Abstract
Human mesenchymal stromal cells (MSCs) are currently the leading candidate for cell-based therapeutics. While the use of MSCs in transplantation therapies is widely expanding, still, there is a lot of scope for better understanding of the mechanisms underlying their effects. We have generated MSCs from pre- and post-natal human tissue sources such as Wharton’s jelly (WJ), stem cells from human exfoliated deciduous teeth (SHED), and bone marrow (BM). We then expanded, banked, and characterized them based on morphology, growth kinetics, senescence, immunophenotype, gene expression, and secretion of growth factors. Although the immunophenotype was very similar across MSCs from the three types of donor tissues, they showed minor variations in their growth kinetics. Further, a higher percentage of senescent cells were observed in BM-MSCs than in WJ-MSCs and SHED. Gene expression analysis showed the increased expression of INF-γ, PDGFA, VEGF, IL10, and SDF in SHED over WJ-MSC and BM-MSC. Comparative secretome profiling by ELISA demonstrated the presence of FGF-2, IL-10, PDGF, SDF-1, Ang-1, TGF-β3, HGF, INF-γ, VEGF, and IL-6 in cell culture supernatants. Based on our findings, WJ-MSC and SHED appear more potent than BM-MSC for managing inflammation, immunomodulation, angiogenesis, fibrosis, and scarring. Due to widespread application of MSCs in cell replacement therapy, these subtle differences need to be taken into consideration while designing stem cell–based clinical trials.
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Acknowledgments
The authors thank Manipal University, Manipal; AMET University, Kanathur, Chennai; and Genes & Life Health Care Pvt. Ltd., Hyderabad, for supporting this study. The authors also would like to thank Dr. Swapna Nandakumar and Dr. Renu Kapoor for proofreading the manuscript.
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All the three protocols were approved by the Institutional (Manipal Hospitals, Bangalore) and Independent ethics committee (Suraksha Independent Ethical Committee, Reg No: IORG 0007193). Informed consent was obtained from all the tissue donors and from parents in case of children.
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Konala, V.B.R., Bhonde, R. & Pal, R. Secretome studies of mesenchymal stromal cells (MSCs) isolated from three tissue sources reveal subtle differences in potency. In Vitro Cell.Dev.Biol.-Animal 56, 689–700 (2020). https://doi.org/10.1007/s11626-020-00501-1
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DOI: https://doi.org/10.1007/s11626-020-00501-1