title: Intraportal injection of insulin-producing cells generated from human bone marrow mesenchymal stem cells decreases blood glucose level in diabetic rats.
abstract: We studied the process of trans-differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) into insulin-producing cells. Streptozotocin (STZ)-induced diabetic rat model was used to study the effect of portal vein transplantation of these insulin-producing cells on blood sugar levels. The BM-MSCs were differentiated into insulin-producing cells under defined conditions. Real-time PCR, immunocytochemistry and glucose challenge were used to evaluate in vitro differentiation. Flow cytometry showed that hBM-MSCs were strongly positive for CD44, CD105 and CD73 and negative for hematopoietic markers CD34, CD38 and CD45. Differentiated cells expressed C-peptide as well as β-cells specific genes and hormones. Glucose stimulation increased C-peptide secretion in these cells. The insulin-producing, differentiated cells were transplanted into the portal vein of STZ-induced diabetic rats using a Port-A catheter. The insulin-producing cells were localized in the liver of the recipient rat and expressed human C-peptide. Blood glucose levels were reduced in diabetic rats transplanted with insulin-producing cells. We concluded that hBM-MSCs could be trans-differentiated into insulin-producing cells in vitro. Portal vein transplantation of insulin-producing cells alleviated hyperglycemia in diabetic rats.
authors.affiliation: Institute of Clinical Medicine, National Yang Ming University, Taipei , Taiwan , R.O.C. .
authors.forename: Pei-Jiun
authors.initials: PJ
authors.lastname: Tsai
authors.forename: Hwai-Shi
authors.initials: HS
authors.lastname: Wang
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Zen-Chung
authors.initials: ZC
authors.lastname: Weng
authors.forename: Tien-Hua
authors.initials: TH
authors.lastname: Chen
authors.forename: Jia-Fwu
authors.initials: JF
authors.lastname: Shyu
mesh_terms: D000818:Animals; D001786:Blood Glucose; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000628:therapy*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000637:transplantation*; D008297:Male; D059630:Mesenchymal Stem Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007328:Insulin