Derivation of Clinically Compliant MSCs from CD105+, CD24− Differentiated Human ESCs

作者：Qizhou Lian, Elia Lye, Keng Suan Yeo, Eileen Khia Way Tan, Manuel Salto‐Tellez, Tongming Liu, Nallasivam Palanisamy, Reida Menshawe El Oakley, Eng Hin Lee, Bing Lim, Sai Kiang Lim · 发表于：Stem Cells · 年份：2006 · DOI：10.1634/stemcells.2006-0420 · 被引用次数：321 · 研究领域：Mesenchymal stem cell research、Pluripotent Stem Cells Research、Tissue Engineering and Regenerative Medicine

Adult tissue-derived mesenchymal stem cells (MSCs) have demonstrated therapeutic efficacy in treating diseases or repairing damaged tissues through mechanisms thought to be mediated by either cell replacement or secretion of paracrine factors. Characterized, self-renewing human ESCs could potentially be an invariable source of consistently uniform MSCs for therapeutic applications. Here we describe a clinically relevant and reproducible manner of generating identical batches of hESC-derived MSC (hESC-MSC) cultures that circumvents exposure to virus, mouse cells, or serum. Trypsinization and propagation of HuES9 or H1 hESCs in feeder- and serum-free selection media generated three polyclonal, karyotypically stable, and phenotypically MSC-like cultures that do not express pluripotency-associated markers but displayed MSC-like surface antigens and gene expression profile. They differentiate into adipocytes, osteocytes, and chondrocytes in vitro. Gene expression and fluorescence-activated cell sorter analysis identified CD105 and CD24 as highly expressed antigens on hESC-MSCs and hESCs, respectively. CD105+, CD24- monoclonal isolates have a typical MSC gene expression profiles and were identical to each other with a highly correlated gene expression profile (r(2) > .90). We have developed a protocol to reproducibly generate clinically compliant and identical hESC-MSC cultures.