ArticleTissue engineering and regenerative medicine2026
Vav1 Sustains the Expression of Insulin, PDX1 and miR-375 During Differentiation of hiPSCs to β Cells: A Potential Target to Improve the In Vitro Generation of Insulin-Producing Cells.
Article in Tissue engineering and regenerative medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backroundHuman-induced pluripotent stem cells (hiPSCs) have emerged as a promising source of transplantable insulinproducing cells (IPCs) to restore insulin levels in Type 1 Diabetes (T1D) patients. Despite progress, obtaining fully functional β cells from hiPSCs remains challenging, underscoring the need to better understand the intracellular mechanisms involved. We investigated here the potential role of Vav1, a multidomain protein that we identified as crucial for the maturation of human biliary stem cells (hBTSCs) into β-like cells and in the trans-differentiation of pancreatic adenocarcinoma (PDAC) cells into IPCs;
methodsLevels and subcellular localization of Vav1 were investigated throughout a seven-step differentiation process of hiPSCs to β cells. Vav1expression was forcedly modulated in pancreatic progenitors, and the potential effects were evaluated on insulin production and on PDX1, miR-375, and Akt, key regulators of β cells generation; RESULTS. Vav1 showed dynamic modulation, with pancreatic precursor cells requiring adequate levels of the protein to generate IPCs.
resultsVav1 sustains the expression of PDX1, a primary regulator of insulin expression, and of its target miR-375, essential for determining β cell mass. Furthermore, Vav1 reduction correlated with increased activation of Akt, which regulates cell survival and insulin secretion in β cells and is down-regulated by miR- 375.
conclusionOur findings suggest the existence of a Vav1/PDX1/miR-375/Akt axis as part of the complex network orchestrating the generation of functional β cells. These insights indicate that strategies aimed at specifically modulating Vav1 levels may positively impact the generation of IPCs in vitro and, ultimately, β cell replacement therapy for T1D.
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