Preeti Viswanathan1, Priya Gupta2, Sorabh Kapoor2, Sanjeev Gupta3. 1. Division of Pediatric Gastroenterology, Department of Pediatrics, Children's Hospital at Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, United States. 2. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, United States. 3. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, United States; Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY, United States. Electronic address: sanjeev.gupta@einstein.yu.edu.
Abstract
BACKGROUND & AIMS: For liver-directed cell therapy, efficient engraftment of transplanted cells is critical. This study delineated whether anti-inflammatory and endothelial disrupting properties of thalidomide could promote transplanted cell engraftment and proliferation in liver. METHODS: We used dipeptidyl peptidase IV-deficient rats for cell transplantation studies, including gene expression analysis, morphological tissue analysis, serological assays, cell culture assays, and assays of transplanted cell engraftment and proliferation. RESULTS: Thalidomide-pretreatment increased engraftment and proliferation of transplanted hepatocytes due to decreased inflammation. Moreover, thalidomide exacerbated cell transplantation-induced endothelial injury. This combined anti-inflammatory and endothelial injury effect of thalidomide was superior to the anti-inflammatory effect alone of repertaxin or etanercept, which block cytokines/chemokines/receptor-dependent inflammation. In thalidomide-pretreated animals, liver repopulation accelerated, including when cells were primed with bosentan to block endothelin-1 receptors. CONCLUSIONS: Thalidomide improved transplanted cell engraftment and liver repopulation. Therefore, this class of drugs will advance applications of liver cell therapy in people. LAY SUMMARY: This work aimed to develop effective drug treatments for improving engraftment of transplanted cells because that constitutes a critical step in rebuilding liver with healthy cells. Studies in animal models of cell transplantation led to identification of an old drug, thalidomide, which blocked inflammation and altered the liver microenvironment to yield superior engraftment and proliferation of transplanted cells. This will be appropriate for liver cell therapy in people.
BACKGROUND & AIMS: For liver-directed cell therapy, efficient engraftment of transplanted cells is critical. This study delineated whether anti-inflammatory and endothelial disrupting properties of thalidomide could promote transplanted cell engraftment and proliferation in liver. METHODS: We used dipeptidyl peptidase IV-deficientrats for cell transplantation studies, including gene expression analysis, morphological tissue analysis, serological assays, cell culture assays, and assays of transplanted cell engraftment and proliferation. RESULTS:Thalidomide-pretreatment increased engraftment and proliferation of transplanted hepatocytes due to decreased inflammation. Moreover, thalidomide exacerbated cell transplantation-induced endothelial injury. This combined anti-inflammatory and endothelial injury effect of thalidomide was superior to the anti-inflammatory effect alone of repertaxin or etanercept, which block cytokines/chemokines/receptor-dependent inflammation. In thalidomide-pretreated animals, liver repopulation accelerated, including when cells were primed with bosentan to block endothelin-1 receptors. CONCLUSIONS:Thalidomide improved transplanted cell engraftment and liver repopulation. Therefore, this class of drugs will advance applications of liver cell therapy in people. LAY SUMMARY: This work aimed to develop effective drug treatments for improving engraftment of transplanted cells because that constitutes a critical step in rebuilding liver with healthy cells. Studies in animal models of cell transplantation led to identification of an old drug, thalidomide, which blocked inflammation and altered the liver microenvironment to yield superior engraftment and proliferation of transplanted cells. This will be appropriate for liver cell therapy in people.
Authors: Ling Lu; Faribourz Payvandi; Lei Wu; Ling-Hua Zhang; Robert J Hariri; Hon-Wah Man; Roger S Chen; George W Muller; Christopher C W Hughes; David I Stirling; Peter H Schafer; J Blake Bartlett Journal: Microvasc Res Date: 2008-09-04 Impact factor: 3.514
Authors: Riccardo Bertini; Marcello Allegretti; Cinzia Bizzarri; Alessio Moriconi; Massimo Locati; Giuseppe Zampella; Maria N Cervellera; Vito Di Cioccio; Maria C Cesta; Emanuela Galliera; Fernando O Martinez; Rosa Di Bitondo; Giulia Troiani; Vilma Sabbatini; Gaetano D'Anniballe; Roberto Anacardio; Juan C Cutrin; Barbara Cavalieri; Fabrizio Mainiero; Raffaele Strippoli; Pia Villa; Maria Di Girolamo; Franck Martin; Marco Gentile; Angela Santoni; Daniela Corda; Giuseppe Poli; Alberto Mantovani; Pietro Ghezzi; Francesco Colotta Journal: Proc Natl Acad Sci U S A Date: 2004-07-28 Impact factor: 11.205