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Therapeutic Potential of Bone Marrow-Derived Stem Cells in Treatment of Genetic Diseases of the Liver

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Stem Cells and Cancer Stem Cells, Volume 7

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 7))

Abstract

Genetic liver diseases are the greatest challenge of modern health care that have no proven treatment. End-stage patients are advised for transplantation of liver. Unlike kidney, donor liver is difficult to obtain. Therefore, an alternate route of generating hepatocytes has been sought. BM-derived stem cells have been shown to differentiate into hepatocytes in culture and in vivo. It has been proposed that small increase in missing protein may cause significant improvement in the pathology of genetic liver diseases. Experimental findings from our and other groups heighten the scope for exploitation of this novel phenomenon of adult stem cells plasticity for the treatment of such disease. It has been presumed that BM-stem cell therapy not only helps for the synthesis of missing protein, it may protect liver from hepatocellular carcinoma or other adverse pathological changes of the liver.

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References

  • Almeida-Porada G, Porada CD, Chamberlain J, Torabi A, Zanjani ED (2004) Formation of human hepatocytes by human hematopoietic stem cells in sheep. Blood 104:2582–2590

    Article  CAS  PubMed  Google Scholar 

  • Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer K, Lois C, Morrison SJ, Alvarez-Buvilla A (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968–973

    Article  CAS  PubMed  Google Scholar 

  • Chakrapani A, Green A (2004) Metabolic liver disease in the infant and older child. In: Kelly D (ed) Diseases of the liver and biliary system in children, vol 1, 2nd edn. Blackwell Publishing, Ltd, Malden, pp 211–242

    Google Scholar 

  • Di Campli C, Wu J, Gasbarrini A, Gasbarrini G, Zern MA (1999) Gene therapy for human liver diseases. Eur J Gastroenterol Hepatol 11:421–429

    Article  PubMed  Google Scholar 

  • Duncan AW, Hickey RD, Paulk NK, Culberson AJ, Olson SB, Finegold MJ, Grompe M (2009) Ploidy reductions in murine fusion-derived hepatocytes. PLoS Genet 5:1–11

    Article  Google Scholar 

  • Elsas LJ, Langley S, Steele E, Evinger J, Fridovich-Keil JL, Brown A, Singh R, Fernhoff P, Hielm LN, Dembure PP (1995) Galactosemia: a strategy to identify new biochemical phenotypes and molecular genotypes. Am J Hum Genet 56:630–639

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fausto N, Campbell JS, Riehle KJ (2006) Liver regeneration. Hepatology 43:S45–S53

    Article  CAS  PubMed  Google Scholar 

  • Fox IJ, Chowdhury JR, Kaufman SS, Goertzen TC, Chowdhury NR, Warkentin PI, Dorko K, Sauter BV, Strom SC (1998) Treatment of the Cliger–Najjar syndrome type 1 with hepatocytes transplantation. N Engl J Med 338:1422–1426

    Article  CAS  PubMed  Google Scholar 

  • Jang YY, Collector MI, Baylin SB, Diehl AM, Sharkis SJ (2004) Hematopoietic stem cells convert into liver cells within days without fusion. Nat Cell Biol 6:532–539

    Article  CAS  PubMed  Google Scholar 

  • Kayler LK, Rasmussen CS, Dykstra DM, Punch JD, Ru-dich SM, Magee JC, Maraschio MA, Arenas JD, Campbell DA Jr, Merion RM (2003) Liver transplantation in children with metabolic disorders in the United States. Am J Transplant 3:334–339

    Article  PubMed  Google Scholar 

  • Khurana S, Mukhopadhyay A (2007) Characterization of the potential subpopulation of bone marrow cells involved in the repair of injured liver tissue. Stem Cells 25:1439–1447

    Article  CAS  PubMed  Google Scholar 

  • Khurana S, Mukhopadhyay A (2008a) Hematopoietic progenitors from early murine fetal liver possess hepatic differentiation potential. Am J Pathol 173:1818–1827

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Khurana S, Mukhopadhyay A (2008b) In vitro transdifferentiation of adult hematopoietic stem cells: an alternative source of engraftable hepatocytes. J Hepatol 49:998–1007

    Article  CAS  PubMed  Google Scholar 

  • Khurana S, Mukhopadhyay A (2010) Hepatocyte nuclear factor-4α induces transdifferentiation of hemato­poietic cells into hepatocytes. J Biol Chem 285:4725–4731

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kren BT, Parashar B, Bandhopadhyaya P, Chowdhury NR, Chowdhury JR, Steer CJ (1999) Correction of UPD-glucuronosyltransferase gene defect in Gunn rat model of Crigler-Najjar syndrome type 1 with a chimwric oligonucleotide. Proc Natl Acad Sci USA 96:10349–10354

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wange X, Finegold M, Weissman IL, Grompe M (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6:1229–1234

    Article  CAS  PubMed  Google Scholar 

  • Mallet VO, Mitchell C, Mezey E, Fabre M, Guidotti JE, Renia L, Coulombel L, Kahn A, Gilgenkrantz H (2002) Bone marrow transplantation in mice leads to a minor population of hepatocytes that can be selectively amplified in vivo. Hepatology 35:799–804

    Article  PubMed  Google Scholar 

  • Matern D, Starzl TE, Arnaout W, Barnard J, Bynon JS, Dhawan A, Emond J, Haagsma EB, Hug G, Lachaux A, Smit GP, Chen YT (1999) Liver transplantation for glycogen storage disease types I, III, and IV. Eur J Pediatr 158:S43–S48

    Article  PubMed Central  PubMed  Google Scholar 

  • Michalopeulos GK, DeFrances MC (1997) Liver regeneration. Science 276:60–66

    Article  Google Scholar 

  • Mitchell GA, Grompe M, Lambert M, Tanguay RM (2001) Hypertyrosinemia. In: Scriver CR, Beaudet AL, Sly W, Valle D (eds) The metabolic and molecular basis of inherited disease, 8th edn. McGraw-Hill, New York, pp 777–1805

    Google Scholar 

  • Overturf K, Al-Dhalimy M, Tanguay R, Brantly M, Ou CN, Finegold M, Grompe M (1996) Hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyroseminaemia type I. Nat Genet 12:266–273

    Article  CAS  PubMed  Google Scholar 

  • Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP (1999) Bone marrow as a potential source of hepatic oval cells. Science 284:1168–1170

    Article  CAS  PubMed  Google Scholar 

  • Roth DA, Kessler CM, Pasi KJ, Rup B, Courter SG, Tubridy KL (2001) Human recombinant factor IX: safety and efficacy studies in hemophilia B patients previously treated with plasma-derived factor IX concentrates. Blood 98:3600–3606

    Article  CAS  PubMed  Google Scholar 

  • Sakamoto T, Ye Q, Lu L, Demetris AJ, Starlz TE, Murase N (1999) Donor haematopoietic progenitor cells in nonmyeloablated rat recipients of allogeneic bone marrow and liver grafts. Transplantation 27:833–840

    Article  Google Scholar 

  • Shafritz DA, Dabeva MD (2002) Liver stem cells and model systems for liver repopulation. J Hepatol 36:552–564

    Article  PubMed  Google Scholar 

  • Strom SC, Rubinstein WS, Barranger JA, Towbin RB, Charron M, Mieles L, Pisarov LA, Dorko K, Thompson MT, Reyes J (1997) Transplantation of human hepatocytes. J Trans Proc 29:2103–2106

    Article  CAS  Google Scholar 

  • Taub R (2004) Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol 5:836–847

    Article  CAS  PubMed  Google Scholar 

  • Teckman JH, Lindblad D (2006) Alpha-1-antitrypsin deficiency diagnosis, pathology, and management. Curr Gastroenterol Rep 8:14–20

    Article  PubMed  Google Scholar 

  • Vassilopoulos G, Wang PR, Russell DW (2003) Transplanted bone marrow regenerates liver by cell fusion. Nature 422:901–904

    Article  CAS  PubMed  Google Scholar 

  • Wang LJ, Chen YM, George D, Smets F, Sokal EM, Bremer EG, Soriano HE (2002) Engraftment assessment in human and mouse liver tissue after sex-­mismatched liver cell transplantation by real-time quantitative PCR for Y chromosome sequences. Liver Transpl 8:822–828

    Article  PubMed  Google Scholar 

  • Wang X, Ge S, McManara G, Hao QL, Crooks GM, Nolta JA (2003) Albumin expressing hepatocyte-like cells develop in the livers of immune deficient mice transplanted with highly purified human hematopoietic stem cells. Blood 101:4201–4208

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Weinstein DA, Correia CE, Conlon T, Specht A, Verstegen J, Onclin-Verstegen K, Campbell-Thompson M, Dhaliwal G, Mirian L, Cossette H, Falk DJ, Germain S, Clement N, Porvasnik S, Fiske L, Struck M, Ramirez HE, Jordan J, Andrutis K, Chou JY, Byrne BJ, Mah CS (2010) Adeno- associated virus-mediated correction of a canine model of glycogen storage disease type Ia. Hum Gene Ther 21:903–910

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Whitington PF, Alonso EM, Boyle JT, Molleston JP, Rosenthal P, Emond JC, Millis JM (1998) Liver transplantation for the treatment of urea cycle disorders. J Inherit Metab Dis 21:112–118

    Article  PubMed  Google Scholar 

  • Yadav N, Kanjirakkuzhiyil S, Kumar S, Jain M, Halder A, Saxena R, Mukhopadhyay A (2009) The therapeutic effect of bone marrow derived liver cells in the phenotypic correction of murine hemophilia A. Blood 114:4552–4556

    Article  CAS  PubMed  Google Scholar 

  • Yadav N, Kanjirakkuzhiyil S, Ramakrishnan M, Das TK, Mukhopadhyay A (2011) Factor VIII can be synthesized in hemophilia A mice liver by bone marrow progenitor cell-derived hepatocytes and sinusoidal endothelial cells. Stem Cells Dev 21:110–120

    Google Scholar 

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Acknowledgement

This work was supported by the special grant of Center for Molecular Medicine, DBT, Government of India, for which the first (PB) and the last (AM) author is grateful.

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Authors and Affiliations

  1. Stem Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India

    Prakash Baligar, Neelam Yadav & Asok Mukhopadhyay

  2. Department of Biochemistry, Dr. Ram Manohar Lohia Avadh University, Faizabad, India

    Neelam Yadav

Authors
  1. Prakash Baligar
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  2. Neelam Yadav
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  3. Asok Mukhopadhyay
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Corresponding author

Correspondence to Asok Mukhopadhyay .

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Editors and Affiliations

  1. Biology, Kean University, Union, New Jersey, USA

    M.A. Hayat

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© 2012 Springer Science+Business Media Dordrecht

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Baligar, P., Yadav, N., Mukhopadhyay, A. (2012). Therapeutic Potential of Bone Marrow-Derived Stem Cells in Treatment of Genetic Diseases of the Liver. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 7. Stem Cells and Cancer Stem Cells, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4285-7_9

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