Skip to main content
SpringerLink
Log in
Book cover

Stem Cells and Cancer Stem Cells, Volume 10 pp 45–57Cite as

Hepatogenic Differentiation: Comparison Between Adipose Tissue-Derived Stem Cells and Bone Marrow Mesenchymal Stem Cells

  • Chapter
  • First Online:

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 10))

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells, able to differentiate into elements of the mesodermal lineage. Bone marrow and adipose tissue represent the main sources for MSCs isolation. In the last decade, several studies have reported the plasticity of MSCs toward a hepatocyte-like phenotype. Both types of cells have been cultured under similar pro-hepatogenic conditions by sequential exposure to cytokines, growth factors and hormones reflecting their temporal expression during in vivo hepatogenesis. The different capacities of hepatic differentiation of the two subsets in vitro have been investigated.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

ADSCs:

adipose tissue-derived stem cells

AFP:

alpha-Fetoprotein

ALB:

Albumin

BMP 2 and 4:

bone morphogenetic protein 2 and 4

BMSCs:

bone marrow-derived stem cells

CYPs:

cytochrome P450 enzymes

DEX:

dexamethasone

FGF:

fibroblastic growth factor

FGF1, 2 and 4:

fibroblastic growth factor 1, 2 and 4

FGFR1 and 2:

fibroblast growth factor receptor 1 and 2

hESCs:

human embryonic stem cells

HGF:

hepatocyte growth factor

IGF-I:

insulin growth factor

LDL:

low-density lipoprotein

MSCs:

mesenchymal stem cells

OSM:

oncostatin

PLGA:

poly lactic glycolic acid

References

  • Amer ME, El-Sayed SZ, El-Kheir WA, Gabr H, Gomaa AA, El-Noomani N, Hegazy M (2011) Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells. Eur J Gastroenterol Hepatol 23:936–941

    Article  PubMed  Google Scholar 

  • Aurich I, Mueller LP, Aurich H, Luetzkendorf J, TisljarK, Dollinger MM, Schormann W, Walldorf J, Hengstler JG, Fleig WE, Christ B (2007) Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers. Gut 56:405–415

    Article  PubMed  CAS  Google Scholar 

  • Aurich H, Sgodda M, Kaltwasser P, Vetter M, Weise A, Liehr T, Brulport M, Hengstler JG, Dollinger MM, Fleig WE, Christ B (2009) Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut 58:570–581

    Article  PubMed  CAS  Google Scholar 

  • Ayatollahi M, Soleimani M, Tabei SZ, Kabir Salmani M (2011) Hepatogenic differentiation of mesenchymal stem cells induced by insulin like growth factor-I. World J Stem Cells 3:113–121

    Article  PubMed  Google Scholar 

  • Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Osaki M, Kawamata M, Kato T, Okochi H, Ochiya T (2008) IFATS collection: in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury. Stem Cells 26:2705–2712

    Article  PubMed  CAS  Google Scholar 

  • Bonora-Centelles A, Jover R, Mirabet V, Lahoz A, Carbonell F, Castell JV, Gomez-Lechon MJ (2009) Sequential hepatogenic transdifferentiation of adipose tissue-derived stem cells: relevance of different extracellular signaling molecules, transcription factors involved, and expression of new key marker genes. Cell Transplant 18:1319–1340

    Article  PubMed  CAS  Google Scholar 

  • Bort R, Signore M, Tremblay K, Martinez Barbera JP, Zaret KS (2006) Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development. Dev Biol 290:44–56

    Article  PubMed  CAS  Google Scholar 

  • di Bonzo LV, Ferrero I, Cravanzola C, Mareschi K, Rustichell D, Novo E, Sanavio F, Cannito S, Zamara E, Bertero M, Davit A, Francica S, Novelli F, Colombatto S, Fagioli F, Parola M (2008) Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine: engraftment and hepatocyte differentiation versus profibrogenic potential. Gut 57:223–231

    Article  PubMed  Google Scholar 

  • Duret C, Gerbal-Chaloin S, Ramos J, Fabre JM, Jacquet E, Navarro F, Blanc P, Sa-Cunha A, Maurel P, Daujat-Chavanieu M (2007) Isolation, characterization, and differentiation to hepatocyte-like cells of nonparenchymal epithelial cells from adult human liver. Stem Cells 25:1779–1790

    Article  PubMed  CAS  Google Scholar 

  • Farre J, Roura S, Prat-Vidal C, Soler-Botija C, Llach A, Molina CE, Hove-Madsen L, Cairo JJ, Godia F, Bragos R, Cinca J, Bayes-Genis A (2007) FGF-4 increases in vitro expansion rate of human adult bone marrow-derived mesenchymal stem cells. Growth Factors 25:71–76

    Article  PubMed  CAS  Google Scholar 

  • Fox IJ, Roy-Chowdhury J (2004) Hepatocyte transplantation. J Hepatol 40:878–886

    Article  PubMed  CAS  Google Scholar 

  • Isabel Z, Miri B, Einav H, Ella BL, Zamir H, Ran O (2006) Isolation, characterization and culture of Thy1-positive cells from fetal rat livers. World J Gastroenterol 12:3841–3847

    PubMed  CAS  Google Scholar 

  • Izadpanah R, Kaushal D, Kriedt C, Tsien F, Patel B, Dufour J, Bunnell BA (2008) Long-term in vitro expansion alters the biology of adult mesenchymal stem cells. Cancer Res 68:4229–4238

    Article  PubMed  CAS  Google Scholar 

  • Kinoshita T, Miyajima A (2002) Cytokine regulation of liver development. Biochim Biophys Acta 1592:303–312

    Article  PubMed  CAS  Google Scholar 

  • Kuo TK, Hung SP, Chuang CH, Chen CT, Shih YR, Fang SC, Yang VW, Lee OK (2008) Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology 134:2111–2121, 2121, e2111–e2113

    Google Scholar 

  • Lee RH, Kim B, Choi I, Kim H, Choi HS, Suh K, Bae YC, Jung JS (2004) Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell Physiol Biochem 14:311–324

    Article  PubMed  CAS  Google Scholar 

  • Li J, Ning G, Duncan SA (2000) Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha. Genes Dev 14:464–474

    PubMed  CAS  Google Scholar 

  • Lue J, Lin G, Ning H, Xiong A, Lin CS, Glenn JS (2010) Transdifferentiation of adipose-derived stem cells into hepatocytes: a new approach. Liver Int 30:913–922

    Article  PubMed  CAS  Google Scholar 

  • Ochiya T, Yamamoto Y, Banas A (2010) Commitment of stem cells into functional hepatocytes. Differentiation 79:65–73

    Article  PubMed  CAS  Google Scholar 

  • Parviz F, Matullo C, Garrison WD, Savatski L, Adamson JW, Ning G, Kaestner KH, Rossi JM, Zaret KS, Duncan SA (2003) Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis. Nat Genet 34:292–296

    Article  PubMed  CAS  Google Scholar 

  • Ruiz JC, Ludlow JW, Sherwood S, Yu G, Wu X, Gimble JM (2010) Differentiated human adipose-derived stem cells exhibit hepatogenic capability in vitro and in vivo. J Cell Physiol 225:429–436

    Article  PubMed  CAS  Google Scholar 

  • Sato Y, Araki H, Kato J, Nakamura K, Kawano Y, Kobune M, Sato T, Miyanishi K, Takayama T, Takahashi M, Takimoto R, Iyama S, Matsunaga T, Ohtani S, Matsuura A, Hamada H, Niitsu Y (2005) Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 106:756–763

    Article  PubMed  CAS  Google Scholar 

  • Seo MJ, Suh SY, Bae YC, Jung JS (2005) Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun 328:258–264

    Article  PubMed  CAS  Google Scholar 

  • Sgodda M, Aurich H, Kleist S, Aurich I, Konig S, Dollinger MM, Fleig WE, Christ B (2007) Hepatocyte differentiation of mesenchymal stem cells from rat peritoneal adipose tissue in vitro and in vivo. Exp Cell Res 313:2875–2886

    Article  PubMed  CAS  Google Scholar 

  • Snykers S, Vanhaecke T, Papeleu P, Luttun A, Jiang Y, Vander Heyden Y, Verfaillie C, Rogiers V (2006). Sequential exposure to cytokines reflecting embryogenesis: the key for in vitro differentiation of adult bone marrow stem cells into functional hepatocyte-like cells. Toxicol Sci 94:330–341; discussion 235–339

    Google Scholar 

  • Snykers S, Vanhaecke T, De Becker A, Papeleu P, Vinken M, Van Riet I, Rogiers V (2007) Chromatin remodeling agent trichostatin A: a key-factor in the hepatic differentiation of human mesenchymal stem cells derived of adult bone marrow. BMC Dev Biol 7:24

    Article  PubMed  Google Scholar 

  • Stock P, Staege MS, Muller LP, Sgodda M, Volker A, Volkmer I, Lutzkendorf J, Christ B (2008) Hepatocytes derived from adult stem cells. Transplant Proc 40:620–623

    Article  PubMed  CAS  Google Scholar 

  • Suzuki A, Iwama A, Miyashita H, Nakauchi H, Taniguchi H (2003) Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells. Development 130:2513–2524

    Article  PubMed  CAS  Google Scholar 

  • Talens-Visconti R, Bonora A, Jover R, Mirabet V, Carbonell F, Castell JV, Gomez-Lechon MJ (2006) Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells. World J Gastroenterol 12:5834–5845

    PubMed  CAS  Google Scholar 

  • Vemuri MC, Chase LG, Rao MS (2011) Mesenchymal stem cell assays and applications. Methods Mol Biol 698:3–8

    Article  PubMed  Google Scholar 

  • Wang PP, Wang JH, Yan ZP, Hu MY, Lau GK, Fan ST, Luk JM (2004) Expression of hepatocyte-like phenotypes in bone marrow stromal cells after HGF induction. Biochem Biophys Res Commun 320:712–716

    Article  PubMed  CAS  Google Scholar 

  • Wang M, Pei H, Zhang L, Guan L, Zhang R, Jia Y, Li B, Yue W, Wang Y, Pei X (2010) Hepatogenesis of adipose-derived stem cells on poly-lactide-co-glycolide scaffolds: in vitro and in vivo studies. Tissue Eng Part C Methods 16:1041–1050

    Article  PubMed  Google Scholar 

  • Wang J, Zong C, Shi D, Wang W, Shen D, Liu L, Tong X, Zheng Q, Gao C (2012) Hepatogenic engineering from human bone marrow mesenchymal stem cells in porous polylactic glycolic acid scaffolds under perfusion culture. J Tissue Eng Regen Med 6:29–39

    Article  PubMed  CAS  Google Scholar 

  • Westmacott A, Burke ZD, Oliver G, Slack JM, Tosh D (2006) C/EBPalpha and C/EBPbeta are markers of early liver development. Int J Dev Biol 50:653–657

    Article  PubMed  CAS  Google Scholar 

  • Zemel R, Bachmetov L, Ad-El D, Abraham A, Tur-Kaspa R (2009) Expression of liver-specific markers in naive adipose-derived mesenchymal stem cells. Liver Int 29:1326–1337

    Article  PubMed  CAS  Google Scholar 

  • Zhao R, Watt AJ, Li J, Luebke-Wheeler J, Morrisey EE, Duncan SA (2005) GATA6 is essential for embryonic development of the liver but dispensable for early heart formation. Mol Cell Biol 25:2622–2631

    Article  PubMed  CAS  Google Scholar 

  • Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank the financial support of the European Union (Innovaliv Project, HEALTH-F4-2011278152). L.T. was a recipient of a Sara Borrell Contract from the “Instituto de Salud Carlos III” from the Spanish Ministry of Economy and Competitiveness.

Author information

Authors and Affiliations

  1. Experimental Hepatology Unit, Research Centre Hospital La Fe, Avda Campanar 21, 46009, Valencia, Spain

    María José Gómez-Lechón & Laia Tolosa

Authors
  1. María José Gómez-Lechón
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laia Tolosa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to María José Gómez-Lechón .

Editor information

Editors and Affiliations

  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Gómez-Lechón, M.J., Tolosa, L. (2013). Hepatogenic Differentiation: Comparison Between Adipose Tissue-Derived Stem Cells and Bone Marrow Mesenchymal Stem Cells. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 10. Stem Cells and Cancer Stem Cells, vol 10. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6262-6_5

Download citation

Publish with us

Policies and ethics

Search

Navigation