The use of a polyelectrolyte fibrous scaffold to deliver differentiated hMSCs to the liver.
Liver transplantation as a therapy for liver failure is often hampered by a shortage of donor tissue. The delivery of liver-differentiated human mesenchymal stem cells (hMSCs) is a potential therapy to aid in liver regeneration. In this study, an RGD-modified chitosan-alginate polyelectrolyte complex (PEC) fibrous non-woven scaffold was employed to deliver differentiated hMSCs in vivo. Bone marrow-derived hMSCs were differentiated in vitro by a combination of extracellular matrix (ECM) and conditioned medium and seeded onto the RGD-modified chitosan-alginate fibrous scaffolds. The cell/scaffold construct was then implanted into the livers of a rat model, where 70% of the liver had been removed. Post-implantation analysis of the cell/scaffold constructs showed positive periodic acid-Schiff (PAS) staining for glycogen, and expression of the hepatic markers, AFP, CK19, CK18, albumin, HNF-3beta and MRP-2 by immunofluorescence labeling. In addition, human albumin was detectable in the rat serum by spot blot. These findings demonstrated that the RGD-modified chitosan-alginate fibrous scaffold was useful for delivering transdifferentiated hMSCs into the liver and maintaining the differentiated phenotype of the cells.
Tai
Benjamin C U
BC
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669.
Du
Chan
C
Gao
Shujun
S
Wan
Andrew C A
AC
Ying
Jackie Y
JY
D000464:Alginates; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D048271:Chitosan; D017077:Culture Media, Conditioned; D017931:DNA Primers; D004573:Electrolytes; D004797:Enzyme-Linked Immunosorbent Assay; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D023421:Models, Animal; D000089762:Multidrug Resistance-Associated Protein 2; D009842:Oligopeptides; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
C000715087:ABCC2 protein, human; D000464:Alginates; D017077:Culture Media, Conditioned; D017931:DNA Primers; D004573:Electrolytes; D006603:Hexuronic Acids; D000089762:Multidrug Resistance-Associated Protein 2; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D020723:Glucuronic Acid; D048271:Chitosan