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 Scopus citations

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)
Pages (from-to)437-445
Number of pages9
JournalNature Biomedical Engineering
Volume4
Issue number4
DOIs
StatePublished - Apr 1 2020

ASJC Scopus subject areas

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

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    Shaheen, M. F., Joo, D. J., Ross, J. J., Anderson, B. D., Chen, H. S., Huebert, R. C., Li, Y., Amiot, B., Young, A., Zlochiver, V., Nelson, E., Mounajjed, T., Dietz, A. B., Michalak, G., Steiner, B. G., Davidow, D. S., Paradise, C. R., van Wijnen, A. J., Shah, V. H., ... Nyberg, S. L. (2020). Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs. Nature Biomedical Engineering, 4(4), 437-445. https://doi.org/10.1038/s41551-019-0460-x