Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix

Basak E. Uygun, Alejandro Soto-Gutierrez, Hiroshi Yagi, Maria Louisa Izamis, Maria A. Guzzardi, Carley Shulman, Jack Milwid, Naoya Kobayashi, Arno Tilles, Francois Berthiaume, Martin Hertl, Yaakov Nahmias, Martin Yarmush, Korkut Uygun

Research output: Contribution to journalArticle

798 Citations (Scopus)

Abstract

Orthotopic liver transplantation is the only available treatment for severe liver failure, but it is currently limited by organ shortage. One technical challenge that has thus far limited the development of a tissue-engineered liver graft is oxygen and nutrient transport. Here we demonstrate a novel approach to generate transplantable liver grafts using decellularized liver matrix. The decellularization process preserves the structural and functional characteristics of the native microvascular network, allowing efficient recellularization of the liver matrix with adult hepatocytes and subsequent perfusion for in vitro culture. The recellularized graft supports liver-specific function including albumin secretion, urea synthesis and cytochrome P450 expression at comparable levels to normal liver in vitro. The recellularized liver grafts can be transplanted into rats, supporting hepatocyte survival and function with minimal ischemic damage. These results provide a proof of principle for the generation of a transplantable liver graft as a potential treatment for liver disease.

Original languageEnglish (US)
Pages (from-to)814-820
Number of pages7
JournalNature Medicine
Volume16
Issue number7
DOIs
StatePublished - Jul 1 2010

Fingerprint

Reengineering
Grafts
Liver
Transplants
Hepatocytes
Liver Failure
Microvessels
Transplantation (surgical)
Liver Transplantation
Cytochrome P-450 Enzyme System
Urea
Liver Diseases
Albumins
Perfusion
Oxygen
Nutrients
Food
Rats
Therapeutics
Tissue

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Uygun, B. E., Soto-Gutierrez, A., Yagi, H., Izamis, M. L., Guzzardi, M. A., Shulman, C., ... Uygun, K. (2010). Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nature Medicine, 16(7), 814-820. https://doi.org/10.1038/nm.2170
Uygun, Basak E. ; Soto-Gutierrez, Alejandro ; Yagi, Hiroshi ; Izamis, Maria Louisa ; Guzzardi, Maria A. ; Shulman, Carley ; Milwid, Jack ; Kobayashi, Naoya ; Tilles, Arno ; Berthiaume, Francois ; Hertl, Martin ; Nahmias, Yaakov ; Yarmush, Martin ; Uygun, Korkut. / Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. In: Nature Medicine. 2010 ; Vol. 16, No. 7. pp. 814-820.
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Uygun, BE, Soto-Gutierrez, A, Yagi, H, Izamis, ML, Guzzardi, MA, Shulman, C, Milwid, J, Kobayashi, N, Tilles, A, Berthiaume, F, Hertl, M, Nahmias, Y, Yarmush, M & Uygun, K 2010, 'Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix', Nature Medicine, vol. 16, no. 7, pp. 814-820. https://doi.org/10.1038/nm.2170

Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. / Uygun, Basak E.; Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Izamis, Maria Louisa; Guzzardi, Maria A.; Shulman, Carley; Milwid, Jack; Kobayashi, Naoya; Tilles, Arno; Berthiaume, Francois; Hertl, Martin; Nahmias, Yaakov; Yarmush, Martin; Uygun, Korkut.

In: Nature Medicine, Vol. 16, No. 7, 01.07.2010, p. 814-820.

Research output: Contribution to journalArticle

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