Hepatogenesis of Adipose-Derived Stem Cells on Poly-Lactide-co-Glycolide Scaffolds: In Vitro and In Vivo Studies

Abstract

Human adipose-derived stem cells (hASCs) have been shown to be multipotent and could be induced into various cell types, which make them the ideal cell source for cell therapy or tissue engineering. However, differentiation of ASCs into hepatocytes on three-dimensional scaffold, an important part of tissue engineering, has not been reported. In this study, to investigate the hepatogenesis of ASCs on porous poly-lactide-co-glycolide (PLGA) scaffolds, we loaded hASCs on these scaffolds. The cell-scaffold complex was implanted into the peritoneal cavity of 70% hepatectomized rats with or without 14 days of induction in hepatic inducing medium. Our results indicated that hASCs cultured on the PLGA scaffolds in the hepatic inducing medium proliferated more efficiently and could be induced into cells with hepatocyte-like phenotypic and functional properties. In vivo studies showed that induced hASCs on PLGA scaffolds survived and maintained hepatic phenotype and function for at least 14 days after implantation; moreover, noninduced hASCs on PLGA scaffolds expressed human albumin 14 days after transplantation. Collectively, these results suggest that porous PLGA scaffolds are suitable for the hepatogenesis of hASCs. These findings might be helpful in the application of hASC-based tissue engineering for liver disease therapy.

Adipose-Derived Stem Cells in Tissue Regeneration: A Review

“…Initial studies in 2003 show increased engraftment of human ASCs into regenerating livers following partial hepatectomy [254]. Indicative of liver regeneration, preinduced human ASCs, loaded onto PLGA scaffolds and implanted into the peritoneum of hepatectomized rats, not only survive on-scaffold at least 14 days after implantation but aslo, like their in vitro counterparts, exhibit increased expression of liver-specific genes [255]. However, this study is unable to confirm differentiation at the functional level.…”

Three-dimensional polymer scaffolds for enhanced differentiation of human mesenchymal stem cells to hepatocyte-like cells: a comparative study

“…Several reports on the differentiation of MSCs isolated from different sources indicate a bias to differentiation towards the hepatic lineage more efficaciously on various 3D surfaces (Kazemnejad et al , ; Tai et al , ; Lin et al , ; Li et al , ; Wang, et al , ; Ghaedi et al , ; Bishi et al ); however, an efficient 3D scaffold has to be established. Recently, it was reported that decellularized liver 3D matrix scaffold supports in vitro hepatic differentiation of rodent MSCs more efficiently than 2D culture (Ji et al , ; Jiang et al , ; Zhang and Dong 2014).…”

Cell–Microsphere Constructs Formed with Human Adipose‐Derived Stem Cells and Gelatin Microspheres Promotes Stemness, Differentiation, and Controlled Pro‐Angiogenic Potential

“…Utilizing such differentiated cells combined with various 3D scaffolds both for fat and bone tissue regeneration have also shown promising results . However, although there are many studies, which show hepatic differentiation of ADSCs using different inducing agents, almost all of these studies were performed on 2D with very few focusing on 3D scaffolds . In this study, along with adipogenic and osteogenic differentiation of ADSCs, we have also shown differentiation of ADSCs to hepatic lineage both on 2D and on GMs.…”