Modulation of the stemness and osteogenic differentiation of human mesenchymal stem cells by controlling RGD concentrations of poly(carboxybetaine) hydrogel
Journal
Biotechnology Journal
Journal Volume
9
Journal Issue
12
Pages
1613-1623
Date Issued
2014
Author(s)
Abstract
In vitro modulation of the differentiation status of mesenchymal stem cells (MSCs) is important for their application to regenerative medicine. We suggested that the morphology and differentiation states of MSCs could be modulated by controlling the cell affinity of a substrate. The objective of this study was to investigate the effects of surface bio-adhesive signals on self-renewal and osteogenic differentiation of MSCs using a low-fouling platform. Cell-resistant poly(carboxybetaine) hydrogel was conjugated with 5 μM or 5 mM of cell-adhesive arginine-glycine-aspartic acid (RGD) peptides in order to control the cells' affinity to the substrate. Human mesenchymal stem cells (hMSCs) were cultured on the RGD-modified poly(carboxybetaine) hydrogel and then the cells' states of stemness and osteogenic differentiation were evaluated using reverse-transcriptase polymerase chain reaction. The hMSCs formed three-dimensional spheroids on the 5 μM RGD substrate, while cells on the 5 mM RGD substrate exhibited spreading morphology. Furthermore, cells on the 5 μM RGD hydrogel maintained a better stemness phenotype, while the hMSCs on the 5 mM RGD hydrogel proliferated faster and underwent osteogenic differentiation. In conclusion, the stemness of hMSCs was best maintained on a low RGD surface, while osteogenic differentiation of hMSCs was enhanced on a high RGD surface. The objective of this study is to investigate the effects of surface bio-adhesive signals, i.e. density of RGD signals, on self-renewal and osteogenic differentiation of human mesenchymal stem cells (hMSCs) using Poly(carboxybetaine methacrylate) (poly(CBMA)) hydrogel as low-fouling platform. hMSCs that are cultured on poly(CMBA) hydrogel with low RGD density form spheroid clusters and maintain cell stemness. hMSCs that are cultured on poly(CMBA) hydrogel with a high RGD density exhibit a spread morphology with enhanced osteogenic differentiation. ? 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Subjects
Mesenchymal stem cells; Osteogenic differentiation; Poly(carboxybetaine); RGD; Stemness
SDGs
Other Subjects
Adhesives; Amino acids; Flowcharting; Hydrogels; Modulation; Morphology; Polymerase chain reaction; Stem cells; Arginine-glycine-aspartic acids; Human mesenchymal stem cells; Human mesenchymal stem cells (hMSCs); Mesenchymal stem cell; Osteogenic differentiation; Polies (carboxybetaine); Reverse transcriptase- polymerase chain reaction; Stemness; Cell culture; arginylglycylaspartic acid; betaine derivative; calcium; octamer transcription factor 4; poly(carboxybetaine); transcription factor NANOG; unclassified drug; arginyl-glycyl-aspartic acid; betaine; hydrogel; oligopeptide; Article; binding affinity; bone development; bone mineralization; cell adhesion; cell culture; cell differentiation; cell function; cell interaction; cell proliferation; cell renewal; cell structure; clinical evaluation; concentration response; conjugation; human; human cell; hydrogel; mesenchymal stem cell; ossification; osteogenic differentiation; phenotypic variation; priority journal; reverse transcription polymerase chain reaction; bone development; cell differentiation; cell line; chemistry; cytology; drug effects; mesenchymal stroma cell; Betaine; Cell Differentiation; Cell Line; Humans; Hydrogels; Mesenchymal Stromal Cells; Oligopeptides; Osteogenesis
Type
journal article