title: Combinatorial treatment of bone marrow stem cells and stromal cell-derived factor 1 improves glycemia and insulin production in diabetic mice.
abstract: Transdifferentiation of stem cells into insulin-producing cells for the treatment of diabetes have shown promising but inconsistent results. We examined the potential for attracting bone marrow stem cells (BMSCs) to the pancreas using a chemokine, stromal cell-derived factor 1 (SDF-1). SDF-1 treatment markedly increased the number of GFP labeled BMSCs in the pancreas, but surprisingly, the majority was observed in liver. The liver cells had typical pancreatic endocrine cell gene expression including insulin I, insulin II, PDX-1, somatostatin, and glucagon. Combined treatment with SDF-1 and BMSC transplant reduced hyperglycemia and prolonged the long-term survival of diabetic mice, and a sub group had complete normoglycemia (<150 mg/dl), restored blood insulin levels, and normal glucose tolerance. Our results suggest that SDF-1 could potentially be used to improve the homing of stem cells and β-cell regeneration. The mechanism appears to involve an increase in insulin producing cells mainly in the liver.
authors.affiliation: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, 70803, USA. hcheng@vetmed.lsu.edu
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.forename: Y C
authors.initials: YC
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Wolfe
authors.forename: V
authors.initials: V
authors.lastname: Valencia
authors.forename: K
authors.initials: K
authors.lastname: Qian
authors.forename: L
authors.initials: L
authors.lastname: Shen
authors.forename: Y L
authors.initials: YL
authors.lastname: Tang
authors.forename: W H
authors.initials: WH
authors.lastname: Hsu
authors.forename: M A
authors.initials: MA
authors.lastname: Atkinson
authors.forename: M I
authors.initials: MI
authors.lastname: Phillips
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002096:C-Peptide / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000008:administration & dosage / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000628:therapy*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications / Q000628:therapy*; D007328:Insulin / Q000096:biosynthesis* / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D016019:Survival Analysis
chemical_list: D002096:C-Peptide; D054377:Chemokine CXCL12; D007328:Insulin