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.

中文翻译：

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HA水凝胶从人多能干细胞两步生成间充质干/基质细胞，增强了对兔关节炎的功效

当前的研究启发了人类多能干细胞（hPSC）衍生的间充质干/基质细胞（MSCs）在再生医学中的美好前景。然而，对它们的签名和其他替代生物材料在骨关节炎（OA）中的应用的系统研究仍不清楚。在本文中，我们最初利用小分子文库介导的编程策略来诱导hPSC-MSC。然后，借助多方面分析，例如流式细胞仪（FCM），染色体核细胞和细胞活力，伤口愈合和微管形成测定以及与T淋巴细胞共培养，我们系统地评估了特征的表征以及hPSC的体内功效-MSCs和HA水凝胶复合物对兔骨关节炎模型的影响 我们发现LLY-507和AZD5153的组合足以从具有干性的hESC和hiPSC（POU5F1 / SOX2 / NANOG）高效诱导CD73 + CD90 + CD105 + CD31-CD34-CD45-HLA-DR-MSC诱导。程序化的hPSC-MSC表现出保守的转录组变异，并经历了具有间充质相关基因表达（NT5E，ENG，VIM和FN1）的异质中间阶段，并表现出典型的细胞形态，免疫表型和正常核型，多系分化潜能，有利的细胞活力，体外促血管生成和免疫调节特性。同时，该细胞群体在体内具有HA水凝胶的OA兔子上表现出较好的恢复和改善功能。总的来说，我们建立了快速，方便的hPSC-MSC生成程序，无需进行多余的操作。