Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Controlling osteogenic stem cell differentiation via soft bioinspired hydrogels.

ABSTRACT: Osteogenic differentiation of human mesenchymal stem cells (hMSCs) is guided by various physical and biochemical factors. Among these factors, modulus (i.e., rigidiy) of the ECM has gained significant attention as a physical osteoinductive signal that can contribute to endochondral ossification of a cartilaginous skeletal template. However, MSCs also participate in intramembranous bone formation, which occurs de novo from within or on a more compliant tissue environment. To further understand the role of the matrix interactions in this process, we evaluated osteogenic differentiation of hMSCs cultured on low moduli (102, 390 or 970 Pa) poly(N-isopropylacrylamide) (p(NIPAAm)) based semi-interpenetrating networks (sIPN) modified with the integrin engaging peptide bsp-RGD(15) (0, 105 or 210 µM). Cell adhesion, proliferation, and osteogenic differentiation of hMSCs, as measured by alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), bone sialoprotein-2 (iBSP), and osteocalcien (OCN) protein expression, was highest on substrates with the highest modulus and peptide concentrations. However, within this range of substrate stiffness, many osteogenic cellular functions were enhanced by increasing either the modulus or the peptide density. These findings suggest that within a compliant and low modulus substrate, a high affinity adhesive ligand serves as a substitute for a rigid matrix to foster osteogenic differentiation.

SUBMITTER: Jha AK

PROVIDER: S-EPMC4060996 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Bioinspired glycosaminoglycan hydrogels via click chemistry for 3D dynamic cell encapsulation.

Project description:Cell encapsulation within 3D hydrogels is an attractive approach to develop effective cell-based therapies. However, little is known about how cells respond to the dynamic microenvironment resulting from hydrogel gelation-based cell encapsulation. Here, a tunable biomimetic hydrogel system that possesses alterable gelation kinetics and biologically relevant matrix stiffness is developed to study 3D dynamic cellular responses during encapsulation. Hydrogels are synthesized by cross-linking thiolated hyaluronic acid and thiolated chondroitin sulfate with polyethylene glycol diacrylate under cell-compatible conditions. Hydrogel properties are tailored by altering thiol substitution degrees of glycosaminoglycans or molecular weights of cross-linkers. Encapsulation of human mesenchymal stem cells through hydrogel gelation reveals high cell viability as well as a three-stage gelation-dependent cellular response in real-time focal adhesion kinase (FAK) phosphorylation in live single cells. Furthermore, stiffer hydrogels result in higher equilibrium FAK activity and enhanced actin protrusions. Our results demonstrate the promise of hydrogel-mediated cellular responses during cell encapsulation.

| S-EPMC6749605 | biostudies-literature

Sustained localized presentation of RNA interfering molecules from in situ forming hydrogels to guide stem cell osteogenic differentiation.

Project description:To date, RNA interfering molecules have been used to differentiate stem cells on two-dimensional (2D) substrates that do not mimic three-dimensional (3D) microenvironments in the body. Here, in situ forming poly(ethylene glycol) (PEG) hydrogels were engineered for controlled, localized and sustained delivery of RNA interfering molecules to differentiate stem cells encapsulated within the 3D polymer network. RNA interfering molecules were released from the hydrogels in a sustained and controlled manner over the course of 3-6 weeks, and exhibited high bioactivity. Importantly, it was demonstrated that the delivery of siRNA and/or miRNA from the hydrogel constructs enhanced the osteogenic differentiation of encapsulated stem cells. Prolonged delivery of siRNA and/or miRNA from this polymeric scaffold permitted extended regulation of cell behavior, unlike traditional siRNA experiments performed in vitro. This approach presents a powerful new methodology for controlling cell fate, and is promising for multiple applications in tissue engineering and regenerative medicine.

| S-EPMC4157362 | biostudies-literature

Engineering elastic bioactive composite hydrogels for promoting osteogenic differentiation of embryonic mesenchymal stem cells.

Project description:The development of bioactive materials with good mechanical properties and promotion of stem cell osteogenic differentiation has important application prospects in bone tissue engineering. In this paper, we designed a novel organic‒inorganic composite hydrogel (FPIGP@BGN-Sr) utilizing diacrylated F127 (DA-PF127), β-glycerophosphate-modified polyitaconate (PIGP) and strontium-doped bioactive glass nanoparticles (BGN-Sr) through free radical polymerization and coordination interactions and then evaluated its promoting effect on the osteogenic differentiation of mouse embryonic mesenchymal stem cells in detail. The results showed that the FPIGP@BGN-Sr hydrogel exhibited a controlled storage modulus by changing the amount of BGN-Sr. Notably, the FPIGP@BGN-Sr hydrogel possessed excellent elastic ability with a compressive strain of up to 98.6% and negligible change in mechanical properties after 10 cycles of compression. In addition, the FPIGP@BGN-Sr hydrogel had good cytocompatibility, maintained the activity and proliferation of mouse embryonic mesenchymal stem cells (C3H10T1/2), and effectively enhanced the activity of alkaline phosphatase, osteogenic gene expression and biomineralization ability of the cells. In conclusion, the excellent mechanical properties and osteogenic biological activity of the FPIGP@BGN-Sr hydrogel make it a promising organic‒inorganic composite bioactive material for stem cell-based bone regeneration.

| S-EPMC9596812 | biostudies-literature

ZEB1 Mediates Bone Marrow Mesenchymal Stem Cell Osteogenic Differentiation Partly via Wnt/β-Catenin Signaling.

Project description:Zinc finger E-box-binding homebox 1 (ZEB1) is a zinc-finger transcription factor best known for its role in promoting the epithelial-mesenchymal transition, which is also related to osteogenesis. Here, ZEB1 was investigated for its role in the commitment of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts. In vitro, ZEB1 expression decreased following osteogenic differentiation. Furthermore, silencing of ZEB1 in BMSCs promoted osteogenic activity and mineralization. The increase in osteogenic differentiation induced by si-ZEB1 could be partly rescued by the inhibition of Wnt/β-catenin (si-β-catenin). In vivo, knockdown of ZEB1 in BMSCs inhibited the rapid bone loss of ovariectomized (OVX) mice. ZEB1 expression has also been negatively associated with bone mass and bone formation in postmenopausal women. In conclusion, ZEB1 is an essential transcription factor in BMSC differentiation and may serve as a potential anabolic strategy for treating and preventing postmenopausal osteoporosis (PMOP).

| S-EPMC8183571 | biostudies-literature

3D gelatin-chitosan hybrid hydrogels combined with human platelet lysate highly support human mesenchymal stem cell proliferation and osteogenic differentiation.

Project description:Bone marrow and adipose tissue human mesenchymal stem cells were seeded in highly performing 3D gelatin-chitosan hybrid hydrogels of varying chitosan content in the presence of human platelet lysate and evaluated for their proliferation and osteogenic differentiation. Both bone marrow and adipose tissue human mesenchymal stem cells in gelatin-chitosan hybrid hydrogel 1 (chitosan content 8.1%) or gelatin-chitosan hybrid hydrogel 2 (chitosan 14.9%) showed high levels of viability (80%-90%), and their proliferation and osteogenic differentiation was significantly higher with human platelet lysate compared to fetal bovine serum, particularly in gelatin-chitosan hybrid hydrogel 1. Mineralization was detected early, after 21 days of culture, when human platelet lysate was used in the presence of osteogenic stimuli. Proteomic characterization of human platelet lysate highlighted 59 proteins mainly involved in functions related to cell adhesion, cellular repairing mechanisms, and regulation of cell differentiation. In conclusion, the combination of our gelatin-chitosan hybrid hydrogels with hPL represents a promising strategy for bone regenerative medicine using human mesenchymal stem cells.

| S-EPMC6507314 | biostudies-literature

Soft Hydrogels Support Differentiation of Induced Pluripotent Stem Cells toward Mesenchymal Stromal Cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-03-13 | GSE95061 | GEO

Hybrid Protein-Glycosaminoglycan Hydrogels Promote Chondrogenic Stem Cell Differentiation.

Project description:Gelatin-hyaluronic acid (Gel-HA) hybrid hydrogels have been proposed as matrices for tissue engineering because of their ability to mimic the architecture of the extracellular matrix. Our aim was to explore whether tyramine conjugates of Gel and HA, producing injectable hydrogels, are able to induce a particular phenotype of encapsulated human mesenchymal stem cells without the need for growth factors. While pure Gel allowed good cell adhesion without remarkable differentiation and pure HA triggered chondrogenic differentiation without cell spreading, the hybrids, especially those rich in HA, promoted chondrogenic differentiation as well as cell proliferation and adhesion. Secretion of chondrogenic markers such as aggrecan, SOX-9, collagen type II, and glycosaminoglycans was observed, whereas osteogenic, myogenic, and adipogenic markers (RUNX2, sarcomeric myosin, and lipoproteinlipase, respectively) were not present after 2 weeks in the growth medium. The most promising matrix for chondrogenesis seems to be a mixture containing 70% HA and 30% Gel as it is the material with the best mechanical properties from all compositions tested here, and at the same time, it provides an environment suitable for balanced cell adhesion and chondrogenic differentiation. Thus, it represents a system that has a high potential to be used as the injectable material for cartilage regeneration therapies.

| S-EPMC5709783 | biostudies-literature

Engineering hydrogels with homogeneous mechanical properties for controlling stem cell lineage specification.

Project description:The extracellular matrix (ECM) is mechanically inhomogeneous due to the presence of a wide spectrum of biomacromolecules and hierarchically assembled structures at the nanoscale. Mechanical inhomogeneity can be even more pronounced under pathological conditions due to injury, fibrogenesis, or tumorigenesis. Although considerable progress has been devoted to engineering synthetic hydrogels to mimic the ECM, the effect of the mechanical inhomogeneity of hydrogels has been widely overlooked. Here, we develop a method based on host-guest chemistry to control the homogeneity of maleimide-thiol cross-linked poly(ethylene glycol) hydrogels. We show that mechanical homogeneity plays an important role in controlling the differentiation or stemness maintenance of human embryonic stem cells. Inhomogeneous hydrogels disrupt actin assembly and lead to reduced YAP activation levels, while homogeneous hydrogels promote mechanotransduction. Thus, the method we developed to minimize the mechanical inhomogeneity of hydrogels may have broad applications in cell culture and tissue engineering.

| S-EPMC8449376 | biostudies-literature

Sustained presentation of BMP-2 enhances osteogenic differentiation of human adipose-derived stem cells in gelatin hydrogels.

Project description:Human adipose-derived stem cells (hASCs) show great potential for healing bone defects. Bone morphogenetic protein-2 (BMP-2) has been reported to stimulate their osteogenic differentiation both in vitro and in vivo. Here, methacrylated gelatin (GelMA) hydrogels were evaluated as a system to deliver BMP-2 to encapsulated hASCs from two different donors, and BMP-2 delivered from the hydrogels was compared to BMP-2 presented exogenously in culture media. GelMA hydrogels were shown to provide sustained, localized presentation of BMP-2 due to electrostatic interactions between the growth factor and biomaterial after an initial burst release. Both donors exhibited similar responses to the loaded and exogenous growth factor; BMP-2 from the hydrogels had a statistically significant effect on hASC osteogenic differentiation compared to exogenous BMP-2. Expression of alkaline phosphatase was accelerated, and cells in hydrogels with loaded BMP-2 deposited more calcium at one, two, and four weeks than cells without BMP-2 or with the growth factor presented in the media. There were no statistically significant differences in calcium content between groups with 25, 50, or 100 µg/mL loaded BMP-2, suggesting that using a lower growth factor dose may be as effective as a higher loading amount in this system. Taken together, these findings suggest that controlled delivery of BMP-2 from the GelMA enhances its osteogenic bioactivity compared to free growth factor presented in the media. Thus, the GelMA system is a promising biomaterial for BMP-2-mediated hASC osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1387-1397, 2016.

| S-EPMC6930142 | biostudies-literature

Soft Hydrogels Support Differentiation of Induced Pluripotent Stem Cells toward Mesenchymal Stromal Cells [expression]

Project description:Induced pluripotent stem cells (iPSCs) can be differentiated toward mesenchymal stromal cells (MSCs), but at least on epigenetic level this transition remains incomplete with the current culture conditions. Hydrogels provide a more physiologic three-dimensional environment for in vitro cell culture than conventional tissue culture plastic (TCP). In this study, we followed the hypothesis that growth and differentiation of primary MSCs and of iPSC-derived MSCs (iMSCs) can be enhanced on hydrogels. To this end, we used a hydrogel made of human platelet lysate (hPL). MSCs were effectively cultured on and inside hPL-gel and demonstrated more structured deposition of extracellular matrix (ECM) components than TCP. Furthermore, hPL-gel supported differentiation of iPSCs toward MSCs. Unexpectedly, the differentiation process seemed to be hardly affected by the substrate: iMSCs generated either on TCP or hPL-gel did not reveal differences in morphology, immunophenotype, or differentiation potential. Moreover, global gene expression and DNA-methylation profiles were almost identical in iMSCs generated on TCP or hPL-gel. Our results indicate that matrix elasticity is less crucial for directed lineage-specific differentiation toward MSCs than expected.

2018-03-13 | GSE95060 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data