ROCK inhibition enhanced hepatocyte liver engraftment by retaining membrane CD59 and attenuating complement activation.

ABSTRACT: Hepatocyte transplantation can be an effective treatment for patients with certain liver-based metabolic disorders and liver injuries. Hepatocytes are usually infused into the portal vein, from which hepatocytes migrate into the liver and integrate into the liver parenchyma. However, early cell loss and poor liver engraftment represent major hurdles to sustaining the recovery of diseased livers after transplantation. In the present study, we found that ROCK (Rho-associated kinase) inhibitors significantly enhanced in vivo hepatocyte engraftment. Mechanistic studies suggested that the isolation of hepatocytes caused substantial degradation of cell membrane proteins, including the complement inhibitor CD59, probably due to shear stress-induced endocytosis. ROCK inhibition by ripasudil, a cli

SUBMITTER: Ma H 

PROVIDER: S-EPMC10277888 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature