PDF(Pubmed)
Abstract：
Over the past decades, mesenchymal stromal cells (MSCs) have been extensively investigated as a potential therapeutic cell source for the treatment of various disorders. Differentiation of MSCs from human induced pluripotent stem cells (iMSCs) has provided a scalable approach for the biomanufacturing of MSCs and related biological products. Although iMSCs shared typical MSC markers and functions as primary MSCs (pMSCs), there is a lack of lineage specificity in many iMSC differentiation protocols. Here, a stepwise hiPSC-to-iMSC differentiation method is employed via intermediate cell stages of neural crest and cytotrophoblast to generate lineage-specific MSCs with varying differentiation efficiencies and gene expression. Through a comprehensive comparison between early developmental cell types (hiPSCs, neural crest, and cytotrophoblast), two lineage-specific iMSCs, and six source-specific pMSCs, are able to not only distinguish the transcriptomic differences between MSCs and early developmental cells, but also determine the transcriptomic similarities of iMSC subtypes to postnatal or perinatal pMSCs. Additionally, it is demonstrated that different iMSC subtypes and priming conditions affected EV production, exosomal protein expression, and cytokine cargo.
摘要：
在过去的几十年里，间充质基质细胞（MSC）已被广泛研究作为治疗各种疾病的潜在治疗细胞来源。MSC从人诱导多能干细胞(iMSC)的分化为MSC和相关生物制品的生物制造提供了可扩展的方法。虽然iMSC共享典型的MSC标记和功能作为主要的MSC（pMSC），许多iMSC分化方案缺乏谱系特异性.这里,通过神经c和细胞滋养层的中间细胞阶段，采用逐步的hiPSC到iMSC分化方法，以产生具有不同分化效率和基因表达的谱系特异性MSC。通过早期发育细胞类型(hiPSCs，神经嵴,和细胞滋养层)，两个谱系特异性的iMSC，和六个来源特异性pMSC，不仅能够区分MSCs和早期发育细胞之间的转录组差异，而且还确定iMSC亚型与出生后或围产期pMSC的转录组相似性。此外,证明了不同的iMSC亚型和启动条件会影响EV的生产，外泌体蛋白表达，和细胞因子货物。
