Soft Hydrogels Support Differentiation of Induced Pluripotent Stem Cells toward Mesenchymal Stromal Cells
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PROVIDER: PRJNA375872 | ENA |
REPOSITORIES: ENA
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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
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 | GSE95058 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-03-13 | GSE95061 | GEO
Project description:D2.0R mouse breast cancer cells cultured on stiff or soft ECM hydrogels
| PRJNA784565 | ENA
Project description:Hippocampal rat neurons have been cultured on very soft (100 Pa) and stiff (10 kPa) hydrogels for 7 days. On DIV7, the RNA has been extracted and sequenced. The goal of this experiment is to understand why neurons mature more quickly on soft gels compared to stiff gels.
2023-12-01 | E-MTAB-11368 | biostudies-arrayexpress
Project description:Soft Hydrogels Support Differentiation of Induced Pluripotent Stem Cells toward Mesenchymal Stromal Cells [expression]
| PRJNA375874 | ENA
Project description:Soft Hydrogels Support Differentiation of Induced Pluripotent Stem Cells toward Mesenchymal Stromal Cells [methylation]
| PRJNA375873 | ENA
Project description:Metastatic breast cancer cells disseminate to organs with a soft microenvironment. Whether and how tissue mechanical properties influence their response to treatment remains unclear. Here we found that a soft ECM empowers redox homeostasis. Cells cultured on a soft ECM display increased peri-mitochondrial F-actin promoted by Spire1C and Arp2/3 nucleation factors, and increased DRP1- and MIEF1/2-dependent mitochondrial fission. Changes in mitochondrial dynamics lead to increased mtROS production and activate the NRF2 antioxidant transcriptional response, including increased cystine uptake and glutathione metabolism. This retrograde response endows cells with resistance to oxidative stress and ROS-dependent chemotherapy drugs. This is relevant in a mouse model of metastatic breast cancer cells dormant in the lung soft tissue, where inhibition of DRP1 and NRF2 restored cisplatin sensitivity and prevented disseminated cancer cell awakening. We propose that targeting this mitochondrial dynamics- and redox-based mechanotransduction pathway could open new avenues to prevent metastatic relapse.
2021-12-21 | GSE189803 | GEO
Project description:FGF-2 is commonly used in culture media when growing mechenchymal stromal cells. Here, we cultured human MSCs from 3 donors with and without 50 ng/ml FGF-2 (Prepotech, human recombinant) in 3D PEG hydrogels, and analysed transcriptome changes by RNA sequencing.
2020-06-02 | E-MTAB-8510 | biostudies-arrayexpress
Project description:Organoid technology has provided unique insights into human organ development, function, and diseases. Patient derived organoids are increasingly used for drug screening, modeling rare disorders, designing regenerative therapies, and understanding pathological changes associated with disease progression. However, the use of Matrigel to grow organoids represents a major challenge in the clinical translation of organoid technology. Matrigel is a poorly defined cocktail of extracellular matrix proteins and growth factors extracted from the Engelbreth Holm Swarm mouse tumor. The extracellular matrix is a major driver of multiple cellular processes and differs significantly between tissues as well as in healthy and diseases states of the same tissue. Therefore, we envisioned that extracellular matrix derived from a native healthy tissue would be sufficient to support organoid growth akin to organogenesis in vivo. Here, we have developed hydrogels from decellularized human and bovine endometrium. These hydrogels supported the growth of mouse and human endometrial organoids, which was comparable to Matrigel. Organoids grown in endometrial hydrogels were proteomically more similar to the native tissue than the organoids cultured in Matrigel. Proteomic and Raman spectroscopy analyses showed that the method of decellularization affects the biochemical composition of hydrogels and subsequently, their ability to support organoid growth. The amount of laminin in hydrogels correlated with the number and the shape of organoids. We also demonstrated the utility of endometrial hydrogels in developing solid scaffolds for supporting high throughput cell culture-based applications. In summary, endometrial hydrogels overcome a major limitation of organoid technology and greatly expand the applicability of organoids to understand endometrial biology and associated pathologies.
2022-03-14 | MSV000089054 | MassIVE