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标题：MSCs derived from iPSCs with a modified protocol are tumor-tropic but have much less potential to promote tumors than bone marrow MSCs
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作者：Qingguo Zhao ; Carl A. Gregory ; Ryang Hwa Lee 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：2
页码：530-535
DOI：10.1073/pnas.1423008112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceMesenchymal stem or stromal cells (MSCs) offer great promise as potential therapies for cancers and other diseases. However, applications of MSCs for cancer therapy are hindered by their protumor potential under certain conditions, considerable donor variations, and limited expandability. Here we report generation of induced pluripotent stem cells (iPSC)-derived MSCs with same tumor homing capacity but much less protumor potential using a modified protocol with high derivation efficiency. Starting from iPSCs with almost unlimited expandability, the protocol can be readily scaled up to provide huge amounts of MSCs with uniform biological properties for multicenter evaluation, large animal experiments, and potential clinical trial. Moreover, therapeutic transgenes can be inserted into safe-harbor loci of iPSCs before derivation of MSCs to eliminate insertional mutation and guarantee stable expression of transgenes during prolonged expansion. Mesenchymal stem or stromal cells (MSCs) have many potential therapeutic applications including therapies for cancers and tissue damages caused by cancers or radical cancer treatments. However, tissue-derived MSCs such as bone marrow MSCs (BM-MSCs) may promote cancer progression and have considerable donor variations and limited expandability. These issues hinder the potential applications of MSCs, especially those in cancer patients. To circumvent these issues, we derived MSCs from transgene-free human induced pluripotent stem cells (iPSCs) efficiently with a modified protocol that eliminated the need of flow cytometric sorting. Our iPSC-derived MSCs were readily expandable, but still underwent senescence after prolonged culture and did not form teratomas. These iPSC-derived MSCs homed to cancers with efficiencies similar to BM-MSCs but were much less prone than BM-MSCs to promote the epithelial-mesenchymal transition, invasion, stemness, and growth of cancer cells. The observations were probably explained by the much lower expression of receptors for interleukin-1 and TGF{beta
关键词：mesenchymal stem cells ; cancer ; iPS cells ; tumor tropism ; protumor effects