title: Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice.
abstract: BACKGROUND
  Aging and aging-related disorders impair the survival and differentiation potential of bone marrow mesenchymal stem cells (MSCs) and limit their therapeutic efficacy. Induced pluripotent stem cells (iPSCs) may provide an alternative source of functional MSCs for tissue repair. This study aimed to generate and characterize human iPSC-derived MSCs and to investigate their biological function for the treatment of limb ischemia.
  
  
  RESULTS
  Human iPSCs were induced to MSC differentiation with a clinically compliant protocol. Three monoclonal, karyotypically stable, and functional MSC-like cultures were successfully isolated using a combination of CD24(-) and CD105(+) sorting. They did not express pluripotent-associated markers but displayed MSC surface antigens and differentiated into adipocytes, osteocytes, and chondrocytes. Transplanting iPSC-MSCs into mice significantly attenuated severe hind-limb ischemia and promoted vascular and muscle regeneration. The benefits of iPSC-MSCs on limb ischemia were superior to those of adult bone marrow MSCs. The greater potential of iPSC-MSCs may be attributable to their superior survival and engraftment after transplantation to induce vascular and muscle regeneration via direct de novo differentiation and paracrine mechanisms.
  
  
  CONCLUSIONS
  Functional MSCs can be clonally generated, beginning at a single-cell level, from human iPSCs. Patient-specific iPSC-MSCs can be prepared as an "off-the-shelf" format for the treatment of tissue ischemia.
authors.affiliation: Cardiology Division, Department of Medicine, University of Hong Kong, Hong Kong, China. qzlian@hkucc.hku.hk
authors.forename: Qizhou
authors.initials: Q
authors.lastname: Lian
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Zhang
authors.forename: Hua Kun
authors.initials: HK
authors.lastname: Zhang
authors.forename: Xingang
authors.initials: X
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Francis Fu-Yuen
authors.initials: FF
authors.lastname: Lam
authors.forename: Sarang
authors.initials: S
authors.lastname: Kang
authors.forename: Jian Chuan
authors.initials: JC
authors.lastname: Xia
authors.forename: Wing-Hong
authors.initials: WH
authors.lastname: Lai
authors.forename: Ka-Wing
authors.initials: KW
authors.lastname: Au
authors.forename: Yen Yen
authors.initials: YY
authors.lastname: Chow
authors.forename: Chung-Wah
authors.initials: CW
authors.lastname: Siu
authors.forename: Chuen-Neng
authors.initials: CN
authors.lastname: Lee
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology; D002999:Clone Cells / Q000637:transplantation; D042783:Endothelial Cells / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D005822:Genetic Vectors / Q000235:genetics; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D007511:Ischemia / Q000601:surgery*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D010011:Osteocytes / Q000166:cytology; D019899:Paracrine Communication; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation; D011993:Recombinant Fusion Proteins / Q000502:physiology; D020127:Recovery of Function; D013724:Teratoma / Q000473:pathology; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins