title: Immune-protected xenogeneic bioartificial livers with liver-specific microarchitecture and hydrogel-encapsulated cells.
abstract: Development of a xenogeneic biological liver support is important in providing a bridge to transplantation or liver regeneration, thus helping to overcome the chronic shortage of liver donors. Among the critical factors in developing biological liver support are the creation of in vivo mimetic micro liver tissue (mLT), especially mLTs containing liver-specific ultrastructure, and an encapsulation method that can package massive numbers of cells while providing immune-protection from the host immune system. We describe here the development of mLTs that include liver microarchitecture and their in situ encapsulation in hydrogel composites. Concave microwells and the tri-culture of three types of primary liver cells were applied for the construction of mLTs showing excellent liver functions and long-term (>1 month) viability in vitro. Large quantities of rat mLTs were encapsulated in collagen-alginate composites, implanted into hepatic failure mice and sustained their survival during regeneration of the remaining liver. The proposed liver support system offers xenogeneic hepatic assistance by mimicking native liver microarchitecture and providing immune-protection without the need for complicated devices or processes, and as such represents a promising system for recovery of organ function.
authors.affiliation: Department of Biomedical Engineering, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Da Yoon
authors.initials: da Y
authors.lastname: No
authors.affiliation: Department of Biomedical Engineering, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Gi Seok
authors.initials: GS
authors.lastname: Jeong
authors.affiliation: Department of Biomedical Engineering, Korea University, Seoul 136-701, Republic of Korea; KU-KIST Graduate School of Converging of Sciences & Technologies, Korea University, Seoul 136-703, Republic of Korea. Electronic address: dbiomed@korea.ac.kr.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000208:Acute Disease; D000464:Alginates / Q000737:chemistry; D000818:Animals; D002470:Cell Survival; D018914:Cells, Immobilized / Q000737:chemistry; D003094:Collagen / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D022781:Hepatocytes / Q000378:metabolism; D064593:Heterografts; D006603:Hexuronic Acids / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D017114:Liver Failure, Acute / Q000601:surgery*; D008115:Liver Regeneration; D016031:Liver Transplantation; D019164:Liver, Artificial; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid; D003094:Collagen
keywords: Bioartificial liver; Hepatocyte; Hydrogel; Microencapsulation; Tissue engineering; Xenotransplantation