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Eradication of donor-dependent variations of mesenchymal stem cells in immunomodulation to enhance their therapeutic values.

ABSTRACT: Mesenchymal stem cells (MSC) are one of the most widely clinically trialed stem cells, due to their abilities to secret regenerative/rejuvenating factors, modulate immune functions, among others. In this study, we analyzed human umbilical-cord-derived MSC from 32 donors and revealed donor-dependent variations in two non-correlated properties, 1) cell proliferation, and 2) immune modulatory functions in vitro and in vivo, which might explain inconsistent clinical efficacies of MSC. Through unbiased transcriptomic analyses, we discovered that IFN- γ and NF-κB signaling were positively associated with immune modulatory function of MSC. Activation of these two pathways via IFN-γ and TNF-α treatment eradicated donor-dependent variations. Additional transcriptomic analyses revealed that treatment with these two factors, while abolished donor-dependent variations in immune modulatory function, did not overall made different donor-derived MSC more similar at whole transcriptomic levels, meaning the cells were still different in many other biological perspectives, and might not perform equally for therapeutic purposes other than immune modulation. Pre-selection or pre-treatment to eradicate MSC variations in a disease-treatment-specific manner would therefore be necessary to assure clinical efficacies. Together this study provided novel insights into the quality control perspective of using different-donor-derived MSC to treat inflammation-related clinical conditions and/or autoimmune diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165811 | GEO | 2021/02/01

REPOSITORIES: GEO

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