Cadaveric Hepatocytes Repopulate Diseased Livers: Life After Death

Hay, David C.

doi:10.1053/j.gastro.2010.07.013

Cited by 8 publications

(3 citation statements)

References 16 publications

(5 reference statements)

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“…Hepatocyte cell therapy is an attractive alternative to liver transplantation 1, 2 . Hepatocytes have a high replicative potential in vivo 3, 4 , however hepatocyte isolation is technically demanding, requires cadaveric liver donation, and hepatocytes cannot be expanded effectively in vitro 5 .…”

Section: Introductionmentioning

confidence: 99%

Hepatic progenitor cells of biliary origin with liver repopulation capacity

et al. 2015

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SummaryHepatocytes and cholangiocytes self renew following liver injury. Following severe injury hepatocytes are increasingly senescent, whether Hepatic Progenitor Cells (HPCs) then contribute to liver regeneration is unclear. Here, we describe a mouse model where Mdm2 is inducibly deleted in over 98% of hepatocytes, causing apoptosis, necrosis and senescence with nearly all hepatocytes expressing p21. This results in florid HPC activation, which is necessary for survival, followed by complete, functional liver reconstitution. HPCs isolated from genetically normal mice, using cell surface markers, were highly expandable and phenotypically stable in vitro. These HPCs were transplanted into adult mouse livers where hepatocyte Mdm2 was repeatedly deleted, creating a non-competitive repopulation assay. Transplanted HPCs contributed significantly to restoration of liver parenchyma, regenerating hepatocytes and biliary epithelia, highlighting their in vivo lineage potency. HPCs are therefore a potential future alternative to hepatocyte or liver transplantation for liver disease.

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Section: Introductionmentioning

confidence: 99%

Hepatic progenitor cells of biliary origin with liver repopulation capacity

et al. 2015

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“…Liver diseases, such as hepatitis virus infection and alcoholic and nonalcoholic steatohepatitis, can lead to severe liver cirrhosis, resulting in liver failure, an irreversible and life-threatening state. [1][2][3] The only treatment for severe liver failure is currently liver transplantation, but donors for liver transplantation are lacking, 4 and there are many problems with transplantation, including technical difficulties and highly invasive surgery, the risk of life-threatening postoperative complications, requirement for immunosuppression after the transplantation, and declining quality of the posttransplant life because of the immunosuppressive status. Thus, liver transplantation is not indicated for all cases with liver failure, suggesting a need to develop novel new therapeutic interventions for liver failure.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Autologous Skeletal Myoblast Cell Sheet Transplantation for Liver Regeneration in Liver Failure

et al. 2023

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Background. No effective therapies have yet been established for liver regeneration in liver failure. Autologous skeletal myoblast cell sheet transplantation has been proven to improve cardiac function in patients with heart failure, and one of the mechanisms has been reported to be a paracrine effect by various growth factors associated with liver regeneration. Therefore, the present study focused on the effect of myoblast cells on liver regeneration in vitro and in vivo. Methods. We assessed the effect of myoblast cells on the cells comprising the liver in vitro in association with liver regeneration. In addition, we examined in vivo effect of skeletal myoblast cell sheet transplantation in C57/BL/6 mouse models of liver failure, such as liver fibrosis induced by thioacetamide and hepatectomy. Results. In vitro, the myoblast cells exhibited a capacity to promote the proliferation of hepatic epithelial cells and the angiogenesis of liver sinusoidal endothelial cells, and suppress the activation of hepatic stellate cells. In vivo, sheet transplantation significantly suppressed liver fibrosis in the induced liver fibrosis model and accelerated liver regeneration in the hepatectomy model. Conclusions. Autologous skeletal myoblast cell sheet transplantation significantly improved the liver failure in the in vitro and in vivo models. Sheet transplantation is expected to have the potential to be a clinically therapeutic option for liver regeneration in liver failure.

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“…The field therefore offers the promise that, in the future, scientists will be able to grow tissues in the laboratory and use them safely as extracorporeal devices to stimulate endogenous repair [1] or implant them when the body cannot heal itself, but only when cell-based therapies are deemed safe and effective [2, 3]. If successful, such an approach would have a significant impact on the problem of the shortage of donor organs available for transplantation.…”

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confidence: 99%