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 L. Yarmush; Korkut Uygun

doi:10.1038/nm.2170

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 L. Yarmush, Korkut Uygun

Research output: Contribution to journal › Article › peer-review

1180 Scopus citations

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 language	English
Pages (from-to)	814-820
Number of pages	7
Journal	Nature Medicine
Volume	16
Issue number	7
DOIs	https://doi.org/10.1038/nm.2170
State	Published - Jul 2010

Bibliographical note

Funding Information:
This work was supported by grants from the US National Institutes of Health, R01DK59766 and R01DK084053 to M.L.Y., K99/R00 DK080942 to K.U. and K99DK083556 to A.S.G., and US National Science Foundation CBET0853569 to K.U. We thank the support of the Shriners Hospitals for Children to B.E.U. (grant no. 8503), the American Liver Foundation to A.S.G. and Massachusetts General Hospital Junior Faculty Grant to K.U. and the Shriners Hospitals for Children. We would like to thank A. Vitalo, C. Calhoun and B. Crowther for technical support.

Access to Document

10.1038/nm.2170

Cite this

Uygun, B. E., Soto-Gutierrez, A., Yagi, H., Izamis, M. L., Guzzardi, M. A., Shulman, C., Milwid, J., Kobayashi, N., Tilles, A., Berthiaume, F., Hertl, M., Nahmias, Y., Yarmush, M. L., & 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

@article{7010129e31114376b919a968f68b9c3f,

title = "Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix",

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.",

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

note = "Funding Information: This work was supported by grants from the US National Institutes of Health, R01DK59766 and R01DK084053 to M.L.Y., K99/R00 DK080942 to K.U. and K99DK083556 to A.S.G., and US National Science Foundation CBET0853569 to K.U. We thank the support of the Shriners Hospitals for Children to B.E.U. (grant no. 8503), the American Liver Foundation to A.S.G. and Massachusetts General Hospital Junior Faculty Grant to K.U. and the Shriners Hospitals for Children. We would like to thank A. Vitalo, C. Calhoun and B. Crowther for technical support.",

year = "2010",

month = jul,

doi = "10.1038/nm.2170",

language = "אנגלית",

volume = "16",

pages = "814--820",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Research",

number = "7",

}

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, ML & 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

TY - JOUR

T1 - Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix

AU - Uygun, Basak E.

AU - Soto-Gutierrez, Alejandro

AU - Yagi, Hiroshi

AU - Izamis, Maria Louisa

AU - Guzzardi, Maria A.

AU - Shulman, Carley

AU - Milwid, Jack

AU - Kobayashi, Naoya

AU - Tilles, Arno

AU - Berthiaume, Francois

AU - Hertl, Martin

AU - Nahmias, Yaakov

AU - Yarmush, Martin L.

AU - Uygun, Korkut

N1 - Funding Information: This work was supported by grants from the US National Institutes of Health, R01DK59766 and R01DK084053 to M.L.Y., K99/R00 DK080942 to K.U. and K99DK083556 to A.S.G., and US National Science Foundation CBET0853569 to K.U. We thank the support of the Shriners Hospitals for Children to B.E.U. (grant no. 8503), the American Liver Foundation to A.S.G. and Massachusetts General Hospital Junior Faculty Grant to K.U. and the Shriners Hospitals for Children. We would like to thank A. Vitalo, C. Calhoun and B. Crowther for technical support.

PY - 2010/7

Y1 - 2010/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77954533642&partnerID=8YFLogxK

U2 - 10.1038/nm.2170

DO - 10.1038/nm.2170

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 20543851

AN - SCOPUS:77954533642

SN - 1078-8956

VL - 16

SP - 814

EP - 820

JO - Nature Medicine

JF - Nature Medicine

IS - 7

ER -

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

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this