Our laboratory focuses on the development of liver cell-based therapies and relevant aspects of stem cell biology. Major goals are directed towards understanding mechanisms by which transplanted cells engraft, proliferate and function in the liver, obtaining insights into cell-cell interactions that may alter the fate of transplanted cells, and addressing the potential of liver cell types that might improve liver repopulation. The laboratory works with stem/progenitor cells isolated from fetal human tissues and uses such cells for studies of gene regulation, cell differentiation and therapeutic gene expression, including induction of pancreatic beta cell function.
A variety of rodent models, including various inbred mouse strains, the hemophilia A mouse, the Gunn rat, the Nagase analbuminemic rat, the dipeptidyl peptidase IV deficient (DPPIV-) rat and the DPPIV- mouse, the Long-Evans Cinnamon rat, etc., are available for studies. Several animals constitute unique genetic models for studying hepatic pathophysiology. Animal models, where acute or chronic liver injury is induced with toxins, including cell cycle regulators, are available. The DPPIV- rat and mouse-based transplantation systems have been very helpful for analyzing the fate of transplanted adult and fetal hepatocytes, as well as stem/progenitor cells. Studies are conducted to examine whether liver repopulation with hepatocyte transplantation could offer metabolic function in chronic liver disease and improve survival in animals with liver failure. Related studies are aimed at propagating subsets of stem/progenitor cells from fetal human tissues and analyzing mechanisms of cell differentiation, including after transplantation in immunodeficient animals. Some studies utilize microarray-based gene expression analysis and others use established cell and molecular biology methods. Further studies concern mechanisms of gene transfer with lentiviral vectors. Additional studies are aimed at developing novel models of human disease. The overall effort is aimed at translating basic research findings into clinical studies in people.
The laboratory collaborates with a number of leading investigators at Einstein or elsewhere as necessary.
- Viswanathan P, Kapoor S, Kumaran V, Joseph B, Gupta S. Etanercept blocks inflammatory responses orchestrated by TNF-a to promote transplanted cell engraftment and proliferation in rat liver. Hepatology 2014;60:1378-88.
- Kapoor S, Berishvili E, Bandi S, Gupta S. Ischemic preconditioning affects long-term cell fate through DNA damage-related molecular signaling and altered proliferation. Am J Pathol 2014;184:2779-90.
- Bahde R, Kapoor S, Bhargava KK, Palestro CJ, Gupta S. Diagnosis of abnormal biliary copper excretion by positron emission tomography with targeting of (64)Copper-asialofetuin complex in LEC rat model of Wilson's disease. Am J Nucl Med Mol Imaging 2014;4:537-47.
- Bandi S, Viswanathan P, Gupta S. Evaluation of cytotoxicity and DNA damage response with analysis of intracellular ATM signaling pathways. Assay Drug Dev Technol 2014;12:272-81.
- Gupta S. Cell therapy to remove excess copper in Wilson's disease. Ann NY Acad Sci 2014;1315:70-80.
- Bahde R, Kapoor S, Gupta S. Nonselective inhibition of prostaglandin-endoperoxide synthases by naproxen ameliorates acute or chronic liver injury in animals. Exp Mol Pathol 2014;96:27-35.
- Bahde R, Kapoor S, Viswanathan P, Spiegel HU, Gupta S. Endothelin-1 receptor A blocker darusentan decreases cell transplantation-induced hepatic perturbations and improves liver repopulation. Hepatology 2014;59:1107-17.
- Kakabadze Z, Gupta S, Pileggi A, Molano RD, Ricordi C, Shatirishvili G, Loladze G, Mardaleishvili K, Kakabadze M, Berishvili E. Correction of diabetes by minimal mass islet transplantation into the small intestinal submucosa. Am J Transplantation 2013;13:2550-57.
- Bahde R, Kapoor S, Bandi S, Bhargava K, Palestro C, Gupta S. Directly acting drugs prostacyclin or nitroglycerine and endothelin receptor blocker bosentan improve cell engraftment in rat liver. Hepatology 2013;57:320-30.
- Kakabadze Z, Shanava K, Ricordi C, Shapiro AMJ, Gupta S, Berishvili E. An isolated venous sac as a novel site for cell therapy in diabetes mellitus. Transplantation 2012;94:319-324.
- Viswanathan P, Gupta S. New directions for cell-based therapies in acute liver failure. J Hepatol 2012; 57:913-915.
- Follenzi A, Raut S, Merlin S, Sarkar R, Gupta S. Role of bone marrow transplantation for correcting hemophilia A in mice. Blood 2012;119;5532-5542. Editorial commentary: 5344-5346.
- Bandi S, Cheng K, Joseph B, Gupta S. Spontaneous origin from human embryonic stem cells of early developmental stage liver cells displaying conjoint meso-endodermal phenotype with hepatic functions. J Cell Sci 2012;125:1274-83.
- Enami Y, Joseph B, Bandi S, Lin J, Gupta S. Molecular perturbations restrict potential for liver repopulation of hepatocytes isolated from nonheart-beating donor rats. Hepatology 2012;55:1182-92.
- Bandi S, Joseph B, Berishvili E, Singhania R, Wu YM, Cheng K, Gupta S. Perturbations in ataxia telangiectasia mutant signaling pathways after drug-induced acute liver failure and their reversal during rescue of animals by cell therapy. Am J Pathol 2011; 178:161-74.
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