Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells

Abstract EN

Activation of the pancreatic lineage in the liver has been suggested as a potential autologous cell replacement therapy for diabetic patients.

Transcription factors-induced liver-to-pancreas reprogramming has been demonstrated in numerous species both in vivo and in vitro.

However, human-derived liver cells capable of acquiring the alternate pancreatic repertoire have never been characterized.

It is yet unknown whether hepatic-like stem cells or rather adult liver cells give rise to insulin-producing cells.

Using an in vitro experimental system, we demonstrate that proliferating adherent human liver cells acquire mesenchymal-like characteristics and a considerable level of cellular plasticity.

However, using a lineage-tracing approach, we demonstrate that insulin-producing cells are primarily generated in cells enriched for adult hepatic markers that coexpress both albumin and mesenchymal markers.

Taken together, our data suggest that adult human hepatic tissue retains a substantial level of developmental plasticity, which could be exploited in regenerative medicine approaches.