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Pancreatic progenitor cells (PPCs) are multipotent cells derived from the definitive endoderm that possess the capacity to differentiate into all pancreatic lineages, including endocrine (e.g., alpha, beta, delta cells), exocrine (acinar cells), and ductal cells (Gittes, 2009). These cells are characterized by the expression of specific transcription factors such as PDX1, SOX9, and NKX6.1, which orchestrate the complex developmental program of the pancreas (Rezania et al., 2014). In the context of regenerative medicine, PPCs are a primary focus for the development of cell-replacement therapies for Type 1 Diabetes, where they are generated in vitro from human pluripotent stem cells and subsequently matured into functional insulin-secreting beta cells (Pagliuca et al., 2014). While not a single molecular target, they represent a cellular therapeutic target for pharmacological modulation and transplantation (Kroon et al., 2008). Various small molecules and growth factors, such as retinoic acid and FGF10, are used to interact with signaling pathways in these cells to drive their maturation (Nostro & Keller, 2012). Challenges in their clinical application include ensuring precise lineage commitment, preventing tumorigenesis from residual undifferentiated cells, and overcoming immune-mediated rejection following transplantation (Agulnick et al., 2015).
Directed differentiation of pluripotent stem cells into pancreatic lineages through sequential activation and inhibition of developmental signaling pathways (e.g., Wnt, Nodal, Hedgehog, BMP, and FGF) to replace lost or dysfunctional beta cells.
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