**7. References**


Cell Based Therapy for Chronic Liver Disease:

Dis. 39: 1071–1076.

Ther. 27: 932–939.

6: 32–40.

100–118.

Gasteroenterology 142: 505-512

Liver Transplant. 10: 1331–1342.

Role of Fetal Liver Cells in Restoration of the Liver Cell Functions 235

[18]. Lorenzini S, Isidori A, Catani L, Gramenzi A, Talarico S, Bonifazi F, Giudice V, Conte R,

[19] Spahr L, Lambert JF, Rubbia-Brandt L, Chalandon Y, Frossard JL, Giostra E, Hadengue A.

[21] Groth CG, Arborgh B, Bjorken C, Sundberg B, Lundgren G (1977) Correction of

[22] Bilir BM, Guinette D, Karrer F, Kumpe DA, Krysl J, Stephens J, McGavran L, Ostrowska

[23] Mito M, Kusano M (1993) Hepatocyte transplantation in man. Cell Transplant 2: 65–74. [24] Strom SC, Fisher RA, Thompson MT, Sanyal AJ, Cole PE, Ham JM, Posner MP (1997)

[25] Kung JW, Forbes SJ (2009) Stem cells and liver repair. Curr. Opin. Biotech. 20: 568–574. [26] Sancho-Bru P, Najimi M, Caruso M et al Pauwelyn K, Cantz T, Forbes S, Roskams T, Ott M,

[28] Demetriou AA, Brown Jr RS, Busuttil RW, Fair J, McGuire BM, Rosenthal P, Am Esch JS

[29] Ellis AJ, Hughes RD, Wendon JA, Dunne J, Langley PG, Kelly JH, Gislason GT,

[30] Piscaglia C, Novi M, Campanale M, Gasbarrini A (2008) Stem cell-based therapy in

[31] Duret C, Gerbal-Chaloin S, Ramos J, Fabre JM, Jacquet E, Navarro F, Blanc P, Sa-Cunha

[32] Schmelzer E, Wauthier E, Reid LM (2006) The phenotypes of pluripotent human

hepatocyte transplantation. Transplant. Proc. 9: 313–316.

terminal liver failure. Transplantation 63: 559–569.

treating acute liver failure. Ann. Surg. 239: 660.

adult human liver. Stem Cells 25: 1779–1790.

hepatic progenitors. Stem Cells 24: 1852–1858.

assist device in acute liver failure. Hepatology 24: 1446–51.

profile of G-CSF therapy in patients with acute on chronic liver failure. Dig. Liv.

Baccarani M, Bernardi M, Forbes SJ, Lemoli RM, Andreone P (2008) Stem cell mobilization and collection in patients with liver cirrhosis. Aliment. Pharmcol.

(2008) Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial. Hepatology 48: 221–229. [20] Garg V, Garg H, Khan A, Trehanpati N, Kumar A, Sharma BC, Sakhuja P, Sarin SK

(2012) Granulocyte Colony-Stimulating Factor Mobilizes CD34(+) Cells and Improves Survival of Patients With Acute-on-Chronic Liver Failure.

hyperbilirubinemia in the glucuronyltransferase deficient rat by intraportal

A, Durham J (2000) Hepatocyte transplantation in acute liver failure. Liver Transpl.

Hepatocyte transplantation as a bridge to orthotopic liver transplantation in

Gehling U, Sokal E, Verfaillie CM, Muraca M (2009) Stem and progenitor cells for liver repopulation: can we standardise the process from bench to bedside? Gut 58: 594– 603. [27] Chan C, Berthiaume F, Nath BD, Tilles AW, Toner M, Yarmush ML (2004) Hepatic

tissue engineering for adjunct and temporary liver support: critical technologies.

2nd, Lerut J, Nyberg SL, Salizzoni M, Fagan EA, de Hemptinne B, Broelsch CE, Muraca M, Salmeron JM, Rabkin JM, Metselaar HJ, Pratt D, De La Mata M, McChesney LP, Everson GT, Lavin PT, Stevens AC, Pitkin Z, Solomon BA (2004) Prospective, randomized, multicenter, controlled trial of a bioartificial liver in

Sussman NL, Williams R (1996) Pilot-controlled trial of the extracorporeal liver

gastroenterology and hepatology. Minimally Invasive Therp. Allied Technol. 17:

A, Maurel P, Daujat-Chavanieu M (2007) Isolation, characterization, and differentiation to hepatocyte-like cells of nonparenchymal epithelial cells from


[3] Seyer JM, Hutcheson ET, Kang AH (1977) Collagen polymorphism in normal and

[4] Taniyama Y, Morishita R, Nakagam H, Moriguchi A, Sakonjo H, Shokei-Kim MD,

[5] Ueki T, Kaneda Y, Tsutsui H, Nakanishi K, Sawa Y, Morishita R, Matsumoto K,

of liver cirrhosis by hepatocyte growth factor in rats. Nat Med. 5: 226 –230. [6] Yaekashiwa M, Nakayama S, Ohnuma K, Sakai T, Abe T, Satoh K, Matsumoto K,

[7] Liu Y (2002) Hepatocyte growth factor and the kidney. Curr. Opin. Nephrol. Hypertens.

[8] Matsumoto K, Nakamura T (2001) Hepatocyte growth factor: renotropic role and potential therapeutics for renal diseases. Kidney Int. 59: 2023– 2038. [9] Janczewska-Kazek E, Marek B, Kajdaniuk D, Ziółkowsk A, Kukla M (2005) Correlation

[10] Kallis YN, Robson AJ, Fallowfield JA, Thomas HC, Alison MR, Wright NA, Goldin RD,

[11] Gehling UM, Willems M, Schlagner K, Benndorf RA, Dandri M, Petersen J, Sterneck M,

[12] Piscaglia C (2008) Stem cells, a two-edged sword: risks and potentials of regenerative

[13] Liongue C, Wright C, Russell AP, Ward AC (2009) Granulocyte colony-stimulating

[14] Piscaglia C, Shupe TD, Oh S, Gasbarrini A, Petersen BE (2007) Granulocyte-colony

[15] Gaia S, Smedile A, Omed`e P Olivero, A, Sanavio F, Balzola F,Ottobrelli A, Abate ML,

[16] Khan AA, Parveen N, Mahaboob VS, Rajendraprasad A, Ravindraprakash HR,

[17] Campli CD, Zocco MA, Saulnier N, Grieco A, Rapaccini G, Addolorato G, Rumi C,

cells in patients with liver cirrhosis, World J. Gastro. 16: 217–224.

the hepatic progenitor cell response. Gut 60: 525–533.

proliferation in rats. Gastroenterology. 133: 619–631.

medicine. World J. Gastro. 14: 4273–4279.

end stage liver disease. J. Hep. 45: 13–19.

preliminary study. Transp. Proc. 40: 1140–1144.

Biol. 41: 2372–2375.

Matsumoto K, Nakamura S, Higaki J, Ogihara T (2000) Potential Contribution of a Novel Antifibrotic Factor, Hepatocyte Growth Factor, to Prevention of Myocardial Fibrosis by Angiotensin II Blockade in Cardiomyopathic Hamsters. J. American

Nakamura T, Takahashi H, Oakamoto E, Fujimoto J (1999) Curative gene therapy

Nakamura T, Takahashi T, Nukiwa T (1997) Simultaneous or delayed administration of hepatocyte growth factor equally represses the fibrotic changes in murine lung injury induced by bleomycin: a morphologic study. Am. J. Respir.

between TGF-beta1, VEGF, HGF, EGF, TGF-alpha and FGF serum levels, necroinflammatory activity and fibrosis in chronic hepatitis C. E&C Hepatology 1:

Iredale JP, Forbes SJ (2011) Remodelling of extracellular matrix is a requirement for

Pollok JM, Hossfeld DK, Rogiers X (2010) Mobilization of hematopoietic progenitor

factor receptor: stimulating granulopoiesis and much more. Int. J. Biochem. Cell

stimulating factor promotes liver repair and induces oval cell migration and

Marzano A, Rizzetto M, Tarella C (2006) Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with

Venkateswarlu J,. Rao SG, Narusu ML, Khaja MN, Pramila R, Habeeb A, Habibullah CM (2008) Safety and efficacy of autologous bone marrow stem cell transplantation through hepatic artery for the treatment of chronic liver failure: A

Santoliquido A, Leone G, Gasbarrini G, Gasbarrini A (2007) Safety and efficacy

cirrhotic human liver. J. Clin. Invest. 59: 241-248.

Heart Association 102: 246-252.

Crit. Care Med. 156: 1937–1944.

11: 23–30.

24-28.

profile of G-CSF therapy in patients with acute on chronic liver failure. Dig. Liv. Dis. 39: 1071–1076.


Cell Based Therapy for Chronic Liver Disease:

*vivo*. Exp. Hematol. 30: 42-48.

Immunol. 57: 11-20.

Role of Fetal Liver Cells in Restoration of the Liver Cell Functions 237

[49] Bahk JY, Piao Z, Jung JH, Han H (2011) Treatment of the end Stage Liver Cirrhosis by

[51] Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringden O (2003) Mesenchymal

[52] Fibbe WE, Noort WA (2003) Mesenchymal stem cells and hematopoietic stem cell

[53] Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O

[54] Maitra B, Szekely E, Gjini K, Laughlin MJ, Dennis J, Haynesworth SE, Koc ON (2004)

[55] Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic

[56] Zaret KS, Grompe M (2008) Generation and regeneration of cells of the liver and

[57] Cai J, Zhao Y, Liu Y, Ye F, Song Z, Qin H, Meng S, Chen Y, Zhou R, Song X, Guo Y,

[58] Yamanaka S (2009) Elite and stochastic models for induced pluripotent stem cell

[59] Sullivan GJ, Hay DC, Park IH, Fletcher J, Hannoun Z, Payne CM, Dalgetty D, Black JR,

[60] Si-Tayeb K, Noto FK, Nagaoka M, Li J, Battle MA, Duris C, North PE, Dalton S, Duncan

[61] Jozefczuk J, Prigione A, Chavez L, Adjaye J (2011). Comparative analysis of human

[62] Inamura M, Kawabata K, Takayama K, Tashiro K, Sakurai F, Katayama K, Toyoda M,

haploidentical mesenchymal stem cells. Lancet 363: 1439-1441.

and suppress T-cell activation. Bon. Marr. Transplant. 33: 597-604.

transplantation. Ann. N. Y. Acad. Sci. 996: 235-244.

immune cell responses. Blood 105:1815-1822.

functional hepatic cells. Hepatology 45: 1229–39.

pluripotent stem cells. Hepatology 51: 297– 305.

trimester. World J. Gastroenterol. 14: 5730-5737.

induced pluripotent stem cells. Hepatology 51: 329–335.

pancreas. Science 322: 1490–1494.

generation. Nature 460: 49–52.

Stem Cells Dev. 20: 1259–1275.

Human Umbilical Cord Blood Stem Cells: Preliminary Results. In: Ali Gholamrezanezhad editor. Stem Cells in Clinic and Research. InTech. pp 469-500. [50] Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W,

Devine S, Ucker D, Deans R, Moseley A, Hoffman R. (2002) Mesenchymal stem cells suppress lymphocyte proliferation *in vitro* and prolong skin graft survival *in* 

stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand. J.

(2004) Treatment of severe acute graft-versus-host disease with third party

Human mesenchymal stem cells support unrelated donor hematopoietic stem cells

Ding M, Deng H (2007) Directed differentiation of human embryonic stem cells into

Ross JA, Samuel K, Wang G, Daley GQ, Lee JH, Church GM, Forbes SJ, Iredale JP, Wilmut I (2010) Generation of functional human hepatic endoderm from human

SA (2010) Highly efficient generation of human hepatocyte-like cells from induced

embryonic stem cell and induced pluripotent stem cell-derived hepatocyte like cells reveals current drawbacks and possible strategies for improved differentiation.

Akutsu H, Miyagawa Y, Okita H, Kiyokawa N, Umezawa A, Hayakawa T, Furue MK, Mizuguchi H (2011) Efficient generation of hepatoblasts from human ES cells and iPS cells by transient overexpression of homeobox gene HEX. Mol. Ther. 19: 400–407. [63] SubbaRao M, Khan AA, Parveen N, Habeeb MA, Habibullah CM, Pande G (2008)

Characterization of hepatic progenitors from human fetal liver during second


[33] Haruna Y, Saito K, Spaulding S, Nalesnik MA, Gerber MA (1996) Identification of bipotential progenitor cells in human liver development. Hepatology 23: 476-481. [34] Badve S, Logdberg L, Sokhi R, Sigal SH, Botros N, Chae S, Das KM, Gupta S (2000) An

[35] Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA,

[36] Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells:

[37] Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida

[38] Ismail, Fouad O, Abdelnasser A, Chowdhury A, Selim A (2010) Stem cell therapy improves the outcome of liver resection in cirrhotics. J. Gastro. Cancer 41: 17–23. [39] Russo FP, Alison MR, Bigger BW, Amofah E, Florou A, Amin F, Bou-Gharios G, Jeffery

[40] Thomas JA, Pope C, Wojtacha D, Robson AJ, Gordon-Walker TT, Hartland S,

[41] Duffield JS, Forbes SJ, Constandinou CM, Clay S, Partolina M, Vuthoori S, Wu S, Lang

[42] Wognum AW, Eaves AC, Thomas TE (2003) Identification and isolation of

[43] Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP,

[44] Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Quinn G, Okochi H,

[45] Tong ML, Martina M, Hutmacher DW, Hui JHPO, Eng HL, and Lim B (2007)

[46] Kern S, Eichler H, Stoeve J, Kl¨uter H, Bieback K (2006) Comparative analysis of

[47] Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R, Ortega J,

fibrosis, regeneration and function. Hepatology 53: 2003–2015.

roles during liver injury and repair. J. Clin. Invest. 115: 56–65.

hematopoietic stem cells. Arch. Med. Res. 34: 461-475.

cell-based therapies. Tissue. Eng. 7: 211–228.

human hepatocytes. Hepatology 46: 219–228.

lineages. Stem Cells 25: 750–760.

tissue. Stem Cells 24: 1294–1301.

nature, biology, and potential applications. Stem Cells 19: 180-192.

among cell lineages. Pathobiology 68: 76-86.

mesenchymal stem cells. Science 284: 143–147.

fibrosis. Gastroenterology 130: 1807–1821.

Stem Cells 24: 2292–2298.

antigen reacting with Das-1 monoclonal antibody is ontogenically regulated in diverse organs including liver and indicates sharing of developmental mechanisms

Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human

K, Yamasaki T, Fujii Y, Okita K, Sakaida I (2006) Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy.

R, Iredale JP, Forbes SJ (2006) The bone marrow functionally contributes to liver

Ramachandran P, Van Deemter M, Hume DA, Iredale JP, Forbes SJ. (2011) Macrophage therapy for murine liver fibrosis recruits host effector cells improving

R, Iredale JP (2005) Selective depletion of macrophages reveals distinct, opposing

Hedrick MH (2001) Multi lineage cells from human adipose tissue: implications for

Ochiya T (2007) Adipose tissue derived mesenchymal stem cells as a source of

Identification of common pathways mediating differentiation of bone marrow and adipose tissue-derived human mesenchymal stem cells into three mesenchymal

mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose

Souillet G, Ferreira E, Laporte JP, Fernandez M, Chastang C (1997) Outcome of cordblood transplantation from related and unrelated donors. N. Engl. J. Med. 337: 373–81. [48] Grewal SS, Barker JN, Davies SM, Wagner JE (2003) Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood. Blood 101: 4233–44.


Cell Based Therapy for Chronic Liver Disease:

Transplant. Proc. 9: 578-584.

type I. Nat. Genet. 12: 266–273.

Cirrhosis. Cell Transplant. 19: 409–418.

World J. Gastroenterol. 13: 1067– 1073.

Adult Hepatocytes in Mice. Hepatology 50: 1194–1203.

Med. 3: 48–53.

Nature 406: 257

S30–S34

Role of Fetal Liver Cells in Restoration of the Liver Cell Functions 239

[83] Blei AT (2005) Selection for acute liver failure: have we got it right? Liver Transpl. 11:

[84] Khan AA, Habeeb A, Parveen N, Naseem B, Babu RP, Capoor AK, Habibullah CM.

[86] Khan AA, Parveen N, Mahaboob VS, Rajendraprasad A, Ravindraprakash HR,

[87] Sokal EM, Smets F, Bourgos A, Van Maldergem L, Buls JP, Reding R (2003) Hepatocyte

[88] Sommer BG, Sutherland DE, MatasAJ, SimmonsRL, Najarian, JS (1979) Hepato cellular

[89] Overturf K, Al-Dhalimy M, Tanguay R, Brantly M, Ou CN (1996) Hepatocytes corrected

[90] Gunsalus JR, Brady DA, Coulter SM, Gray BM, Edge AS (1997) Reduction of serum

[91] Khan AA, Shaik MV, Parveen N, Rajendraprasad A, Aleem MA, Aejaz Habeeb M,

[92] Nagata H, Ito M, Shirota C, Edge A, McCowan TC (2003) Route of hepatocyte delivery affects hepatocyte engraftment in the spleen. Transplantation 76: 732–734. [93] Cheng K, Benten D, Bhargava K, Inada M, Joseph B, Palestro C, Gupta S (2009) Hepatic

[94] Alison MA, Poulsom R, Jeffery R (2000) Hepatocytes from non-hepatic adult stem cells.

[95] Yannaki E, Anagnostopoulos A, Kapetanos D, Xagorari A, Iordanidis F, Batsis I,

[97] Kim JK, Park YN, Kim JS, Park MS, Paik YH, Seok JY, Chung YE, Kim HO, Kim KS, Ahn

patients with advanced liver cirrhosis. Cell Transplant. 19: 1237–1246.

acute fatty liver pregnancy; a case report. Trop. Gastroenterol. 25: 141-3. [85] Fox IJ, Roy Chowdhary J, Kauffman SS (1998) Treatment of the Crigler-Najjar syndrome

type I with hepatocyte transplantation. N Engl. J. Med. 338: 1422-6.

hyperbilirubinemia. Transplant Proc. 40: 1148-50.

safety and metabolic follow-up. Transplantation. 76: 735-43.

(2004) Peritoneal transplantation of human fetal hepatocytes for the treatment of

Venkateswarlu J, Rao P, Pande G, Narusu ML, Khaja MN, Pramila R, Habeeb A, Habibullah CM (2008) Treatment of Crigler-Najjar Syndrome type 1 by hepatic progenitor cell transplantation: a simple procedure for management of

transplantation in a 4-year girl with peroxisomal biogenesis disease: technique,

transplantation for treatment of galactosamine induced acute liver failure in rats.

by gene therapy are selected *in vivo* in a murine model of hereditary tyrosinaemia

cholesterol in Watanabe rabbits by xenogeneic hepatocellular transplantation. Nat.

Srinivas G, Avinash Raj T, Tiwari SK, Kumaresan K, Venkateswarlu, Pande G, Habibullah CM (2010) Human Fetal Liver-Derived Stem Cell Transplantation as Supportive Modality in the Management of End-Stage Decompensated Liver

Targeting and Biodistribution of Human Fetal Liver Stem/ Progenitor Cells and

Kaloyannidis P, Athanasiou E, Dourvas G, Kitis G, Fassas A (2006) Lasting amelioration in the clinical course of decompensated alcoholic cirrhosis with boost infusions of mobilized peripheral blood stem cells Exper. Hematol. 34: 1583–1587. [96] Lyra AC, Soares MB, Silva (2007) Feasiblity and safety of autologous bone marrow

mononuclear cell transplantation in patients with advanced chronic liver disease.

SH, Kim do Y, Kim MJ, Lee KS, Chon CY, Kim SJ, Terai S, Sakaida I, Han KH (2010) Autologous bone marrow infusion activates the progenitor cell compartment in


[64] Nyamath P, Alvi A, Habeeb A, Khosla S, Khan AA, Habibullah CM (2007)

[65] Malhi H, Irani AN, Gagandeep S, Gupta S (2002). Isolation of human progenitor liver

[66] Petersen BE, Goff JP, Greenberger Michalopoulos GK (1998) Hepatic oval cells express the hematopoietic stem cell marker Thy-1 in the rat. Hepatology 27: 433–445. [67] Fujio K, Evarts RP, Hu Z, Marsden ER, Thorgeirsson SS (1994) Expression of stem cell

[68] Weiss TS, Lichtenauer M, Kirchner S, Stock P, Aurich H, Christ B, Brockhoff G, Kunz-

[69] Harrison MF (1953) Composition of the liver cell. Proc R Soc Lond B Biol Sci. 141: 203-16 [70] Anderson NG (1953) The mass isolation of whole cells from rat liver.Science. 117: 627-8. [71] Castagna M, Chauveau J (1963) Dispersion of hepatic tissue in the state of isolated cells.

[72] Gallai-Hatchard JJ, Gray GM (1971) A method of obtaining a suspension of intact

[73] Hommes FA, Draisma MI, Molenaar I (1970) Preparation and some properties of

[74] Gridelli B, Vizzini G, Pietrosi G, Luca A, Spada M, Gruttadauria S, Cintorino D, Amico

[75] Yaswen P, Hayner NT, Fausto N (1984) Isolation of oval cells by centrifugal elutriation

[76] Balzar M, Winter MJ, de Boer CJ, Litvinov SV (1999) The biology of the 17-1A antigen

[77] Schmelzer E, Wauthier E, Reid LM (2006) The phenotypes of pluripotent human hepatic

[78] Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC (1996) Isolation and

[79] Uchida N, Fujisaki T, Eaves AC, Eaves CJ (2001) Transplantable hematopoietic stem

[80] Khan AA, Parveen N, Habeeb MA, Habibullah CM (2006) Journey from hepatocyte

[81] Liu Y-N, Zhang J, He Q-H, Dai X, and Shen L (2008) Isolation and characterization of epithelial progenitor cells from human fetal liver. Hepatol Res. 38: 103–113. [82] Habibullah CM, Syed IH, Qamar A, Taher-Uz Z (1994) Human fetal hepatocyte transplantation in patients with fulminant hepatic failure. Transplantation 58: 951-2.

G, Chinnici C, Miki T, Schmelzer E, Conaldi PG, Triolo F, Gerlach JC (2012) Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell-based therapy and case report on cell transplantation. Liver Transpl.

and compersion with other cell types purified from normal and preneoplastic

functional properties of murine hematopoietic stem cells that are replicating *in vivo*.

cells in human fetal liver have a CD34(+) side population (SP)phenotype. J Clin

transplantation to hepatic stem cells: A novel treatment strategy for liver diseases.

from adult human livers for cell transplantation. Gut. 57:1129-38.

parenchymal cells from adult rat liver. J Cell Sci. 8: 73-86.

isolated rat liver cells. Biochim. Biophys Acta. 222: 361–371.

hepatic progenitor marker. World J. Gastroenterol. 13: 2319-2323.

hepatocytes. J. Cell Sci. 115: 2679-2688.

adult rat. Lab. Invest. 70: 511–516.

C R Hebd Seances Acad Sci. 22: 969-977.

livers. Cancer Res. 44: 324-331.

J Exp Med. 183: 1797-806

Invest. 108: 1071-7

(Ep-CAM). J. Mol. Med. 77: 699–712.

progenitors. Stem Cells 24:1852-1858.

Indian. J. Med. Res. 123: 601-614.

18:226-37.

Characterization of hepatic progenitors from human fetal liver using CD34 as a

epithelial cells with extensive replication capacity and differentiation into mature

factor and its receptor, c-kit, during liver regeneration from putative stem cells in

Schughart LA, Jauch KW, Schlitt HJ, Thasler WE (2008) Hepatic progenitor cells


**13** 

*USA*

**Liver Regeneration and Bioengineering –** 

**The Emergence of Whole Organ Scaffolds** 

Every year an estimated two million people die of advanced liver disease. The World Health Organization estimates that over six hundred and fifty million people worldwide are affected by some form of liver disease, including thirty million Americans. On a worldwide base, the bleak cenario of one to two million deaths are accounted to liver related diseases annually. From all the countries, China has the world's largest population of Hepatitis B patients (approx. 120 million) with five hundred thousand people dying of the liver disease every year(1, 2). In the US alone, there are around five hundred thousand critical episodes of liver problems every year requiring hospitalization with a huge burden to the patients and an enormous cost to the health care system. In the European Union and United States of America alone, over eighty one thousand and twenty six thousand people died of chronic liver disease in 2006, respectively(1, 3). For these patients, liver transplantation is currently the only therapy proven to extend survival for end-stage liver disease, as it is also the only treatment for severe acute liver failure and the some forms of inborn errors of metabolism. However, the waiting list for liver transplants is extensive and many on the list will not

receive an organ due to a dramatic shortage of donors or not being eligible(1).

A good example of this is that in 2007 there were nearly seventeen thousand individuals on the US waiting list for a liver transplant. Only 30% of those in need were transplanted. The average waiting time was more than 400 days. The same year, about one thousand and three hundred people died while waiting for a suitable donor with no available medical option for saving their life. Also, for those patients with fulminant hepatic failure, a severe liver disease with 60-90% mortality, depending on the cause, only 10% received a transplant. Nevertheless, liver transplantation still has a relatively high mortality of 30-40% at 5-8 years with 65% of the deaths occurring in the first 6 months. In addition, patients who have undergone transplantation have to use lifelong immunosuppressive therapy, with

The etiologies of end-stage chronic liver disease that lead to transplantation are numerous and ~80% of people in the liver transplant waiting list have as primary diagnosis a cirrhotic liver. Fortunately, some of the causes of the disease are nowadays preventable. A good example is the successful vaccination programs in many countries in the world against Hepatitis B virus that have considerably reduced the incidence of chronic carriers and viral

**1. Introduction** 

sometimes severe side effects(4).

*Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC,* 

Pedro M. Baptista, Dipen Vyas and Shay Soker

*Wake Forest University Health Sciences,* 

