Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs

Mohammed F. Shaheen, Dong Jin Joo, Jeffrey J. Ross, Brett D. Anderson, Harvey S. Chen, Robert C. Huebert, Yi Li, Bruce Amiot, Anne Young, Viviana Zlochiver, Erek Nelson, Taofic Mounajjed, Allan B. Dietz, Gregory Michalak, Benjamin G. Steiner, Dominique Seetapun Davidow, Christopher R. Paradise, Andre J. van Wijnen, Vijay H. Shah, Mengfei LiuScott L. Nyberg

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Implanted bioengineered livers have not exceeded three days of continuous perfusion. Here we show that decellularized whole porcine livers revascularized with human umbilical vein endothelial cells and implanted heterotopically into immunosuppressed pigs whose spleens had been removed can sustain perfusion for up to 15 days. We identified peak glucose consumption rate as a main predictor of the patency of the revascularized bioengineered livers (rBELs). Heterotopic implantation of rBELs into pigs in the absence of anticoagulation therapy led to sustained perfusion for three days, followed by a pronounced immune responses directed against the human endothelial cells. A 10 day steroid-based immunosuppression protocol and a splenectomy at the time of rBEL implantation reduced the immune responses and resulted in continuous perfusion of the rBELs for over two weeks. We also show that the human endothelial cells in the perfused rBELs colonize the liver sinusoids and express sinusoidal endothelial markers similar to those in normal liver tissue. Revascularized liver scaffolds that can maintain blood perfusion at physiological pressures might eventually help to overcome the chronic shortage of transplantable human livers.

Original languageEnglish (US)
JournalNature Biomedical Engineering
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Liver
Swine
Perfusion
Endothelial cells
Endothelial Cells
Human Umbilical Vein Endothelial Cells
Splenectomy
Scaffolds (biology)
Immunosuppression
Glucose
Blood
Spleen
Steroids
Tissue
Pressure

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

Cite this

Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs. / Shaheen, Mohammed F.; Joo, Dong Jin; Ross, Jeffrey J.; Anderson, Brett D.; Chen, Harvey S.; Huebert, Robert C.; Li, Yi; Amiot, Bruce; Young, Anne; Zlochiver, Viviana; Nelson, Erek; Mounajjed, Taofic; Dietz, Allan B.; Michalak, Gregory; Steiner, Benjamin G.; Davidow, Dominique Seetapun; Paradise, Christopher R.; van Wijnen, Andre J.; Shah, Vijay H.; Liu, Mengfei; Nyberg, Scott L.

In: Nature Biomedical Engineering, 01.01.2019.

Research output: Contribution to journalArticle

Shaheen, MF, Joo, DJ, Ross, JJ, Anderson, BD, Chen, HS, Huebert, RC, Li, Y, Amiot, B, Young, A, Zlochiver, V, Nelson, E, Mounajjed, T, Dietz, AB, Michalak, G, Steiner, BG, Davidow, DS, Paradise, CR, van Wijnen, AJ, Shah, VH, Liu, M & Nyberg, SL 2019, 'Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs', Nature Biomedical Engineering. https://doi.org/10.1038/s41551-019-0460-x
Shaheen, Mohammed F. ; Joo, Dong Jin ; Ross, Jeffrey J. ; Anderson, Brett D. ; Chen, Harvey S. ; Huebert, Robert C. ; Li, Yi ; Amiot, Bruce ; Young, Anne ; Zlochiver, Viviana ; Nelson, Erek ; Mounajjed, Taofic ; Dietz, Allan B. ; Michalak, Gregory ; Steiner, Benjamin G. ; Davidow, Dominique Seetapun ; Paradise, Christopher R. ; van Wijnen, Andre J. ; Shah, Vijay H. ; Liu, Mengfei ; Nyberg, Scott L. / Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs. In: Nature Biomedical Engineering. 2019.
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