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Immunomodulatory function of whole human umbilical cord derived mesenchymal stem cells
Institution:1. Department of Hematology, Affiliated Hospital of Jining Medical University, No. 79, Guhuai Road, Jining, Shandong 272000, China;2. Department of Pediatrics, The Affiliated Hospital of Jining Medical College, Jining, Shandong 272000, China;3. Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China;4. Department of Graduate School, Jining Medical University, Jining 272000, Shandong Province, China;5. Cell and Gene Therapy Center of Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China;1. Laboratory of Virology (Laboratório de Virologia), Institute of Biological Sciences (Instituto de Ciências Biológicas), Federal University of Pará (Universidade Federal do Pará), Guamá, 66075-110 Belém, Pará, Brazil;2. Tropical Medicine Unit (Núcleo de Medicina Tropical), Federal University of Pará (Universidade Federal do Para), Umarizal, 66050-240 Belém, Pará, Brazil;1. LUNAM, Neurology Department, University Hospital, Angers, France;2. LUNAM, Neurobiology and Transgenesis Laboratory – UPRES EA 3143, University Hospital, Angers, France;1. Institute for Neurophysiology, University of Cologne, Robert-Koch Straße 39, D-50931 Cologne, Germany;2. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch Straße 39, D-50931 Cologne, Germany;3. Department of Neurosurgery, University Hospital, Heinrich-Heine-University, Düsseldorf, Moorenstraße 5, D-40225 Düsseldorf, Germany;1. Héma-Québec, Research and Development, Quebec City, Canada;2. Department of Biochemistry, Microbiology and Bioinformatics, Laval University, Quebec City, Canada;3. Laboratory for Biomaterials and Bioengineering, Department of Mining-Metallurgical and Materials Engineering & University Hospital Research Center, Laval University, Quebec City, Canada;4. Canadian Blood Services, Center for Innovation, Ottawa, Canada;5. Centre de Recherche Hôpital Maisonneuve-Rosemont, Montreal, Canada;6. Division of Hematology-Oncology, Department of Medicine, University of Montréal, Montreal, Canada
Abstract:Bone marrow derived mesenchymal stem cells (MSCs) play a critical role in immune modulation. However, immunomodulatory function of whole human umbilical cord derived mesenchymal stem cells (UC-MSCs) remains unclear. In this study, UC-MSCs were separated from whole umbilical cord using a single enzyme digestion. UC-MSCs (CD73+, CD90+, CD105+, and CD34, CD45, HLA-DR) were differentiated into adipocytes, osteocytes and chondrocytes in vitro under specific stimulatory environments. UC-MSCs suppressed umbilical cord blood lymphocyte proliferation stimulated by mitogen, and ELISA showed that the secretion of INF-γ was downregulated, and the secretion of IL-4 was upregulated, with CD8+ T cells markedly decreased and CD4+ T cells changed lightly. Moreover, the infusion of UC-MSCs in recipient mice transplanted with donor bone marrow cells ameliorated acute graft-versus host disease (aGVHD) and extended survival. In conclusion, UC-MSCs might negatively modulate immunoreactions, and have application potential in the treatment of aGVHD caused by allogeneic stem cells transplantation.
Keywords:Umbilical cord  Mesenchymal stem cells  Hematopoietic stem cells  Graft-versus-host disease  Immune modulation
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