Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into insulin-producing cells (IPCs). Bio-scaffolds derived from decellularized organs can act as a carrier for seed cells and may have broad applications in regenerative medicine. This study investigated the effect of native pancreatic stroma obtained from decellularized pancreas on the proliferation, migration and differentiation of BMSCs into IPCs, and explored the potential underlying molecular mechanism. The decellularized pancreas bio-scaffold was obtained by perfusion with Triton X-100/ammonium hydroxide, followed by digestion with a mixture of pepsin and hydrochloric acid to prepare the stroma solution. Islet-like cells were differentiated from BMSCs by a three-step induction method. The differences on the cytological behavior with or without stroma were evaluated by morphological observation, insulin release assay, qRT-PCR assay and western blot analysis. Our results showed that, stroma derived from decellularized pancreas could promote the proliferation and migration of BMSCs. Furthermore, the formation of IPCs could also be promoted, which possessed similar morphology to endogenous islets. During the induced differentiation process, the presence of stroma significantly increased the expression of insulin 1, insulin 2 and Pdx-1, as well as insulin release. This was accompanied by an increase in the phosphorylation of Akt and ERK in third stage cell clusters, which was prevented by the addition of the inhibitors PD98059 and LY294002, respectively. In summary, decellularized pancreatic stroma could promote the proliferation, migration and differentiation of BMSCs into IPCs, and this involved the activation of Akt and ERK signal pathways.

中文翻译：

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脱细胞和增溶的胰腺基质可促进BMSC在体外增殖，迁移和分化为IPC。

骨髓间充质干细胞（BMSC）具有分化为胰岛素产生细胞（IPC）的能力。源自脱细胞器官的生物支架可以充当种子细胞的载体，并在再生医学中具有广泛的应用。这项研究调查了从脱细胞胰腺获得的天然胰腺基质对BMSCs向IPCs增殖，迁移和分化的影响，并探讨了潜在的潜在分子机制。通过用Triton X-100 /氢氧化铵灌注，然后用胃蛋白酶和盐酸的混合物消化以制备基质溶液，从而获得脱细胞的胰腺生物支架。通过三步诱导法将胰岛样细胞从骨髓间充质干细胞中分化出来。通过形态学观察，胰岛素释放测定，qRT-PCR测定和蛋白质印迹分析评估有无基质细胞行为的差异。我们的结果表明，来自脱细胞胰腺的基质可以促进骨髓间充质干细胞的增殖和迁移。此外，还可以促进IPC的形成，其具有与内源胰岛相似的形态。在诱导分化过程中，基质的存在显着增加了胰岛素1，胰岛素2和Pdx-1的表达以及胰岛素的释放。这伴随着第三阶段细胞簇中Akt和ERK的磷酸化的增加，这分别通过添加抑制剂PD98059和LY294002来阻止。总之，脱细胞的胰腺基质可以促进增殖，