Retracted: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 WJMSCs + scaffold group than in the carbon tetrachloride (CCl 4 ) 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 CCl 4 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 WJMSCs significantly promoted the recovery of injured liver and could be further studied for liver tissue engineering.

Hydrogels for Liver Tissue Engineering

“…The matrices derived were loaded with human umbilical cord multipotent stromal cells (MSCs) and hepatocyte-like cells, and after 28 days the tissue generated looked very similar to the native organ. A study reported the recovery of injured mouse liver when a PHBVHHx scaffold loaded with human umbilical cord Wharton’s jelly (WJ) MSCs was transplanted [133]. Chemically modified PHAs also find use as films, pins, sutures, screws, and scaffolds for repairing skin, cartilage and LTE [111].…”

Recent Advances in the Use of Polyhydroyalkanoates in Biomedicine

“…PHBVHHx is considered a promising PHA member for the growth of stem cells, and certain studies utilized it as biomaterial for the preparation of three-dimensional supportive scaffolds for organ tissue. In some works [50,51], PHBVHHx films and scaffolds were developed and loaded with mesenchymal stem cells from human umbilical cord (UC-MSCs) to recover injured liver. Biopolymer scaffolds were transplanted into liver-injured mice, and the results demonstrated that the PHA scaffold significantly promoted the recovery of injured liver and could be used for liver tissue engineering.…”

“…Biopolymer scaffolds were transplanted into liver-injured mice, and the results demonstrated that the PHA scaffold significantly promoted the recovery of injured liver and could be used for liver tissue engineering. In the case of the work by Li et al [50], differences between PHBVHHx and some other commonly used biopolymers such as PLA, PHB4HB, and PHBHHx were examined by loading them with stem cells into their scaffolds (Figure 2d). They concluded that the PHBVHHx structures exhibited the highest cell attachment and, when loaded with mesenchymal stem cells, significantly improved the recovery of injured liver.…”

“…( c ) Scheme of the asymmetric PHA membranes entrapping an anti-biofilm protein (dispersin B) for wound healing [49]. ( d ) SEM micrographs of biopolymers scaffolds from Li et al [50]. The biopolymer structures displayed different pore sizes where stem cells were loaded into, and the PHBVHHx ones exhibited the highest cell attachment.…”

Silver Nanoparticle-Coated Polyhydroxyalkanoate Based Electrospun Fibers for Wound Dressing Applications

“…However, one drawback of the mcl-PHAs for electrospinning is their low glass transition temperature (T g ), which limits their spinnability and causes sticky and fused fibers. Several groups have investigated the electrospinning of different scl-PHAs, including P(3HB), poly(3-hydroxybutyrate- co -3-hydroxyvalerate) P(3HB- co -3HV), poly(3-hydroxybutyrate- co -4-hydroxybutyrate) (P3HB- co -4HB), poly(3-hydroxybutyrate- co -3-hydroxyhexanoate) P(HB- co -3HHx) and poly(3-hydroxybutyrate- co -3-hydroxyvalerate- co -3-hydroxyhexanoate) P(3HB- co -3HV- co -3HHx) [ 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Recent examples by Liu and coworkers introduced both single-nozzle and coaxial electrospinning of mcl-PHA poly (3-hydroxyoctanoate- co -3-hydroxyhexanoate) P(3HO- co -3HHx) nanofibers by blending with a scl-PHA, P(3HB- co -3HV) [ 30 , 31 ].…”