ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
ROCK inhibition enhanced hepatocyte liver engraftment by retaining membrane CD59 and attenuating complement activation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- Advances and challenges in developing expandable human hepatocytes for regenerative medicine.Histology and histopathology · 2026Review
- Cell-intrinsic insulin signaling defects in human iPS cell-derived hepatocytes in type 2 diabetes.The Journal of clinical investigation · 2025Article
- Generation of self-renewing neuromesodermal progenitors with neuronal and skeletal muscle bipotential from human embryonic stem cells.Cell reports methods · 2024Article
- Evaluation of Rho kinase inhibitor effects on neuroprotection and neuroinflammation in an ex-vivo retinal explant model.Acta neuropathologica communications · 2024Article
- Chemical approaches targeting the hurdles of hepatocyte transplantation: mechanisms, applications, and advances.Frontiers in cell and developmental biology · 2024Review
- Liver Extracellular Vesicles and Particles Enriched β-Sitosterol Effectively Promote Liver Regeneration in Mice.International journal of nanomedicine · 2024Article
- Dysregulated Cyclic Nucleotide Metabolism in Alcohol-Associated Steatohepatitis: Implications for Novel Targeted Therapies.Biology · 2023Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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 clinically used ROCK inhibitor, can protect transplanted hepatocytes by retaining cell membrane CD59 and blocking the formation of the membrane attack complex. Knockdown of CD59 in hepatocytes eliminates ROCK inhibition-enhanced hepatocyte engraftment. Ripasudil can accelerate liver repopulation of fumarylacetoacetate hydrolase-deficient mice. Our work reveals a mechanism underlying hepatocyte loss after transplantation and provides immediate strategies to enhance hepatocyte engraftment by inhibiting ROCK.
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