title: Efficient differentiation of human pluripotent stem cells into mesenchymal stem cells by modulating intracellular signaling pathways in a feeder/serum-free system.
abstract: Mesenchymal stem cells (MSCs) derived from human pluripotent stem cells (hPSC-derived MSCs) will be one promising alternative cell source for MSC-based therapies. Here, an efficient protocol is demonstrated for generating hPSC-derived MSCs under a feeder-free culture system by regulating signaling pathways. Simultaneous treatments with Activin A, BIO (6-bromoindirubin-3'-oxime), and bone morphogenetic protein 4 (ABB) activated the transcription of mesoderm-lineage genes such as T, MIXL1, and WNT3 in hPSCs. The ABB-treated hPSCs could develop into CD105(+) cells with a high efficiency of 20% in the MSC-induction medium. The properties of the hPSC-derived CD105(+) cells were similar to those of adult MSCs in terms of surface antigens. Also, hPSC-derived MSCs had the potential to differentiate into adipocytes, osteoblasts, and chondrocytes in vitro. The results demonstrated that functional MSCs could be generated efficiently from hPSCs by the combined modulation of signaling pathways.
authors.affiliation: Department of Biological Sciences and Center for Stem Cell Differentiation, KAIST (Korean Advance Institute of Sciences and Technology), Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Ngoc-Tung
authors.initials: NT
authors.lastname: Tran
authors.forename: Quynh-Mai
authors.initials: QM
authors.lastname: Trinh
authors.forename: Gyun Min
authors.initials: GM
authors.lastname: Lee
authors.forename: Yong-Mahn
authors.initials: YM
authors.lastname: Han
mesh_terms: D028341:Activins / Q000494:pharmacology; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D016895:Culture Media, Serum-Free; D004357:Drug Synergism; D000071063:Endoglin; D020869:Gene Expression Profiling; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010091:Oximes / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: C483321:6-bromoindirubin-3'-oxime; D015703:Antigens, CD; C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D016895:Culture Media, Serum-Free; C064206:ENG protein, human; D000071063:Endoglin; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D010091:Oximes; D011956:Receptors, Cell Surface; C422405:activin A; D028341:Activins