible patient with end stage renal disease. The number of renal transplants has increased rapidly over the last two decades. However, the demand for organs has increased even more. This disparity between the availability of organs and waitlisted patients for transplants has forced many transplant centers across the world to use marginal kidneys and donors. We performed a Medline search to establish the current status of marginal kidney donors in the world. Transplant programs using marginal deceased renal grafts is well established. The focus is now on efforts to improve their results. Utilization of non-heart-beating donors is still in a plateau phase and comprises a minor percentage of deceased donations. The main concern is primary non-function of the renal graft apart from legal and ethical issues. Transplants with living donors outnumbered cadaveric transplants at many centers in the last decade. There has been an increased use of marginal living kidney donors with some acceptable medical risks. Our primary concern is the safety of the living donor. There is not enough scientific data available to quantify the risks involved for such donation. The definition of marginal living donor is still not clear and there are no uniform recommendations. The decision must be tailored to each donor who in turn should be actively involved at all levels of the decision-making process. In the current circumstances, our responsibility is very crucial in making decisions for either accepting or rejecting a marginal living donor.

Infrapatellar Fat Pad Stem Cells: From Developmental Biology to Cell Therapy

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Ronaldo J. F. C. do Amaral

2017-01-01

Full Text Available The ideal cell type to be used for cartilage therapy should possess a proven chondrogenic capacity, not cause donor-site morbidity, and should be readily expandable in culture without losing their phenotype. There are several cell sources being investigated to promote cartilage regeneration: mature articular chondrocytes, chondrocyte progenitors, and various stem cells. Most recently, stem cells isolated from joint tissue, such as chondrogenic stem/progenitors from cartilage itself, synovial fluid, synovial membrane, and infrapatellar fat pad (IFP have gained great attention due to their increased chondrogenic capacity over the bone marrow and subcutaneous adipose-derived stem cells. In this review, we first describe the IFP anatomy and compare and contrast it with other adipose tissues, with a particular focus on the embryological and developmental aspects of the tissue. We then discuss the recent advances in IFP stem cells for regenerative medicine. We compare their properties with other stem cell types and discuss an ontogeny relationship with other joint cells and their role on in vivo cartilage repair. We conclude with a perspective for future clinical trials using IFP stem cells.

Infrapatellar Fat Pad Stem Cells: From Developmental Biology to Cell Therapy.

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do Amaral, Ronaldo J F C; Almeida, Henrique V; Kelly, Daniel J; O'Brien, Fergal J; Kearney, Cathal J

2017-01-01

The ideal cell type to be used for cartilage therapy should possess a proven chondrogenic capacity, not cause donor-site morbidity, and should be readily expandable in culture without losing their phenotype. There are several cell sources being investigated to promote cartilage regeneration: mature articular chondrocytes, chondrocyte progenitors, and various stem cells. Most recently, stem cells isolated from joint tissue, such as chondrogenic stem/progenitors from cartilage itself, synovial fluid, synovial membrane, and infrapatellar fat pad (IFP) have gained great attention due to their increased chondrogenic capacity over the bone marrow and subcutaneous adipose-derived stem cells. In this review, we first describe the IFP anatomy and compare and contrast it with other adipose tissues, with a particular focus on the embryological and developmental aspects of the tissue. We then discuss the recent advances in IFP stem cells for regenerative medicine. We compare their properties with other stem cell types and discuss an ontogeny relationship with other joint cells and their role on in vivo cartilage repair. We conclude with a perspective for future clinical trials using IFP stem cells.

Data mining of mental health issues of non-bone marrow donor siblings.

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Takita, Morihito; Tanaka, Yuji; Kodama, Yuko; Murashige, Naoko; Hatanaka, Nobuyo; Kishi, Yukiko; Matsumura, Tomoko; Ohsawa, Yukio; Kami, Masahiro

2011-07-20

Allogenic hematopoietic stem cell transplantation is a curative treatment for patients with advanced hematologic malignancies. However, the long-term mental health issues of siblings who were not selected as donors (non-donor siblings, NDS) in the transplantation have not been well assessed. Data mining is useful in discovering new findings from a large, multidisciplinary data set and the Scenario Map analysis is a novel approach which allows extracting keywords linking different conditions/events from text data of interviews even when the keywords appeared infrequently. The aim of this study is to assess mental health issues on NDSs and to find helpful keywords for the clinical follow-up using a Scenario Map analysis. A 47-year-old woman whose younger sister had undergone allogenic hematopoietic stem cell transplantation 20 years earlier was interviewed as a NDS. The text data from the interview transcriptions was analyzed using Scenario Mapping. Four clusters of words and six keywords were identified. Upon review of the word clusters and keywords, both the subject and researchers noticed that the subject has had mental health issues since the disease onset to date with being a NDS. The issues have been alleviated by her family. This single subject study suggested the advantages of data mining in clinical follow-up for mental health issues of patients and/or their families.

ODMR of shallow donors in Zn-doped LEC-grown InP

International Nuclear Information System (INIS)

Trombetta, J.M.; Kennedy, T.A.

1990-01-01

ODMR spectra observed while monitoring the shallow donor-shallow acceptor pair emission in Zn-doped LEC-grown InP display strong features in the region near the conduction electron value of g = 1.20. In addition to a previously observed narrow line, the authors observe a much broader resonance which dominates at low photoexcitation intensity. This broader line is interpreted as the unresolved exchange split resonances of electrons bound to residual shallow donors. The exchange broadening arises from interaction with nearby paramagnetic centers. Both resonances result in a decrease in the shallow-donor-to shallow-acceptor radiative recombination and give evidence for pair recombination processes which compete with this emission

What is the role of biosimilar G-CSF agents in hematopoietic stem cell mobilization at present?

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Korkmaz, Serdal; Altuntas, Fevzi

2017-12-01

Mobilization of hematopoietic stem cells, which has largely replaced bone marrow harvesting as a source of hematopoietic stem cells, using recombinant agents such as filgrastim or lenograstim has become a standard procedure in both patients and healthy donors prior to peripheral blood stem cell collection for autologous and allogeneic stem cell transplantation. Published literature data suggest that mobilization with recombinant granulocyte-colony stimulating factor (G-CSF) is safe and mobilization outcomes are satisfactory. In recent years, besides G-CSF originators, biosimilar G-CSF agents have been approved by the regulatory agencies for the same indications. Current data showed that by using the biosimilar G-CSF, similar results regarding safety and efficacy of hematopoietic stem cell mobilization may be achieved compared to the originator G-CSF. Although the issues such as the similarity to a licenced biological medicine, differences in manufacturing processes, the potential to cause immunogenicity, extrapolation and interchangeability of these biosimilar products are still being discussed by the scientific area, however, more experience with these agents now exists in approved endications and there seems to be no reason to expect significant differences between biosimilar G-CSF and originator G-CSF regarding their efficacy and safety in both patients and healthy donors. Also, the significant cost savings of biosimilars in real life setting may enhance the use of these agents in the future. Nonetheless, the collection of long-term follow-up data is mandatory for both patients and healthy donors, and multicentre randomized clinical trials that directly compare biosimilar G-CSF with the originator G-CSF are needed in order to allow the transplant community to make informed decisions regarding the choice of G-CSF. Copyright © 2017 Elsevier Ltd. All rights reserved.

Limbal Stem Cell-Sparing Corneoscleroplasty with Peripheral Intralamellar Tuck: A New Surgical Technique for Keratoglobus

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Elias Jarade

2017-04-01

Full Text Available Purpose: To describe the technique of limbal stem cell-sparing corneoscleroplasty for the management of advanced keratoglobus. Methods: A patient with bilateral advanced keratoglobus, with best-corrected visual acuity of 20/400 in the right eye and 20/200 in the left eye, underwent limbal stem cell-sparing corneoscleroplasty of the right eye. Initially, a 360-degree limbal incision with 200-μm depth was created, followed by a sublimbal tunnel dissection into the sclera, in order to conserve stem cells. Next, a limbus-to-limbus lamellar keratectomy at 200-μm depth was performed. Meanwhile, a donor corneoscleral button with preserved endothelium of the central 8 mm was fashioned. Prior to suturing the donor corneoscleral graft using a modified suturing technique to cover its scleral component, a full-thickness trephination of 8-mm diameter was completed in the central host cornea. Results: Reepithelialization occurred within the first week. No episodes of rejection, intraocular pressure spikes, or epithelial breakdown were observed postoperatively. At the 6-month follow-up, the patient had 20/70 best-corrected vision and a smooth cornea with regular astigmatism on topography. Conclusion: Limbal stem cell-sparing corneoscleroplasty is a single-step technique for restoring the structural integrity of the cornea in advanced keratoglobus while preserving the host limbal stem cells.

Donor Retention in Online Crowdfunding Communities: A Case Study of DonorsChoose.org.

Science.gov (United States)

Althoff, Tim; Leskovec, Jure

2015-05-01

Online crowdfunding platforms like DonorsChoose.org and Kick-starter allow specific projects to get funded by targeted contributions from a large number of people. Critical for the success of crowdfunding communities is recruitment and continued engagement of donors. With donor attrition rates above 70%, a significant challenge for online crowdfunding platforms as well as traditional offline non-profit organizations is the problem of donor retention. We present a large-scale study of millions of donors and donations on DonorsChoose.org, a crowdfunding platform for education projects. Studying an online crowdfunding platform allows for an unprecedented detailed view of how people direct their donations. We explore various factors impacting donor retention which allows us to identify different groups of donors and quantify their propensity to return for subsequent donations. We find that donors are more likely to return if they had a positive interaction with the receiver of the donation. We also show that this includes appropriate and timely recognition of their support as well as detailed communication of their impact. Finally, we discuss how our findings could inform steps to improve donor retention in crowdfunding communities and non-profit organizations.

Scripts for TRUMP data analyses. Part II (HLA-related data): statistical analyses specific for hematopoietic stem cell transplantation.

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Kanda, Junya

2016-01-01

The Transplant Registry Unified Management Program (TRUMP) made it possible for members of the Japan Society for Hematopoietic Cell Transplantation (JSHCT) to analyze large sets of national registry data on autologous and allogeneic hematopoietic stem cell transplantation. However, as the processes used to collect transplantation information are complex and differed over time, the background of these processes should be understood when using TRUMP data. Previously, information on the HLA locus of patients and donors had been collected using a questionnaire-based free-description method, resulting in some input errors. To correct minor but significant errors and provide accurate HLA matching data, the use of a Stata or EZR/R script offered by the JSHCT is strongly recommended when analyzing HLA data in the TRUMP dataset. The HLA mismatch direction, mismatch counting method, and different impacts of HLA mismatches by stem cell source are other important factors in the analysis of HLA data. Additionally, researchers should understand the statistical analyses specific for hematopoietic stem cell transplantation, such as competing risk, landmark analysis, and time-dependent analysis, to correctly analyze transplant data. The data center of the JSHCT can be contacted if statistical assistance is required.

Intravital imaging of donor allogeneic effector and regulatory T cells with host dendritic cells during GVHD.

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Lin, Kaifeng Lisa; Fulton, LeShara M; Berginski, Matthew; West, Michelle L; Taylor, Nicholas A; Moran, Timothy P; Coghill, James M; Blazar, Bruce R; Bear, James E; Serody, Jonathan S

2014-03-06

Graft-versus-host disease (GVHD) is a systemic inflammatory response due to the recognition of major histocompatibility complex disparity between donor and recipient after hematopoietic stem cell transplantation (HSCT). T-cell activation is critical to the induction of GVHD, and data from our group and others have shown that regulatory T cells (Tregs) prevent GVHD when given at the time of HSCT. Using multiphoton laser scanning microscopy, we examined the single cell dynamics of donor T cells and dendritic cells (DCs) with or without Tregs postallogeneic transplantation. We found that donor conventional T cells (Tcons) spent very little time screening host DCs. Tcons formed stable contacts with DCs very early after transplantation and only increased velocity in the lymph node at 20 hours after transplant. We also observed that Tregs reduced the interaction time between Tcons and DCs, which was dependent on the generation of interleukin 10 by Tregs. Imaging using inducible Tregs showed similar disruption of Tcon-DC contact. Additionally, we found that donor Tregs induce host DC death and down-regulate surface proteins required for donor T-cell activation. These data indicate that Tregs use multiple mechanisms that affect host DC numbers and function to mitigate acute GVHD.

A Photo-triggered and photo-calibrated nitric oxide donor: Rational design, spectral characterizations, and biological applications.

Science.gov (United States)

He, Haihong; Liu, Yuxin; Zhou, Zhongneng; Guo, Chunlei; Wang, Hong-Yin; Wang, Zhuang; Wang, Xueli; Zhang, Ziqian; Wu, Fu-Gen; Wang, Haolu; Chen, Daijie; Yang, Dahai; Liang, Xiaowen; Chen, Jinquan; Zhou, Shengmin; Liang, Xin; Qian, Xuhong; Yang, Youjun

2018-04-27

Nitric oxide (NO) donors are valuable tools to probe the profound implications of NO in health and disease. The elusive nature of NO bio-relevance has largely limited the use of spontaneous NO donors and promoted the development of next generation NO donors, whose NO release is not only stimulated by a trigger, but also readily monitored via a judiciously built-in self-calibration mechanism. Light is without a doubt the most sensitive, versatile and biocompatible method of choice for both triggering and monitoring, for applications in complex biological matrices. Herein, we designed and synthesized an N-nitroso rhodamine derivative (NOD560) as a photo-triggered and photo-calibrated NO donor to address this need. NOD560 is essentially non-fluorescent. Upon irradiation by green light (532 nm), it efficiently release NO and a rhodamine dye, the dramatic fluorescence turn-on from which could be harnessed to conveniently monitor the localization, flux, and dose of NO release. The potentials of NOD560 for in vitro biological applications were also exemplified in in vitro biological models, i.e. mesenchymal stem cell (MSC) migration suppression. NOD560 is expected to complement the existing NO donors and find widespread applications in chemical biological studies. Copyright © 2018 Elsevier Inc. All rights reserved.

Evolution of the clonogenic potential of human epidermal stem/progenitor cells with age

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Zobiri O

2012-02-01

Full Text Available Olivia Zobiri, Nathalie Deshayes, Michelle Rathman-JosserandDepartment of Biological Research, L'Oréal Advanced Research, Clichy Cedex, FranceAbstract: A number of clinical observations have indicated that the regenerative potential and overall function of the epidermis is modified with age. The epidermis becomes thinner, repairs itself less efficiently after wounding, and presents modified barrier function recovery. In addition, the dermal papillae flatten out with increasing age, suggesting a modification in the interaction between epidermal and dermal compartments. As the epidermal regenerative capacity is dependent upon stem and progenitor cell function, it is naturally of interest to identify and understand age-related changes in these particular keratinocyte populations. Previous studies have indicated that the number of stem cells does not decrease with age in mouse models but little solid evidence is currently available concerning human skin. The objective of this study was to evaluate the clonogenic potential of keratinocyte populations isolated from the epidermis of over 50 human donors ranging from 18 to 71 years old. The data indicate that the number of epidermal cells presenting high regenerative potential does not dramatically decline with age in human skin. The authors believe that changes in the microenvironment controlling epidermal basal cell activity are more likely to explain the differences in epidermal function observed with increasing age.Keywords: skin, epidermal stem cells, aging, colony-forming efficiency test

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

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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.

Is There Any Reason to Prefer Cord Blood Instead of Adult Donors for Hematopoietic Stem Cell Transplants?

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Beksac, Meral

2015-01-01

As cord blood (CB) enables rapid access and tolerance to HLA mismatches, a number of unrelated CB transplants have reached 30,000. Such transplant activity has been the result of international accreditation programs maintaining highly qualified cord blood units (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 CB transplants success by decreasing transplant-related mortality. CB progenitor/stem cell content has been compared with adult stem cells revealing higher long-term repopulating capacity compared to bone marrow-mesenchymal stromal cells and lesser oncogenic potential than progenitor-induced stem cells. This chapter summarizes the advantages and disadvantages of CB compared to adult stem cells within the context of stem cell biology and transplantation.

High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation.

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Ciurea, Stefan O; de Lima, Marcos; Cano, Pedro; Korbling, Martin; Giralt, Sergio; Shpall, Elizabeth J; Wang, Xuemei; Thall, Peter F; Champlin, Richard E; Fernandez-Vina, Marcelo

2009-10-27

BACKGROUND.: Although donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been implicated in graft rejection in solid organ transplantation, their role in hematopoietic stem-cell transplantation remains unclear. METHODS.: To address the hypothesis that the presence of DSA contributes to the development graft failure, we tested 24 consecutive patients for the presence of anti-HLA antibodies determined by a sensitive and specific solid-phase/single-antigen assay. The study included a total of 28 haploidentical transplants, each with 2 to 5 HLA allele mismatches, at a single institution, from September 2005 to August 2008. RESULTS.: DSA were detected in five patients (21%). Three of four (75%) patients with DSA before the first transplant failed to engraft, compared with 1 of 20 (5%) without DSA (P=0.008). All four patients who experienced primary graft failure had second haploidentical transplants. One patient developed a second graft failure with persistent high DSA levels, whereas three engrafted, two of them in the absence of DSA. No other known factors that could negatively influence engraftment were associated with the development of graft failure in these patients. CONCLUSIONS.: These results suggest that donor-specific anti-HLA antibodies are associated with a high rate of graft rejection in patients undergoing haploidentical stem-cell transplantation. Anti-HLA sensitization should be evaluated routinely in hematopoietic stem-cell transplantation with HLA mismatched donors.

Umbilical cord blood banking in the worldwide hematopoietic stem cell transplantation system: perspectives for Ukraine.

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Kalynychenko, T O

2017-09-01

Significant progress in the promotion of procedural technologies associated with the transplantation of hematopoietic stem cells caused a rapid increase in activity. The exchange of hematopoietic stem cells for unrelated donor transplantations is now much easier due to the relevant international professional structures and organizations established to support cooperation and standard setting, as well as rules for the functioning of both national donor registries and cord blood banks. These processes are increasing every year and are contributing to the outpacing rates of development in this area. Products within their country should be regulated by the competent government authorities. This study analyzes the work of international and national levels of support for transplantation activity in the field of unrelated hematopoietic stem cell transplantation, the standardization order of technologies, as well as data that justify the need to create a network of donated umbilical cord blood banks in Ukraine as a factor in the development of allogeneic transplantation. This will promote the accessibility of international standards for the treatment of serious diseases for Ukrainian citizens.

[Absolute numbers of peripheral blood CD34+ hematopoietic stem cells prior to a leukapheresis procedure as a parameter predicting the efficiency of stem cell collection].

Science.gov (United States)

Galtseva, I V; Davydova, Yu O; Gaponova, T V; Kapranov, N M; Kuzmina, L A; Troitskaya, V V; Gribanova, E O; Kravchenko, S K; Mangasarova, Ya K; Zvonkov, E E; Parovichnikova, E N; Mendeleeva, L P; Savchenko, V G

To identify a parameter predicting a collection of at least 2·106 CD34+ hematopoietic stem cells (HSC)/kg body weight per leukapheresis (LA) procedure. The investigation included 189 patients with hematological malignancies and 3 HSC donors, who underwent mobilization of stem cells with their subsequent collection by LA. Absolute numbers of peripheral blood leukocytes and CD34+ cells before a LA procedure, as well as a number of CD34+ cells/kg body weight (BW) in the LA product stored on the same day were determined in each patient (donor). There was no correlation between the number of leukocytes and that of stored CD34+ cells/kg BW. There was a close correlation between the count of peripheral blood CD34+ cells prior to LA and that of collected CD34+ cells calculated with reference to kg BW. The optimal absolute blood CD34+ cell count was estimated to 20 per µl, at which a LA procedure makes it possible to collect 2·106 or more CD34+ cells/kg BW.

Role of Killer Immunoglobulin-Like Receptor and Ligand Matching in Donor Selection

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Meral Beksaç

2012-01-01

Full Text Available Despite all efforts to improve HLA typing and immunosuppression, it is still impossible to prevent severe graft versus host disease (GVHD which can be fatal. GVHD is not always associated with graft versus malignancy and can prevent stem cell transplantation from reaching its goals. Overall T-cell alloreactivity is not the sole mechanism modulating the immune defense. Innate immune system has its own antigens, ligands, and mediators. The bridge between HLA and natural killer (NK cell-mediated reactions is becoming better understood in the context of stem cell transplantation. Killer immunoglobulin-like receptors (KIRs constitute a wide range of alleles/antigens segregated independently from the HLA alleles and classified into two major haplotypes which imprints the person's ability to suppress or to amplify T-cell alloreactivity. This paper will summarize the impact of both activating and inhibitory KIRs and their ligands on stem cell transplantation outcome. The ultimate goal is to develop algorithms based on KIR profiles to select donors with maximum antileukemic and minimum antihost effects.

Nyretransplantation med levende donor

DEFF Research Database (Denmark)

Kamper, A L; Løkkegaard, H; Rasmussen, F

2000-01-01

In recent years transplantation from living donors has accounted for 25-30% of all kidney transplants in Denmark corresponding to 40-45 per year. Most of these living donors are parents or siblings, although internationally an increasing number are unrelated donors. Donor nephrectomy is associate...... in cadaver transplantation. The ethical and psychological aspects related to transplantation from a living donor are complex and need to be carefully evaluated when this treatment is offered to the patients....

Generation of human induced pluripotent stem cell lines from human dermal fibroblasts using a modified RNA system

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Kyung-Ok Uhm

2017-10-01

Full Text Available We generated human induced pluripotent stem cells (KSCBi002-B and KSCBi002-B-1 from the dermal fibroblasts of a donor using a modified RNA-based gene delivery method. According to GTG-banding analysis, the generated KSCBi002-B line has a cytogenetic abnormality (46,XY, t(1;4(q21;q25 that is distinct from that of the donor, whereas KSCBi002-B-1 has a normal karyotype (46,XY. These cell lines can be useful as a model for characterizing the hiPSCs generated by a non-viral and non-integrative system, or as a chromosomal balanced translocation model. These two cell lines are registered and available from the National Stem Cell Bank, Korea National Institute of Health.

Milestones of Hematopoietic Stem Cell Transplantation – From First Human Studies to Current Developments

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Juric, Mateja Kralj; Ghimire, Sakhila; Ogonek, Justyna; Weissinger, Eva M.; Holler, Ernst; van Rood, Jon J.; Oudshoorn, Machteld; Dickinson, Anne; Greinix, Hildegard T.

2016-01-01

Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation (HSCT) has become an established curative treatment for an increasing number of patients with life-threatening hematological, oncological, hereditary, and immunological diseases. This has become possible due to worldwide efforts of preclinical and clinical research focusing on issues of transplant immunology, reduction of transplant-associated morbidity, and mortality and efficient malignant disease eradication. The latter has been accomplished by potent graft-versus-leukemia (GvL) effector cells contained in the stem cell graft. Exciting insights into the genetics of the human leukocyte antigen (HLA) system allowed improved donor selection, including HLA-identical related and unrelated donors. Besides bone marrow, other stem cell sources like granulocyte-colony stimulating-mobilized peripheral blood stem cells and cord blood stem cells have been established in clinical routine. Use of reduced-intensity or non-myeloablative conditioning regimens has been associated with a marked reduction of non-hematological toxicities and eventually, non-relapse mortality allowing older patients and individuals with comorbidities to undergo allogeneic HSCT and to benefit from GvL or antitumor effects. Whereas in the early years, malignant disease eradication by high-dose chemotherapy or radiotherapy was the ultimate goal; nowadays, allogeneic HSCT has been recognized as cellular immunotherapy relying prominently on immune mechanisms and to a lesser extent on non-specific direct cellular toxicity. This chapter will summarize the key milestones of HSCT and introduce current developments. PMID:27881982

T cell reconstitution in allogeneic haematopoietic stem cell transplantation

DEFF Research Database (Denmark)

Kielsen, K; Jordan, K K; Uhlving, H H

2015-01-01

Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although...... it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We...... in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : β = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : β = -8.4 × 10(6) cells/l, P = 0.061; CD4...

Marked in Vivo Donor Regulatory T Cell Expansion via Interleukin-2 and TL1A-Ig Stimulation Ameliorates Graft-versus-Host Disease but Preserves Graft-versus-Leukemia in Recipients after Hematopoietic Stem Cell Transplantation.

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Wolf, Dietlinde; Barreras, Henry; Bader, Cameron S; Copsel, Sabrina; Lightbourn, Casey O; Pfeiffer, Brent J; Altman, Norman H; Podack, Eckhard R; Komanduri, Krishna V; Levy, Robert B

2017-05-01

Regulatory T cells (Tregs) are critical for self-tolerance. Although adoptive transfer of expanded Tregs limits graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT), ex vivo generation of large numbers of functional Tregs remains difficult. Here, we demonstrate that in vivo targeting of the TNF superfamily receptor TNFRSF25 using the TL1A-Ig fusion protein, along with IL-2, resulted in transient but massive Treg expansion in donor mice, which peaked within days and was nontoxic. Tregs increased in multiple compartments, including blood, lymph nodes, spleen, and colon (GVHD target tissue). Tregs did not expand in bone marrow, a critical site for graft-versus-malignancy responses. Adoptive transfer of in vivo-expanded Tregs in the setting of MHC-mismatched or MHC-matched allogeneic HSCT significantly ameliorated GVHD. Critically, transplantation of Treg-expanded donor cells facilitated transplant tolerance without GVHD, with complete sparing of graft-versus-malignancy. This approach may prove valuable as a therapeutic strategy promoting transplantation tolerance. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Overweight young female kidney donors have low renal functional reserve post-donation.

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van Londen, Marco; Schaeffers, Anouk W M A; de Borst, Martin H; Joles, Jaap A; Navis, Gerjan; Lely, A Titia

2018-01-03

Maintenance of adequate renal function after living kidney donation is important for donor outcome. Overweight donors in particular may have an increased risk for end stage kidney disease (ESKD), and young female donors have an increased preeclampsia risk. Both of these risks may associate with low post-donation renal functional reserve (RFR). Because we previously found that higher BMI and lower post-donation RFR were associated, we now studied the relationship between BMI and RFR in young female donors. RFR, the rise in GFR (125I-Iothalamate clearance) during dopamine, was measured in female donors (donation. Donors who are overweight (BMI>25) and non-overweight donors were compared by t-test; the association was subsequently explored with regression analysis. We included 105 female donors (age 41 [36-44] (median[IQR])) with a BMI of 25 [22-27] kg/m2. Pre-donation GFR was 118 (17) ml/min (mean(SD)) rising to 128 (19) ml/min during dopamine; mean RFR was 10 (10) ml/min. Post-donation GFR was 76 (13) ml/min, rising to 80 (12); RFR was 4 (6) ml/min (pdonation). In overweight donors, RFR was fully lost after donation (1 ml/min vs. 10 ml/min pre-donation, pdonation, independent of confounders (St. β 0.37, p=0.02). Reduced RFR might associate with the risk of preeclampsia and ESKD in kidney donors. Prospective studies should explore whether RFR is related to preeclampsia and whether BMI reduction prior to conception is of benefit to overweight female kidney donors during and after pregnancy.

Stem cell therapy for end-stage heart failure : indispensable role for the cell?

NARCIS (Netherlands)

Vrijsen, K. R.; Chamuleau, S. A. J.; Noort, W. A.; Doevendans, P. A.; Sluijter, J. P. G.

2009-01-01

Purpose of review For heart failure patients, the urgent need for heart transplantation exceeds the availability of donor hearts. Therefore, cell transplantation has emerged as an interesting and potential solution. This review will focus on the capability of different types of stem cells to

Donating umbilical cord blood to a public bank or storing it in a private bank: knowledge and preference of blood donors and of pregnant women.

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Screnci, Maria; Murgi, Emilia; Pirrè, Guglielma; Valente, Elisabetta; Gesuiti, Paola; Corona, Francesca; Girelli, Gabriella

2012-07-01

Umbilical cord blood (UCB) is a source of stem cells for allogeneic haematopoietic transplantation in paediatric and adult patients with haematological malignancies and other indications. Voluntary donation is the basis for the success of unrelated UCB transplantation programmes. In the last few years a growing number of private banks offer their services to expectant parents, to store UCB for future use. The debate concerning UCB donation and private preservation has been ongoing for several years. The aims of this single centre study were to explore knowledge about UCB stem cells and attitudes towards voluntary UCB donation or private UCB preservation among both blood donors and pregnant women. This study was conducted at the "Sapienza" University of Rome. Two types of anonymous questionnaires were prepared: one type was administered to 1,000 blood donors while the other type was distributed to 300 pregnant women. Most blood donors as well as the majority of pregnant women had some general knowledge about UCB (89% and 93%, respectively) and were aware of the possibility of donating it (82% and 95%). However, the level of knowledge regarding current therapeutic use resulted generally low, only 91 (10%) among informed blood donors and 69 (31%) among informed pregnant women gave a correct answer. The survey revealed a preference for voluntary donation both among blood donors (76%) and among pregnant woman (55%). Indeed, a minority of blood donors (6.5%) and of pregnant women (9%) would opt to store UCB for private use. The study raises the following considerations: (i) the large support for UCB donation expressed by blood donors and by pregnant women suggests that UCB preservation does not represent an obstacle to the expansion of UCB donation and to development of unrelated transplantation programmes; (ii) information about UCB donation and preservation should be carefully given by professionals and institutions.

Adipose tissue-derived microvascular fragments from aged donors exhibit an impaired vascularisation capacity

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MW Laschke

2014-10-01

Full Text Available Adipose tissue-derived microvascular fragments are promising vascularisation units for applications in the field of tissue engineering. Elderly patients are the major future target population of such applications due to an increasing human life expectancy. Therefore, we herein investigated the effect of aging on the fragments’ vascularisation capacity. Microvascular fragments were isolated from epididymal fat pads of adult (8 months and aged (16 months C57BL/6 donor mice. These fragments were seeded onto porous polyurethane scaffolds, which were implanted into dorsal skinfold chambers to study their vascularisation using intravital fluorescence microscopy, histology and immunohistochemistry. Scaffolds seeded with fragments from aged donors exhibited a significantly lower functional microvessel density and intravascular blood flow velocity. This was associated with an impaired vessel maturation, as indicated by vessel wall irregularities, constantly elevated diameters and a lower fraction of CD31/α-smooth muscle actin double positive microvessels in the implants’ border and centre zones. Additional in vitro analyses revealed that microvascular fragments from adult and aged donors do not differ in their stem cell content as well as in their release of angiogenic growth factors, survival and proliferative activity under hypoxic conditions. However, fragments from aged donors exhibit a significantly lower number of matrix metalloproteinase -9-positive perivascular cells. Taken together, these findings demonstrate that aging is a crucial determinant for the vascularisation capacity of isolated microvascular fragments.

Influence of kinship on donors' mental burden in living donor liver transplantation.

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Erim, Yesim; Beckmann, Mingo; Kroencke, Sylvia; Sotiropoulos, Georgios C; Paul, Andreas; Senf, Wolfgang; Schulz, Karl-Heinz

2012-08-01

In the context of living donor liver transplantation (LDLT), German transplantation law stipulates that donor candidates should primarily be relatives of the recipients or persons with distinct and close relationships. In this study, we investigated the influence of the relationship between the donor and the recipient on the donor's emotional strain before transplantation. Donors were categorized according to the following subgroups: (1) parents donating for their children, (2) children donating for their parents, (3) siblings, (4) spouses, (5) other relatives, and (6) nonrelatives. The sample consisted of 168 donor candidates. Anxiety (F = 2.8, P = 0.02), depression (F = 2.6, P = 0.03), and emotional quality of life (F = 3.1, P = 0.01) differed significantly according to the relationship between the donor and the recipient. In comparison with healthy controls, parents donating for their children were significantly less stressed before LDLT and demonstrated fewer anxiety (P depression symptoms (P < 0.05). Adult children donating for their parents demonstrated the highest mental burden and the lowest emotional quality of life. However, this was not due to the responsibility of these children for their own families because differences between donors with children and donors without children could not be ascertained. This group should be given special attention before LDLT and during follow-up visits, and psychological help should be provided when it is necessary. Copyright © 2012 American Association for the Study of Liver Diseases.

Concise review: stem cell-derived erythrocytes as upcoming players in blood transfusion.

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Zeuner, Ann; Martelli, Fabrizio; Vaglio, Stefania; Federici, Giulia; Whitsett, Carolyn; Migliaccio, Anna Rita

2012-08-01

Blood transfusions have become indispensable to treat the anemia associated with a variety of medical conditions ranging from genetic disorders and cancer to extensive surgical procedures. In developed countries, the blood supply is generally adequate. However, the projected decline in blood donor availability due to population ageing and the difficulty in finding rare blood types for alloimmunized patients indicate a need for alternative red blood cell (RBC) transfusion products. Increasing knowledge of processes that govern erythropoiesis has been translated into efficient procedures to produce RBC ex vivo using primary hematopoietic stem cells, embryonic stem cells, or induced pluripotent stem cells. Although in vitro-generated RBCs have recently entered clinical evaluation, several issues related to ex vivo RBC production are still under intense scrutiny: among those are the identification of stem cell sources more suitable for ex vivo RBC generation, the translation of RBC culture methods into clinical grade production processes, and the development of protocols to achieve maximal RBC quality, quantity, and maturation. Data on size, hemoglobin, and blood group antigen expression and phosphoproteomic profiling obtained on erythroid cells expanded ex vivo from a limited number of donors are presented as examples of the type of measurements that should be performed as part of the quality control to assess the suitability of these cells for transfusion. New technologies for ex vivo erythroid cell generation will hopefully provide alternative transfusion products to meet present and future clinical requirements. Copyright © 2012 AlphaMed Press.

Iron deficiency in blood donors

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Rodolfo Delfini Cançado

Full Text Available CONTEXT: Blood donation results in a substantial loss of iron (200 to 250 mg at each bleeding procedure (425 to 475 ml and subsequent mobilization of iron from body stores. Recent reports have shown that body iron reserves generally are small and iron depletion is more frequent in blood donors than in non-donors. OBJECTIVE: The aim of this study was to evaluate the frequency of iron deficiency in blood donors and to establish the frequency of iron deficiency in blood donors according to sex, whether they were first-time or multi-time donors, and the frequency of donations per year. DESIGN: From September 20 to October 5, 1999, three hundred blood donors from Santa Casa Hemocenter of São Paulo were studied. DIAGNOSTIC TESTS: Using a combination of biochemical measurements of iron status: serum iron, total iron-binding capacity, transferrin saturation index, serum ferritin and the erythrocyte indices. RESULTS: The frequency of iron deficiency in blood donors was 11.0%, of whom 5.5% (13/237 were male and 31.7% (20/63 female donors. The frequency of iron deficiency was higher in multi-time blood donors than in first-time blood donors, for male blood donors (7.6% versus 0.0%, P < 0.05 and female ones (41.5% versus 18.5%, P < 0.05. The frequency of iron deficiency found was higher among the male blood donors with three or more donations per year (P < 0.05 and among the female blood donors with two or more donations per year (P < 0.05. CONCLUSIONS: We conclude that blood donation is a very important factor for iron deficiency in blood donors, particularly in multi-time donors and especially in female donors. The high frequency of blood donors with iron deficiency found in this study suggests a need for a more accurate laboratory trial, as hemoglobin or hematocrit measurement alone is not sufficient for detecting and excluding blood donors with iron deficiency without anemia.

Correlation between donor age and organs transplanted per donor: our experience in Japan.

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Ashikari, J; Omiya, K; Konaka, S; Nomoto, K

2014-05-01

The shortage of available organs for transplantation is a worldwide issue. To maximize the number of transplantations, increasing the number of organs transplanted per donor (OTPD) is widely recognized as an important factor for improving the shortage. In Japan, we have had 211 donors, 1112 organs transplanted, and 924 recipients receiving the transplants, resulting in 4.4 ± 1.4 recipients receiving transplants per donor and 5.3 ± 1.6 OTPD as of February 2013. Because donor age is a well-recognized factor of donor suitability, we analyzed the correlation between donor age group and OTPD. Only the age group 60 to 69 years and the age group 70 to 79 years were significantly different (P donor under age 70 years has the potential to donate 4.6 to 6.7 organs. Copyright © 2014 Elsevier Inc. All rights reserved.

Achieving donor management goals before deceased donor procurement is associated with more organs transplanted per donor.

Science.gov (United States)

Malinoski, Darren J; Daly, Michael C; Patel, Madhukar S; Oley-Graybill, Chrystal; Foster, Clarence E; Salim, Ali

2011-10-01

There is a national shortage of organs available for transplantation. Implementation of preset donor management goals (DMGs) to improve outcomes is recommended, but uniform practices and data are lacking. We hypothesized that meeting DMGs before organ procurement would result in more organs transplanted per donor (OTPD). The eight organ procurement organization in United Network for Organ Sharing Region 5 selected 10 critical care end points as DMGs. Each organ procurement organization submitted retrospective data from 40 standard criteria donors. "DMGs met" was defined as achieving any eight DMGs before procurement. The primary outcome was ≥4 OTPD. Binary logistic regression was used to determine independent predictors of ≥4 OTPD with a pdonors had 3.6±1.6 OTPD. Donors with DMGs met had more OTPD (4.4 vs. 3.3, p50% (OR=4.0), Pao2:FIO2>300 (OR=4.6), and serum sodium 135 to 160 mEq/L (OR=3.4). Meeting DMGs before procurement resulted in more OTPD. Donor factors and critical care end points are independent predictors of organ yield. Prospective studies are needed to determine the true impact of each DMG on the number and function of transplanted organs.

The Japan Marrow Donor Program, 25 years of experience in achieving 20,000 bone marrow transplantations: organization structure, activity, and financial basis.

Science.gov (United States)

Saito, Hidehiko; Ito, Masaharu; Kato, Shunichi; Kodera, Yoshihisa; Okamoto, Shinichiro; Taniguchi, Shuichi; Takanashi, Minoko; Kanamori, Heiwa; Masaoka, Toru; Takaku, Fumimaro

2018-01-24

The Japan Marrow Donor Program (JMDP), established in 1991, has continued to grow in its capacity to facilitate unrelated bone marrow (BMT) and peripheral blood stem cell transplantation (PBSCT) for the past 25 years in Japan. The current donor pool is 463,465 (as of 31 December 2016) and 20,237 transplants were performed with the help of the Japanese Red Cross, government, and supporters. As JMDP introduced PBSCT in 2010, the vast majority of transplants are BMT. All donors are fully typed for HLA-A, B, C, and DR. The peak age of registered donors is around 40 years. The 8/8 HLA-matched donors are found in our registry for 96% of the patients and 54% of the patients receive a transplant. The median time between the initiation of donor search and the transplantation is approximately 122 days. The median interval between the initiation of donor search and identification of the first potential donor is 40 days. The most common diseases for which unrelated BMT/PBSCT is indicated are acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), and malignant lymphoma. In recent years we have seen a marked increase in elderly patients who received BMT.

A simplified donor risk index for predicting outcome after deceased donor kidney transplantation.

Science.gov (United States)

Watson, Christopher J E; Johnson, Rachel J; Birch, Rhiannon; Collett, Dave; Bradley, J Andrew

2012-02-15

We sought to determine the deceased donor factors associated with outcome after kidney transplantation and to develop a clinically applicable Kidney Donor Risk Index. Data from the UK Transplant Registry on 7620 adult recipients of adult deceased donor kidney transplants between 2000 and 2007 inclusive were analyzed. Donor factors potentially influencing transplant outcome were investigated using Cox regression, adjusting for significant recipient and transplant factors. A United Kingdom Kidney Donor Risk Index was derived from the model and validated. Donor age was the most significant factor predicting poor transplant outcome (hazard ratio for 18-39 and 60+ years relative to 40-59 years was 0.78 and 1.49, respectively, Pinformed consent.

[Results of hematopoietic stem cell transplantation in hemoglobinopathies: thalassemia major and sickle cell disease].

Science.gov (United States)

Hladun, R; Elorza, I; Olivé, T; Dapena, J L; Llort, A; Sánchez de Toledo, J; Díaz de Heredia, C

2013-08-01

The prevalence of hemoglobinopathies in Spain is increasing as a result of immigration. Thalassemia major presents with chronic hemolytic anemia that requires regular red blood cell transfusions within the first year of life. Patients with sickle cell disease suffer from chronic anemia, vasculopathy and progressive damage in almost any organ. There is decreased life expectancy in both conditions. Allogeneic hematopoietic stem cell transplantation represents the only potentially curative option. Seventeen patients (fourteen thalassemia major, and three sickle cell disease) underwent allogeneic hematopoietic stem cell transplantations. In the thalassemia group, nine donors were HLA-geno-identical siblings, two were partially matched related donors (one HLA allele mismatch), and three unrelated donors. All three patients with sickle cell disease were transplanted from HLA-geno-identical siblings. The source of stem cells was bone marrow in sixteen cases. Median patient age at transplant was six years (range: 1-16) in the thalassemia group, and twelve years (range: 8-15) in the sickle cell disease group. The graft was successful in all patients. Secondary graft rejection was observed in two thalassemia patients rendering them dependent on blood transfusions. Complete chimerism was observed in thirteen patients and, although mixed chimerism occurred in two, with all of them showing normal hemoglobin levels after transplantation and not requiring further transfusion support. Patients affected by sickle cell disease did not present with new vaso-occlusive crises, and stabilization of pulmonary and neurological function was observed. Chronic graft-versus-host disease was detected in three patients affected by thalassemia, and hypogonadotrophic hypogonadism in five patients. We conclude that for thalassemia major and sickle cell disease, allogenic hematopoietic stem cell transplantation from HLA-geno-identical siblings offers a high probability of complication-free survival

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

Science.gov (United States)

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

2015-03-01

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

The impact of disclosure on donor gamete participants: donors, intended parents and offspring.

Science.gov (United States)

Greenfeld, Dorothy A

2008-06-01

The present review examines recent publications that provide insight into how the trend toward nonanonymity and disclosure in gamete donation impacts donors, intended parents, and their donor-conceived children. Recent findings show an increase in donor programs that offer open-identity between donors and offspring. The psychological needs of gamete donors and their attitudes toward disclosure are increasingly given consideration. Qualitative research on how parents of donor gamete offspring make decisions about disclosure reveals that even when couples initially disagree about disclosing to offspring, most ultimately come to a united disclosure decision. The literature on the impact of disclosure on donor gamete offspring has extended to include children conceived through embryo donation and children born as a result of surrogacy. The absence of genetic or gestational link between parents and their child does not have a negative impact on parent-child relationships. Parents through surrogacy tend to disclose the method of family creation to their child, whereas parents through embryo donation tend to be secretive about their child's origins. The trend toward greater openness in gamete donation has been accompanied by an increase in programs offering open-identity donation. In addition, the psychological needs of gamete donors and their attitudes toward disclosure are increasingly being given consideration. Parents of donor gamete offspring give careful thought to their disclosure decisions, and the psychological well being of donor-conceived children does not seem to be impacted by those decisions.

A Comparative Reference Study for the Validation of HLA-Matching Algorithms in the Search for Allogeneic Hematopoietic Stem Cell Donors and Cord Blood Units

Science.gov (United States)

2016-08-15

donors and cord blood units W. Bochtler1, L. Gragert2, Z. I. Patel3, J. Robinson3,4, D. Steiner5, J. A. Hofmann6, J. Pingel6, A. Baouz7, A. Melis8, J...cord blood units for individual patients is of primary importance. This challenging search process is routinely performed in a donor registry or cord...term ‘ donor ’ to refer to donors of HSCs from bone marrow or peripheral blood and cord blood units and the term ‘ donor registry’ shall include cord blood

Organ utilization from increased infectious risk donors: An observational study.

Science.gov (United States)

L'Huillier, Arnaud G; Humar, Atul; Payne, Clare; Kumar, Deepali

2017-12-01

Donors with an increased risk of transmitting human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) (increased risk donors [IRDs]) are a potential source of organs for transplant. Organs from IRDs can be utilized with appropriate recipient consent and post-transplant follow-up. We reviewed the characteristics and utilization of IRDs in our Organ Procurement Organization (OPO) over a 2-year period. Donor information from April 1, 2013 to March 31, 2015 was obtained through the OPO database. Only consented donors were included. Donors were categorized as IRDs according to Health Canada/Canadian Standards Association (CSA) criteria. A total of 494 potential donors were identified, of which 92 (18.6%) were IRDs. Of these, at least one organ was transplanted from 76 (82.6%). Risk factors for IRDs included injection drug user (IDU) (12%), men having sex with men (MSM) (7%), commercial sex worker (CSW) (4%), and incarceration (24%). Fifty-nine percent (253/429) of IRD organs were utilized. The most frequently used organ was kidney, followed by liver. Median number of organs recovered per IRD was 3 (interquartile range: 2-5). Nucleic acid testing (NAT) was performed in 18.5% (17/92) of IRDs. Reasons for NAT were IDU (n = 2), MSM (n = 2), CSW (n = 2), and previous incarceration (n = 7). Organ utilization from donors that had NAT was similar to donors who did not (94% vs 80%, P = .29). Follow-up NAT was done in multiple factors contribute to the perception of infectious risk from such organs. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Differences in social representation of blood donation between donors and non-donors: an empirical study.

Science.gov (United States)

Guarnaccia, Cinzia; Giannone, Francesca; Falgares, Giorgio; Caligaris, Aldo Ozino; Sales-Wuillemin, Edith

2015-11-04

Both donors and non-donors have a positive image of blood donation, so donors and non-donors do not differ regarding their views on donation but do differ in converting their opinion into an active deed of donation. Several studies have identified altruism and empathy as the main factors underlying blood donation. However, a mixture of various motivational factors mould the complex behaviour of donation. This paper presents an exploratory study on differences of social representations of blood donation between blood donors and non-donors, in order to understand the reasons that bring someone to take the decision to become a blood donor. Participants filled in the Adapted Self-Report Altruism Scale, Toronto Empathy Questionnaire and answered a test of verbal association. Descriptive and correlation analyses were carried out on quantitative data, while a prototypic analysis was used for qualitative data. The study was carried out on a convenience sample of 786 individuals, 583 donors (mean age: 35.40 years, SD: 13.01 years; 39.3% female) and 203 non-donors (mean age: 35.10 years, SD: 13.30 years; 67.5% female). Social representations of donors seem to be more complex and articulated than those of non-donors. The terms that appear to be central were more specific in donors (life, needle, blood, help, altruism were the words most associated by non-donors; life, aid, altruism, solidarity, health, love, gift, generosity, voluntary, control, needed, useful, needle were the words most associated by donors). Furthermore, non-donors associated a larger number of terms referring to negative aspects of blood donation. Aspects related to training and the accuracy of any information on blood donation seem to be important in the decision to become a donor and stabilise the behaviour of donation over time, thus ensuring the highest levels of quality and safety in blood establishments.

The effect of repeated blood donations on the iron status of male Saudi blood donors

Science.gov (United States)

Abdullah, Saleh M.

2011-01-01

Background. Regular blood donation can lead to iron deficiency. Screening donors’ serum ferritin levels at the time of first donation and subsequently once every year is a very rational way to pick up iron deficiency in a voluntary blood donor population. The aim of this study was to determine the effect of blood donation and the prevalence of erythropoiesis with iron deficiency (sideropenia) in Saudi male blood donors. Materials and methods. The study was prospectively conducted, between December 2008 and March 2009, on 182 male native Saudi blood donors at King Fahd Central Hospital in Jazan region, Saudi Arabia. Each donor gave 450±50 mL of whole blood. Following the donation, samples were removed into 2.5 mL EDTA tubes for measurement of mean cell volume (MCV) and mean corpuscular haemoglobin (MCH) and into 7.5 mL plain tubes for estimation of iron and serum ferritin concentrations. The blood donors were divided into five groups, according to the number of donations they had given in the preceding 3 years. The blood donors in group I were first-time donors, with no previous history of blood donation. Group II donors had donated once in the last 3 years. Subjects in groups III, IV and V had donated more than once in the preceding 3 years and were considered regular donors. Results. The mean serum iron was significantly higher among subjects with no previous history of blood donation (group I) than among regular donors who had donated twice or more. The difference in serum ferritin concentration was statistically significant (pdonated once in the last 3 years, and in first-time blood donors (131.4 μg/L) was not statistically significant (pdonated between two to five times had iron deficiency. The prevalence of erythropoiesis with iron deficiency in regular blood donors was 4.3%. Conclusion. The results of this study show that an increase in the number of donations results in an increase in the frequency of depleted iron stores and subsequently in

Cloning from stem cells: different lineages, different species, same story.

Science.gov (United States)

Oback, Björn

2009-01-01

Following nuclear transfer (NT), the most stringent measure of extensive donor cell reprogramming is development into viable offspring. This is referred to as cloning efficiency and quantified as the proportion of cloned embryos transferred into surrogate mothers that survive into adulthood. Cloning efficiency depends on the ability of the enucleated recipient cell to carry out the reprogramming reactions ('reprogramming ability') and the ability of the nuclear donor cell to be reprogrammed ('reprogrammability'). It has been postulated that reprogrammability of the somatic donor cell epigenome is inversely proportional to its differentiation status. In order to test this hypothesis, reprogrammability was compared between undifferentiated stem cells and their differentiated isogenic progeny. In the mouse, cells of divergent differentiation status from the neuronal, haematopoietic and skin epithelial lineage were tested. In cattle and deer, skeletal muscle and antler cells, respectively, were used as donors. No conclusive correlation between differentiation status and cloning efficiency was found, indicating that somatic donor cell type may not be the limiting factor for cloning success. This may reflect technical limitations of the NT-induced reprogramming assay. Alternatively, differentiation status and reprogrammability may be unrelated, making all cells equally difficult to reprogramme once they have left the ground state of pluripotency.

Periarteriolar Glioblastoma Stem Cell Niches Express Bone Marrow Hematopoietic Stem Cell Niche Proteins

NARCIS (Netherlands)

Hira, Vashendriya V. V.; Wormer, Jill R.; Kakar, Hala; Breznik, Barbara; van der Swaan, Britt; Hulsbos, Renske; Tigchelaar, Wikky; Tonar, Zbynek; Khurshed, Mohammed; Molenaar, Remco J.; van Noorden, Cornelis J. F.

2018-01-01

In glioblastoma, a fraction of malignant cells consists of therapy-resistant glioblastoma stem cells (GSCs) residing in protective niches that recapitulate hematopoietic stem cell (HSC) niches in bone marrow. We have previously shown that HSC niche proteins stromal cell-derived factor-1α (SDF-1α),

Transplantation Dose Alters the Differentiation Program of Hematopoietic Stem Cells.

Science.gov (United States)

Brewer, Casey; Chu, Elizabeth; Chin, Mike; Lu, Rong

2016-05-24

Hematopoietic stem cell (HSC) transplantation is the most prevalent stem cell therapy, but it remains a risky procedure. To improve this treatment, it is important to understand how transplanted stem cells rebuild the blood and immune systems and how this process is impacted by transplantation variables such as the HSC dose. Here, we find that, in the long term following transplantation, 70%-80% of donor-HSC-derived clones do not produce all measured blood cell types. High HSC doses lead to more clones that exhibit balanced lymphocyte production, whereas low doses produce more T-cell-specialized clones. High HSC doses also produce significantly higher proportions of early-differentiating clones compared to low doses. These complex differentiation behaviors uncover the clonal-level regeneration dynamics of hematopoietic regeneration and suggest that transplantation dose can be exploited to improve stem cell therapy. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

In-Vivo Imaging Of Transplanted Human Hepatic Stem Cells: Negative Contrast Labeling And 7t Micro-MRI Tracking

National Research Council Canada - National Science Library

McClelland, Randall E; Wauthier, Eliane; Reid, Lola; Hsu, Edward

2004-01-01

Stem cell therapies have great potential as alternative options to whole organ transplantations in treating dysfunction or failure, and alleviating the chronic shortage of donor availability of organs such as the...

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors.

Science.gov (United States)

Taniguchi, K; Yoshihara, S; Maruya, E; Ikegame, K; Kaida, K; Hayashi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Onuma, T; Fujii, N; Kusunoki, Y; Soma, T; Saji, H; Ogawa, H

2012-10-01

Pre-existing donor-specific HLA antibodies in patients undergoing HLA-mismatched SCT have increasingly been recognized as a risk factor for primary graft failure. However, the clinical implications of the presence of HLA antibodies in donors remain unknown. We prospectively examined 123 related donors for the presence of HLA antibodies by using a Luminex-based single antigen assay. Of these, 1/57 (1.8%) male, 6/27 (22%) parous female and 0/39 (0%) nonparous female donors were HLA antibody-positive. Then, we determined the presence of HLA antibodies in seven patients who received SCT from antibody-positive donors. Of these, four became HLA antibody-positive after SCT. The specificities of the antibodies that emerged in the patients closely resembled those of the antibodies found in the donors, indicating their production by donor-derived plasma cells. Moreover, the kinetics of the HLA antibody levels were similar in all four patients: levels started increasing within 1 week after SCT and peaked at days 10-21, followed by a gradual decrease. These results suggest that donor-derived HLA antibody production frequently occurs in patients undergoing SCT from antibody-positive donors. Further studies are warranted for clarifying the clinical significance of donor-derived HLA antibodies, including the role of these antibodies in post transplant platelet transfusion refractoriness.

Conformationally superarmed S-ethyl glycosyl donors as effective building blocks for chemoselective oligosaccharide synthesis in one pot

DEFF Research Database (Denmark)

Bandara, Mithila D.; Yasomanee, Jagodige P.; Rath, Nigam P.

2017-01-01

A new series of superarmed glycosyl donors has been investigated. It was demonstrated that the S-ethyl leaving group allows for high reactivity, which is much higher than that of equally equipped S-phenyl glycosyl donors that were previously investigated by our groups. The superarmed S......-ethyl glycosyl donors equipped with a 2-O-benzoyl group gave complete β-stereoselectivity. Utility of the new glycosyl donors has been demonstrated in a one-pot one-addition oligosaccharide synthesis with all of the reaction components present from the beginning...

The effect of whole-blood donor adverse events on blood donor return rates.

Science.gov (United States)

Newman, Bruce H; Newman, Daniel T; Ahmad, Raffat; Roth, Arthur J

2006-08-01

Some blood donation-related adverse events (AEs) can negatively impact the blood donor return rate (BDRR) and decrease donor retention. One-thousand randomly selected whole-blood donors were interviewed 3 weeks after a 525-mL index whole-blood donation for seven AEs. The number of return visits and duration of follow-up were recorded for each of the 1000 donors. A negative binomial regression analysis was used to determine the contribution of the four most common AEs to the BDRR, and interactions between these AEs were also evaluated. The four most common AEs were bruise alone (15.1%), sore arm "alone" (7.0%), fatigue "alone" (5.1%), and donor reaction "alone" (4.2%), where "alone" is defined to also include donors who had a bruise but no other AE. The estimated BDRR for donations without AEs was 1.32 visits per year. The estimated BDRRs for the four most common AEs were: bruise alone, 1.32 visits per year; sore arm alone, 1.30 visits per year (2% reduction in BDRR); fatigue alone, 1.06 visits per year (20% reduction in BDRR); and donor reaction alone, 0.87 visits per year (34% reduction in BDRR). The BDRR for donor reaction, fatigue, and sore arm together was 0.20 visits per year (85% reduction in BDRR). Donor reaction had the most negative impact on the BDRR. There appears to be a synergistic effect between donor reaction, fatigue, and sore arm. Theoretically, amelioration of some AEs has the potential to improve BDRRs.

Modified extracorporeal photopheresis with cells from a healthy donor for acute graft-versus-host disease in a mouse model.

Directory of Open Access Journals (Sweden)

Holger Budde

Full Text Available Graft-versus-host disease (GvHD is a major challenge after hematopoietic stem cell transplantation but treatment options for patients are still limited. In many cases first-line treatment with glucocorticoids is not successful. Among second-line therapies the extracorporeal photopheresis (ECP is frequently performed, due to induction of selective tolerance instead of general immunosuppression. However, for some patients with severe acute GvHD the leukapheresis step of the ECP procedure is physically exhausting and limits the number of ECP cycles.We hypothesized that leukocytes from healthy cell donors could be used as a replacement for ECP leukocytes gained from the GvHD patient. For this purpose we used a well established mouse model of acute GvHD. The ECP therapy was based on cells with the genetic background of the initial donor of the stem cell transplantation. As a precondition we developed a protocol representing conventional ECP in mice equivalent to clinical used ECP setup.We could demonstrate that conventional, clinically derived ECP setup is able to alleviate acute GvHD. By using leukocytes obtained from healthy mice with the bone marrow donor's genetic background we could not observe a statistically significant therapeutic effect.Conventional human ECP setup is effective in the mouse model of severe acute GvHD. In addition we could not prove that ECP cells from healthy mice with bone marrow donor's genetic background are as effective as ECP cells derived from GvHD mice. Based on our findings, new questions arise for further studies, in which the cellular characteristics for ECP mediated immune tolerance are a matter of investigation.

ِAnalysis of donor motivations in living donor liver transplantation

Directory of Open Access Journals (Sweden)

Hesham eAbdeldayem

2014-07-01

Full Text Available Objectives: The introduction of the living donor liver transplantation (LDLT in Egypt as in elsewhere, has raised important psychological conflicts and ethical questions. The objective of this study was to get better understanding of the potential donors’ motives towards LDLT.Methods:This study was conducted on consecutive 193 living –liver donors who underwent partial hepatectomy as donors for LDLT during the period between April 2003 and January 2013, at the National Liver Institute Menoufeyia University, Egypt. Potential donors were thoroughly evaluated preoperatively through a screening questionnaire and interviews as regard their demographic data, relationship to the potential recipient and motives towards proceeding to surgery. They were assured that the information shared between them and the transplant centre is confidential. Results.The donors’ mean age was 25.53± 6.39 years with a range of 18-45 years. Males represented 64.7 % and females were 35.3%. The most common donors (32.1%, n_62, were sons and daughters to their parents (sons: n_43, daughters: n_19 while parents to their offsprings represent 15% (mothers: n_21, fathers: n_8. Brothers and sisters represent 16.5 % (brothers: n_22, sisters: n_10. Nephews & nieces giving their uncles or aunts were 14%. The number of wives donating to their husbands was 11 (5.7%. Interestingly, there was no single husband who donated his wife. Among the remaining donors, there were 11 cousins & one uncle. Unrelated donors were 20 (10.4%. Several factors seemed to contribute to motivation for donation: the seriousness of the potential recipient condition, the relationship and personal history of the donor to the potential recipient, the religious beliefs, the trust in the health care system, and family dynamics and obligations.Conclusions. Absolute absence of coercion on the living-liver donor’s motives may not be realistic because of the serious condition of the potential recipient. It is

The donor star of the X-ray pulsar X1908+075

Science.gov (United States)

Martínez-Núñez, S.; Sander, A.; Gímenez-García, A.; Gónzalez-Galán, A.; Torrejón, J. M.; Gónzalez-Fernández, C.; Hamann, W.-R.

2015-06-01

High-mass X-ray binaries consist of a massive donor star and a compact object. While several of those systems have been well studied in X-rays, little is known for most of the donor stars as they are often heavily obscured in the optical and ultraviolet regime. There is an opportunity to observe them at infrared wavelengths, however. The goal of this study is to obtain the stellar and wind parameters of the donor star in the X1908+075 high-mass X-ray binary system with a stellar atmosphere model to check whether previous studies from X-ray observations and spectral morphology lead to a sufficient description of the donor star. We obtained H- and K-band spectra of X1908+075 and analysed them with the Potsdam Wolf-Rayet (PoWR) model atmosphere code. For the first time, we calculated a stellar atmosphere model for the donor star, whose main parameters are: Mspec = 15 ± 6 M⊙, T∗ = 23-3+6 kK, log geff = 3.0 ± 0.2 and log L/L⊙ = 4.81 ± 0.25. The obtained parameters point towards an early B-type (B0-B3) star, probably in a supergiant phase. Moreover we determined a more accurate distance to the system of 4.85 ± 0.50 kpc than the previously reported value. Based on observations made with the William Herschel Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias.Appendix A is available in electronic form at http://www.aanda.org

Allogeneic stem cell transplantation in acute myeloid leukemia

Directory of Open Access Journals (Sweden)

Natasha Ali

2012-11-01

Full Text Available We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients. Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

Segregation of genes from donor strain during the production of recombinant congenic strains.

Science.gov (United States)

van Zutphen, L F; Den Bieman, M; Lankhorst, A; Demant, P

1991-07-01

Recombinant congenic strains (RCS) constitute a set of inbred strains which are designed to dissect the genetic control of multigenic traits, such as tumour susceptibility or disease resistance. Each RCS contains a small fraction of the genome of a common donor strain, while the majority of genes stem from a common background strain. We tested at two stages of the inbreeding process in 20 RCS, derived from BALB/cHeA and STS/A, to see whether alleles from the STS/A donor strain are distributed over the RCS in a ratio as would theoretically be expected. Four marker genes (Pep-3; Pgm-1; Gpi-1 and Es-3) located at 4 different chromosomes were selected and the allelic distribution was tested after 3-4 and after 12 generations of inbreeding. The data obtained do not significantly deviate from the expected pattern, thus supporting the validity of the concept of RCS.

Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts.

Science.gov (United States)

Gary, Regina; Aigner, Michael; Moi, Stephanie; Schaffer, Stefanie; Gottmann, Anja; Maas, Stefanie; Zimmermann, Robert; Zingsem, Jürgen; Strobel, Julian; Mackensen, Andreas; Mautner, Josef; Moosmann, Andreas; Gerbitz, Armin

2018-05-09

A major complication after allogeneic hematopoietic stem cell transplantation (aSCT) is the reactivation of herpesviruses such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Both viruses cause significant mortality and compromise quality of life after aSCT. Preventive transfer of virus-specific T cells can suppress reactivation by re-establishing functional antiviral immune responses in immunocompromised hosts. We have developed a good manufacturing practice protocol to generate CMV/EBV-peptide-stimulated T cells from leukapheresis products of G-CSF mobilized and non-mobilized donors. Our procedure selectively expands virus-specific CD8+ und CD4+ T cells over 9 days using a generic pool of 34 CMV and EBV peptides that represent well-defined dominant T-cell epitopes with various HLA restrictions. For HLA class I, this set of peptides covers at least 80% of the European population. CMV/EBV-specific T cells were successfully expanded from leukapheresis material of both G-CSF mobilized and non-mobilized donors. The protocol allows administration shortly after stem cell transplantation (d30+), storage over liquid nitrogen for iterated applications, and protection of the stem cell donor by avoiding a second leukapheresis. Our protocol allows for rapid and cost-efficient production of T cells for early transfusion after aSCT as a preventive approach. It is currently evaluated in a phase I/IIa clinical trial.

Rhizomucor and Scedosporium Infection Post Hematopoietic Stem-Cell Transplant

Directory of Open Access Journals (Sweden)

Dânia Sofia Marques

2011-01-01

Full Text Available Hematopoietic stem-cell transplant recipients are at increased risk of developing invasive fungal infections. This is a major cause of morbidity and mortality. We report a case of a 17-year-old male patient diagnosed with severe idiopathic acquired aplastic anemia who developed fungal pneumonitis due to Rhizomucor sp. and rhinoencephalitis due to Scedosporium apiospermum 6 and 8 months after undergoing allogeneic hematopoietic stem-cell transplant from an HLA-matched unrelated donor. Discussion highlights risk factors for invasive fungal infections (i.e., mucormycosis and scedosporiosis, its clinical features, and the factors that must be taken into account to successfully treat them (early diagnosis, correction of predisposing factors, aggressive surgical debridement, and antifungal and adjunctive therapies.

Increasing Stem Cell Dose Promotes Posttransplant Immune Reconstitution.

Science.gov (United States)

Xu, Ning; Shen, Sylvie; Dolnikov, Alla

2017-04-01

Umbilical cord blood (UCB) transplantation can provide a successful therapeutic option for patients that have no suitable related donor. UCB transplantation is often limited by the relatively small hematopoietic stem cell (HSC) numbers in UCB especially for adult recipients. Early neutrophil and platelet engraftment correlates with the stem cell numbers in UCB transplant. Compared to other HSC sources, immune reconstitution following UCB transplant is slower and complicated by increased frequency of opportunistic infections. The effect of HSC numbers in UCB transplant on immune reconstitution was not thoroughly examined. Using immunocompromised mice transplanted with purified UCB CD34+ stem cells, we have demonstrated that increasing the numbers of CD34+ cells in the transplant promotes hematopoietic and immune reconstitution. At early stages posttransplant, high stem cell dose generated relatively more B cells, while lower dose generated more myeloid and T cells. Thus, the size of the stem cell graft appears to modulate the differentiation potential of infused stem cells. In addition, increasing stem cell dose in the transplant improved CD8+ T cell development and delayed late memory T cell skewing in expense of naive T cells highlighting the importance of HSC dose to maintain the pool of naive T cells able to develop strong immune responses. Transplantation of ex vivo expanded CD34+ cells did not promote, but rather delayed immune reconstitution suggesting the loss of primitive lymphoid precursor cells during ex vivo expansion.

Stem Cells Transplantation in the Treatment of Patients with Liver Failure.

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Tao, Ya-Chao; Wang, Meng-Lan; Chen, En-Qiang; Tang, Hong

2018-02-23

Liver failure is a life-threatening liver disease encompassing severe acute deterioration of liver function. Emergency liver transplantation is the only curative treatment for liver failure, but is restricted by the severe shortage of organ donors. Stem cell, including embroyonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells and hepatic progenitor cells, have capacity to proliferate and differentiate and could be used in a variety of liver diseases including hereditary liver diseases, cirrhosis and liver failure. We summarized the basic experimental and clinical advances of stem cell transplantation in liver failure treatment, and also discussed the advantages and disadvantage of different stem cells subtype in this field, aiming to provide a perspective on the stem cell-based therapy for liver failure. Stem cells, especially mesenchymal stem cells (mainly low immunogenicity and paracrine characteristics) and induced pluripotent stem cells (generation of desired cell type from somatic cell), are feasible candidates for cell therapy in the treatment of liver failure, but there are some drawbacks remaining to be resolved, such as low engraftment, cryotpreservation methods and tumorigenesis. Stem cell transplantation is a promising but challenging strategy and paves a new way for curing liver failure. But more efforts need to be made to overcome problems before this new strategy could be safely and effectively applied to humans. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

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Katja M. Piltti

2015-09-01

Full Text Available The effect of transplantation dose on the spatiotemporal dynamics of human neural stem cell (hNSC engraftment has not been quantitatively evaluated in the central nervous system. We investigated changes over time in engraftment/survival, proliferation, and migration of multipotent human central nervous system-derived neural stem cells (hCNS-SCns transplanted at doses ranging from 10,000 to 500,000 cells in spinal cord injured immunodeficient mice. Transplant dose was inversely correlated with measures of donor cell proliferation at 2 weeks post-transplant (WPT and dose-normalized engraftment at 16 WPT. Critically, mice receiving the highest cell dose exhibited an engraftment plateau, in which the total number of engrafted human cells never exceeded the initial dose. These data suggest that donor cell expansion was inversely regulated by target niche parameters and/or transplantation density. Investigation of the response of donor cells to the host microenvironment should be a key variable in defining target cell dose in pre-clinical models of CNS disease and injury.

Fanconi Anemia Mesenchymal Stromal Cells-Derived Glycerophospholipids Skew Hematopoietic Stem Cell Differentiation Through Toll-Like Receptor Signaling.

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Amarachintha, Surya; Sertorio, Mathieu; Wilson, Andrew; Li, Xiaoli; Pang, Qishen

2015-11-01

Fanconi anemia (FA) patients develop bone marrow (BM) failure or leukemia. One standard care for these devastating complications is hematopoietic stem cell transplantation. We identified a group of mesenchymal stromal cells (MSCs)-derived metabolites, glycerophospholipids, and their endogenous inhibitor, 5-(tetradecyloxy)-2-furoic acid (TOFA), as regulators of donor hematopoietic stem and progenitor cells. We provided two pieces of evidence that TOFA could improve hematopoiesis-supporting function of FA MSCs: (a) limiting-dilution cobblestone area-forming cell assay revealed that TOFA significantly increased cobblestone colonies in Fanca-/- or Fancd2-/- cocultures compared to untreated cocultures. (b) Competitive repopulating assay using output cells collected from cocultures showed that TOFA greatly alleviated the abnormal expansion of the donor myeloid (CD45.2+Gr1+Mac1+) compartment in both peripheral blood and BM of recipient mice transplanted with cells from Fanca-/- or Fancd2-/- cocultures. Furthermore, mechanistic studies identified Tlr4 signaling as the responsible pathway mediating the effect of glycerophospholipids. Thus, targeting glycerophospholipid biosynthesis in FA MSCs could be a therapeutic strategy to improve hematopoiesis and stem cell transplantation. © 2015 AlphaMed Press.

Chimeric animal models in human stem cell biology.

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Glover, Joel C; Boulland, Jean-Luc; Halasi, Gabor; Kasumacic, Nedim

2009-01-01

The clinical use of stem cells for regenerative medicine is critically dependent on preclinical studies in animal models. In this review we examine some of the key issues and challenges in the use of animal models to study human stem cell biology-experimental standardization, body size, immunological barriers, cell survival factors, fusion of host and donor cells, and in vivo imaging and tracking. We focus particular attention on the various imaging modalities that can be used to track cells in living animals, comparing their strengths and weaknesses and describing technical developments that are likely to lead to new opportunities for the dynamic assessment of stem cell behavior in vivo. We then provide an overview of some of the most commonly used animal models, their advantages and disadvantages, and examples of their use for xenotypic transplantation of human stem cells, with separate reviews of models involving rodents, ungulates, nonhuman primates, and the chicken embryo. As the use of human somatic, embryonic, and induced pluripotent stem cells increases, so too will the range of applications for these animal models. It is likely that increasingly sophisticated uses of human/animal chimeric models will be developed through advances in genetic manipulation, cell delivery, and in vivo imaging.

Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia.

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Hill, Brian T; Ahn, Kwang Woo; Hu, Zhen-Huan; Aljurf, Mahmoud; Beitinjaneh, Amer; Cahn, Jean-Yves; Cerny, Jan; Kharfan-Dabaja, Mohamed A; Ganguly, Siddhartha; Ghosh, Nilanjan; Grunwald, Michael R; Inamoto, Yoshihiro; Kindwall-Keller, Tamila; Nishihori, Taiga; Olsson, Richard F; Saad, Ayman; Seftel, Matthew; Seo, Sachiko; Szer, Jeffrey; Tallman, Martin; Ustun, Celalettin; Wiernik, Peter H; Maziarz, Richard T; Kalaycio, Matt; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Saber, Wael

2018-03-01

Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the only known curative treatment for CLL. The potential benefit of transplantation is most likely due to the presence of alloreactive donor T cells that mediate the graft-versus-leukemia (GVL) effect. The recognition of potentially tumor-specific antigens in the context of class I and II major histocompatibility complex on malignant B lymphocytes by donor T cells may be influenced by subtle differences in the highly polymorphic HLA locus. Given previous reports of specific HLA alleles impacting the incidence of CLL and the clinical outcomes of allo-HCT for CLL, we sought to study the overall survival and progression-free survival of a large cohort of patients with CLL who underwent allo-HCT from fully HLA-matched related and unrelated donors at Center for International Blood and Marrow Transplant Research transplantation centers. We found no statistically significant association of allo-HCT outcomes in CLL based on previously reported HLA combinations. Additional study is needed to further define the immunologic features that portend a more favorable GVL effect after allo-HCT for CLL. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

HLA engineering of human pluripotent stem cells.

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Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

2013-06-01

The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I-negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8(+) T cell responses were reduced in class I-negative cells that had undergone differentiation in embryoid bodies. These B2M(-/-) ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines.

HLA Engineering of Human Pluripotent Stem Cells

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Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

2013-01-01

The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I–negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8+ T cell responses were reduced in class I–negative cells that had undergone differentiation in embryoid bodies. These B2M−/− ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines. PMID:23629003

Donor bound excitons in ZnSe nanoresonators - Applications in quantum information science

Energy Technology Data Exchange (ETDEWEB)

Pawlis, A. [Department of Physics, University of Paderborn, Warburger Str. 100, 33098 Paderborn, Germany and Edward L. Ginzton Laboratory, Stanford University, Stanford, California 94305-4088 (United States); Lischka, K. [Department of Physics, University of Paderborn, Warburger Str. 100, 33098 Paderborn (Germany); Sanaka, K.; Yamamoto, Y. [Edward L. Ginzton Laboratory, Stanford University, Stanford, California 94305-4088, USA and National Institute of Informatics, 2-1-2 Hitotsubashi, Chiyoda-ku, Tokyo 101-8430 (Japan); Sleiter, D. [Edward L. Ginzton Laboratory, Stanford University, Stanford, California 94305-4088 (United States)

2014-05-15

Here we summarize the advantages of excitons bound to isolated fluorine donor in ZnSe/ZnMgSe quantum well nano-structures. Devices based on these semiconductors, are particularly suited to implement concepts of the optical manipulation of quantum states in solid-state material. The fluorine donor in ZnSe provides a physical qubit with potential advantages over previously researched qubits. In this context we show several initial demonstrations of devices, such as a low-threshold microdisk laser and an indistinguishable single photon source. Additionally we demonstrate the realization of a controllable three-level-system qubit consisting of a single Fluorine donor in a ZnSe nano-pillar, which provides an optical accessible single electon spin qubit.

Clonal dominance and transplantation dynamics in hematopoietic stem cell compartments.

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Peter Ashcroft

2017-10-01

Full Text Available Hematopoietic stem cells in mammals are known to reside mostly in the bone marrow, but also transitively passage in small numbers in the blood. Experimental findings have suggested that they exist in a dynamic equilibrium, continuously migrating between these two compartments. Here we construct an individual-based mathematical model of this process, which is parametrised using existing empirical findings from mice. This approach allows us to quantify the amount of migration between the bone marrow niches and the peripheral blood. We use this model to investigate clonal hematopoiesis, which is a significant risk factor for hematologic cancers. We also analyse the engraftment of donor stem cells into non-conditioned and conditioned hosts, quantifying the impact of different treatment scenarios. The simplicity of the model permits a thorough mathematical analysis, providing deeper insights into the dynamics of both the model and of the real-world system. We predict the time taken for mutant clones to expand within a host, as well as chimerism levels that can be expected following transplantation therapy, and the probability that a preconditioned host is reconstituted by donor cells.

Blood donor incentives: A step forward or backward

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Abolghasemi Hassan

2010-01-01

Full Text Available Dramatic increase in blood usage and critical seasonal blood shortages are faced by various countries. Countries which previously reached 100% voluntary nonremunerated donation have been led to offer different kinds of incentives to recruit blood donors and meet their blood demands. In some cases, these incentives are considered monetary and are in complete contrast with International standards like World Health Organization (WHO. It seems that attitudes toward sole dependency on nonremunerated voluntary blood donation have been changed in recent years and experts in some developed countries are reevaluating partial reliance on paid donation. On the other hand, besides the effects of such incentives on blood safety, several economic and psychological studies have shown that incentives have discouraging effects on pro-social behaviors like blood donation and will reduce the number of blood donors in long term. With regard to the results of such studies, it seems that implementing incentive-based blood donor recruitment programs to meet blood requirements by some countries is becoming a challenge for blood banks.

Early outcomes of liver transplants in patients receiving organs from hypernatremic donors.

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Khosravi, Mohammad Bagher; Firoozifar, Mohammad; Ghaffaripour, Sina; Sahmeddini, Mohammad Ali; Eghbal, Mohammad Hossien

2013-12-01

Uncorrected hypernatremia in organ donors has been associated with poor graft or patient survival during liver transplants. However, recent studies have found no association between the donor serum sodium and transplant outcome. This study sought to show the negative effect donor hypernatremia has on initial liver allograft function. This is the first study to investigate international normalized ratio and renal factors of patients with normal and those with hypernatremic donor livers. This study was conducted at the Shiraz Transplant Research Center in Shiraz, Iran, between May 2009, and July 2011. Four hundred seven consecutive adult orthotopic liver transplants were performed at the University of Shiraz Medical Center. There were 93 donors in the group with hypernatremia with terminal serum sodium of 155 mEq/L or greater (group 1), and 314 with terminal serum sodium less than 155 mEq/L (group 2). Posttransplant data after 5 days showed that aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and kidney function did not differ between the groups. Hypernatremia is the most important complication after brain death. Previous studies have suggested donor hypernatremia results in a greater incidence of early postoperative graft dysfunction in liver transplant and is considered one of the extended criteria donor. However, in recent years, this hypothesis has been questioned. Our study shows no difference between patients' initial results of liver and kidney functioning with normal and hypernatremic donor livers. This is the first study to investigate international normalized ratio as a fundamental factor in defining early allograft dysfunction and renal factors between patients with normal and hypernatremic donor's livers.

Biobanking human embryonic stem cell lines: policy, ethics and efficiency.

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Holm, Søren

2015-12-01

Stem cell banks curating and distributing human embryonic stem cells have been established in a number of countries and by a number of private institutions. This paper identifies and critically discusses a number of arguments that are used to justify the importance of such banks in policy discussions relating to their establishment or maintenance. It is argued (1) that 'ethical arguments' are often more important in the establishment phase and 'efficiency arguments' more important in the maintenance phase, and (2) that arguments relating to the interests of embryo and gamete donors are curiously absent from the particular stem cell banking policy discourse. This to some extent artificially isolates this discourse from the broader discussions about the flows of reproductive materials and tissues in modern society, and such isolation may lead to the interests of important actors being ignored in the policy making process.

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

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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.

A phase I/II minor histocompatibility antigen-loaded dendritic cell vaccination trial to safely improve the efficacy of donor lymphocyte infusions in myeloma

NARCIS (Netherlands)

Franssen, L.E.; Roeven, M.W.; Hobo, W.A.; Doorn, R. van; Oostvogels, R.; Falkenburg, J.H.; Donk, N.W. van de; Kester, M.G.; Fredrix, H.; Westinga, K.; Slaper-Cortenbach, I.; Spierings, E.; Kersten, M.J.; Dolstra, H.; Mutis, T; Schaap, N.P.; Lokhorst, H.M.

2017-01-01

Allogeneic stem cell transplantation (allo-SCT) with or without donor lymphocyte infusions (DLI) is the only curative option for several hematological malignancies. Unfortunately, allo-SCT is often associated with GvHD, and patients often relapse. We therefore aim to improve the graft-versus-tumor

Inter- and Intrapersonal Barriers to Living Donor Kidney Transplant among Black Recipients and Donors.

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Davis, LaShara A; Grogan, Tracy M; Cox, Joy; Weng, Francis L

2017-08-01

End-stage renal disease (ESRD) is more common among Blacks, but Blacks are less likely to receive a live donor kidney transplant (LDKT). The objective of this study is to identify barriers and coping mechanisms that Black LDKT recipients and donors experienced while receiving or donating a kidney. A qualitative study was conducted using structured interviews. Thematic analysis was used for data interpretation. All 20 participants identified as Black, with two participants identifying themselves as multiracial. The mean age for the 14 recipients was 60, and the average age for the 6 living donors was 47. Themes emerging from the data suggest both recipients and donors faced barriers in the LDKT experience. Recipients faced barriers associated with their denial and avoidance of the severity of their ESRD, their desire to maintain the privacy of their health status, and their refusal to approach potential donors. Donors encountered negative responses from others about the donors' desire to donate and the initial refusal of recipients to accept a LDKT offer. Recipients identified faith as a coping mechanism, while donors identified normalization of donation as their method of coping. Various types of social support helped donors and recipients navigate the transplant process. Black LDKT recipients and donors must overcome barriers prior to receiving or donating a kidney. Most of these barriers arise from communication and interactions with others that are either lacking or undesirable. Future interventions to promote LDKT among Blacks may benefit by specifically targeting these barriers.

Inherent Immunogenicity or Lack Thereof of Pluripotent Stem Cells: Implications for Cell Replacement Therapy

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Arvind Chhabra

2017-08-01

Full Text Available Donor-specific induced pluripotent stem cells (iPSCs offer opportunities for personalized cell replacement therapeutic approaches due to their unlimited self-renewal potential and ability to differentiate into different somatic cells. A significant progress has been made toward generating iPSC lines that are free of integrating viral vectors, development of xeno-free culture conditions, and differentiation of pluripotent stem cells (PSCs into functional somatic cell lineages. Since donor-specific iPSC lines are genetically identical to the individual, they are expected to be immunologically matched and these iPSC lines and their cellular derivatives are not expected to be immunologically rejected. However, studies in mouse models, utilizing rejection of teratomas as a model, have claimed that syngenic iPSC lines, especially the iPSC lines derived with integrating viral vectors, could be inherently immunogenic. This manuscript reviews current understanding of inherent immunogenicity of PSC lines, especially that of the human iPSC lines and their cellular derivatives, and strategies to overcome it.

Hematopoietic Stem Cell Transplantation—50 Years of Evolution and Future Perspectives

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Israel Henig

2014-10-01

Full Text Available Hematopoietic stem cell transplantation is a highly specialized and unique medical procedure. Autologous transplantation allows the administration of high-dose chemotherapy without prolonged bone marrow aplasia. In allogeneic transplantation, donor-derived stem cells provide alloimmunity that enables a graft-versus-tumor effect to eradicate residual disease and prevent relapse. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then the field has evolved and expanded worldwide. New indications beside acute leukemia and aplastic anemia have been constantly explored and now include congenital disorders of the hematopoietic system, metabolic disorders, and autoimmune disease. The use of matched unrelated donors, umbilical cord blood units, and partially matched related donors has dramatically extended the availability of allogeneic transplantation. Transplant-related mortality has decreased due to improved supportive care, including better strategies to prevent severe infections and with the incorporation of reduced-intensity conditioning protocols that lowered the toxicity and allowed for transplantation in older patients. However, disease relapse and graft-versus-host disease remain the two major causes of mortality with unsatisfactory progress. Intense research aiming to improve adoptive immunotherapy and increase graft-versus-leukemia response while decreasing graft-versus-host response might bring the next breakthrough in allogeneic transplantation. Strategies of graft manipulation, tumor-associated antigen vaccinations, monoclonal antibodies, and adoptive cellular immunotherapy have already proved clinically efficient. In the following years, allogeneic transplantation is likely to become more complex, more individualized, and more efficient.

Donor-Derived Myeloid Sarcoma in Two Kidney Transplant Recipients from a Single Donor

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Amudha Palanisamy

2015-01-01

Full Text Available We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ. Fluorescence in situ hybridization (FISH and molecular genotyping analyses confirmed that the malignant cells were of donor origin in each patient. Allograft nephrectomy and immediate withdrawal of immunosuppression were performed in both cases; systemic chemotherapy was subsequently administered to one patient. Both recipients were in remission at least one year following the diagnosis of donor-derived myeloid sarcoma. These cases suggest that restoration of the immune system after withdrawal of immunosuppressive therapy and allograft nephrectomy may be sufficient to control HLA-mismatched donor-derived myeloid sarcoma without systemic involvement.

Energy status of pig donor organs after ischemia is independent of donor type.

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Stadlbauer, Vanessa; Stiegler, Philipp; Taeubl, Philipp; Sereinigg, Michael; Puntschart, Andreas; Bradatsch, Andrea; Curcic, Pero; Seifert-Held, Thomas; Zmugg, Gerda; Stojakovic, Tatjana; Leopold, Barbara; Blattl, Daniela; Horki, Vera; Mayrhauser, Ursula; Wiederstein-Grasser, Iris; Leber, Bettina; Jürgens, Günther; Tscheliessnigg, Karlheinz; Hallström, Seth

2013-04-01

Literature is controversial whether organs from living donors have a better graft function than brain dead (BD) and non-heart-beating donor organs. Success of transplantation has been correlated with high-energy phosphate (HEP) contents of the graft. HEP contents in heart, liver, kidney, and pancreas from living, BD, and donation after cardiac death in a pig model (n=6 per donor type) were evaluated systematically. BD was induced under general anesthesia by inflating a balloon in the epidural space. Ten hours after confirmation, organs were retrieved. Cardiac arrest was induced by 9V direct current. After 10min of ventricular fibrillation without cardiac output, mechanical and medical reanimation was performed for 30min before organ retrieval. In living donors, organs were explanted immediately. Freeze-clamped biopsies were taken before perfusion with Celsior solution (heart) or University of Wisconsin solution (abdominal organs) in BD and living donors or with Histidine-Tryptophan-Ketoglutaric solution (all organs) in non-heart-beating donors, after perfusion, and after cold ischemia (4h for heart, 6h for liver and pancreas, and 12h for kidney). HEPs (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, and phosphocreatine), xanthine, and hypoxanthine were measured by high-performance liquid chromatography. Energy charge and adenosine triphosphate-to-adenosine diphosphate ratio were calculated. After ischemia, organs from different donor types showed no difference in energy status. In all organs, a decrease of HEP and an increase in hypoxanthine contents were observed during perfusion and ischemia, irrespective of the donor type. Organs from BD or non-heart-beating donors do not differ from living donor organs in their energy status after average tolerable ischemia. Copyright © 2013 Elsevier Inc. All rights reserved.

Frequency and risk factors for donor reactions in an anonymous blood donor survey.

Science.gov (United States)

Goldman, Mindy; Osmond, Lori; Yi, Qi-Long; Cameron-Choi, Keltie; O'Brien, Sheila F

2013-09-01

Adverse donor reactions can result in injury and decrease the likelihood of donor return. Reaction reports captured in the blood center's database provide an incomplete picture of reaction rates and risk factors. We performed an anonymous survey, mailed to 40,000 donors in 2008, including questions about symptoms, height, weight, sex, and donation status. Reaction rates were compared to those recorded in our database. Possible risk factors were assessed for various reactions. The response rate was 45.5%. A total of 32% of first-time and 14% of repeat donors reported having any adverse symptom, most frequently bruising (84.9 per 1000 donors) or feeling faint or weak (66.2 per 1000). Faint reactions were two to eight times higher than reported in our database, although direct comparison was difficult. Younger age, female sex, and first-time donation status were risk factors for systemic and arm symptoms. In females, low estimated blood volume (EBV) was a risk factor for systemic symptoms. Only 51% of donors who consulted an outside physician also called Canadian Blood Services. A total of 10% of first-time donors with reactions found adverse effects information inadequate. This study allowed us to collect more information about adverse reactions, including minor symptoms and delayed reactions. Based on our findings of the risk factors and frequency of adverse reactions, we are implementing more stringent EBV criteria for younger donors and providing more detailed information to donors about possible adverse effects and their management. © 2012 American Association of Blood Banks.

Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: Similar outcomes with umbilical cord blood and unrelated donor peripheral blood

NARCIS (Netherlands)

C.A. Rodrigues (Celso Arrais); V. Rocha (Vanderson); P. Dreger (Peter); C.G. Brunstein (Claudio); H. Sengeloev (Henrik); J. Finke (Jürgen); M. Mohty (Mohamad); B. Rio (Bernard); E. Petersen (Eefke); F. Guilhot (François); D. Niederwieser (Dietger); J.J. Cornelissen (Jan); P. Jindra (Pavel); A. Nagler (Arnon); N. Fegueux (Nathalie); H. Schoemans (Hélène); A. Ruggeri (Annelisa); S.P. Robinson (Stephen); E. Gluckman (Eliane); C. Canals (Carmen); A. Sureda (Anna)

2014-01-01

textabstractWe have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who

T cells for viral infections after allogeneic hematopoietic stem cell transplant.

Science.gov (United States)

Bollard, Catherine M; Heslop, Helen E

2016-06-30

Despite recent advances in the field of allogeneic hematopoietic stem cell transplantation (HSCT), viral infections are still a major complication during the period of immune suppression that follows the procedure. Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Early proof of principle studies demonstrated that the administration of donor-derived T cells specific for cytomegalovirus or Epstein-Barr virus (EBV) could effectively restore virus-specific immunity and control viral infections. Subsequent studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported response rates of 60% to 70%. Current efforts have focused on broadening the applicability of this approach by: (1) extending the number of viral antigens being targeted, (2) simplifying manufacture, (3) exploring strategies for recipients of virus-naïve donor grafts, and (4) developing and optimizing "off the shelf" approaches. © 2016 by The American Society of Hematology.

Modulation of Host Osseointegration during Bone Regeneration by Controlling Exogenous Stem Cells Differentiation Using a Material Approach.

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Yu, Xiaohua; Wang, Liping; Xia, Zengmin; Chen, Li; Jiang, Xi; Rowe, David; Wei, Mei

2014-02-01

Stem cell-based tissue engineering for large bone defect healing has attracted enormous attention in regenerative medicine. However, sufficient osseointegration of the grafts combined with exogenous stem cells still remains a major challenge. Here we developed a material approach to modulate the integration of the grafts to the host tissue when exogenous bone marrow stromal cells (BMSCs) were used as donor cells. Distinctive osseointegration of bone grafts was observed as we varied the content of hydroxyapatite (HA) in the tissue scaffolds implanted in a mouse femur model. More than 80% of new bone was formed in the first two weeks of implantation in high HA content scaffold but lack of host integration while only less than 5% of the new bone was formed during this time period in the no HA group but with much stronger host integration. Cell origin analysis leveraging GFP reporter indicates new bone in HA containing groups was mainly derived from donor BMSCs. In comparison, both host and donor cells were found on new bone surface in the no HA groups which led to seamless bridging between host tissue and the scaffold. Most importantly, host integration during bone formation is closely dictated to the content of HA present in the scaffolds. Taken together, we demonstrate a material approach to modulate the osseointegration of bone grafts in the context of exogenous stem cell-based bone healing strategy which might lead to fully functional bone tissue regeneration.

Autologous Bone Marrow Stem Cell Infusion (AMBI therapy for Chronic Liver Diseases

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Rajkumar JS

2007-01-01

Full Text Available Liver Cirrhosis is the end stage of chronic liver disease which may happen due to alcoholism, viral infections due to Hepatitis B, Hepatitis C viruses and is difficult to treat. Liver transplantation is the only available definitive treatment which is marred by lack of donors, post operative complications such as rejection and high cost. Autologous bone marrow stem cells have shown a lot of promise in earlier reported animal studies and clinical trials. We have in this study administered in 22 patients with chronic liver disease, autologous bone marrow stem cell whose results are presented herewith.

Specificities of transplantation of kidneys procured from donors with situs inversus totalis: A case report and review of the literature

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Petrović Milica

2015-01-01

Full Text Available Introduction. Situs inversus totalis (SIT represents a total vertical transposition of the thoracic and abdominal organs which are arranged in a mirror image reversal of the normal positioning 1. We presented a successful pre-dialysis kidney transplantation from a living sibling donor with SIT and the longest donor follow-up period, along with analysis of the reviewed literature. Case report. The pair for pre-dialysis kidney transplantation included a 68-year-old mother and 34-year-old daughter at low immunological risk. Comorbidities evidenced in kidney donors with previously diagnosed SIT, included moderate arterial hypertension and borderline blood glucose level. Explantation of the left donor kidney and its placement into the right iliac fossa of the recipient were performed in the course of the surgical procedure. A month after nephrectomy, second degree renal failure was noticed in the donor. A 20-month follow-up of the donor’s kidney and graft in the recipient proved that their functions were excellent. Conclusion. In donors with previously diagnosed SIT the multidisciplinary approach, preoperative evaluation of the patient and detection of possible vascular anomalies are required to provide maximum safety for the donor.

Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation.

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Leventhal, Joseph; Abecassis, Michael; Miller, Joshua; Gallon, Lorenzo; Ravindra, Kadiyala; Tollerud, David J; King, Bradley; Elliott, Mary Jane; Herzig, Geoffrey; Herzig, Roger; Ildstad, Suzanne T

2012-03-07

The toxicity of chronic immunosuppressive agents required for organ transplant maintenance has prompted investigators to pursue approaches to induce immune tolerance. We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSCs) and tolerogenic graft facilitating cells (FCs) combined with nonmyeloablative conditioning; this approach resulted in engraftment, durable chimerism, and tolerance induction in recipients with highly mismatched related and unrelated donors. Eight recipients of human leukocyte antigen (HLA)-mismatched kidney and FC/HSC transplants underwent conditioning with fludarabine, 200-centigray total body irradiation, and cyclophosphamide followed by posttransplant immunosuppression with tacrolimus and mycophenolate mofetil. Subjects ranged in age from 29 to 56 years. HLA match ranged from five of six loci with related donors to one of six loci with unrelated donors. The absolute neutrophil counts reached a nadir about 1 week after transplant, with recovery by 2 weeks. Multilineage chimerism at 1 month ranged from 6 to 100%. The conditioning was well tolerated, with outpatient management after postoperative day 2. Two subjects exhibited transient chimerism and were maintained on low-dose tacrolimus monotherapy. One subject developed viral sepsis 2 months after transplant and experienced renal artery thrombosis. Five subjects experienced durable chimerism, demonstrated immunocompetence and donor-specific tolerance by in vitro proliferative assays, and were successfully weaned off all immunosuppression 1 year after transplant. None of the recipients produced anti-donor antibody or exhibited engraftment syndrome or graft-versus-host disease. These results suggest that manipulation of a mobilized stem cell graft and nonmyeloablative conditioning represents a safe, practical, and reproducible means of inducing durable chimerism and donor-specific tolerance in solid organ transplant recipients.

Adipose Tissue-Derived Mesenchymal Stem Cells as a New Host Cell in Latent Leishmaniasis

Science.gov (United States)

Allahverdiyev, Adil M.; Bagirova, Melahat; Elcicek, Serhat; Koc, Rabia Cakir; Baydar, Serap Yesilkir; Findikli, Necati; Oztel, Olga N.

2011-01-01

Some protozoan infections such as Toxoplasma, Cryptosporidium, and Plasmodium can be transmitted through stem cell transplantations. To our knowledge, so far, there is no study about transmission of Leishmania parasites in stem cell transplantation and interactions between parasites and stem cells in vitro. Therefore, the aim of this study was to investigate the interaction between different species of Leishmania parasites and adipose tissue-derived mesenchymal stem cells (ADMSCs). ADMSCs have been isolated, cultured, characterized, and infected with different species of Leishmania parasites (L. donovani, L. major, L. tropica, and L. infantum). Infectivity was examined by Giemsa staining, microculture, and polymerase chain reaction methods. As a result, infectivity of ADMSCs by Leishmania parasites has been determined for the first time in this study. According to our findings, it is very important that donors are screened for Leishmania parasites before stem cell transplantations in regions where leishmaniasis is endemic. PMID:21896818

Donor genotype in the Interleukin-7 receptor α-chain predicts risk of graft-versus-host disease and cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation

DEFF Research Database (Denmark)

Kielsen, Katrine; Enevold, Christian; Heilmann, Carsten

2018-01-01

The efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by acute and chronic graft-versus-host disease (aGVHD and cGVHD) and viral infections due to long-lasting immunodeficiency. Interleukin-7 (IL-7) is a cytokine essential for de novo T cell generation in thymus.......1-3.8, P = 0.034) and with significantly increased risk of extensive cGVHD (HR = 2.0, 95% CI = 1.1-3.6, P = 0.025) after adjustment for potential risk factors. In addition, the TT genotype was associated with a higher risk of cytomegalovirus (CMV) infection post-transplant (HR = 2.4, 95% CI = 1.2-4.3, P.......7, 95% CI = 1.2-2.3, P = 0.0027) and increased treatment-related mortality (HR = 2.3, 95% CI = 1.3-4.0, P = 0.0047), but was not associated with the risk of relapse (P = 0.35). In conclusion, the IL-7Rα rs6897932 genotype of the donor is predictive of aGVHD and cGVHD, CMV infection, and mortality...

Impression management during evaluation and psychological reactions post-donation of living kidney donors.

Science.gov (United States)

Hildebrand, Lee; Melchert, Timothy P; Anderson, Rebecca C

2014-08-01

Many healthcare providers have been concerned about the extent to which potential kidney donors use impression management or concealment of important information regarding their medical history, current functioning, or other circumstances that could affect whether they are accepted as donors. To date, however, there has been very little empirical examination of these questions. It is also not known whether donors' use of impression management pre-donation is related to their reactions and adjustment post-donation. This study surveyed 76 individuals who had donated a kidney one to six yr previously regarding their use of impression management and their concealing of information during their psychological evaluations. They were also asked about their reactions to the donation and whether they would make the same decision again. In addition, 21 of these donors participated in focus groups that explored these questions in depth. Many of the kidney donors reported that they possessed very strong motivation to donate and consequently used impression management in their interactions with medical professionals pre-donation. Very few donors, however, indicated that they concealed information during their pre-donation evaluations. The donors' psychological reactions post-donation were generally positive, and nearly all indicated that they would make the same decision again. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Indian egg donors' characteristics, motivations and feelings towards the recipient and resultant child.

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Jadva, V; Lamba, N; Kadam, K; Golombok, S

2015-12-01

This is the first study to examine characteristics, motivations and experiences of Indian egg donors. In-depth interviews were conducted with 25 egg donors who had donated during the previous 8 months at a fertility clinic in Mumbai. The semi-structured interviews were conducted in Hindi and English. In addition to demographic information, data were collected on donors' motivations for donating, with whom they had discussed donation, and feelings towards the recipients. The response rate was 66%. All participants were literate and had attended school. Twenty (80%) egg donors had children and five (20%) did not. The most common motivation (19, 76%) for donating was financial need. Egg donors had discussed their donation with their husband or with close family/friends, with almost all mentioning that wider society would disapprove. The majority (20, 80%) had no information about the recipients and 11 (44%) preferred not to. The findings highlight the similarities and differences between egg donors from India and those from other countries and that egg donors are of a more varied demographic background than surrogates in India. Given that India has been a popular destination for fertility treatment, the findings have important implications for regulation and practice within India and internationally.

Is there a place for human fetal-derived stem cells for cell replacement therapy in Huntington's disease?

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Precious, Sophie V; Zietlow, Rike; Dunnett, Stephen B; Kelly, Claire M; Rosser, Anne E

2017-06-01

Huntington's disease (HD) is a neurodegenerative disease that offers an excellent paradigm for cell replacement therapy because of the associated relatively focal cell loss in the striatum. The predominant cells lost in this condition are striatal medium spiny neurons (MSNs). Transplantation of developing MSNs taken from the fetal brain has provided proof of concept that donor MSNs can survive, integrate and bring about a degree of functional recovery in both pre-clinical studies and in a limited number of clinical trials. The scarcity of human fetal tissue, and the logistics of coordinating collection and dissection of tissue with neurosurgical procedures makes the use of fetal tissue for this purpose both complex and limiting. Alternative donor cell sources which are expandable in culture prior to transplantation are currently being sought. Two potential donor cell sources which have received most attention recently are embryonic stem (ES) cells and adult induced pluripotent stem (iPS) cells, both of which can be directed to MSN-like fates, although achieving a genuine MSN fate has proven to be difficult. All potential donor sources have challenges in terms of their clinical application for regenerative medicine, and thus it is important to continue exploring a wide variety of expandable cells. In this review we discuss two less well-reported potential donor cell sources; embryonic germ (EG) cells and fetal neural precursors (FNPs), both are which are fetal-derived and have some properties that could make them useful for regenerative medicine applications. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Promoting Organ Donor Registries Through Public Education: What Is the Cost of Securing Organ Donors?

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Razdan, Manik; Smith, Kenneth J; Bryce, Cindy L; Degenholtz, Howard B

2016-06-01

Transplant medicine's impact on America's public health is seriously limited by acute shortage of transplantable organs. Consequently, the United Sates has witnessed considerable investment in the promotion of organ donor registries. Although there is no evidence to support that donor registry promotion alleviates organ shortage, this belief continues to drive investments into registry promotion. In this study, return on investment in donor registry promotion was examined using cost-outcomes analysis. Cost of promoting the donor registry was estimated in US dollars whereas the outcome was measured as the number of individuals who join the registry (registrants) and their value in terms of organ donors. The study was conducted from the perspective of a regional Organ Procurement Organization (OPO). Costs were directly obtained from the OPO. The number of new registrants was obtained from the OPO and the departments of motor vehicles that maintain the donor registry. The value of registrants in terms of organ donors was computed based on a registrant's age-dependent risk of dying and age-dependent probability of becoming an organ donor. Six thousand seven hundred eight individuals joined the organ donor registry (95% confidence interval [95% CI], 5429-7956) at a cost of $455 per registrant (95% CI, US $383-US $562). These individuals result in 4.2 present-day donors (95% CI, 2.5-6.6) at a cost of US $726 000 (95% CI, US $462000-US $1.2 million). Because the cost per registrant and cost per donor is less than society's willingness to pay, donor registry promotion offers positive return on investment. Investment in registry promotion should at the minimum be maintained at current levels.

Normal function of immunologic stem cells from aged mice

International Nuclear Information System (INIS)

Harrison, D.E.; Doubleday, J.W.

1975-01-01

Marrow or spleen grafts from aged donor mice produced antibody-forming cells as effectively as did grafts from younger controls in recipients tested 3 to 10 months after the transplantation. All recipients were lethally irradiated, and the T6 chromosome marker was used to demonstrate that they were populated by donor cell lines. Recipients of aged or younger control grafts gave similar responses when stimulated with varying doses of antigen and when tested at different times after the transplantation except in two cases. Recipients of aged spleen grafts gave significantly lower responses than younger controls for the first few weeks after the transplantation. If recipients had been thymectomized before lethal irradiation, aged cell lines (pooled marrow and spleen cells) gave only 37 percent of the responses of younger controls. Given sufficient time and intact young recipients, immunologic stem cell lines from old donors populated recipients with cells having normal immune responses. These results suggest that age-related immunologic defects are not intrinsically timed in the precursor cell lines that populate the immune system. (U.S.)

Pre-Transplantation Blockade of TNF-α-Mediated Oxygen Species Accumulation Protects Hematopoietic Stem Cells.

Science.gov (United States)

Ishida, Takashi; Suzuki, Sachie; Lai, Chen-Yi; Yamazaki, Satoshi; Kakuta, Shigeru; Iwakura, Yoichiro; Nojima, Masanori; Takeuchi, Yasuo; Higashihara, Masaaki; Nakauchi, Hiromitsu; Otsu, Makoto

2017-04-01

Hematopoietic stem cell (HSC) transplantation (HSCT) for malignancy requires toxic pre-conditioning to maximize anti-tumor effects and donor-HSC engraftment. While this induces bone marrow (BM)-localized inflammation, how this BM environmental change affects transplanted HSCs in vivo remains largely unknown. We here report that, depending on interval between irradiation and HSCT, residence within lethally irradiated recipient BM compromises donor-HSC reconstitution ability. Both in vivo and in vitro we demonstrate that, among inflammatory cytokines, TNF-α plays a role in HSC damage: TNF-α stimulation leads to accumulation of reactive oxygen species (ROS) in highly purified hematopoietic stem/progenitor cells (HSCs/HSPCs). Transplantation of flow-cytometry-sorted murine HSCs reveals damaging effects of accumulated ROS on HSCs. Short-term incubation either with an specific inhibitor of tumor necrosis factor receptor 1 signaling or an antioxidant N-acetyl-L-cysteine (NAC) prevents TNF-α-mediated ROS accumulation in HSCs. Importantly, pre-transplantation exposure to NAC successfully demonstrats protective effects in inflammatory BM on graft-HSCs, exhibiting better reconstitution capability than that of nonprotected control grafts. We thus suggest that in vivo protection of graft-HSCs from BM inflammation is a feasible and attractive approach, which may lead to improved hematopoietic reconstitution kinetics in transplantation with myeloablative conditioning that inevitably causes inflammation in recipient BM. Stem Cells 2017;35:989-1002. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Declining prevalence of hepatitis E antibodies among Danish blood donors

DEFF Research Database (Denmark)

Holm, Dorte K; Moessner, Belinda K; Engle, Ronald E

2015-01-01

BACKGROUND: The increasing incidence of reported hepatitis E cases in Europe has focused attention on hepatitis E virus (HEV) and the risk of transfusion-transmitted hepatitis E. The aim of this study was to investigate the prevalence of antibodies to HEV (anti-HEV) among Danish blood donors...... in 2013 and to compare it to previous studies in Denmark. In addition we wanted to compare the relative reactivity of two different assays. STUDY DESIGN AND METHODS: Samples from 504 blood donors were collected and analyzed for anti-HEV with an in-house assay developed at the National Institutes of Health...... (NIH). In addition the samples were analyzed with the Wantai anti-HEV assay. Demographic information and possible HEV exposure was collected by self-administered questionnaire. RESULTS: Using the NIH assay the prevalence of anti-HEV among Danish blood donors was 10.7% and with the Wantai assay...

Donor selection criteria and procurement

International Nuclear Information System (INIS)

Agcaoili, N.R.

1999-01-01

Donor selection is one of the most important aspects of tissue banking practice. Without a good donor selection criteria, the results of any effort of trying to preserve tissues will have disastrous outcome for the recipient of these tissues. While with a very good and strict donor selection the Tissue Bank can guarantee safe and effective tissue allografts. There are significant aspects in the history and physical examination of the donor that must be emphasized. A donor exclusion criteria has also been formulated together with a list of all the needed laboratory examinations to eliminate possible diseases that may be transferred from the donor. The methods of procurement of tissue allografts from living and cadaver donors will be described. The limitations and advantages of each will be taken.There are also special restrictions that are important in the practice of removing the tissues from the donors. All the necessary equipment should be ready and the potential risk on the personnel should be known to all doing Tissue Banking

[Survey of blood donors on the topic of "reimbursement for blood donors"].

Science.gov (United States)

Zeiler, T; Kretschmer, V

1995-02-01

Remuneration for blood donors, in the way as presently handled by governmental and communal blood transfusion services in Germany, is not generally accepted. It is feared that donors are recruited with increased risk to transmit infectious diseases, especially AIDS. Alternative incentives are discussed. After the so-called AIDS scandal in Germany, a change in the donor motivation was to be expected, associated with an increased willingness to renounce remuneration. Therefore, we performed the present survey, in which we evaluated the donor's willingness to renounce remuneration, possibilities of cashless remuneration and other alternative incentives. During March and April 1994, a total of 1,157 blood donors of the University Blood Bank Marburg were questioned anonymously by a questionnaire in the framework of whole-blood donations. Beside the above-mentioned aspects demoscopic data were included (age, sex, profession, journey). Cutting of remuneration without any other compensation was refused by 86.1% of the donors, 77% would not want to further donate blood in this case. Transfer of money to a bank account instead of cash payment was accepted by 78.6%, the use of non-negotiable cheques by 68.7%. Alternative compensation by tickets for theater, concert, cinema or coupons for restaurants met with the approval of only 27.3%; under these circumstances, 36.9% would be willing to continue blood donation. With increasing age and number of donations, but largely independent of social status, donors attached greater importance to retention of remuneration. Cutting of remuneration would result in a considerable reduction of the willingness to donate blood within the population of donors of the governmental and communal blood transfusion services. However, an increase of virus safety of the blood products would not be reached in this way, since especially the long-term donors would be driven away. Considerable bottlenecks, particularly in the specific blood supply of

Decisions to register for the National Marrow Donor Program: rational vs emotional appeals.

Science.gov (United States)

Studts, J L; Ruberg, J L; McGuffin, S A; Roetzer, L M

2010-03-01

Little research has examined how the content of health communications regarding the need for BM and stem cell donation affects the intentions and attitudes of potential National Marrow Donor Program (NMDP) donors. This study used an experimental design to test the hypothesis that an emotional appeal (EA) to potential donors would lead to higher rates of NMDP registration than a rational appeal (RA). Participants were randomly assigned to receive either a RA or an EA and then asked if they would (1) register with the NMDP and (2) talk with family members about NMDP registration. A total of 85% of individuals receiving the EA agreed to register for the NMDP, whereas only 49% of the participants receiving the RA agreed to register. The EA (72%) and RA (54%) groups did not differ significantly in their reported willingness to talk with family members about NMDP registration. However, multivariate logistic regression analyses indicated that the EA group endorsed significantly greater willingness to engage in both outcomes. Results suggest that an EA was more effective in motivating participants, but other sociodemographic factors were also associated with decisions about NMDP registration. EA may provide a useful and cost-effective method for increasing NMDP registration.

The impact of meeting donor management goals on the number of organs transplanted per donor: results from the United Network for Organ Sharing Region 5 prospective donor management goals study.

Science.gov (United States)

Malinoski, Darren J; Patel, Madhukar S; Daly, Michael C; Oley-Graybill, Chrystal; Salim, Ali

2012-10-01

Many organ procurement organizations have implemented critical care end points as donor management goals in efforts to increase organs transplanted per donor after neurologic determination of death. Although retrospective studies have demonstrated an association between meeting donor management goals and organ yield, prospective studies are lacking. In June 2008, nine donor management goals were prospectively implemented as a checklist and every donor after neurologic determination of death was managed to meet them. The donor management goals represented normal cardiovascular, pulmonary, renal, and endocrine end points. Data were collected for 7 months. Donor management goals "met" was defined a priori as achieving any seven of the nine donor management goals, and this was recorded at the time of consent, 12-18 hrs later, and prior to organ recovery. The primary outcome measure was ≥4 organs transplanted per donor, and binary logistic regression was used to identify independent predictors of this outcome with a porgan procurement organizations in the five Southwestern United States (United Network for Organ Sharing Region 5). All standard criteria donors after neurologic determination of deaths. Prospective implementation of a donor management goal checklist. There were 380 standard criteria donors with 3.6±1.7 organs transplanted per donor. Fifteen percent had donor management goals met at the time of consent, 33% at 12-18 hrs, and 38% prior to organ recovery. Forty-eight percent had ≥4 organs transplanted per donor. Donors with ≥4 organs transplanted per donor had significantly more individual donor management goals met at all three time points. Independent predictors of ≥4 organs transplanted per donor were age (odds ratio=0.95 per year), final creatinine (odds ratio=0.75 per 1-unit increase), donor management goals "met" at consent (odds ratio=2.03), donor management goals "met" prior to organ recovery (odds ratio=2.34), and a change in the number of

Development of Organ-Specific Donor Risk Indices

Science.gov (United States)

Akkina, Sanjeev K.; Asrani, Sumeet K.; Peng, Yi; Stock, Peter; Kim, Ray; Israni, Ajay K.

2012-01-01

Due to the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival using various combinations of donor and recipient characteristics. We will review the kidney donor risk index (KDRI) and liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The Kidney Donor Risk Index has a potential role in developing new kidney allocation algorithms. The Liver Donor Risk Index allows for greater appreciation of the importance of donor factors, particularly for hepatitis C-positive recipients; as the donor risk index increases, rates of allograft and patient survival among these recipients decrease disproportionately. Use of livers with high donor risk index is associated with increased hospital costs independent of recipient risk factors, and transplanting livers with high donor risk index into patients with Model for End-Stage Liver Disease scores Donor Risk Index has limited this practice. Significant regional variation in donor quality, as measured by the Liver Donor Risk Index, remains in the United States. We also review other potential indices for liver transplant, including donor-recipient matching and the retransplant donor risk index. While substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival. PMID:22287036

Amniotic fluid as a source of engraftable stem cells

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Cesar V Borlongan

2017-01-01

Full Text Available The ability of stem cells to differentiate into various lineages has made them powerful tools of regenerative medicine and applicable to multiple human diseases. Of particular interest, amniotic fluid-derived stem cells (AFSC have been characterized to express both adult and embryonic cell markers, indicating them as cells within an intermediate stage between embryonic and adult phenotype. AFSC can differentiate into cells of all three germ layers, including hepatic, myogenic, osteogenic, and neurogenic cell types. Furthermore, AFSC have minimal replicative senescence, retaining the ability to divide effectively for over 250 doublings. These facts indicate that amniotic fluid may exist as a promising donor source of stem cells for the treatment of multiple clinically relevant conditions. Of particular interest is the convenience of harvesting stem cells from the amniotic fluid stem for the treatment of newborns, as well as for banking or cryopreserving purposes to be used at a later date. Importantly, the promise of amniotic fluid as a source of stem cells merits ongoing research into their potential therapeutic applications. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

Enhancement by dimethyl myleran of donor type chimerism in murine recipients of bone marrow allografts

International Nuclear Information System (INIS)

Lapidot, T.; Terenzi, A.; Singer, T.S.; Salomon, O.; Reisner, Y.

1989-01-01

A major problem in using murine models for studies of bone marrow allograft rejection in leukemia patients is the narrow margin in which graft rejection can be analyzed. In mice irradiated with greater than 9 Gy total body irradiation (TBI) rejection is minimal, whereas after administration of 8 Gy TBI, which spares a significant number of clonable T cells, a substantial frequency of host stem cells can also be detected. In current murine models, unlike in humans, bone marrow allograft rejection is generally associated with full autologous hematopoietic reconstitution. In the present study, we investigated the effect of the myeloablative drug dimethyl myleran (DMM) on chimerism status following transplantation of T cell-depleted allogenic bone marrow (using C57BL/6 donors and C3H/HeJ recipients, conditioned with 8 Gy TBI). Donor type chimerism 1 to 2 months post-transplant of 1 to 3 x 10(6) bone marrow cells was markedly enhanced by using DMM one day after TBI and prior to transplantation. Conditioning with cyclophosphamide instead of DMM, in combination with 8 Gy TBI, did not enhance engraftment of donor type cells. Artificial reconstitution of T cells, after conditioning with TBI plus DMM, by adding mature thymocytes, or presensitization with irradiated donor type spleen cells 1 week before TBI and DMM, led to strong graft rejection and consequently to severe anemia. The anti-donor responses in these models were proportional to the number of added T cells and to the number of cells used for presensitization, and they could be neutralized by increasing the bone marrow inoculum

Novel agents and approaches for stem cell mobilization in normal donors and patients.

Science.gov (United States)

Bakanay, Ş M; Demirer, T

2012-09-01

In spite of the safety and efficiency of the classical mobilization protocols, recombinant human G-CSF±chemotherapy, there is still a considerable amount of mobilization failures (10-30%), which warrant novel agents and approaches both in an autologous and an allogeneic transplant setting. Attempts to improve CD34+ yields by using several cytokines and growth factors as adjuncts to G-CSF could not change the standard approaches during the last decade, either because of inefficiency or the adverse events encountered with these agents. As a long-acting G-CSF analog, pegfilgrastim has the advantages of an earlier start of apheresis, reduction in the number of apheresis procedures as well as a reduced number of injections as compared with unconjugated G-CSF. However, dosing and cost-effectiveness especially in cytokine-only mobilizations require further investigation. As interactions between hematopoietic stem cells and the BM microenvironment are better understood, new molecules targeting these interactions are emerging. Plerixafor, which started its journey as an anti-HIV drug, recently ended up being a popular stem cell mobilizer with the ability of rapid mobilization and gained approval as an adjunct to G-CSF for poor mobilizers. At present, it is challenging to search for the best approach by using the available drugs with appropriate timing to provide sufficient CD34+ yield after an initial mobilization attempt, and in a cost-effective manner thereby avoiding further mobilization attempts and exposure to chemotherapy. Approaches not only for increasing stem cell yield, but also aiming to improve the quality of graft content and the associated transplantation outcomes are promising areas of research.

Facilitation of syngeneic stem cell engraftment by anti-class I monoclonal antibody pretreatment of unirradiated recipients

International Nuclear Information System (INIS)

Voralia, M.; Semeluk, A.; Wegmann, T.G.

1987-01-01

We have established a murine model of syngeneic bone marrow transplantation based on the use of monoclonal antibody as the sole conditioning regimen in unirradiated recipients. Administration of a single injection of monoclonal antibody directed against major histocompatibility complex-encoded class I determinants facilitated permanent hemopoietic stem cell engraftment without any apparent side-effects. Whereas untreated hosts exhibited a maximal chimerism of 15% at donor cell doses of up to 12 X 10(7) bone marrow cells, pretreatment by 2 mg of anti-class I antibody one week prior to transplantation of 3 X 10(7) syngeneic bone marrow cells resulted in a mean donor representation of about 80%. The antibody can be given up to four weeks prior to transplantation, and the degree of donor engraftment observed is a function of the dose of antibody administered. The fact that specific antibody enhanced engraftment in two strain combinations indicates that antibody is the active agent in facilitating engraftment and that facilitation is not strain-restricted. Anti-class I antibodies of the IgG2a, but not IgG1, isotype are effective in promoting engraftment. Although the isotype requirement suggests a role for antibody-mediated cytotoxicity in promoting stem cell engraftment, the extensive time-frame of facilitation suggests that other effects of the antibody may also be involved. The model of syngeneic bone marrow transplantation we describe here will be useful in studying the mechanisms regulating stem cell engraftment and may have potential clinical application as an approach to autologous marrow transplantation

Derivation of Insulin Producing Cells From Human Endometrial Stromal Stem Cells and Use in the Treatment of Murine Diabetes

OpenAIRE

Santamaria, Xavier; Massasa, Efi E; Feng, Yuzhe; Wolff, Erin; Taylor, Hugh S

2011-01-01

Pancreatic islet cell transplantation is an effective approach to treat type 1 diabetes, however the shortage of cadaveric donors and limitations due to rejection require alternative solutions. Multipotent cells derived from the uterine endometrium have the ability to differentiate into mesodermal and ectodermal cellular lineages, suggesting the existence of mesenchymal stem cells in this tissue. We differentiated human endometrial stromal stem cells (ESSC) into insulin secreting cells using ...

Hematopoietic stem cell transplantation for chronic lymphocytic leukemia.

Science.gov (United States)

Gladstone, Douglas E; Fuchs, Ephraim

2012-03-01

Although hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many aggressive hematologic malignancies, the role of HSCT in chronic lymphocytic leukemia (CLL) has remained controversial. Now in the era of improved conventional treatment and better prognostication of long-term outcome, a review of autologous and allogeneic HSCT in CLL treatment is warranted. Despite an improved disease-free survival in some patients, multiple, prospective, randomized autologous HSCT CLL trials fail to demonstrate an overall survival benefit as compared to conventional therapy. Allogeneic bone marrow transplantation, although limited by donor availability, can successfully eradicate CLL with adverse prognostic features. In the older CLL patients, nonmyeloablative allogeneic transplants are better tolerated than myeloablative transplants. Nonmyeloablative allogeneic transplants are less effective in heavily diseased burdened patients. Outside of a clinical protocol, autologous HSCT for CLL cannot be justified. Nonmyeloablative allogeneic transplantation should be considered in high-risk populations early in the disease process, when disease burden is most easily controlled. Alternative donor selection using haploidentical donors and posttransplantation cyclophosphamide has the potential to vastly increase the availability of curative therapy in CLL while retaining a low treatment-related toxicity.

Probability of Finding Marrow Unrelated Donor (MUD) for an Indian patient in a Multi-national Human Leukocyte Antigen (HLA) Registry.

Science.gov (United States)

Tiwari, Aseem K; Bhati-Kushwaha, Himakshi; Kukreja, Pooja; Mishra, Vikash C; Tyagi, Neetu; Sharma, Ashish; Raina, Vimarsh

2015-06-01

With an increase in the number of transplants happening globally, hematopoietic stem cells (HSC) transplantation from matched unrelated donor (MUD) has begun. The increasing trend of MUD transplants across countries has been largely facilitated with the conspicuous growth of volunteer HSC donor noted in the last decade i.e. 8 million HSC donors in 2002 to more than 22 million in 2013 registered in 71 member registries of the Bone Marrow Donor Worldwide (BMDW). Some populations of the world are still very poorly represented in these registries. Since, the chances of successful engraftment and disease free survival are directly proportional to the HLA compatibility between the recipient and the prospective donor, the diversity of the HLA system at the antigenic and allelic level and the heterogeneity of HLA data of the registered donors has a bearing on the probability of finding a volunteer unrelated HSC donor for patients from such populations. In the present study 126 patients were identified suffering from hematological diseases requiring MUD transplant. Their HLA typing was performed and search was done using BMDW database. The search results for these Indian patients in the multinational registry as well as in the Indian Registries were analyzed using mean, range, standard deviation and finally evaluated in terms of probability for finding matched donor (MUD). Total Asian population is only 11 % in the BMDW making it difficult to find a MUD for an Asian patient. The current study supports this, experimentally; revealing that the probability of finding an allele match for an Indian patient in the multinational Human Leukocyte Antigen (HLA) registries is 16 % and a dismal 0.008 % in the Indian registries (donors in Indian registries is just 33,678 as compared to 22.5 million in BMDW). This greatly, emphasizes on enhancing the number of Indian donors in Indian and multi-national registries.

Allogenic banking of dental pulp stem cells for innovative therapeutics.

Science.gov (United States)

Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

2015-08-26

Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

Concise review: stem cell-based approaches to red blood cell production for transfusion.

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Shah, Siddharth; Huang, Xiaosong; Cheng, Linzhao

2014-03-01

Blood transfusion is a common procedure in modern medicine, and it is practiced throughout the world; however, many countries report a less than sufficient blood supply. Even in developed countries where the supply is currently adequate, projected demographics predict an insufficient supply as early as 2050. The blood supply is also strained during occasional widespread disasters and crises. Transfusion of blood components such as red blood cells (RBCs), platelets, or neutrophils is increasingly used from the same blood unit for multiple purposes and to reduce alloimmune responses. Even for RBCs and platelets lacking nuclei and many antigenic cell-surface molecules, alloimmunity could occur, especially in patients with chronic transfusion requirements. Once alloimmunization occurs, such patients require RBCs from donors with a different blood group antigen combination, making it a challenge to find donors after every successive episode of alloimmunization. Alternative blood substitutes such as synthetic oxygen carriers have so far proven unsuccessful. In this review, we focus on current research and technologies that permit RBC production ex vivo from hematopoietic stem cells, pluripotent stem cells, and immortalized erythroid precursors.

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

Directory of Open Access Journals (Sweden)

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

Compliance with donor age recommendations in oocyte donor recruitment advertisements in the USA.

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Alberta, Hillary B; Berry, Roberta M; Levine, Aaron D

2013-04-01

IVF using donated oocytes offers benefits to many infertile patients, yet the technique also raises a number of ethical concerns, including worries about potential physical and psychological risks to oocyte donors. In the USA, oversight of oocyte donation consists of a combination of federal and state regulations and self-regulatory guidelines promulgated by the American Society for Reproductive Medicine. This study assesses compliance with one of these self-regulatory guidelines - specifically, ASRM's preferred minimum age for donors of 21. To assess compliance, 539 oocyte donor recruitment advertisements from two recruitment channels (Craigslist and college newspapers) were collected and evaluated. Of these, 61% in the Craigslist dataset and 43% in the college newspaper dataset listed minimum ages between 18 and 20, which is inconsistent with ASRM's preferred minimum age recommendation of 21. Advertisements placed by oocyte donor recruitment agencies were more likely than advertisements placed by clinics to specify minimum ages between 18 and 20. These results indicate that ASRM should evaluate and consider revising its donor age guidelines. IVF using donated human eggs can help many patients who have difficulty having children. However, the technique also raises ethical concerns, including concerns about potential physical and psychological harms to egg donors. In the USA, oversight of egg donation relies on a combination of federal and state regulation and professional self-regulation. Governmental regulations address only limited aspects of egg donation, such as the potential spread of infectious diseases and the reporting of success rates, leaving voluntary guidelines developed by an association of medical professionals to address most issues, including ethical concerns raised by the practice. One of these voluntary guidelines recommends that egg donors should be at least 21 years of age. In this article, we analysed 539 egg donor recruitment advertisements

First Danish experience with ex vivo lung perfusion of donor lungs before transplantation

DEFF Research Database (Denmark)

Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold

2014-01-01

INTRODUCTION: The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its...... otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. RESULTS: In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died......% improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. CONCLUSION: In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted...

Development of Organ-Specific Donor Risk Indices

OpenAIRE

Akkina, Sanjeev K.; Asrani, Sumeet K.; Peng, Yi; Stock, Peter; Kim, Ray; Israni, Ajay K.

2012-01-01

Due to the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival using various combinations of donor and recipient characteristics. We will review the kidney donor risk index (KDRI) and liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The Kidney Donor Risk Index has a potential role in devel...

Suicidal hanging donors for lung transplantation

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Ananiadou, Olga; Schmack, Bastian; Zych, Bartlomiej; Sabashnikov, Anton; Garcia-Saez, Diana; Mohite, Prashant; Weymann, Alexander; Mansur, Ashham; Zeriouh, Mohamed; Marczin, Nandor; De Robertis, Fabio; Simon, Andre Rüdiger; Popov, Aron-Frederik

2018-01-01

Abstract In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group. Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed. No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation. PMID:29620623

Laparoscopic versus open nephrectomy for live kidney donors.

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Wilson, Colin H; Sanni, Aliu; Rix, David A; Soomro, Naeem A

2011-11-09

Waiting lists for kidney transplantation continue to grow and live organ donation has become more important as the number of brain stem dead cadaveric organ donors continues to fall. The major disincentive to potential kidney donors is the pain and morbidity associated with open surgery. To identify the benefits and harms of using laparoscopic compared to open nephrectomy techniques to recover kidneys from live organ donors. We searched the online databases CENTRAL (in The Cochrane Library 2010, Issue 2), MEDLINE (January 1966 to January 2010) and EMBASE (January 1980 to January 2010) and handsearched textbooks and reference lists. Randomised controlled trials comparing laparoscopic donor nephrectomy (LDN) with open donor nephrectomy (ODN). Two review authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We contacted study authors for additional information where necessary. Six studies were identified that randomised 596 live kidney donors to either LDN or ODN arms. All studies were assessed as having low or unclear risk of bias for selection bias, allocation bias, incomplete outcome data and selective reporting bias. Four of six studies had high risk of bias for blinding. Various different combinations of techniques were used in each study, resulting in heterogeneity in the results. The conversion rate from LDN to ODN ranged from 1% to 1.8%. LDN was generally found to be associated with reduced analgesia use, shorter hospital stay, and faster return to normal physical functioning. The extracted kidney was exposed to longer warm ischaemia periods (2 to 17 minutes) with no associated short-term consequences. ODN was associated with shorter duration of procedure. For those outcomes that could be meta-analysed there were no significant differences between LDN or ODN for perioperative complications (RR 0.87, 95% CI 0.47 to 4.59), reoperations (RR 0.57, 95% CI 0.09 to 3.64), early graft loss (RR 0.31, 95% CI 0

The Psychosocial and Independent Living Donor Advocate Evaluation and Post-surgery Care of Living Donors.

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Rudow, Dianne LaPointe; Swartz, Kathleen; Phillips, Chelsea; Hollenberger, Jennifer; Smith, Taylor; Steel, Jennifer L

2015-09-01

Solid organ transplantation as a treatment for end stage organ failure has been an accepted treatment option for decades. Despite advances in medicine and technology, and increased awareness of organ donation and transplantation, the gap between supply and demand continues to widen. Living donation has been an option that has increased the number of transplants despite the continued shortage of deceased organs. In the early 2000s live donor transplantation reached an all-time high in the United States. As a result, a consensus meeting was convened in 2000 to increase the oversight of living donor transplantation. Both the Centers for Medicare and Medicaid Services and the United Network for Organ Sharing developed regulations that transplant programs performing live donor transplantation. These regulations and guidelines involve the education, evaluation, informed consent process and living donor follow-up care. Two areas in which had significant changes included the psychosocial and the independent living donor advocate (ILDA) evaluation. The purpose of this paper was to outline the current regulations and guidelines associated with the psychosocial and ILDA evaluation as well as provide further recommendations for the administration of a high quality evaluation of living donors. The goals and timing of the evaluation and education of donors; qualifications of the health care providers performing the evaluation; components of the evaluation; education provided to donors; documentation of the evaluation; participation in the selection committee meeting; post-decline and post-donation care of donors is described. Caveats including the paired donor exchange programs and non-directed and directed donation are also considered.

Q-FISH measurement of hepatocyte telomere lengths in donor liver and graft after pediatric living-donor liver transplantation: donor age affects telomere length sustainability.

Directory of Open Access Journals (Sweden)

Youichi Kawano

Full Text Available Along with the increasing need for living-donor liver transplantation (LDLT, the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved. Furthermore, since contradictory data have been reported with regard to the relationship between donor age and LT/LDLT outcome, the question of whether the use of elderly donors influences the long-term outcome of a graft after LT/LDLT remains unsettled. To address whether hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere lengths of hepatocytes in informative biopsy samples from 12 paired donors and recipients (grafts of pediatric LDLT more than 5 years after adult-to-child LDLT because of primary biliary atresia, using quantitative fluorescence in situ hybridization (Q-FISH. The telomere lengths in the paired samples showed a robust relationship between the donor and grafted hepatocytes (r = 0.765, p = 0.0038, demonstrating the feasibility of our Q-FISH method for cell-specific evaluation. While 8 pairs showed no significant difference between the telomere lengths for the donor and the recipient, the other 4 pairs showed significantly shorter telomeres in the recipient than in the donor. Multiple regression analysis revealed that the donors in the latter group were older than those in the former (p = 0.001. Despite the small number of subjects, this pilot study indicates that donor age is a crucial factor affecting telomere length sustainability in hepatocytes after pediatric LDLT, and that the telomeres in grafted livers may be elongated somewhat longer when the grafts are immunologically well controlled.

Epstein-Barr virus lymphoproliferative disease after hematopoietic stem cell transplant.

Science.gov (United States)

Rouce, Rayne H; Louis, Chrystal U; Heslop, Helen E

2014-11-01

Epstein-Barr virus (EBV) reactivation can cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplant. Delays in reconstitution of EBV-specific T lymphocyte activity can lead to life-threatening EBV lymphoproliferative disease (EBV-PTLD). This review highlights recent advances in the understanding of pathophysiology, risk factors, diagnosis, and management of EBV viremia and PTLD. During the past decade, early detection strategies, such as serial measurement of EBV-DNA load, have helped identify high-risk patients and diagnose early lymphoproliferation. The most significant advances have come in the form of innovative treatment options, including manipulation of the balance between outgrowing EBV-infected B cells and the EBV cytotoxic T lymphocyte response, and targeting infected B cells with monoclonal antibodies, chemotherapy, unmanipulated donor lymphocytes, and donor or more recently third-party EBV cytotoxic T lymphocytes. Defining criteria for preemptive therapy remains a challenge. EBV reactivation is a significant complication after stem cell transplant. Continued improvements in risk stratification and treatment options are required to improve the morbidity and mortality caused by EBV-associated diseases. Current approaches use rituximab to deplete B cells or adoptive transfer of EBV cytotoxic T lymphocyte to reconstitute immunity. The availability of rapid EBV-specific T cell products offers the possibility of improved outcomes.

Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation.

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Bryant, Jane; Hlavaty, Kelan A; Zhang, Xiaomin; Yap, Woon-Teck; Zhang, Lei; Shea, Lonnie D; Luo, Xunrong

2014-10-01

Human islet cell transplantation is a promising treatment for type 1 diabetes; however, long-term donor-specific tolerance to islet allografts remains a clinically unmet goal. We have previously shown that recipient infusions of apoptotic donor splenocytes chemically treated with 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (donor ECDI-SP) can mediate long-term acceptance of full major histocompatibility complex (MHC)-mismatched murine islet allografts without the use of immunosuppression. In this report, we investigated the use of poly(lactide-co-glycolide) (PLG) particles in lieu of donor ECDI-SP as a synthetic, cell-free carrier for delivery of donor antigens for the induction of transplant tolerance in full MHC-mismatched murine allogeneic islet transplantation. Infusions of donor antigen-coupled PLG particles (PLG-dAg) mediated tolerance in ∼20% of recipient mice, and the distribution of cellular uptake of PLG-dAg within the spleen was similar to that of donor ECDI-SP. PLG-dAg mediated the contraction of indirectly activated T cells but did not modulate the direct pathway of allorecognition. Combination of PLG-dAg with a short course of low dose immunosuppressant rapamycin at the time of transplant significantly improved the tolerance efficacy to ∼60%. Furthermore, altering the timing of PLG-dAg administration to a schedule that is more feasible for clinical transplantation resulted in equal tolerance efficacy. Thus, the combination therapy of PLG-dAg infusions with peritransplant rapamycin represents a clinically attractive, biomaterials-based and cell-free method for inducing long-term donor-specific tolerance for allogeneic cell transplantation, such as for allogeneic islet transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Renal Transplantation from Elderly Living Donors

Directory of Open Access Journals (Sweden)

Jacob A. Akoh

2013-01-01

Full Text Available Acceptance of elderly living kidney donors remains controversial due to the higher incidence of comorbidity and greater risk of postoperative complications. This is a review of publications in the English language between 2000 and 2013 about renal transplantation from elderly living donors to determine trends and effects of donation, and the outcomes of such transplantation. The last decade witnessed a 50% increase in living kidney donor transplants, with a disproportionate increase in donors >60 years. There is no accelerated loss of kidney function following donation, and the incidence of established renal failure (ERF and hypertension among donors is similar to that of the general population. The overall incidence of ERF in living donors is about 0.134 per 1000 years. Elderly donors require rigorous assessment and should have a predicted glomerular filtration rate of at least 37.5 mL/min/1.73 m2 at the age of 80. Though elderly donors had lower glomerular filtration rate before donation, proportionate decline after donation was similar in both young and elderly groups. The risks of delayed graft function, acute rejection, and graft failure in transplants from living donors >65 years are significantly higher than transplants from younger donors. A multicentred, long-term, and prospective database addressing the outcomes of kidneys from elderly living donors is recommended.

[Analysis of factors related to the number of mesenchymal stem cells derived from synovial fluid of the temporomandibular joint].

Science.gov (United States)

Sun, Y P; Zheng, Y H; Zhang, Z G

2017-06-09

Objective: To analyze related factors on the number of mesenchymal stem cells in the synovial fluid of the temporomandibular joint (TMJ) and provide an research basis for understanding of the source and biological role of mesenchymal stem cells derived from synovial fluid in TMJ. Methods: One hundred and twenty-two synovial fluid samples from 91 temporomandibular disorders (TMD) patients who visited in Department of TMJ Center, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University from March 2013 to December 2013 were collected in this study, and 6 TMJ synovial fluid samples from 6 normal volunteers who were studying in the North Campus of Sun Yat-sen University were also collected, so did their clinical information. Then the relation between the number of mesenchymal stem cells derived from synovial fluid and the health status of the joints, age of donor, disc perforation, condylar bony destruction, blood containing and visual analogue scale score of pain were investigated using Mann-Whitney U test and Spearman rank correlation test. Results: The number of mesenchymal stem cells derived from synovial fluid had no significant relation with visual analogue scale score of pain ( r= 0.041, P= 0.672), blood containing ( P= 0.063), condylar bony destruction ( P= 0.371). Linear correlation between the number of mesenchymal stem cells derived from synovial fluid and age of donor was very week ( r= 0.186, P= 0.043). The number of mesenchymal stem cells up-regulated when the joint was in a disease state ( P= 0.001). The disc perforation group had more mesenchymal stem cells in synovial fluid than without disc perforation group ( P= 0.042). Conclusions: The number of mesenchymal stem cells derived from synovial fluid in TMJ has no correlation with peripheral blood circulation and condylar bony destruction, while has close relation with soft tissue structure damage of the joint.

Donor hematopoiesis in mice following total lymphoid irradiation requires host T-regulatory cells for durable engraftment

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Müller, Antonia M. S.; Poyser, Jessica; Küpper, Natascha J.; Burnett, Cassandra; Ko, Rose M.; Kohrt, Holbrook E.K.; Florek, Mareike; Zhang, Pei; Negrin, Robert S.

2014-01-01

Total lymphoid irradiation (TLI) with antithymocyte globulin (ATG) is a unique regimen that prepares recipients for allogeneic hematopoietic cell transplantation by targeting lymph nodes, while sparing large areas of the bone marrow. TLI is reported to increase the frequency of CD4+CD25+FoxP3+ T-regulatory cells (Treg) relative to conventional T cells. In this study, barriers to hematopoietic stem cell (HSC) engraftment following this nonmyeloablative conditioning were evaluated. TLI/ATG resulted in profound lymphoablation but endogenous host HSC remained. Initial donor HSC engraftment occurred only in radiation exposed marrow sites, but gradually distributed to bone marrow outside the radiation field. Sustained donor engraftment required host lymphoid cells insofar as lymphocyte deficient Rag2γc−/− recipients had unstable engraftment compared with wild-type. TLI/ATG treated wild-type recipients had increased proportions of Treg that were associated with increased HSC frequency and proliferation. In contrast, Rag2γc−/− recipients who lacked Treg did not. Adoptive transfer of Treg into Rag2γc−/− recipients resulted in increased cell cycling of endogenous HSC. Thus, we hypothesize that Treg influence donor engraftment post-TLI/ATG by increasing HSC cell cycling, thereby promoting the exit of host HSC from the marrow niche. Our study highlights the unique dynamics of donor hematopoiesis following TLI/ATG, and the effect of Treg on HSC activity. PMID:24591203

Skin Recurrence of Transformed Mycosis Fungoides Postumbilical Cord Blood Transplant despite Complete Donor Chimerism

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Rahul Pawar

2014-01-01

Full Text Available Background. Allogeneic stem cell transplant is the treatment of choice for systemic cutaneous T-cell lymphoma (CTCL which provides graft-versus-lymphoma effect. Herein we discuss a case of recurrence of CTCL skin lesions after cord blood transplant in a patient who continued to have 100% donor chimerism in bone marrow. Case Presentation. A 48-year-old female with history of mycosis fungoides (MF presented with biopsy proven large cell transformation of MF. PET scan revealed multiple adenopathy in abdomen and chest suspicious for lymphoma and skin biopsy showed large cell transformation. She was treated with multiple cycles of chemotherapy. Posttherapy PET scan showed resolution of lymphadenopathy. Later she underwent ablative preparative regimen followed by single cord blood transplant. Bone marrow chimerism studies at day +60 after transplant showed 100% donor cells without presence of lymphoma. However 5 months after transplant she had recurrence of MF with the same genotype as prior skin lesion. Bone marrow chimerism study continued to show 100% donor cells. Conclusion. A differential graft-versus-lymphoma effect in our case prevented lymphoma recurrence systemically but failed to do so in skin. We hypothesize that this response may be due to presence of other factors in the bone marrow and lymph node microenvironments preventing recurrence in these sites.

Development of organ-specific donor risk indices.

Science.gov (United States)

Akkina, Sanjeev K; Asrani, Sumeet K; Peng, Yi; Stock, Peter; Kim, W Ray; Israni, Ajay K

2012-04-01

Because of the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival with various combinations of donor and recipient characteristics. Here we review the kidney donor risk index (KDRI) and the liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The KDRI has a potential role in developing new kidney allocation algorithms. The LDRI allows a greater appreciation of the importance of donor factors, particularly for hepatitis C virus-positive recipients; as the donor risk index increases, the rates of allograft and patient survival among these recipients decrease disproportionately. The use of livers with high donor risk indices is associated with increased hospital costs that are independent of recipient risk factors, and the transplantation of livers with high donor risk indices into patients with Model for End-Stage Liver Disease scores indices for liver transplantation, including donor-recipient matching and the retransplant donor risk index. Although substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival. Copyright © 2012 American Association for the Study of Liver Diseases.

Predominant or complete recipient T-cell chimerism following alemtuzumab-based allogeneic transplantation is reversed by donor lymphocytes and not associated with graft failure.

Science.gov (United States)

Mohamedbhai, Sajir G; Edwards, Noha; Morris, Emma C; Mackinnon, Stephen; Thomson, Kirsty J; Peggs, Karl S

2012-02-01

The clinical significance of mixed chimerism following allogeneic haematopoietic stem cell transplantation (HSCT) remains controversial. Its relevance and incidence are probably influenced by the conditioning regimen and incorporation of T-cell depletion. The presence of recipient chimerism levels >40-50% following T-cell replete reduced intensity transplantation correlates with a high risk of graft rejection, regardless of donor-lymphocyte infusions, but it is unclear whether this finding translates to T-cell depleted transplants. We conducted a retrospective single-institution analysis of patients receiving alemtuzumab-based HSCT. 27/152 (18%) evaluable cases had predominantly recipient T-cell chimerism at 3 months or beyond. By contrast, coincident chimerism in the granulocyte lineage was predominantly of donor origin (median 100%) in all but one patient. Donor lymphocyte infusion effectively converted predominantly recipient T-cell chimerism to ful donor chimerism in all evaluable cases including three cases with no detectable donor T cells. The only graft failure occurred in the patient with predominantly recipient myeloid chimerism in whom rejection occurred rapidly before donor lymphocytes could be administered. We conclude that predominant or complete recipient T-cell chimerism following alemtuzumab-based regimens does not have the same clinical implications as that following T-cell replete transplants and can be effectively converted with donor lymphocytes without the need for lympho-depleting agents or re-conditioning. © 2011 Blackwell Publishing Ltd.

Expanding the live kidney donor pool: ethical considerations regarding altruistic donors, paired and pooled programs.

Science.gov (United States)

Patel, Shaneel Rajendra; Chadha, Priyanka; Papalois, Vassilios

2011-06-01

In renal transplant, there is a well-known deficiency in organ supply relative to demand. Live donation provides superior results when compared with deceased donation including a better rate of graft success and fewer immunologic complications. This deficiency in organs leads to significant morbidity and mortality rates. Alternative avenues have been extensively explored that may expand the live donor pool. They include altruistic donation as well as paired and pooled exchange programs. Altruistic donation is a truly selfless act from a donor unknown to the recipient. Kidney paired donation involves 2 incompatible donor-recipient pairs swapping donors to produce compatibility. Pooled donation involves at least 2 pairs, and can take the form of domino chains in which altruistic input sets up a chain of transplants, in which each recipient's incompatible donor makes a donation for the next recipient. Despite application of these various methods, there lie extensive ethical issues surrounding them. Misconceptions frequently occur; for instance, the perceived benefit that donating an organ to a loved one is greater for a related donor than for an altruistic one. Additionally, it is frequently believed that immunologic incompatibility offers coerced donors liberation from surgery, and that overcoming these barriers by introducing exchange programs provides vulnerable donors less protection. This article explores these and other complex ethical issues surrounding the various methods of expanding the donor pool. The authors offer opinions that challenge the ethical issues and attempt to overcome those views that hinder progress in the field.

Gamete donors' reasons for, and expectations and experiences of, registration with a voluntary donor linking register.

Science.gov (United States)

Blyth, Eric; Crawshaw, Marilyn; Frith, Lucy; van den Akker, Olga

2017-12-01

This paper reports on a study of the views and experiences of 21 sperm donors and five egg donors registered with UK DonorLink (UKDL), a voluntary DNA-based contact register established to facilitate contact between adults who wish to identify and locate others to whom they are genetically related following donor conception. Specifically, the paper examines donors' reasons for searching for, or making information about themselves available to donor-conceived offspring. Their expectations of registration with UKDL, experiences of being registered and finally, the experiences of those who had contacted donor-conceived offspring and other genetic relatives are investigated. While most respondents reported largely positive experiences of registration, the study found significant issues relating to concerns about donation, DNA testing, possible linking with offspring and expectations of any relationship that might be established with offspring that have implications for support, mediation and counselling. Research that puts the experiences, perceptions and interests of gamete donors as the central focus of study is a relatively recent phenomenon. This study contributes to this debate and highlights directions for future research in this area.

Qualidade de vida do doador após transplante hepático intervivos Donor quality of life after living donor liver transplantation

Directory of Open Access Journals (Sweden)

Júlio Cezar Uili Coelho

2005-06-01

of living donors. All donors with less than 6 months of follow-up and those who did not want to participate were excluded from the study. The donors answered a questionnaire contained 28 questions about several aspects of donation. Demographic and clinical data from the donors were also evaluated. RESULTS: Thirty-seven donors were included in the study. Thirty-two were first or second degree relatives of the receptor. Only one donor would not donate again. Twenty-two donors (59% experienced more postoperative pain than they had previously anticipated. Return to regular activities occurred in less than 3 months for 21 donors (57%. Twenty-one donors (57% referred financial loss with the donation due to expenses with medications, exams, transportation or lost wages. Thirty-three (89% had no modification or limitation in their lives after donation. The most negative aspects of donation were postoperative pain and the presence of a surgical scar. Most postoperative complications resolved with clinical treatment, but severe or potentially fatal complications occurred in two patients. CONCLUSIONS: Most donors had good recovery and returned to regular activities few months after donation. The most negative aspect of donation was postoperative pain.

Thermodynamics of synergistic extraction of hexavalent plutonium with HPMBP and neutral donors: monodentate versus bidentate

International Nuclear Information System (INIS)

Lohithakshan, K.V.; Mithapara, P.D.; Pai, S.A.; Aggarwal, S.K.; Jain, H.C.

1996-01-01

Synergistic extraction of hexavalent plutonium was studied from HNO 3 medium (0.05 M) with 1-phnyl, 3-methyl, 4-benzoyl, pyrazolone-5 (HPMBP) and different monodentate neutral donors viz. diphenyl sulphoxide (DPSO), tri-n-butyl phosphate (TBP) and tri-n-octyl phosphine oxide (TOPO) using benzene as a diluent. Thermodynamic parameters (ΔG, ΔH, ΔS) evaluated by performing the experiments at various fixed temperatures (288 K to 318 K) were compared with those reported previously for the bidentate neutral donors (DBDECMP, DHDECMP and CMPO). The net enthalpy changes were negative and comparable. The monodentate neutral donors, however, showed a larger decrease in the entropy values. Further, the negative values of enthalpy and entropy changes indicated that the organic adduct formation is an addition reaction as reported ealier for the bidentate donors. (orig.)

Enhanced neuro-therapeutic potential of Wharton's Jelly-derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture.

Science.gov (United States)

Drela, Katarzyna; Lech, Wioletta; Figiel-Dabrowska, Anna; Zychowicz, Marzena; Mikula, Michał; Sarnowska, Anna; Domanska-Janik, Krystyna

2016-04-01

Substantial inconsistencies in mesenchymal stem (stromal) cell (MSC) therapy reported in early translational and clinical studies may indicate need for selection of the proper cell population for any particular therapeutic purpose. In the present study we have examined stromal stem cells derived either from umbilical cord Wharton's Jelly (WJ-MSC) or bone marrow (BM-MSC) of adult, healthy donors. The cells characterized in accordance with the International Society for Cellular Therapy (ISCT) indications as well as other phenotypic and functional parameters have been compared under strictly controlled culture conditions. WJ-MSC, in comparison with BM-MSC, exhibited a higher proliferation rate, a greater expansion capability being additionally stimulated under low-oxygen atmosphere, enhanced neurotrophic factors gene expression and spontaneous tendency toward a neural lineage differentiation commitment confirmed by protein and gene marker induction. Our data suggest that WJ-MSC may represent an example of immature-type "pre-MSC," where a substantial cellular component is embryonic-like, pluripotent derivatives with the default neural-like differentiation. These cells may contribute in different extents to nearly all classical MSC populations adversely correlated with the age of cell donors. Our data suggest that neuro-epithelial markers, like nestin, stage specific embryonic antigens-4 or α-smooth muscle actin expressions, may serve as useful indicators of MSC culture neuro-regeneration-associated potency. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Why Should Donors Care about Corruption?

OpenAIRE

Kolstad, Ivar

2008-01-01

Corruption is bad for donor business. Corruption reduces popular support for aid in donor countries. However, aid agencies should pay attention to corruption because it is the right thing to do, rather than just the smart thing to do. Donor anti-corruption policies require a strong grounding in ethics. Corruption produces bad development outcomes. This is the reasoning largely underlying donor anti-corruption efforts. The focus on consequences of corruption makes donor anticorruptioneffo...

Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency

DEFF Research Database (Denmark)

Qasim, Waseem; Cavazzana-Calvo, Marina; Davies, E Graham

2009-01-01

OBJECTIVES: Leukocyte adhesion deficiency is a rare primary immune disorder caused by defects of the CD18 beta-integrin molecule on immune cells. The condition usually presents in early infancy and is characterized by deep tissue infections, leukocytosis with impaired formation of pus, and delayed...... of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International......, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases. CONCLUSIONS: Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early...

The Impact of Total Ischemic Time, Donor Age and the Pathway of Donor Death on Graft Outcomes After Deceased Donor Kidney Transplantation.

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Wong, Germaine; Teixeira-Pinto, Armando; Chapman, Jeremy R; Craig, Jonathan C; Pleass, Henry; McDonald, Stephen; Lim, Wai H

2017-06-01

Prolonged ischemia is a known risk factor for delayed graft function (DGF) and its interaction with donor characteristics, the pathways of donor death, and graft outcomes may have important implications for allocation policies. Using data from the Australian and New Zealand Dialysis and Transplant registry (1994-2013), we examined the relationship between total ischemic time with graft outcomes among recipients who received their first deceased donor kidney transplants. Total ischemic time (in hours) was defined as the time of the donor renal artery interruption or aortic clamp, until the time of release of the clamp on the renal artery in the recipient. A total of 7542 recipients were followed up over a median follow-up time of 5.3 years (interquartile range of 8.2 years). Of these, 1823 (24.6%) experienced DGF and 2553 (33.9%) experienced allograft loss. Recipients with total ischemic time of 14 hours or longer experienced an increased odd of DGF compared with those with total ischemic time less than 14 hours. This effect was most marked among those with older donors (P value for interaction = 0.01). There was a significant interaction between total ischemic time, donor age, and graft loss (P value for interaction = 0.03). There was on average, a 9% increase in the overall risk of graft loss per hour increase in the total ischemic time (adjusted hazard ratio, 1.09; 95% confidence interval, 1.01-1.18; P = 0.02) in recipients with older donation after circulatory death grafts. There is a clinically important interaction between donor age, the pathway of donor death, and total ischemic time on graft outcomes, such that the duration of ischemic time has the greatest impact on graft survival in recipients with older donation after circulatory death kidneys.

GAMBARAN ANTI HBc POSITIF PADA DONOR DARAH DENGAN HbsAG NEGATIF

Directory of Open Access Journals (Sweden)

Susila Sastri

2009-09-01

Ag negatif dan antiHbc positif untuk memastikan darah donor tersebut tidak boleh ditransfusikan.Kata kunci: Skrining, HBV, HBsAg, Anti-HBc, donor darah  Abstract            HBsAg examination alone to screen for hepatitis B (HBV has not been able to guarantee freedom from HBV blood donor so that blood donors have not fulfilled the requirements to be transfused. Blood donors will be transfused donors should qualify them have never suffered from HBV. Screening of blood donors against HBV in the PMI only with HBsAg alone where the HBsAg test is negative at certain stages of HBV, in terms of donors suffering or recovering in HBV. Anti-HBc can provide information on HBV trip when combined with other HBV markers and anti-HBc last longer in the blood compared with other markers. HBsAg negative blood donors with anti-HBc positive than some previous research is still exist that contain HBV-DNA and can transmit HBV.Has done research on blood donors with anti-HBc test descriptively against HBsAg negative blood donors (n = 100 on the UTD PMI Branch of Padang in cross sectional study. Samples taken by proportional random sampling. Blood samples were HBsAg negative blood VDRL, HCV, HIV negative, all examined by the ELISA. The aim is to see the picture of positive anti-HBc in blood donors with HBsAg negative and look at the relationship between the index of HBsAg with anti-HBc index. Examination of anti-HBc by ELISA, equipment and reagents the same output. The results showed the frequency of positive anti-HBc in HBsAg negative blood donors by 27%, especially in men aged between 20-29 years (44.4%. There is a positive correlation between the index of negative HBsAg with anti-HBc index (r = 0.02. Anti-HBc positive are found in HBsAg negative index of 0.21 to 0.60 (76%. In conclusion, blood donors with negative HBsAg have been considered safe for transfusion is still likely to transmit HBV proven by the discovery of anti-HBc positive. Because it needs a further examination of HBV

High mortality in diabetic recipients of high KDPI deceased donor kidneys.

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Pelletier, Ronald P; Pesavento, Todd E; Rajab, Amer; Henry, Mitchell L

2016-08-01

Deceased donor (DD) kidney quality is determined by calculating the Kidney Donor Profile Index (KDPI). Optimizing high KDPI (≥85%) DD transplant outcome is challenging. This retrospective study was performed to review our high KDPI DD transplant results to identify clinical practices that can improve future outcomes. We retrospectively calculated the KDPI for 895 DD kidney recipients transplanted between 1/2002 and 11/2013. Age, race, body mass index (BMI), retransplantation, gender, diabetes (DM), dialysis time, and preexisting coronary artery disease (CAD) (previous myocardial infarction (MI), coronary artery bypass (CABG), or stenting) were determined for all recipients. About 29.7% (266/895) of transplants were from donors with a KDPI ≥85%. By Cox regression older age, diabetes, female gender, and dialysis time >4 years correlated with shorter patient survival time. Diabetics with CAD who received a high KDPI donor kidney had a significantly increased risk of death (HR 4.33 (CI 1.82-10.30), P=.001) compared to low KDPI kidney recipients. The Kaplan-Meier survival curve for diabetic recipients of high KDPI kidneys was significantly worse if they had preexisting CAD (P<.001 by log-rank test). Patient survival using high KDPI donor kidneys may be improved by avoiding diabetic candidates with preexisting CAD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Donor conversion and procurement failure: the fate of our potential organ donors.

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Branco, Bernardino C; Inaba, Kenji; Lam, Lydia; Salim, Ali; Barmparas, Galinos; Teixeira, Pedro G R; Talving, Peep; Demetriades, Demetrios

2011-02-01

Donor availability remains the primary limiting factor for organ transplantation today. The purpose of this study was to examine the causes of procurement failure amongst potential organ donors. After Institutional Review Board approval, all surgical intensive care unit (SICU) patients admitted to the LAC+USC Medical Center from 01/2006 to 12/2008 who became potential organ donors were identified. Demographics, clinical data, and procurement data were abstracted. In non-donors, the causes of procurement failure were documented. During the 3-year study period, a total of 254 patients were evaluated for organ donation. Mean age was 44.8±18.7 years; 191 (75.2%) were male, 136 (53.5%) were Hispanic, and 148 (58.3%) were trauma patients. Of the 254 patients, 116 (45.7%) were not eligible for donation: 34 had multi-system organ failure, 24 did not progress to brain death and had support withdrawn, 18 had uncontrolled sepsis, 15 had malignancy, 6 had human immunodeficiency virus or hepatitis B or C, and 19 patients had other contraindications to organ donation. Of the remaining 138 eligible patients, 83 (60.2%) did not donate: 56 because the family denied consent, 9 by their own choice. In six, next of kin could not be located, five died because of hemodynamic instability before organ procurement was possible, four had organs that could not be placed, and three had their organs declined by the organ procurement organization. The overall consent rate was 57.5% (n=67). From the 55 donors, 255 organs were procured (yield 4.6 organs/donor). Of all patients screened for organ donation, only a fifth actually donated. Denial of consent was the major potentially preventable cause of procurement failure, whereas hemodynamic instability accounted for only a small percentage of donor losses. With such low conversion rates, the preventable causes of procurement failure warrant further study.

First-Line Matched Related Donor Hematopoietic Stem Cell Transplantation Compared to Immunosuppressive Therapy in Acquired Severe Aplastic Anemia

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Peinemann, Frank; Grouven, Ulrich; Kröger, Nicolaus; Bartel, Carmen; Pittler, Max H.; Lange, Stefan

2011-01-01

Introduction Acquired severe aplastic anemia (SAA) is a rare and progressive disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells is a first-line treatment option if HLA-matched related donors are available. First-line immunosuppressive therapy may be offered as alternative. The aim was to compare the outcome of these patients in controlled trials. Methods A systematic search was performed in the bibliographic databases MEDLINE, EMBASE, and The Cochrane Library. To show an overview of various outcomes by treatment group we conducted a meta-analysis on overall survival. We evaluated whether studies reported statistically significant factors for improved survival. Results 26 non-randomized controlled trials (7,955 patients enrolled from 1970 to 2001) were identified. We did not identify any RCTs. Risk of bias was high except in 4 studies. Young age and recent year of treatment were identified as factors for improved survival in the HSCT group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the IST group. In 19 studies (4,855 patients), summary statistics were sufficient to be included in meta-analysis. Considerable heterogeneity did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. Conclusions Young age and recent year of treatment were identified as factors for improved survival in the transplant group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the immunosuppressive group. Considerable heterogeneity of non-randomized controlled studies did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. PMID:21541024

Advances in Bone Marrow Stem Cell Therapy for Retinal Dysfunction

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Park, Susanna S.; Moisseiev, Elad; Bauer, Gerhard; Anderson, Johnathon D.; Grant, Maria B.; Zam, Azhar; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan A.

2016-01-01

The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34+ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34+ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy. PMID:27784628

Philanthropic Motivations of Community College Donors

Science.gov (United States)

Carter, Linnie S.; Duggan, Molly H.

2011-01-01

This descriptive study surveyed current, lapsed, and major gift donors to explore the impact of college communications on donors' decisions to contribute to the college, the likelihood of donor financial support for various college projects, and the philanthropic motivation profiles of the donors of a midsized, multicampus community college in…

Heart transplantation from older donors

Directory of Open Access Journals (Sweden)

V. N. Poptsov

2017-01-01

Full Text Available In the current situation of the shortage of suitable donor organs, heart transplantation from older donors is one of the ways to increase the performance of more heart transplants, particularly, in patients with urgent need of transplantation. While planning a heart transplantation from older donor one should consider increased risk of early cardiac allograft dysfunction, preexisting coronary artery disease, accelerated transplant vasculopathy which may adversely affect early and long-term survival of recipients. Subject to careful selection of donor–recipient pairs, effective prevention and treatment of early cardiac allograft dysfunction, pre-existing atherosclerosis and transplant vasculopathy the early and long-term survival of heart transplant recipients from older donors is comparable to heart transplantation from young donors.