Bioengineering (Oct 2023)

Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure

  • Victoria L. Nelson,
  • Aron R. Stumbras,
  • R. Noelle Palumbo,
  • Shawn A. Riesgraf,
  • Marie S. Balboa,
  • Zachary A. Hannah,
  • Isaac J. Bergstrom,
  • Christopher J. Fecteau,
  • John R. Lake,
  • John J. Barry,
  • Jeff J. Ross

DOI
https://doi.org/10.3390/bioengineering10101201
Journal volume & issue
Vol. 10, no. 10
p. 1201

Abstract

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Acute Liver Failure (ALF) is a life-threatening illness characterized by the rapid onset of abnormal liver biochemistries, coagulopathy, and the development of hepatic encephalopathy. Extracorporeal bioengineered liver (BEL) grafts could offer a bridge therapy to transplant or recovery. The present study describes the manufacture of clinical scale BELs created from decellularized porcine-derived liver extracellular matrix seeded entirely with human cells: human umbilical vein endothelial cells (HUVECs) and primary human liver cells (PHLCs). Decellularized scaffolds seeded entirely with human cells were shown to adhere to stringent sterility and safety guidelines and demonstrated increased functionality when compared to grafts seeded with primary porcine liver cells (PPLCs). BELs with PHLCs were able to clear more ammonia than PPLCs and demonstrated lower perfusion pressures during patency testing. Additionally, to determine the full therapeutic potential of BELs seeded with PHLCs, longer culture periods were assessed to address the logistical constraints associated with manufacturing and transporting a product to a patient. The fully humanized BELs were able to retain their function after cold storage simulating a product transport period. Therefore, this study demonstrates the manufacture of bioengineered liver grafts and their potential in the clinical setting as a treatment for ALF.

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