title: Multiple intravenous infusions of bone marrow mesenchymal stem cells reverse hyperglycemia in experimental type 2 diabetes rats.
abstract: The worldwide rapid increase in diabetes poses a significant challenge to current therapeutic approaches. Single-dose mesenchymal stem cell (MSC) infusion ameliorates hyperglycemia but fails to restore normoglycemia in diabetic animals. We therefore hypothesized that multiple intravenous MSC infusions may reverse hyperglycemia in type 2 diabetes (T2D) rats. We administered serial allogenous bone-marrow derived MSC infusions (1 × 10(6)cells/infusion) via the tail vein once every 2 weeks to T2D rats, induced by high-fat diet and streptozocin (STZ) administration. Hyperglycemia decreased only transiently after a single infusion in early-phase (1 week) T2D rats, but approximated normal levels after at least three-time infusions. This normal blood level was maintained for at least 9 weeks. Serum concentrations of both insulin and C-peptide were dramatically increased after serial MSC infusions. Oral glucose tolerance tests revealed that glucose metabolism was significantly ameliorated. Immunofluorescence analysis of insulin/glucagon staining revealed the restoration of islet structure and number after multiple MSC treatments. When multiple-MSC treatment was initiated in late-phase (5 week) T2D rats, the results were slightly different. The results of this study suggested that a multiple-MSC infusion strategy offers a viable clinical option for T2D patients.
authors.affiliation: Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Hao
authors.forename: Jiejie
authors.initials: J
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhao
authors.forename: Huilin
authors.initials: H
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Hou
authors.forename: Chuan
authors.initials: C
authors.lastname: Tong
authors.forename: Dongdong
authors.initials: D
authors.lastname: Ti
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.forename: Yu
authors.initials: Y
authors.lastname: Cheng
authors.forename: Yiming
authors.initials: Y
authors.lastname: Mu
authors.forename: Jianping
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D017077:Culture Media, Conditioned / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000628:therapy; D059305:Diet, High-Fat / Q000009:adverse effects; D005934:Glucagon / Q000378:metabolism; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000628:therapy*; D007004:Hypoglycemic Agents; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D017077:Culture Media, Conditioned; D007004:Hypoglycemic Agents; D007328:Insulin; D013311:Streptozocin; D005934:Glucagon
keywords: BM-MSCs; Bone marrow; Hyperglycemia; IPITTs; MSCs; Mesenchymal stem cells; Multiple infusion; OGTTs; STZ; T1D; T2D; Type 2 diabetes; bone-marrow-derived MSC; intraperitoneal insulin tolerance tests; mesenchymal stem cells; oral glucose tolerance tests; streptozocin; type 1 diabetes; type 2 diabetes