ABSTRACT
Objective To study the biological characteristics of arsenic resistance cell model chronic arsenic exposure human bone marrow mesenchymal stem cells (CAsE-hFBMSCs) and discuss the consequence of chronic arsenite exposure to human mesenchymal stem cells (hFBMSCs). Methods hFBMSCs cultivated under general conditions,hFBMSC cell survival rate was detected in 48 hours with arsenite toxicity test under different doses arsenic [0(control),0.25,0.50,1.00,2.00,4.00,8.00,20.00,40.00,80.00,120.00 μmol/L]of the fist 2-generation(P2). According to the test results,1.00 μmol/L sodium arsenite was chosen to stimulate hFBMSCs for 14 weeks as experimental group,simultaneous 0 μmol/L sodium arsenite as the control group. And then,the phenotype was detected by fluorescence-activated cell sorting,and the cell cycle by flow cytometry. Finally,the cell malignant transformation was detected by soft-agar assay. Results Arsenite low than 10 μmol/L promoted cell proliferation,but inhibited cell proliferation when exceeding 10 μmol/L. Half of the lethal dose (LC_(50)) in experimental and control groups were (89.42±0.64),(52.48±0.71)μmol/L. The difference between two groups was statistically significant(t = 123.89,P < 0.05). The phenotype of CAsE-hFBMSCs was CD29,CD90,CD166 positive and CD34,CD45 negative. The phenotype of CAsE-hFBMSCs was the same as the control. Comparing to control group[(8.44±0.45)%,(9.14μ0.14)%,(82.42±0.60)%],G2/M phage[(17.72±5.47)%]and S phage [(25.34±3.36)%]cell increased,G0/G1 phage[(56.96±8.83)%]cell decreased in P2 CAsE-hFBMSCs. The cell cycle became nearly the same as the control group after adaption. CAsE-hFBMSCs did not show clone formation in soft agar clone formation assay. Conclusion Long last and low level exposure to arsenite does not influence the biologic features of hFBMSCs.
ABSTRACT
Diabetes mellitus has become one of the diseases which threaten the heath of human being in the 21st century.A goal of research in diabetes is to find a way to increase the number of functional insulin-producing cells. Islet transplantation has been considered to be the most effective approach to cure type Ⅰ and part of type Ⅱ diabetes mellitus.This approach, however, is severely limited by an inadequate supply of donor islets available for transplantation.Moreover, recent progress of stem cells research has shown that stem cells may act as a new source of islet transplantation in diabetes mellitus treatment. Recent evidence indicates that Glucagon-Like PeptideⅠ(GLP-1) plays a very important role in targeted differentiation of stem cells into Insulin-Producing Cells and pancreatic development. GLP-1 is an intestine-derived insulinotropic hormone that stimulates glucose dependent insulin production and secretion. GLP-1 can induce differentiation of stem cells into insulin-producing cells, which is achieved by up regulation of PDX-1 expression.PDX-1 is a transcription factor critical for pancreatic development and endocrine cell neogenesis and a marker for pancreatic stem cells. These new findings suggest an approach to create Insulin-Producing cells in vitro by expanding stem/progenitor cells and then to convert them into Insulin-Producing cells by treatment with GLP-1. Thus GLP-1 may be a means by which to create Insulin-Producing cells ex vivo for transplantation into patients with insulinopenic type Ⅰ diabetes and severe forms of type Ⅱ diabetes. This article reviews recent progress about GLP-1 and targeted differentiation of stem cells induced by GLP-1.