title: Discarded Livers Find a New Life: Engineered Liver Grafts Using Hepatocytes Recovered From Marginal Livers.
abstract: Treatment for end-stage liver failure is restricted by the critical shortage of donor organs; about 4000 people die in the USA while waiting for a transplantable organ. This situation has been a major driving force behind the rise of tissue engineering to build artificial tissues/organs. Recent advancements in creating transplantable liver grafts using decellularized liver scaffolds bring the field closer to clinical translation. However, a source of readily available and highly functional adult hepatocytes in adequate numbers for regenerative liver therapies still remains unclear. Here, we describe a new method to utilize discarded livers to make transplantable new liver grafts. We show that marginal donor livers damaged due to warm ischemia could be treated with machine perfusion to yield 39 million viable hepatocytes per gram of liver, similar to fresh livers, and these cells could be used to repopulate decellularized liver matrix (DLM) scaffolds to make transplantable liver grafts. The hepatocytes from recovered livers sustained their characteristic epithelial morphology while they exhibited slightly lower protein synthesis functions both in plate cultures and in recellularized liver grafts. The dampened protein synthesis was attributed to residual endoplasmic reticulum stress found in recovered cells. The results here represent a unique approach to reengineer transplantable liver grafts solely from discarded organs.
authors.affiliation: Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and the Shriners Burns Hospital, Boston, MA.
authors.forename: Basak E
authors.identifier: http://orcid.org/0000-0002-2600-7900
authors.initials: BE
authors.lastname: Uygun
authors.affiliation: Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and the Shriners Burns Hospital, Boston, MA.
authors.forename: Maria-Louisa
authors.initials: ML
authors.lastname: Izamis
authors.affiliation: Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and the Shriners Burns Hospital, Boston, MA.
authors.forename: Maria
authors.initials: M
authors.lastname: Jaramillo
authors.affiliation: Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and the Shriners Burns Hospital, Boston, MA.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and the Shriners Burns Hospital, Boston, MA.
authors.forename: Gavrielle
authors.initials: G
authors.lastname: Price
authors.affiliation: Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and the Shriners Burns Hospital, Boston, MA.
authors.forename: Sinan
authors.initials: S
authors.lastname: Ozer
authors.affiliation: Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and the Shriners Burns Hospital, Boston, MA.|Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
mesh_terms: D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry; D022781:Hepatocytes / Q000166:cytology*; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D008115:Liver Regeneration; D010477:Perfusion; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
keywords: -Endoplasmic reticulum stress; -Hepatocytes; -Liver recellularization; Machine perfusion