title: Contribution of murine bone marrow mesenchymal stem cells to pancreas regeneration after partial pancreatectomy in mice.
abstract: The implantation of BMSCs (bone marrow mesenchymal stem cells) has emerged as a potential method of treating tissue damage, but the in vivo differentiation of BMSCs in an injured pancreas and its therapeutic effects have not been determined. Our aim has been to investigate the potential of BMSCs to contribute to the parenchyma and mesenchymal components of the pancreas during rapid regeneration, with preliminary exploration of the molecular mechanisms of this process. GFP(+) (green fluorescent protein(+) ) BMSCs were intravenously infused into the tail veins of mice that had received a 65-70% partial pancreatectomy, while mice that had only received a partial pancreatectomy and mice that had only been injected with BMSCs served as controls. Four weeks later, the injected GFP(+) BMSCs were diffusely engrafted in the pancreatic parenchyma and mesenchyma of the recipient mice with pancreatic injuries and had differentiated into pancreatic ductal epithelial cells (accounting for 1.7±0.3%), vascular endothelial cells (3.2±0.6%) and PSCs (pancreatic stellate cells) (5.2±1.6%), but no β or neural cells. Significantly, more engrafted and differentiated GFP(+) BMSCs were observed in the regenerating pancreas than in the normal pancreas. For the mice that received a partial pancreatectomy, the pancreatic weight/body weight of the mice with BMSC treatment was greater than mice without BMSC treatment (P<0.05). In addition, real-time RT-PCR (reverse transcription-PCR) showed that the expression levels of miR-9 (microRNA 9) and miR-204 in the engrafted BMSCs (5.2- and 2.6-fold, P<0.05, respectively) were increased compared with wild-type BMSCs. We also observed a significant reduction in the expression of miR-375 (0.71-fold, P<0.05) in engrafted GFP(+) BMSCs compared with wild-type BMSCs. BMSCs can therefore be a potential cell bank for treating pancreatic injuries by contributing to a variety of cell types. This process might be related to the expression of miR-9, miR-204 and miR-375.
authors.affiliation: Pancreatic Centre, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Ave 1277, Wuhan City, Hubei Province 430022, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.forename: Chun-You
authors.initials: CY
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Su-Dong
authors.initials: SD
authors.lastname: Zhan
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Kui
authors.initials: K
authors.lastname: Tian
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002478:Cells, Cultured; D049452:Green Fluorescent Proteins / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D010179:Pancreas / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D010180:Pancreatectomy; D012038:Regeneration / Q000502:physiology
chemical_list: C574692:MIRN204 microRNA, mouse; C551804:MIRN9 microRNA, mouse; D035683:MicroRNAs; C540349:Mirn375 microRNA, mouse; D049452:Green Fluorescent Proteins