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Mouse bone marrow-derived mesenchymal stem cells acquire immunogenicity concurrent with differentiation to insulin-producing cells
Institution:1. Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;2. Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;3. Amol Faculty of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran;4. Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran;1. Department of Experimental Immunology, Medical University of Lodz, 92-213, Lodz, Poland;2. Department of Medical Psychology, Medical University of Lodz, 90-131, Lodz, Poland;1. Department of Chemistry, University of Zanjan, P.O. Box 45195-313, Zanjan, Iran;2. Research Institute of Modern Biological Techniques, University of Zanjan, 45371-38791, Zanjan, Iran;3. Department of Plant Protection, Faculty of Agriculture, University of Zanjan, 45371-38791, Zanjan, Iran;1. Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará – UFPA), Belém, Pará, Brazil;2. João de Barros Barreto Hospital, Federal University of Pará (Universidade Federal do Pará – UFPA), Belém, Pará, Brazil;3. School of Medicine, Institute of Health Sciences, Federal University of Pará (Universidade Federal do Pará – UFPA), Belém, Pará, Brazil;4. Laboratory of Human Genetics, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará – UFPA), Belém, Pará, Brazil;5. Graduate Program in Virology, Evandro Chagas Institute/SVS/MS, Brazil;1. Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan;2. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan;3. Taipei City Hospital, Taipei, Taiwan;4. Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan;5. Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan;1. Department of Pediatrics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;2. AmCare Genomics Lab (V.W.Z.), Guangzhou, China;3. Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, USA
Abstract:BackgroundAlthough mesenchymal stem cells (MSCs) are regarded as immune-elusive and even immunosuppressive, recent evidence suggests that allogeneic immune response might is inevitable in the case of some lineages differentiated from MSCs. Regarding the importance of allogeneic IPCs and MSCs in pre-clinical and clinical studies, the present study aimed to investigate the possible changes in the immunogenicity of MSCs during the differentiation to IPCs in a murine model of allogeneic transplantation.Material and methodsTwo mouse strains, C57BL/6 (H2Db) and BALB/c (H2Dd) were selected to establish an allogeneic cell transplantation model. Bone marrow MSCs were differentiated into IPCs and the expression of H2D, CD80, and Qa-2 molecules were evaluated via flowcytometry on MSCs and IPCs. The differentiated and undifferentiated MSCs were encountered to allogeneic splenocytes and the proliferation, CD44 activation marker, and cytokine release in the splenocytes were evaluated.ResultsIPCs exhibited increased expression of MHC-I and CD80 that elicited an allogenic response including the activation-induced proliferation of splenocytes, activation of CD4+ T cells, and IFNγ response.ConclusionsMSCs acquire immunogenicity after differentiation to functional IPCs, which might cause decreased efficacy in the case of allogeneic transplantation. Careful precautions might be critical for saving the IPCs against the detrimental allogeneic responses.
Keywords:Mesenchymal stem cells  Insulin producing cells  MHC  CD80  Immunogenicity
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