The use of a polyelectrolyte fibrous scaffold to deliver differentiated hMSCs to the liver.

Abstract

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.