TITLE

Under non-adherent state, bone marrow mesenchymal stem cells can be efficiently induced into functional islet-like cell-clusters to normalize hyperglycemia in mice: a control study

AUTHOR(S)
Yihua Zhang; Zhongying Dou
PUB. DATE
June 2014
SOURCE
Stem Cell Research & Therapy;2014, Vol. 5 Issue 3, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Introduction It has been demonstrated that bone marrow mesenchymal stem cells (BMSCs) possess low immunogenicity and immunosuppression as an allograft, can differentiate into insulinproducing cells (IPCs) by in vitro induction, and may be a valuable cell source to regenerate pancreatic islets. However, thus far, the very low differentiation efficiency of BMSCs towards IPCs under adherent induction has hindered the clinical exploitation of these cells. The aim of this study is to explore a new way to efficiently induce BMSCs into IPCs and lay the groundwork for their clinical exploitation. Methods In comparison with adherent induction, BMSCs of human first-trimester abortus (hfBMSCs) under non-adherent state were induced towards IPCs in non-coated plastic dishes using a three-stage induction procedure developed by us. Induction effects were evaluated by statistics of cell-clustering rate of induced cells, and ultrastructural observation, dithizone staining, qPCR and Immunofluorescence assay, insulin and c-peptide release under glucose stimulus of cell-clusters, as well as transplantation test of the cell-clusters in diabetic model mice. Results With (6.175 ± 0.263) × 105 cells in 508.5 ± 24.5 cell-clusters, (3.303 ± 0.331) × 105 singlecells and (9.478 ± 0.208) × 105 total cell count averagely, 65.08 ± 2.98% hfBMSCs differentiated into pancreatic islet-like cell-clusters after non-adherent induction. With (3.993 ± 0.344) × 105 cells in 332.3 ± 41.6 cell-clusters, (5.437 ± 0.434) × 105 single-cells and (9.430 ± 0.340) × 105 total cell count averagely, 42.37 ± 3.70% hfBMSCs differentiated into pancreatic islet-like cell-clusters after adherent induction (P < 0.01, n = 10). The former is significantly higher than the latter. Calculated according to the cell-clustering rate and IPCs percentage in the cell-clusters, 29.80 ± 3.95% hfBMSCs differentiated into IPCs after nonadherent induction, 18.40 ± 2.08% hfBMSCs differentiated into IPCs after adherent induction (P < 0.01, n = 10), and the former is significantly higher than the latter. The cell-clusters expressed broad gene profile related to pancreatic islet cells, released insulin and c-peptide in a glucose concentration-dependent manner, and normalized hyperglycemia of streptozocininduced mice for at least 80 days following xenograft. Blood glucose of grafted-mice rose again after their graft removed. A series of examination of the grafts showed that transplanted cells produced human insulin in recipients. Conclusions Our studies demonstrate that non-adherent induction can greatly promote BMSCs to form pancreatic islet-like cell-clusters, thereby improving the differentiation efficiency of BMSCs towards IPCs.
ACCESSION #
96369251

 

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