title: Promoting the recovery of injured liver with poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) scaffolds loaded with umbilical cord-derived mesenchymal stem cells.
abstract: Cell-based therapies are major focus of current research for treatment of liver diseases. In this study, mesenchymal stem cells were isolated from human umbilical cord Wharton's jelly (WJ-MSCs). Results confirmed that WJ-MSCs isolated in this study could express the typical MSC-specific markers and be induced to differentiate into adipocytes, osteoblasts, and chondrocytes. They could also be induced to differentiate into hepatocyte-like cells. Poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PHBVHHx) is a new member of polyhydroxyalkanoate family and biodegradable polyester produced by bacteria. PHBVHHx scaffolds showed much higher cell attachment and viability than the other polymers tested. PHBVHHx scaffolds loaded with WJ-MSCs were transplanted into liver-injured mice. Liver morphology improved after 30 days of transplantation and looked similar to normal liver. Concentrations of serum alanine aminotransferase and total bilirubin were significantly lower, and albumin was significantly higher on days 14 and 30 in the WJ-MSCs+scaffold group than in the carbon tetrachloride (CCl4) group. Hematoxylin-eosin staining showed that liver had similar structure of normal liver lobules and similar size and shape of normal hepatic cells, and Masson staining demonstrated that liver had less blue staining for collagen after 30 days of transplantation. Real-time reverse transcription-polymerase chain reaction (RT-PCR) showed that the expression of the bile duct epithelial cell gene CK-19 in mouse liver is significantly lower on days 14 and 30 in the WJ-MSCs+scaffold group than in the CCl4 group. Real-time RT-PCR, immunocytochemistry, and periodic acid-Schiff staining showed that WJ-MSCs in scaffolds differentiated into hepatocyte-like cells on days 14 and 30 in the WJ-MSCs+scaffold group. Real-time RT-PCR also demonstrated that WJ-MSCs in scaffolds expressed endothelial cell genes Flk-1, vWF, and VE-cadherin on days 14 and 30 in the WJ-MSCs+scaffold group, indicating that WJ-MSCs also differentiated into endothelial-like cells. These results demonstrated that PHBVHHx scaffolds loaded with WJ-MSCs significantly promoted the recovery of injured liver and could be further studied for liver tissue engineering.
authors.affiliation: 1 Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University , Guangzhou, China .
authors.forename: Pengshan
authors.initials: P
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Huan
authors.initials: H
authors.lastname: Ma
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Puchang
authors.initials: P
authors.lastname: Lie
authors.forename: Yuechun
authors.initials: Y
authors.lastname: Wang
authors.forename: Gexiu
authors.initials: G
authors.lastname: Liu
authors.forename: Huilan
authors.initials: H
authors.lastname: Zeng
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Li
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis; D002208:Caproates / Q000737:chemistry*; D036101:Cord Blood Stem Cell Transplantation / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D008107:Liver Diseases / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D008115:Liver Regeneration / Q000502:physiology*; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D011091:Polyesters; D020127:Recovery of Function / Q000502:physiology; D023822:Tissue Engineering / Q000295:instrumentation; D054457:Tissue Scaffolds; D016896:Treatment Outcome; D000094122:Polyhydroxybutyrates
chemical_list: D020155:3-Hydroxybutyric Acid; D001672:Biocompatible Materials; D002208:Caproates; D011091:Polyesters; C512913:poly(3-hydroxybutyrate)-block-poly(3-hydroxybutyrate-co-3-hydroxyvalerate); D000094122:Polyhydroxybutyrates; C115940:poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)