한빛사 논문
Mohammed F. Shaheena,b, DongJin Jooa,c, Jeffrey J. Rossd,*, Brett D. Andersond, Harvey S. Chena,b, Robert C. Hueberte, Yi Lia, Bruce Amiota, Anne Youngd, Viviana Zlochiverd, Erek Nelsona,b, Taofic Mounajjedf, Allan B. Dietzf, Gregory Michalakg, Benjamin G. Steinerd, Dominique Seetapun Davidowd, Christopher R. Paradiseh, Andre J. van Wijneni,j, Vijay H. Shahe, Mengfei Liue & Scott L. Nyberga,b,*
aWilliam J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA
bDepartment of Surgery, Mayo Clinic, Rochester, MN, USA
cDepartment of Surgery, Yonsei University College of Medicine, Seoul, South Korea
dMiromatrix Medical Inc., Eden Prairie, MN, USA
eDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
fDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
gDepartment of Radiology, Mayo Clinic, Rochester, MN, USA
hCenter for Regenerative Medicine, Mayo Clinic, Rochester, MN, USA
iDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
jDepartment of Orthopedics, Mayo Clinic, Rochester, MN, USA
These authors contributed equally: Mohammed F. Shaheen, DongJin Joo.
*Correspondence to Jeffrey J. Ross or Scott L. Nyberg
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.
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