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Cell Journal، جلد ۱۵، شماره Suppl ۱، صفحات ۷-۷
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عنوان انگلیسی Is-14: Immunomodulatory Effects of Mesenchymal Stem Cells and Use in Allogeneic Hematopoietic
چکیده انگلیسی مقاله Objective: Mesenchymal stem cells (MSC) can differentiate into several tissues, including bone, cartilage and fat, in vitro and in vivo. MSC may be important in regenerative medicine for tissue repair. Materials and Methods: In vitro, we studied MSC in mixed lymphocyte culture (MLC), mitogenic stimulation and in cell-mediated lympholysis with chromiumlabelled target cells. In vivo, MSC were studied in patients with acute and chronic graft-versus-host disease (GVHD), hemorrhagic cystitis and hemorrhages following hematopoietic stem cell transplantation. Results: MSC have low immunogenicity and immunomodulatory effects. In vitro, MSC suppress alloantigen- induced T-cell functions in vitro in mixed lymphocyte culture (MLC) and cytotoxic T-cells (CTL). This effect was seen regardless of HLA compatibility between MSC and responder or stimulatory cells in alloreactivity. Pooling of MSC from several donors generated higher and more stable suppression in both MLC and after mitogenic stimulation. We have found that MSC from different individuals have varying capacity to inhibit alloreactivity. Furthermore, single clones from the same individual also differ regarding capacity to induce immunosuppression. Suppressive MSC also seems to differ from non-suppressive MSC regarding the phenotype and gene profiles. We found that Epstein- Barr virus and cytomegalovirus induced proliferation and interferon-γ (IFNγ) production from blood lymphocytes was less affected by third party MSC than response to alloantigen. Furthermore, MSC had no effect on expansion of EBV and CMV pentamer specific Tcells. This suggests that the effect of functions of virus specific T-cells may be retained after MSC infusion. Clinically, we found that MSC can reverse severe acute graft-versus-host disease (GVHD). MSC were found to home to target organs of GVHD. In 55 allogeneic hematopoietic stem cell transplant patients treated for severe acute GVHD, 30 patients had a complete response and survival was 52%. For patients with partial or no response (n=25), 2-year survival was 15% (p=0.02). MSC showed positive effects in autoimmune disease models. Because chronic GVHD resembles autoimmune disorders, MSC were used also to treat chronic GVHD. Response to MSC therapy was seen in around half of the patients with chronic GVHD. We have also used MSC for tissue repair, such as hemorrhagic cystitis and perforated colon in allogeneic HSCT patients. MSC also interfere with coagulation and were found to stop major hemorrhages following stem cell transplantation. MSC have also been used to enhance engraftment in HSCT patients and for graft failure. Conclusion: Possible clinical applications to the immunomodulatory and tissue repairing effects of MSC include acute and chronic GVHD, tissue repair, treatment of rejection of organ allografts, hemorrhages and autoimmune disorders.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/779
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