Improving Hepatocyte Engraftment Following Hepatocyte Transplantation Using Repeated Reversible Portal Vein Embolization in Rats

Gaillard, M.; Tranchart, Hadrien; Laïnas, Panagiotis; Trassard, Olivier; Remy, Séverine; Dubart‐Kupperschmitt, Anne; Dagher, Ibrahim

doi:10.1002/lt.25364

Cited by 9 publications

(7 citation statements)

References 39 publications

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“…Thus, an interest of RPVE is that recanalization of the portal embolized territory allows an early second embolization, that could maximize liver hypertrophy by providing an additional regenerative stimulus. This hypothesis was recently reported in rodents [11, 12], in which repeated RPVE (RRPVE) showed additional hepatocyte proliferation and a cumulative increase in liver hypertrophy in the non-occluded lobes compared with a single RPVE.…”

Section: Introductionsupporting

confidence: 61%

Liver Regeneration and Recanalization Time Course following Repeated Reversible Portal Vein Embolization in Swine

et al. 2020

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Introduction: Portal vein embolization (PVE) is an accepted technique to preoperatively increase the volume of the future remnant liver before major hepatectomy. A permanent material is usually preferred since its superiority to induce liver hypertrophy over absorbable material has been demonstrated. Nevertheless, the use of an absorbable material generates a reversible PVE (RPVE) capable of inducing significant liver hypertrophy. In small animal models, the possibility to proceed to a repeated RPVE (RRPVE) has shown to boost liver hypertrophy further. The aim of this preliminary study was to assess the feasibility and the tolerance of RRPVE in a large animal model, in comparison with permanent PVE (PPVE) and single RPVE. Methods: Six swine (2 per group) were assigned either to single RPVE group (using powdered gelatin sponge), RRPVE group (2 RPVEs separated by 14 days) or PPVE group (using N-butyl-cyanoacrylate). The feasibility and tolerance of the procedures were evaluated using portography, liver function tests and histological analysis. Evolution of liver volumes was assessed with volumetric imaging by computed tomography. Results: Embolization of portal branches corresponding to 75% of total liver volume was performed successfully in all animals. Procedures were well tolerated, inducing moderate changes in portal pressure and transient aminotransferase increase. None of the animals developed portal vein thrombosis. After RPVE, complete recanalization occurred at day 11. RRPVE showed a trend for higher hypertrophy, the non-embolized liver to total liver ratio reaching 5.2 ± 1.0% in the RPVE group, 6.8 ± 0.1% in the RRPVE group and 5.0 ± 0.3% in the PPVE group. Discussion/Conclusion: In this preliminary comparative study, RRPVE was as feasible and as well tolerated as the other procedures, and resulted in higher liver hypertrophy.

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Section: Introductionsupporting

confidence: 61%

Liver Regeneration and Recanalization Time Course following Repeated Reversible Portal Vein Embolization in Swine

et al. 2020

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“…[47][48][49] Specific liver insults, such as portal vein embolisation and partial hepatectomy can pre-condition remaining host hepatocytes to proliferate, positively influencing donor hepatocyte engraftment and proliferation. 50,51 Irradiation-induced apoptosis of sinusoidal endothelial cells allows for greater engraftment and integration of donor hepatocytes into hepatic cords. 52 Irradiating individual liver lobes to give donor hepatocytes a competitive advantage has been performed in primates and a patient with phenylketonuria.…”

Section: Overcoming the Challenges Of Cell Therapy For Liver Diseasementioning

confidence: 99%

Cell therapy for advanced liver diseases: Repair or rebuild

Dwyer¹,

Macmillan²,

Brennan³

et al. 2021

Journal of Hepatology

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Advanced liver disease presents a significant worldwide health and economic burden and accounts for 3.5% of global mortality. When liver disease progresses to organ failure the only effective treatment is liver transplantation, which necessitates lifelong immunosuppression and carries associated risks. Furthermore, the shortage of suitable donor organs means patients may die waiting for a suitable transplant organ. Cell therapies have made their way from animal studies to a small number of early clinical trials. Herein, we review the current state of cell therapies for liver disease and the mechanisms underpinning their actions (to repair liver tissue or rebuild functional parenchyma). We also discuss cellular therapies that are on the clinical horizon and challenges that must be overcome before routine clinical use is a possibility.

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“…Moreover engraftment could be partly impaired in ZSD mice liver due to Cxcl12 and Hgf downregulation (GSE145524), chemokines implicated in mesenchymal stromal cells recruitment and hepatocyte proliferation, respectively [41]. Several strategies have been developed to improve hepatocyte engraftment such as hepatotoxic drugs [35], preparative hepatic irradiation [42] combined or not with partial hepatectomy [25] and (repeated) reversible portal vein embolization [43]. The vast majority were evaluated in rat models of HT.…”

Section: Discussionmentioning

confidence: 99%

High Dose Versus Low Dose Syngeneic Hepatocyte Transplantation in Pex1-G844D NMRI Mouse Model is Safe but Does Not Achieve Long Term Engraftment

Demaret

Evraerts

Ravau

et al. 2020

Cells

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Genetic alterations in PEX genes lead to peroxisome biogenesis disorder. In humans, they are associated with Zellweger spectrum disorders (ZSD). No validated treatment has been shown to modify the dismal natural history of ZSD. Liver transplantation (LT) improved clinical and biochemical outcomes in mild ZSD patients. Hepatocyte transplantation (HT), developed to overcome LT limitations, was performed in a mild ZSD 4-year-old child with encouraging short-term results. Here, we evaluated low dose (12.5 million hepatocytes/kg) and high dose (50 million hepatocytes/kg) syngeneic male HT via intrasplenic infusion in the Pex1-G844D NMRI mouse model which recapitulates a mild ZSD phenotype. HT was feasible and safe in growth retarded ZSD mice. Clinical (weight and food intake) and biochemical parameters (very long-chain fatty acids, abnormal bile acids, etc.) were in accordance with ZSD phenotype but they were not robustly modified by HT. As expected, one third of the infused cells were detected in the liver 24 h post-HT. No liver nor spleen microchimerism was detected after 7, 14 and 30 days. Future optimizations are required to improve hepatocyte engraftment in Pex1-G844D NMRI mouse liver. The mouse model exhibited the robustness required for ZSD liver-targeted therapies evaluation.

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Improving Hepatocyte Engraftment Following Hepatocyte Transplantation Using Repeated Reversible Portal Vein Embolization in Rats

Cited by 9 publications

References 39 publications

Liver Regeneration and Recanalization Time Course following Repeated Reversible Portal Vein Embolization in Swine

Liver Regeneration and Recanalization Time Course following Repeated Reversible Portal Vein Embolization in Swine

Cell therapy for advanced liver diseases: Repair or rebuild

High Dose Versus Low Dose Syngeneic Hepatocyte Transplantation in Pex1-G844D NMRI Mouse Model is Safe but Does Not Achieve Long Term Engraftment

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