Efficient Hepatocyte Engraftment in a Nonhuman Primate Model After Partial Portal Vein Embolization

Dagher, Ibrahim; Boudechiche, Lyes; Branger, Julie; Coulomb-L’Herminé, Aurore; Parouchev, Alexandre; Sentilhes, Loïc; Lin, Tao; Groyer-Picard, Marie-Thérèse; Vons, C.; Hadchouel, Michelle; Pariente, D.; Andreoletti, Marion; Franco, Dominique; Weber, Anne

doi:10.1097/01.tp.0000236103.99456.8f

Cited by 56 publications

(47 citation statements)

References 29 publications

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“…However, new indications for PVE are currently emerging in patients for whom resection of the embolized liver may not ultimately be required. Temporary regeneration may be sought in multi-step approaches for liver cancer treatment, to improve cell and gene therapy [15,19], or even to induce lobar liver hypertrophy in living organ donors. In the present study, we evaluated the time course of portal revascularization after temporary PVE with Curaspon powder -an absorbable agent -and its efficiency for increasing hepatocyte proliferation and liver hypertrophy in a preclinical primate model.…”

Section: Discussionmentioning

confidence: 99%

“…Surgery was performed as previously described [15], under general anesthesia. Acetaminophen was used for analgesia (10 mg/kg orally every 6 h for 3 days).…”

Section: Reversible Pve and Assessment Of Recanalizationmentioning

confidence: 99%

“…Reversible PVE may also be more suitable for cirrhotic patients, as the associated functional decline would be transient. In addition, we have used PVE before hepatocyte transplantation, to improve engraftment and induce hepatocyte proliferation in primates [15]. The use of an absorbable material for PVE would certainly be safer in similar clinical situations in which the embolized liver is not resected.…”

Section: Introductionmentioning

confidence: 98%

“…Liver regeneration following permanent embolization occurs rapidly, within 11-17 days [16][17][18]. The precise time course of regeneration after PVE has been evaluated in experimental studies showing early liver regeneration [15,19]. The use of reversible PVE to ensure vascular occlusion over 2 weeks should therefore induce the required hypertrophy without long-term deleterious effects.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Liver regeneration and recanalization time course following reversible portal vein embolization

Laïnas

Boudechiche

Osorio

et al. 2008

Journal of Hepatology

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Section: Discussionmentioning

confidence: 99%

“…Surgery was performed as previously described [15], under general anesthesia. Acetaminophen was used for analgesia (10 mg/kg orally every 6 h for 3 days).…”

Section: Reversible Pve and Assessment Of Recanalizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Liver regeneration and recanalization time course following reversible portal vein embolization

Laïnas

Boudechiche

Osorio

et al. 2008

Journal of Hepatology

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“…Attempts at improving engraftment include temporary embolisation of the portal vein [30], liver irradiation [31] and the administration of growth factors [32].…”

Section: Regenerative Medicine and Cell Therapy Of Liver Diseasementioning

confidence: 99%

New Horizons in Pediatric Hepatology: A Glimpse of the Future

Fitzpatrick

Dhawan

2015

Textbook of Pediatric Gastroenterology, Hepatology and Nutrition

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Efficient hepatocyte engraftment and long-term transgene expression after reversible portal embolization in nonhuman primates

et al. 2008

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The feasibility of ex vivo gene therapy as an alternative to liver transplantation for the treatment of liver metabolic diseases needs to be analyzed in large animal models. This approach requires appropriate gene transfer vectors and effective hepatocyte engraftment. Lentiviral vectors have the ability to transduce nondividing differentiated cells, such as hepatocytes, and portal vein occlusion increases hepatocyte engraftment. We investigated whether reversible portal vein embolization combined with ex vivo lentivirus-mediated gene transfer is an effective approach for successful hepatocyte engraftment in nonhuman primates and whether the transgene remains expressed in the long term in transplanted hepatocytes in situ. Simian hepatocytes were isolated after left lobe resection, and the left and right anterior portal branches of animals were embolized with absorbable material. Isolated hepatocytes were labeled with Hoechst dye or transduced in suspension with lentiviruses expressing green fluorescent protein under the control of the human apolipoprotein A-II promoter and transplanted via the inferior mesenteric vein. The whole procedure was well tolerated. The embolized liver was revascularized within 2 weeks. The volume of nonembolized liver increased from 38.7% ؎ 0.8% before embolization to 55.9% ؎ 1% after embolization and hepatocytes significantly proliferated (10.5% ؎ 0.4% on day 3 after embolization). Liver repopulation after transplantation with Hoechst-labeled hepatocytes was 7.4% ؎ 1.2%. Liver repopulation was 2.1% ؎ 0.2% with transduced hepatocytes, a proportion similar to that obtained with Hoechst-labeled cells, given that the mean transduction efficacy of simian hepatocyte population was 34%. Transgene expression persisted at 16 weeks after transplantation. Conclusion: We have developed a new approach to improve hepatocyte engraftment and to express a transgene in the long term in nonhuman primates. This strategy could be suitable for clinical applications. (HEPATOLOGY 2009;49: 950-959.)O rthotopic liver transplantation is the only available curative treatment for various liver diseases and genetic metabolic disorders. Owing to the limited availability of donor livers, alternative approaches such as hepatocyte transplantation have been proposed. 1,2 However, the increasing organ shortage makes the supply of tissue for cell transplantation very limited. 3 There are often no unused donor livers available when a patient requires cell transplantation; most patients therefore receive cryopreserved cells, the functionality of which remains lower than that of freshly isolated hepatocytes.

show abstract

Efficient Hepatocyte Engraftment in a Nonhuman Primate Model After Partial Portal Vein Embolization

Abstract: These data suggest that partial portal embolization of the recipient liver improves engraftment of transplanted hepatocytes in a primate preclinical model providing a new strategy for hepatocyte transplantation.

Cited by 56 publications

References 29 publications

Liver regeneration and recanalization time course following reversible portal vein embolization

Liver regeneration and recanalization time course following reversible portal vein embolization

New Horizons in Pediatric Hepatology: A Glimpse of the Future

Efficient hepatocyte engraftment and long-term transgene expression after reversible portal embolization in nonhuman primates

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