Enhanced liver regeneration via targeted mRNA delivery for partial in vivo reprogramming

Utilizing Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc: OSKM) for in vivo partial reprogramming generates ‘injury-responsive cells’ in the intestine, mirroring those derived from injury-induced dedifferentiation. Thus, the transgene induction of OSKM or viral delivery of Oct4, Sox2, and Klf4 shows promise in facilitating tissue regeneration in the intestine, liver, skeletal muscle, and retina.

Herein, we demonstrated that transient OSKM induction produces two distinct liver progenitor-like cell populations. One of these populations resembles liver progenitor-like cells (LPLCs) generated by acute acetaminophen (APAP) injury without triggering immune responses. To explore in vivo reprogramming as a viable strategy for tissue regeneration, we employed lipid nanoparticles (LNP) carrying OSKM mRNA (OSKM-mRNA-LNP) to stimulate LPLCs formation.