title: Construction of bioengineered hepatic tissue derived from human umbilical cord mesenchymal stem cells via aggregation culture in porcine decellularized liver scaffolds.
abstract: An individualized, tissue-engineered liver suitable for transplanting into a patient with liver disease would be of great benefit to the patient and the healthcare system. The tissue-engineered liver would possess the functions of the original healthy organ. Two fields of study, (i) using decellularized tissue as cell scaffolding, and (ii) stem cell differentiation into functional cells, are coming together to make this concept feasible. The decellularized liver scaffolds (DLS) can interact with cells to promote cell differentiation and signal transduction and three-dimensional (3D) stem cell aggregations can maintain the phenotypes and improve functions of stem cells after differentiation by undergoing cell-cell contact. Although the effects of DLS and stem cell aggregation culture have been intensively studied, few observations about the interaction between the two have been achieved.
  
  
  
  We established a method that combines the use of decellularized liver scaffolds and aggregation culture of MSCs (3D-DLS) and explored the effects of the two on hepatic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) in bioengineered hepatic tissue.
  
  
  
  A higher percentage of albumin-producing cells, higher levels of liver-specific transcripts, higher urea cycle-related transcripts, and lower levels of stem cell-specific transcripts were observed in the 3D-DLS group when compared to that of hUC-MSCs in monolayer culture (2D), aggregation culture (3D), monolayer on DLS culture (2D-DLS). The gene arrays also indicated that 3D-DLS induced the differentiation from the hUC-MSC phenotype to the PHH phenotype. Liver-specific proteins albumin, CK-18, and glycogen storage were highly positive in the 3D-DLS group. Albumin secretion and ammonia conversion to urea were more effective with a higher cell survival rate in the 3D-DLS group for 14 days.
  
  
  
  This DLS and aggregation combination culture system provides a novel method to improve hepatic differentiation, maintain phenotype of hepatocyte-like cells and sustain survival for 14 days in vitro. This is a promising strategy to use to construct bioengineered hepatic tissue.
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Division of Transplant Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Division of Transplant Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Bao
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Bu
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D008099:Liver / Q000166:cytology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D013552:Swine; D023822:Tissue Engineering / Q000379:methods; D059467:Transcriptome; D014183:Transplantation, Heterologous / Q000379:methods; D014470:Umbilical Cord / Q000166:cytology*
keywords: aggregation culture; bioengineered hepatic tissue; decellularized liver scaffolds; hepatic differentiation; umbilical cord mesenchymal stem cells