Human mesenchymal stem cell-derived matrices for enhanced osteoregeneration
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ABSTRACT:
PROVIDER: PRJNA152309 | ENA |
REPOSITORIES: ENA
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Project description:The methodology for the repair of critical-sized or non-union bone lesions has unpredictable efficacy due in part to our incomplete knowledge of bone repair and the biocompatibility of bone substitutes. Although human mesenchymal stem cells (hMSCs) differentiate into osteoblasts, which promote bone growth, their ability to repair bone has been unpredictable. We hypothesized that given the multi-stage process of osteogenesis, hMSC-mediated repair might be maximal at a specific time-point of healing. Utilizing a mouse model of calvarial healing, we demonstrate that the osteo-repair capacity of hMSCs can be substantially augmented by treatment with an inhibitor of peroxisome-proliferator-activated-receptor-γ, but efficacy is confined to the rapid osteogenic phase. Upon entry into the bone-remodeling phase, hMSC retention signals are lost, resulting in truncation of healing. To solve this limitation, we prepared a scaffold consisting of hMSC-derived extracellular matrix (ECM) containing the necessary biomolecules for extended site-specific hMSC retention. When inhibitor-treated hMSCs were co-administered with ECM, they remained at the injury well into the remodeling phase of healing, which resulted in reproducible and complete repair of critical-sized defects in 3 weeks. These data suggest that hMSC-derived ECM and inhibitor-treated hMSCs could be employed at optimal times to substantially and reproducibly improve bone repair. To gain insight into the superior healing potential of GW-hMSCs and also what might be accounting for their extended engraftment, microarray analyses on the RNA extracted from the calvarial tissue recovered after days 5 and 14 were performed. Equal amounts of total RNA from 4 animals per group and time point were pooled and animals receiving control (DMSO) or peroxisome proliferator-activated receptor-gamma inhibitor GW9662-treated hMSCs were compared with the assumption that murine cross-hybridization would be constant throughout the samples and thus be subtracted from the analysis.
2012-02-17 | E-GEOD-35503 | biostudies-arrayexpress
Project description:The methodology for the repair of critical-sized or non-union bone lesions has unpredictable efficacy due in part to our incomplete knowledge of bone repair and the biocompatibility of bone substitutes. Although human mesenchymal stem cells (hMSCs) differentiate into osteoblasts, which promote bone growth, their ability to repair bone has been unpredictable. We hypothesized that given the multi-stage process of osteogenesis, hMSC-mediated repair might be maximal at a specific time-point of healing. Utilizing a mouse model of calvarial healing, we demonstrate that the osteo-repair capacity of hMSCs can be substantially augmented by treatment with an inhibitor of peroxisome-proliferator-activated-receptor-γ, but efficacy is confined to the rapid osteogenic phase. Upon entry into the bone-remodeling phase, hMSC retention signals are lost, resulting in truncation of healing. To solve this limitation, we prepared a scaffold consisting of hMSC-derived extracellular matrix (ECM) containing the necessary biomolecules for extended site-specific hMSC retention. When inhibitor-treated hMSCs were co-administered with ECM, they remained at the injury well into the remodeling phase of healing, which resulted in reproducible and complete repair of critical-sized defects in 3 weeks. These data suggest that hMSC-derived ECM and inhibitor-treated hMSCs could be employed at optimal times to substantially and reproducibly improve bone repair.
2012-02-17 | GSE35503 | GEO
Project description:In the stem-cell niche, the extracellular matrix (ECM) serves as a structural support that additionally provides stem cells with signals that contribute to the regulation of stem-cell function, via reciprocal interactions between cells and components of the ECM. Recently, cell-derived ECMs have emerged as in vitro cell culture substrates to better recapitulate the native stem-cell microenvironment outside the body. Significant changes in cell number, morphology and function have been observed when mesenchymal stem cells (MSC) were cultured on ECM substrates as compared to standard tissue-culture polystyrene (TCPS). As select ECM components are known to regulate specific stem-cell functions, a robust characterization of cell-derived ECM proteomic composition is critical to better comprehend the role of the ECM in directing cellular processes. Here, we characterized and compared the protein composition of ECM produced in vitro by bone marrow-derived MSC, adipose-derived MSC and neonatal fibroblasts isolated from different donors, employing quantitative proteomic methods. Each cell-derived ECM displayed a specific and unique matrisome signature, yet they all shared a common set of proteins. We evaluated the biological response of cells cultured on the different matrices and compared them to cells on standard TCPS. The matrices lead to differential survival and gene-expression profiles among the cell types and as compared to TCPS, indicating that the cell-derived ECMs influence each cell type in a different manner. This general approach to understanding the protein composition of different tissue-specific and cell-derived ECM will inform the rational design of defined systems and biomaterials that recapitulate critical ECM signals for stem-cell culture and tissue engineering.
2017-03-07 | GSE94667 | GEO
Project description:The objective of this project is secreening the constituent of adipose derived mesenchymal stem cell secretome.
2023-09-11 | PXD045254 |
Project description:We reported a specialized protocol to produce human cardiac cell-derived matrices without the introduction of exogenous matrix proteins. Human cardiac fibroblasts cultured under conditions to produced cell-derived matrices were harvested at the beginning, middle and completion of the experiment - corresponding to days 0, 5 and 10. Fetal and adult human cardiac fibroblasts were cultured densely in the presence of ficoll as a macromolecular crowder on the adhesive biopolymer l-polydopamine, and sampled throughout matrix deposition to determine the age-specific responses of primary human cardiac fibroblasts to macromolecular crowders and enhanced matrix deposition.
2021-07-25 | GSE155225 | GEO
Project description:We characterized and compared the proteomic composition of ECM produced in vitro by bone marrow-derived MSC, adipose-derived MSC and neonatal fibroblasts isolated from different donors, employing a multidimensional proteomic approach coupled with label-based quantitative proteomics. Each cell-derived ECM displayed a specific and unique matrisome signature, yet they all shared a common set of proteins. We evaluated the biological response of cells cultured on the different matrices and compared them to cells on standard TCPS. The matrices lead to differential proliferation and gene expression profiles between the cell types and as compared to TCPS, indicating that the cell-derived ECM influence each cell type in a unique manner.
2017-03-08 | PXD005521 | Pride
Project description:We compared the differential proteins between Mesenchymal stem cells-derived exosomes MRC-5 cell-derived exosomes.
2024-05-21 | PXD033839 | Pride
Project description:We characterized and compared the proteomic composition of ECM produced in vitro by bone marrow-derived MSC, adipose-derived MSC and neonatal fibroblasts isolated from different donors, employing a multidimensional proteomic approach coupled with label-based quantitative proteomics. Each cell-derived ECM displayed a specific and unique matrisome signature, yet they all shared a common set of proteins. We evaluated the biological response of cells cultured on the different matrices and compared them to cells on standard TCPS. The matrices lead to differential proliferation and gene expression profiles between the cell types and as compared to TCPS, indicating that the cell-derived ECM influence each cell type in a unique manner.
2017-03-29 | MSV000080731 | MassIVE
Project description:Stem Cell-Derived Matrices Provide Improved Isolation and Maintenance of hMSC Characteristics
| PRJNA488086 | ENA
Project description:Recently, mesenchymal stem cells-derived microvesicles (MMVs) attract much attention as a strategy of cell-free treatment. In our study, we found that MMVs could improve the organ dysfunction during sepsis. To investigate the mechanism, we harvested MMVs from mesenchymal stem cells to perform proteomic analysis, and chondrocyte-derived microvesicles (CMVs) were used as a negative control, and PGC-1α overexpressed-MMVs were used as a positive control. A total of 5411 proteins were identified in this study, and differentially expressed (DE) proteins were further identified with a cut-off of absolute fold change >1.5 and a significance p-value <0.05. Compared with CMV group, 321 proteins were upregulated and 209 proteins were downregulated in MMVs. This study illustrated the differences between MMVs and CMVs, and provided a sight for investigating the protective effect of MMVs.
2021-06-08 | PXD026344 | Pride