title: Niche-dependent regulations of metabolic balance in high-fat diet-induced diabetic mice by mesenchymal stromal cells.
abstract: Mesenchymal stromal cells (MSCs) have great potential to maintain glucose homeostasis and metabolic balance. Here, we demonstrate that in mice continuously fed with high-fat diet (HFD) that developed non-insulin-dependent diabetes, two episodes of systemic MSC transplantations effectively improve glucose tolerance and blood glucose homeostasis and reduce body weight through targeting pancreas and insulin-sensitive tissues and organs via site-specific mechanisms. MSCs support pancreatic islet growth by direct differentiation into insulin-producing cells and by mitigating the cytotoxicity of interleukin 1 (IL-1) and tumor necrosis factor-α (TNF-α) in the pancreas. Localization of MSCs in the liver and skeletal muscles in diabetic animals is also enhanced and therefore improves glucose tolerance, although long-term engraftment is not observed. MSCs prevent HFD-induced fatty liver development and restore glycogen storage in hepatocytes. Increased expression of IL-1 receptor antagonist and Glut4 in skeletal muscles after MSC transplantation results in better blood glucose homeostasis. Intriguingly, systemic MSC transplantation does not alter adipocyte number, but it decreases HFD-induced cell infiltration in adipose tissues and reduces serum levels of adipokines, including leptin and TNF-α. Taken together, systemic MSC transplantation ameliorates HFD-induced obesity and restores metabolic balance through multisystemic regulations that are niche dependent. Such findings have supported systemic transplantation of MSCs to correct metabolic imbalance.
authors.affiliation: Center for Stem Cell Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Andrea Tung-Qian
authors.initials: AT
authors.lastname: Ji
authors.affiliation: Center for Stem Cell Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yun-Chuang
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Center for Stem Cell Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Fu
authors.affiliation: Department of Orthopaedic Surgery, Taipei City Hospital, Taipei, Taiwan Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan wh9801@yahoo.com.tw kslee@vghtpe.gov.tw.
authors.forename: Oscar K
authors.initials: OK
authors.lastname: Lee
authors.affiliation: Center for Stem Cell Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan Department of Ophthalmology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan wh9801@yahoo.com.tw kslee@vghtpe.gov.tw.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Ho
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D006801:Humans; D007328:Insulin / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D007328:Insulin; D007375:Interleukin-1; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha