Mesenchymal stem cells (MSCs) can be successfully induced to differentiate into insulin-producing cells （IPCs) by a variety of small molecules and cytokines in vitro. However, problems remain, such as low transdifferentiation efficiency and poor maturity of trans-differentiated cells. The damaged pancreatic cells secreted a large amount of soluble proteins, which were able to promote pancreative islet regeneration and MSCs differentiation. In this study, we utilized the rat injured pancreatic tissue extract to modulate rat bone marrow-derived MSCs differentiation into IPCs by the traditional two-step induction. Our results showed that injured pancreatic tissue extract could effectively promote the trans-differentiation efficiency and maturity of IPCs by the traditional induction. Moreover, IPCs were able to release more insulin in a glucose-dependent manner and ameliorate better the diabetic conditions of streptozotocin (STZ)-treated rats. Our study provides a new strategy to induce an efficient and directional differentiation of MSCs into IPCs.

Mesenchymal stem cells (MSCs) are self-renewing cells that exhibit differentiation capacity and immune regulation ability. These versatile cells have a wide range of potential applications. However, the spontaneous differentiation and aging of MSCs during long-term culturing restrict the amount of cells available for therapies and tissue engineering. Thus, maintaining the biological characteristics of MSCs during long-term culturing is crucial. Chromatic modification via epigenetic regulatory mechanisms (e.g., histone acetylation, deacetylation, and methylation) is crucial in stem cell pluripotency. We investigated the effects of largazole or trichostatin A (TSA), a novel histone deacetylase inhibitor (HDACi), against human umbilical cord (hUC)-MSCs aging. Results show that low concentrations of largazole or TSA can significantly improve hUC-MSCs proliferation and delay hUC-MSCs aging. Largazole can better improve MSCs proliferation than TSA. HDAC is modulate histone H3 acetylation and methylation in the telomerase reverse-transcriptase, octamer-binding transcription factor 4, Nanog, C-X-C chemokine receptor 4, alkaline phosphatase, and osteopontin genes. HDACis can promote hUC-MSCs proliferation and suppress hUC-MSCs spontaneous osteogenic differentiation. HDACis can affect histone H3 lysine 9 or 14 acetylation and histone H3 lysine 4 dimethylation, thus increasing the mRNA expression of pluripotent and proliferative genes and suppressing the spontaneous differentiation of hUC-MSCs.

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