Swati Chitrangi, Prabha Nair and Aparna Khanna
Sunandan Divatia School of Science, India
Shree Chitra Tirunal Institute for Medical Sciences and Technology, India
Posters & Accepted Abstracts: J Cell Sci Ther
Stem cell-based tissue engineering has emerged as a promising avenue for treatment of liver diseases and as drug metabolism and toxicity models in drug discovery and development. In vitro simulation of microenvironment niche for hepatic differentiation remains elusive, due to lack of information about crucial factors for the stem cell niche. For generation of functional hepatocytes, an in vivo three-dimensional (3D) microenvironment and architecture should be reproduced. Towards this, we fabricated three scaffolds as DG1 (Dextran-Gelatin), CH1 (Chitosan-Hyaluronic acid) and GEVAC (Gelatin-Vinyl Acetate). Hepatic differentiation of human umbilical cord derived mesenchymal stem cells (hUC-MSCs) was induced by culturing hUC-MSCs on these scaffolds. The scaffolds support hepatic differentiation by mimicking the native extracellular matrix (ECM) microenvironment and architecture to facilitate 3D cell-cell and cell-matrix interactions. The expression of hepatic markers, glycogen storage, urea production, albumin secretion and cytochrome P450 (CYP450) activity indented hepatic differentiation of hUC-MSCs. The differentiated hUC-MSCs on the 3D scaffolds formed hepatospheroids (three dimensional hepatocyte aggregate) as illustrated by scanning electron microscopy, immunoflourescent staining and cytoskeleton organization. It was observed that the 3D scaffolds supported improved cell morphology, expression of hepatic markers and metabolic activities as compared to matrigel coated plates. To the best of our knowledge, this is the first report demonstrating the use of well characterized scaffold (GEVAC) for enhanced differentiation of hUC-MSCs to hepatocytelike cells (HLCs).
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