title: Mesenchymal stem cell-like cells derived from mouse induced pluripotent stem cells ameliorate diabetic polyneuropathy in mice.
abstract: BACKGROUND
  Although pathological involvements of diabetic polyneuropathy (DPN) have been reported, no dependable treatment of DPN has been achieved. Recent studies have shown that mesenchymal stem cells (MSCs) ameliorate DPN. Here we demonstrate a differentiation of induced pluripotent stem cells (iPSCs) into MSC-like cells and investigate the therapeutic potential of the MSC-like cell transplantation on DPN.
  
  
  METHODS
  For induction into MSC-like cells, GFP-expressing iPSCs were cultured with retinoic acid, followed by adherent culture for 4 months. The MSC-like cells, characterized with flow cytometry and RT-PCR analyses, were transplanted into muscles of streptozotocin-diabetic mice. Three weeks after the transplantation, neurophysiological functions were evaluated.
  
  
  RESULTS
  The MSC-like cells expressed MSC markers and angiogenic/neurotrophic factors. The transplanted cells resided in hindlimb muscles and peripheral nerves, and some transplanted cells expressed S100 β in the nerves. Impairments of current perception thresholds, nerve conduction velocities, and plantar skin blood flow in the diabetic mice were ameliorated in limbs with the transplanted cells. The capillary number-to-muscle fiber ratios were increased in transplanted hindlimbs of diabetic mice.
  
  
  CONCLUSIONS
  These results suggest that MSC-like cell transplantation might have therapeutic effects on DPN through secreting angiogenic/neurotrophic factors and differentiation to Schwann cell-like cells.
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan ; Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
authors: Tatsuhito
authors: T
authors: Himeno
authors: Hideki
authors: H
authors: Kamiya
authors: Keiko
authors: K
authors: Naruse
authors: Zhao
authors: Z
authors: Cheng
authors: Sachiko
authors: S
authors: Ito
authors: Masaki
authors: M
authors: Kondo
authors: Tetsuji
authors: T
authors: Okawa
authors: Atsushi
authors: A
authors: Fujiya
authors: Jiro
authors: J
authors: Kato
authors: Hirohiko
authors: H
authors: Suzuki
authors: Tetsutaro
authors: T
authors: Kito
authors: Yoji
authors: Y
authors: Hamada
authors: Yutaka
authors: Y
authors: Oiso
authors: Kenichi
authors: K
authors: Isobe
authors: Jiro
authors: J
authors: Nakamura
mesh_terms: D043925:Angiogenesis Inducing Agents; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002196:Capillaries / Q000473:pathology; D002454:Cell Differentiation; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D005121:Extremities / Q000098:blood supply / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism; D009431:Neural Conduction; D010465:Perception; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; D001786:Blood Glucose; C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009414:Nerve Growth Factors; D049452:Green Fluorescent Proteins; D001616:beta-Galactosidase