Characterization and response to inflammatory stimulation of human endometrial-derived mesenchymal stem/stromal cells |
| |
| Affiliation: | 1. Department of Orthopedics, UHealth Sports Medicine Institute, University of Miami Miller School of Medicine, Miami, Florida, USA;2. Diabetes Research Institute & Cell Transplant Center, University of Miami Miller School of Medicine, Miami, Florida, USA;3. Department of Biomedical Engineering, University of Miami College of Engineering, Miami, Florida, USA;4. CryoVida Banco de Células Madre Adultas, Guadalajara, México;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. 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. Department of Intensive Care Medicine, The Third Xiangya Hospital of Central South University, Changsha, China;2. Department of Preparations, The First Hospital of Hunan University of Chinese Medicine, Changsha, China;1. Cancer and Blood Disease Institute, Children''s Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California, USA;2. Center for Cancer and Blood Disorders, Children''s National Hospital, George Washington School of Medicine, Washington, DC, USA;3. Department of Immunology and Microbiology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, USA;4. Seattle Children''s Therapeutics, Seattle Children''s Research Institute, Seattle, Washington, USA;1. SymphonyTech Biologics, Philadelphia, Pennsylvania, USA;2. BioInnovat, New Delhi, India;3. Biofusion Therapeutics, Bangalore, India |
| |
| Abstract: | Background aimsThe human endometrium has emerged as an attractive source of endometrial-derived mesenchymal stem/stromal cells (eMSCs) that can be easily isolated by non-invasive procedures. The prominent capacity of the endometrium for efficient and scarless regeneration each menstrual cycle indicates the increased eMSC immunomodulatory and pro-angiogenic properties. Herein the authors investigated the molecular responses of eMSCs to an inflammatory environment and whether those intrinsic responses affected their functional attributes.MethodsHuman eMSCs immunophenotypic, transcriptional and secretory profiles were evaluated at passage three (P3) and passage eight (P8) to determine culture effects. Functionally, P3 and P8 non-induced and TNF-α/IFN-γ-induced eMSCs were interrogated for their capacity to suppress stimulated peripheral blood mononuclear cell (PBMC) proliferation, whereas non-induced eMSCs were assessed for their support to vascular network formation in co-cultures with human umbilical vein endothelial cells in vitro.ResultsNon-induced P3 and P8 eMSCs exhibited similar spindle-shaped morphology and clonogenic capacity. Nevertheless, P8 eMSCs showed reduced growth rate capacity and telomere length. The eMSCs displayed the typical MSC-related immunophenotypic profile, with P3 and P8 eMSCs expressing high levels (>98%) of CD140β, intermediate levels (35–60%) of CD146 and SUSD2 and low levels (～8%) of NG2 pericytic markers. Non-induced P3 and P8 showed similar transcriptional and secretory profiles, though the expression of immunomodulatory HLA-G and IL-8 genes was significantly downregulated in P8 compared with P3 eMSCs. Upon TNF-α/IFN-γ induction, eMSCs showed an immunophenotypic profile similar to that of non-induced eMSCs, except for significant upregulation of HLA-DR protein expression in both induced P3 and P8 eMSCs. However, induced P3 and P8 eMSCs showed significant upregulation of CD10, HLA-G, IDO, IL-6, IL-8, LIF and TSG gene expression compared with non-induced cultures. TNF-α/IFN-γ induction strongly increased the secretion of inflammatory-/angiogenesis-related molecules, whereas growth factor secretion was similar to the non-induced eMSCs. Functionally, P3 and P8 eMSCs showed a strong inhibitory effect on stimulated PBMC proliferation and the capacity to support neovascularization in vitro.ConclusionsThe authors’ study suggests that serial expansion does not affect eMSC immunophenotypic, transcriptional and secretory profiles. This is directly reflected by the functional immunomodulatory and pro-angiogenic properties of eMSCs, which remain unaltered until P8 in vitro. However, exposure of eMSCs to inflammatory environments enhances their immunomodulatory transcriptional and inflammatory-/angiogenesis-related secretory profiles. Therefore, the resulting evidence of eMSCs serial expansion and exposure to inflammation could serve as a foundation for improved eMSCs manufacturing and potential clinical translation efforts. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
