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Title: Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma

Abstract

Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local disease control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects,more » including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the treatment of HCC.« less

Authors:
 [1]; ;  [2];  [3];  [4];  [2];  [4]
  1. Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)
  2. Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)
  3. Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)
  4. (United States)
Publication Date:
OSTI Identifier:
22420365
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 89; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ASCITES; BIOLOGICAL REGENERATION; BONE MARROW; CHEMOTHERAPY; HEPATOMAS; INJURIES; LIVER; LIVER CIRRHOSIS; PATIENTS; RADIATION DOSES; RADIOTHERAPY; STEM CELLS; SURGERY

Citation Formats

Vainshtein, Jeffrey M., Kabarriti, Rafi, Mehta, Keyur J., Roy-Chowdhury, Jayanta, Department of Genetics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, Guha, Chandan, E-mail: cguhamd@gmail.com, and Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma. United States: N. p., 2014. Web. doi:10.1016/J.IJROBP.2014.02.017.
Vainshtein, Jeffrey M., Kabarriti, Rafi, Mehta, Keyur J., Roy-Chowdhury, Jayanta, Department of Genetics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, Guha, Chandan, E-mail: cguhamd@gmail.com, & Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma. United States. doi:10.1016/J.IJROBP.2014.02.017.
Vainshtein, Jeffrey M., Kabarriti, Rafi, Mehta, Keyur J., Roy-Chowdhury, Jayanta, Department of Genetics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, Guha, Chandan, E-mail: cguhamd@gmail.com, and Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Tue . "Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma". United States. doi:10.1016/J.IJROBP.2014.02.017.
@article{osti_22420365,
title = {Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma},
author = {Vainshtein, Jeffrey M. and Kabarriti, Rafi and Mehta, Keyur J. and Roy-Chowdhury, Jayanta and Department of Genetics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York and Guha, Chandan, E-mail: cguhamd@gmail.com and Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York},
abstractNote = {Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local disease control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the treatment of HCC.},
doi = {10.1016/J.IJROBP.2014.02.017},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 89,
place = {United States},
year = {Tue Jul 15 00:00:00 EDT 2014},
month = {Tue Jul 15 00:00:00 EDT 2014}
}