Differential immunomodulation of human mesenchymal stromal cells from various sources in an inflammation mimetic milieu |
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| Institution: | 1. Stem Cell Research Centre, Government Stanley Hospital, Chennai, India;2. Stem Cell and Molecular Biology Lab, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India;3. Government Medical College Hospital, Karur, India;4. Hepato-Pancreato Biliary Centre for Surgery and Transplantation, MIOT International Hospital, Chennai, India;1. Institute of Computer Sciences, Foundation for Research and Technology Hellas, Heraklion, Greece;2. Public Cord Blood Bank of Crete, Department of Hematology, University Hospital of Heraklion, Heraklion, Greece;3. Haemopoiesis Research Laboratory, School of Medicine, University of Crete, Heraklion, Greece;4. CeMIA SA, Larissa, Greece;1. Air Force Medical Center, People''s Liberation Army, Beijing, People''s Republic of China;2. Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, People''s Republic of China;3. Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People''s Republic of China;4. Beijing Institute of Basic Medical Sciences, Beijing, People''s Republic of China;5. The Fifth Medical Center of Chinese People''s Liberation Army General Hospital, Beijing, People''s Republic of China;6. Graduate School of Anhui Medical University, Hefei, People''s Republic of China;1. Institute for Translational Medicine, The Affiliated Hospital, College of Medicine, Qingdao University, Qingdao, China;2. School of Basic Medical Sciences, College of Medicine, Qingdao University, Qingdao, China;1. The State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China;2. Department of Central Lab, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China;1. SymphonyTech Biologics, Philadelphia, Pennsylvania, USA;2. BioInnovat, New Delhi, India;3. Biofusion Therapeutics, Bangalore, India |
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| Abstract: | Mesenchymal stromal cells (MSCs) are very advantageous in the field of regenerative medicine because of their immunomodulatory properties. However, reports show that these properties vary from source to source. Hence, understanding the source-dependent specificity of MSCs and their immunomodulatory abilities will enable optimal use of MSCs in cell-based therapies. Here, we studied human MSCs from three different sources, adipose tissue (AT), bone marrow (BM) and Wharton's jelly (WJ), with respect to phenotypic responses of human peripheral blood mononuclear immune cells (hPBMCs/MNCs) and the concurrent changes in cytokine expression in MSCs, under mitogen-stimulated co-culture conditions. We used cytometric analysis to study the immunoregulatory properties of MSCs on MNCs and cytokine profiling of MSCs using a customized PCR array and solid-phase sandwich enzyme-linked immunosorbent assay. Our results reveal differential modulation of immune cells as well as MSCs upon activation by the mitogen phytohemagglutinin, independently and in co-culture. Notably, we observed source-specific MSC-cytokine signatures under stimulated conditions. Our results show that AT-MSCs up-regulate VEGF, BM-MSCs up-regulate PTGS-2 and WJ-MSCs increase expression of IDO considerably compared with controls. This remarkable modulation in source-specific cytokine expression was also validated at a functional level by quantitative protein expression studies. In our hands, even though MSCs from AT, BM and WJ sources exhibit characteristic immunomodulatory properties, our results highlight that MSCs sourced from different tissues may exhibit unique cytokine signatures and thus may be suitable for specific regenerative applications. |
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