Co-culture of Human Fetal Bone Marrow-Derived Mesenchymal Stem Cells Promotes the Proliferation and Differentiation of Human Pancreatic Progenitor Cells into Islet-like Cell Clusters
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香港中文大學研究人員

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摘要The application of clinical islet transplantation is hindered by the inherent lack of human donors; however, directed differentiation of human pancreatic progenitor cells (PPCs) into islet-like cell clusters (ICCs) opens an avenue to providing transplantable islets for diabetic patients. Recent reports showed that rat mesenchyme acts on the upstream and downstream of Ngn3 to direct the lineage of pancreatic β-cell fate, while co-transplantation of mouse mesenchymal stem cells (MSCs) enhances islet revascularization and function. Besides, co-culture with MSCs promotes the proliferation and differentiation of human cardiac stem cells. However, the effects of MSCs co-culture on the development of human PPCs into ICCs and its functionality are largely ambiguous.
We thus co-cultured our two established human cell models of fetal bone marrow-derived MSCs and fetal pancreas-derived PPCs/ICCs to examine the effects on the development of the PPCs into ICCs.
Results showed that co-culture of MSCs increased the expression of PPC differentiation markers, such as Pdx1, Insulin and Nkx2.2; the resultant ICCs exhibited higher insulin content compared with the cocktail control. In addition, MSC conditioned medium (CM) stimulated PPCs proliferation while reducing cell death. Apoptosis was detected in serum-free condition, which was further confirmed by arrested cell growth in G0/G1 phase and these effects were blocked by the MSC-CM. Moreover, Bcl-2 was upregulated whereas BAX was downregulated by the MSC-CM compared with the starvation condition.
Our data indicate that MSCs can promote the proliferation and differentiation of human PPCs into ICCs, thus offering an insight into the co-culture approach to generating functional -cells for diabetic patients. To this end, we are undertaking ICCs transplantation and microarray to further assess the in vivo functionality and molecular signaling involved.
著者Li X, Wu S, Leung PS
會議名稱American Diabetes Association 77th Scientific Sessions
會議開始日09.06.2017
會議完結日13.06.2017
會議地點San Diego, CA
會議國家/地區美國
出版年份2017
月份6
語言美式英語

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