Three-dimensional culture of hepatocytes on porcine liver tissue-derived extracellular matrix

Ren Lang, Matthew M. Stern, Leona Smith, Yan Liu, Shantaram Bharadwaj, Guihua Liu, Pedro M. Baptista, Christopher R. Bergman, Shay Soker, James J. Yoo, Anthony Atala, Yuanyuan Zhang

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

There is currently no optimal system to expand and maintain the function of human adult hepatocytes in culture. Recent studies have demonstrated that specific tissue-derived extracellular matrix (ECM) can serve as a culture substrate and that cells tend to proliferate and differentiate best on ECM derived from their tissue of origin. The goal of this study was to investigate whether three-dimensional (3D) ECM derived from porcine liver can facilitate the growth and maintenance of physiological functions of liver cells. Optimized decellularization/oxidation procedures removed up to 93% of the cellular components from porcine liver tissue and preserved key molecular components in the ECM, including collagen-I, -III, and -IV, proteoglycans, glycosaminoglycans, fibronectin, elastin, and laminin. When HepG2 cells or human hepatocytes were seeded onto ECM discs, uniform multi-layer constructs of both cell types were formed. Dynamic culture conditions yielded better cellular infiltration into the ECM discs. Human hepatocytes cultured on ECM discs expressed significantly higher levels of albumin over a 21-day culture period compared to cells cultured in traditional polystyrene cultureware or in a collagen gel " sandwich" The culture of hepatocytes on 3D liver-specific ECM resulted in considerably improved cell growth and maintained cell function; therefore, this system could potentially be used in liver tissue regeneration, drug discovery or toxicology studies.

Original languageEnglish
Pages (from-to)7042-7052
Number of pages11
JournalBiomaterials
Volume32
Issue number29
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

Fingerprint

Liver
Extracellular Matrix
Hepatocytes
Swine
Tissue
Collagen
Elastin
Tissue regeneration
Optimal systems
Liver Regeneration
Polystyrenes
Hep G2 Cells
Cell growth
Laminin
Proteoglycans
Drug Discovery
Growth
Glycosaminoglycans
Fibronectins
Infiltration

Keywords

  • 3D
  • Albumin
  • Cell culture
  • ECM (extracellular matrix)
  • Hepatocyte
  • Liver

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Lang, R., Stern, M. M., Smith, L., Liu, Y., Bharadwaj, S., Liu, G., ... Zhang, Y. (2011). Three-dimensional culture of hepatocytes on porcine liver tissue-derived extracellular matrix. Biomaterials, 32(29), 7042-7052. https://doi.org/10.1016/j.biomaterials.2011.06.005

Three-dimensional culture of hepatocytes on porcine liver tissue-derived extracellular matrix. / Lang, Ren; Stern, Matthew M.; Smith, Leona; Liu, Yan; Bharadwaj, Shantaram; Liu, Guihua; Baptista, Pedro M.; Bergman, Christopher R.; Soker, Shay; Yoo, James J.; Atala, Anthony; Zhang, Yuanyuan.

In: Biomaterials, Vol. 32, No. 29, 01.10.2011, p. 7042-7052.

Research output: Contribution to journalArticle

Lang, R, Stern, MM, Smith, L, Liu, Y, Bharadwaj, S, Liu, G, Baptista, PM, Bergman, CR, Soker, S, Yoo, JJ, Atala, A & Zhang, Y 2011, 'Three-dimensional culture of hepatocytes on porcine liver tissue-derived extracellular matrix', Biomaterials, vol. 32, no. 29, pp. 7042-7052. https://doi.org/10.1016/j.biomaterials.2011.06.005
Lang, Ren ; Stern, Matthew M. ; Smith, Leona ; Liu, Yan ; Bharadwaj, Shantaram ; Liu, Guihua ; Baptista, Pedro M. ; Bergman, Christopher R. ; Soker, Shay ; Yoo, James J. ; Atala, Anthony ; Zhang, Yuanyuan. / Three-dimensional culture of hepatocytes on porcine liver tissue-derived extracellular matrix. In: Biomaterials. 2011 ; Vol. 32, No. 29. pp. 7042-7052.
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