Two-step generation of mesenchymal stem/stromal cells from human pluripotent stem cells with reinforced efficacy upon osteoarthritis rabbits by HA hydrogel
Open Access
- 6 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell & Bioscience
- Vol. 11 (1), 1-17
- https://doi.org/10.1186/s13578-020-00516-x
Abstract
Current studies have enlightened the rosy prospects of human pluripotent stem cell (hPSC)-derived mesenchymal stem/stromal cells (MSCs) in regenerative medicine. However, systematic investigation of their signatures and applications with alternative biomaterials in osteoarthritis (OA) remains indistinct. Herein, we initially took advantage of a small molecule library-mediated programming strategy for hPSC-MSC induction. Then, with the aid of multifaceted analyses such as flow cytometry (FCM), chromosome karyocyte and cell vitality, wound healing and microtubule formation assay and coculturing with T lymphocytes, we systematically evaluated the characterizations of signatures in vitro and the in vivo efficacy of hPSC-MSCs and HA hydrogel composite on rabbit osteoarthritis model. We found the combination of LLY-507 and AZD5153 was sufficient for high-efficiency CD73+CD90+CD105+CD31−CD34−CD45−HLA-DR− MSC induction from both hESCs and hiPSCs with stemness (POU5F1/SOX2/NANOG). The programmed hPSC-MSCs revealed conservative transcriptome variations and went through a heterogeneous intermediate-stage with mesenchymal-associated gene expression (NT5E, ENG, VIM and FN1) as well as displayed typical cytomorphology, immunophenotypes and normal karyotyping, multilineage differentiation potential, favorable cell vitality, proangiogenic and immunoregulatory properties in vitro. Meanwhile, the cell population exhibited preferable restorative and ameliorative function on OA rabbits with HA hydrogel in vivo. Collectively, we established a rapid and convenient procedure for hPSC-MSC generation without redundant manipulations. The fundamental and clinical studies upon osteoarthritis (OA) treatment would benefit tremendously from the combination of the inexhaustible hPSC-MSCs and advantageous biomaterials.Keywords
Funding Information
- Natural Science Foundation of Tianjin City (19JCQNJC12500)
- Project Funded by China Postdoctoral Science Foundation (2019M661033)
- Major Program of the National Natural Science Foundation of China (81330015)
- National Science and Technology Major Projects of China for "Major New Drugs Innovation and Development" (2014ZX09508002-003)
- National Natural Science Foundation of China (81900126)
- Natural Science Foundation of Shandong Province (2020, to LSZ)
- Emergency project funded by Department of Science and Technology of Jiangxi Province (2020, to ZCH)
- Key project funded by Department of Science and Technology of Shangrao City (2020)
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