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.
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669.
Benjamin C U
BC
Tai
Chan
C
Du
Shujun
S
Gao
Andrew C A
AC
Wan
Jackie Y
JY
Ying
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