title: Transplantation of mesenchymal stem cells recruits trophic macrophages to induce pancreatic beta cell regeneration in diabetic mice.
abstract: Alleviation of hyperglycemia in chemical-induced diabetic mice has been reported after bone marrow transplantation. Nevertheless, the underlying mechanism remains elusive. In the present study, we transplanted genetically labeled primary mouse mesenchymal stem cells into the pancreas of the streptozotocin-treated hyperglycemic isogeneic mice, resulting in a decrease in blood glucose due to a recovery in beta cell mass. Further analysis revealed that the increase in beta cell mass was predominantly attributable to beta cell replication. The grafted mesenchymal stem cells did not transdifferentiate into beta cells themselves but recruited and polarized macrophages in a Stromal cell-derived factor 1-dependent manner, which in turn promoted beta cell replication. Our finding thus suggests that transplantation of autogenic mesenchymal stem cells may increase functional beta cell mass by boosting beta cell replication in diabetes.
authors.affiliation: Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China. Electronic address: caoxc@tijmu.edu.cn.
authors.forename: Xiaocang
authors.initials: X
authors.lastname: Cao
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin, China.
authors.forename: Zhi-Bo
authors.initials: ZB
authors.lastname: Han
authors.affiliation: Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000628:therapy*; D006943:Hyperglycemia / Q000473:pathology / Q000628:therapy*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008264:Macrophages / Q000637:transplantation; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000503:physiopathology; D012038:Regeneration
chemical_list: D001786:Blood Glucose
keywords: Diabetes; M2 macrophages; Mesenchymal stem cells; SDF-1; Wnt3a