title: Pancreatic islet-like clusters from bone marrow mesenchymal stem cells of human first-trimester abortus can cure streptozocin-induced mouse diabetes.
abstract: Bone marrow mesenchymal stem cells (BMSCs) have been reported to possess low immunogenicity and cause immunosuppression of recipients when allografted. They can differentiate into insulin-producing cells and may be a valuable source for islet formation. However, the extremely low differentiating rate of adult BMSCs toward insulin-producing cells and the insufficient insulin secretion of the differentiated BMSCs in vitro prevent their clinical use in diabetes treatment. Little is known about the potential of cell replacement therapy with human BMSCs. Previously, we isolated and identified human first-trimester fetal BMSCs (hfBMSCs). Under a novel four-step induction procedure established in this study, the hfBMSCs effectively differentiated into functional pancreatic islet-like cell clusters that contained 62 ± 14% insulin-producing cells, expressed a broad gene profile related to pancreatic islet β-cell development, and released high levels of insulin (2.245 ± 0.222 pmol/100 clusters per 30 min) and C-peptide (2.200 ± 0.468 pmol/100 clusters per 30 min) in response to 25 mmol/L glucose stimulus in vitro. The pancreatic islet-like cell clusters normalized the blood glucose level of diabetic model mice for at least 9 weeks when xenografted; blood glucose levels in these mice rose abnormally again when the grafts were removed. Examination of the grafts indicated that the transplanted cells survived in recipients and produced human insulin and C-peptide in situ. These results demonstrate that hfBMSCs derived from a human first-trimester abortus can differentiate into pancreatic islet-like cell clusters following an established four-step induction. The insulin-producing clusters present advantages in cell replacement therapy of type 1 diabetic model mice.
authors.affiliation: Shaanxi Branch of National Stem Cell Engineering and Technology Centre, College of Veterinary Medicine, Northwest A & F University, Yangling, Shaanxi, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Shen
authors.forename: Jinlian
authors.initials: J
authors.lastname: Hua
authors.forename: Anmin
authors.initials: A
authors.lastname: Lei
authors.forename: Changrong
authors.initials: C
authors.lastname: Lv
authors.forename: Huayan
authors.initials: H
authors.lastname: Wang
authors.forename: Chunrong
authors.initials: C
authors.lastname: Yang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Gao
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Dou
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002096:C-Peptide / Q000378:metabolism; D002449:Cell Aggregation; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D042541:Intracellular Space / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D016381:Islets of Langerhans Transplantation; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011384:Proinsulin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin