Communications Biology · 20 authors, 13 centres
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This study describes a laboratory protocol that uses five transcription factors to directly convert human skin fibroblasts into insulin-producing, β-like cells. The reprogrammed cells showed activation of β-cell genes and functional responses to glucose, including insulin secretion.
This preclinical study established a direct reprogramming protocol to convert human fibroblasts into insulin-producing cells. The researchers identified that a sequential combination of five transcription factors (Pdx1, Neurog3, MafA, Pax4, Nkx2-2) delivered via a single polycistronic adenovirus, followed by a 3D culture system, was effective. Reprogrammed cells exhibited transcriptomic changes consistent with β-cell identity, including the repression of fibroblast-specific genes and β-cell disallowed genes. Functionally, the cells mobilized intracellular calcium and secreted insulin in response to glucose stimulation, though levels were lower than in human islets. The study demonstrates proof-of-concept for generating β-like cells from an accessible human somatic cell source. Limitations include the need for further optimization to improve cell maturity and the poor long-term survival of transplanted cells in a mouse model.
