2-Chloro-2'-deoxyadenosine (2-CdA) combined with cyclosporine A successfully prevents rejection of fetal brain stem allograft in rabbits.
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Immunosuppression
Synaptogenesis
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The prevalence of autoimmune diseases (ADs) in Western countries is estimated to be from 3-7%, and the treatment of severe, relapsing/refractory cases is still not satisfactory. The concept of utilizing intense immunosuppression followed by allogeneic or even autologous hemolymphopoietic stem cells (HSCs) to treat AD is based on encouraging results in experimental animals and from serendipitous cases of patients with both ADs and malignancies who were allotransplanted for the latter. However, rare unexpected relapses despite donor immune engraftment have been reported following HSC transplantation for AD. Autologous transplantation is a more feasible procedure with lower toxicity than allogeneic transplantation. This article analyzes the experimental basis for stem cell transplantation in AD and discusses the most important clinical results of both allogeneic and autologous HSC transplants.
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Refractory (planetary science)
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Fetal stem-cell transplantation is an attractive approach to the treatment of a variety of hematological, metabolic and immunological diseases before birth. The possibility of delivering a large number of cells in an early stage of life, and of taking advantage of normal fetal stem-cell migration and development, is promising. During fetal life, the capacity to mount an immune response to allogeneic cells is impaired compared with adult life. This provides an opportunity to induce tolerance to alloantigens without the need for myeloablation, although there are possible immune barriers to foreign cells in the fetus.
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Undigested fetal pancreatic tissue has been previously shown to have immunogenic properties, even after transplantation into the adult rat brain, a relatively immunoprivileged site. In the present study, iso-, allo-, and xenografts of fetal pancreas were placed into neonatal rat brain parenchyma and ventricles in order to determine the extent and quality of its survival in this environment. Adult recipients of the same tissue types were used as controls. Selective survival of insulin-staining beta cells was observed in neonates (n=33) over the 6-week period of the experiment. Ducts and acini were gradually destroyed in allo- and xenografts, disappearing completely by the 42nd day, while there were no such changes in the isografts. The absence of an acute inflammatory reaction was noted, but there were varying degrees of lymphocytic infiltration, though small (20 ± 4 lymphocytes per average graft area of 0.16 mm) in all but one graft. This infiltrate was greatest in allografts, with a significant increase observed after 14 days, corresponding to the time when the ducts started to disappear. Other structures present included fibroblasts and blood vessels. The latter increased significantly with time after transplantation. Unlike isografts placed in the parenchyma of adult rats, allo- and xenografts were rejected from the earliest time observed, 7 days postoperatively. In summary, these data show that beta cells in rat fetal pancreas will survive when grafted across major allogeneic and xenogeneic barriers for up to 6 weeks, without utilization of any form of immunosuppression, provided the recipients are neonates.
Parenchyma
Immunosuppression
Cellular infiltration
Infiltration (HVAC)
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▪ Abstract The prevalence of autoimmune diseases (ADs) in Western countries is estimated to be from 3–7%, and the treatment of severe, relapsing/refractory cases is still not satisfactory. The concept of utilizing intense immunosuppression followed by allogeneic or even autologous hemolymphopoietic stem cells (HSCs) to treat AD is based on encouraging results in experimental animals and from serendipitous cases of patients with both ADs and malignancies who were allotransplanted for the latter. However, rare unexpected relapses despite donor immune engraftment have been reported following HSC transplantation for AD. Autologous transplantation is a more feasible procedure with lower toxicity than allogeneic transplantation. This article analyzes the experimental basis for stem cell transplantation in AD and discusses the most important clinical results of both allogeneic and autologous HSC transplants.
Immunosuppression
Refractory (planetary science)
Autologous stem-cell transplantation
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Citations (104)