Journal
THERANOSTICS
Volume 9, Issue 6, Pages 1683-1697Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.30487
Keywords
neuromesodermal progenitors; mesenchymal stem cells; human pluripotent stem cells; differentiation; immunomodulatory activity
Categories
Funding
- National Key Research and Development Program of China [2017YFA0103802, 2018YFA01072 00, 2017YFA0103403]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16020701, XDA16010102]
- National Natural Science Foundation of China [U1501245, 81501901, 81570487, 81730005, 31771616, 81570161]
- Key Scientific and Technological Program of Guangzhou City [201704020223, 201604020010, 201604020008, 20160402 0189]
- Frontier and Innovation of Key Technology Project in Science and Technology Department of Guangdong Province [2016B030229002, 2015B020228 001, 2017B020231001, 2016B030230001]
- Natural Science Foundation of Guangdong Province [2016A 030310158]
- Fundamental Research Funds for the Central Universities [17ykzd07]
- China Postdoctoral Science Foundation [2015M572407]
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Rationale: Mesenchymal stem cells (MSC) hold great promise in the treatment of various diseases including autoimmune diseases, inflammatory diseases, etc., due to their pleiotropic properties. However, largely incongruent data were obtained from different MSC-based clinical trials, which may be partially due to functional heterogeneity among MSC. Here, we attempt to derive homogeneous mesenchymal stem cells with neuromesodermal origin from human pluripotent stem cells (hPSC) and evaluate their functional properties. Methods: Growth factors and/or small molecules were used for the differentiation of human pluripotent stem cells (hPSC) into neuromesodermal progenitors (NMP), which were then cultured in animal component-free and serum-free induction medium for the derivation and long-term expansion of MSC. The resulted NMP-MSC were detailed characterized by analyzing their surface marker expression, proliferation, migration, multipotency, immunomodulatory activity and global gene expression profile. Moreover, the in vivo therapeutic potential of NMP-MSC was detected in a mouse model of contact hypersensitivity (CHS). Results: We demonstrate that NMP-MSC express posterior HOX genes and exhibit characteristics similar to those of bone marrow MSC (BMSC), and NMP-MSC derived from different hPSC lines show high level of similarity in global gene expression profiles. More importantly, NMP-MSC display much stronger immunomodulatory activity than BMSC in vitro and in vivo, as revealed by decreased inflammatory cell infiltration and diminished production of pro-inflammatory cytokines in inflamed tissue of CHS models. Conclusion: Our results identify NMP as a new source of MSC and suggest that functional and homogeneous NMP-MSC could serve as a candidate for MSC-based therapies.
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