PMID- 27121646 OWN - NLM STAT- MEDLINE DCOM- 20180501 LR - 20181202 IS - 1932-7005 (Electronic) IS - 1932-6254 (Linking) VI - 11 IP - 8 DP - 2017 Aug TI - Three-dimensional polymer scaffolds for enhanced differentiation of human mesenchymal stem cells to hepatocyte-like cells: a comparative study. PG - 2359-2372 LID - 10.1002/term.2136 [doi] AB - Stem cell-based tissue engineering has emerged as a promising avenue for the treatment of liver diseases and as drug metabolism and toxicity models in drug discovery and development. The in vitro simulation of a micro-environmental 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) micro-environment and architecture should be reproduced. Towards this, we fabricated three scaffolds as dextran-gelatin (DG1), chitosan-hyaluronic acid (CH1) and gelatin-vinyl acetate (GEVAC). 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) micro-environment 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 indicated the hepatic differentiation of hUC-MSCs. The differentiated hUC-MSCs on the 3D scaffolds formed hepatospheroids (3D hepatocyte aggregates), as illustrated by scanning electron microscopy (SEM), confocal microscopy 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 a well-characterized scaffold (GEVAC) for enhanced differentiation of hUC-MSCs to hepatocyte-like cells (HLCs). Copyright (c) 2016 John Wiley & Sons, Ltd. CI - Copyright (c) 2016 John Wiley & Sons, Ltd. FAU - Chitrangi, Swati AU - Chitrangi S AD - Department of Biological Sciences, Sunandan Divatia School of Science, SVMK'S NMIMS University, Mumbai, Maharashtra, India. FAU - Nair, Prabha AU - Nair P AD - Division of Tissue Engineering and Regeneration Technologies, Shree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India. FAU - Khanna, Aparna AU - Khanna A AD - Department of Biological Sciences, Sunandan Divatia School of Science, SVMK'S NMIMS University, Mumbai, Maharashtra, India. LA - eng PT - Comparative Study PT - Journal Article DEP - 20160428 PL - England TA - J Tissue Eng Regen Med JT - Journal of tissue engineering and regenerative medicine JID - 101308490 RN - 0 (Dextrans) RN - 9000-70-8 (Gelatin) RN - 9004-61-9 (Hyaluronic Acid) RN - 9012-76-4 (Chitosan) SB - IM MH - Biomimetic Materials/*chemistry MH - *Cell Differentiation MH - Chitosan/chemistry MH - Dextrans/chemistry MH - Extracellular Matrix/*chemistry MH - Gelatin/chemistry MH - Hepatocytes/cytology/*metabolism MH - Humans MH - Hyaluronic Acid/chemistry MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Tissue Scaffolds/*chemistry OTO - NOTNLM OT - F-actin cytoskeleton organization OT - hepatic differentiation OT - hepatocyte-like cells (HLCs) OT - hepatospheroid OT - human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) OT - polymer scaffold OT - three-dimensional (3D) culture system EDAT- 2016/04/29 06:00 MHDA- 2018/05/02 06:00 CRDT- 2016/04/29 06:00 PHST- 2015/06/25 00:00 [received] PHST- 2015/11/19 00:00 [revised] PHST- 2015/12/10 00:00 [accepted] PHST- 2016/04/29 06:00 [pubmed] PHST- 2018/05/02 06:00 [medline] PHST- 2016/04/29 06:00 [entrez] AID - 10.1002/term.2136 [doi] PST - ppublish SO - J Tissue Eng Regen Med. 2017 Aug;11(8):2359-2372. doi: 10.1002/term.2136. Epub 2016 Apr 28.