Modulating Mesenchymal Stromal Cell Microenvironment Alters Exosome RNA Content and Ligament Healing Capacity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1030361 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26451331_1.fastq.gz | Fastqsanger.gz | |||
| SRR26451331_2.fastq.gz | Fastqsanger.gz | |||
| SRR26451332_1.fastq.gz | Fastqsanger.gz | |||
| SRR26451332_2.fastq.gz | Fastqsanger.gz | |||
| SRR26451333_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 85 |
Similar Datasets
Project description:Mesenchymal stromal cells (MSCs) hold great promise in regenerative medicine due to their potential to promote tissue repair and regeneration. However, applying MSC-based cell therapy in actual clinical settings remains challenging due to issues such as immunocompatibility and cell stability. Recent shifts in therapeutic strategies have highlighted MSC-derived exosomes, small vesicles carrying various bioactive molecules, as a promising cell-free therapy to promote tissue regeneration. However, it remains largely unknown regarding the ability to customize the content of MSC-derived exosomes, how alterations in the MSC microenvironment influence exosome content, and the effects of such alterations on healing efficiency and mechanical properties in tissue repair when utilized as a therapy. In this study, we used an in vitro system of human MSC-derived exosomes and an in vivo rat ligament injury model to address these questions. We found a context-dependent correlation between exosomal and parent cell RNA content. Under native conditions, the correlation was moderate but heightened with microenvironmental changes. In vivo rat ligament injury model showed that MSC-derived exosomes increased ligament max load and stiffness. We also found that changes in the MSCs' microenvironment significantly influence the mechanical properties driven by exosome treatment. Additionally, a link was identified between altered exosomal microRNA levels and expression changes in microRNA targets in ligaments. These findings elucidate the nuanced interplay between MSCs, their exosomes, and tissue regeneration.
2024-07-17 | GSE245884 | GEO
Project description:Although mesenchymal stromal cell (MSC) based therapies hold promise in regenerative medicine, their clinical application remains challenging due to issues such as immunocompatibility. MSC-derived exosomes are a promising off-the-shelf therapy for promoting wound healing in a cell-free manner. However, the potential to customize the content of MSC-exosomes, and understanding how such modifications influence exosome effects on tissue regeneration remain underexplored. In this study, we used an in vitro system to compare the priming of human MSCs by 2 inflammatory inducers TNF-α and CRX-527 (a highly potent synthetic TLR4 agonist that can be used as a vaccine adjuvant or to induce anti-tumor immunity) on exosome molecular cargo, as well as on an in vivo rat ligament injury model to validate exosome potency. Different microenvironmental stimuli used to prime MSCs in vitro affected their exosomal microRNAs and mRNAs, influencing ligament healing. Exosomes derived from untreated MSCs significantly enhance the mechanical properties of healing ligaments, in contrast to those obtained from MSCs primed with inflammation-inducers, which not only fail to provide any improvement but also potentially deteriorate the mechanical properties. Additionally, a link was identified between altered exosomal microRNA levels and expression changes in microRNA targets in ligaments. These findings elucidate the nuanced interplay between MSCs, their exosomes, and tissue regeneration.
| S-EPMC11228621 | biostudies-literature
Project description:The objective of the study was to better understand the mechanism behind scar formation by identifying ECM factors and other unique genes differentially expressed during rat ligament healing via microarray. Rat medial collateral ligaments (MCL) were surgically transected or left intact. MCLs were collected at day 3 or 7 post-injury and used for microarray analysis. Results were compared to the normal intact ligaments.
2013-06-06 | GSE47676 | GEO
Project description:The objective of the study was to better understand the mechanism behind scar formation by identifying ECM factors and other unique genes differentially expressed during rat ligament healing via microarray. Rat medial collateral ligaments (MCL) were surgically transected or left intact. MCLs were collected at day 3 or 7 post-injury and used for microarray analysis. Results were compared to the normal intact ligaments. A total of 27 rats were used in the study. Animals were randomly placed in 1 of 3 groups (day 3, day 7, intact CX) with nine animals included with each time (9 rats/group). At the time of collection, MCLs from each time were placed into 3 pools (3 MCLs/pool), resulting in 3 reps per time, and usd for microarray analysis. A total of 9 gene chips were used for the experiment (3 chips/day).
2013-06-06 | E-GEOD-47676 | biostudies-arrayexpress
Project description:Maresin-1 (MaR1) and Resolvin E1 (RvE1) are specialized pro-resolving lipid mediators (SPMs) that regulate inflammatory processes. We have previously demonstrated the hard and soft tissue regenerative capacity of RvE1 in an in vivo model of periodontal disease characterized by inflammatory tissue destruction. Regeneration of periodontal tissues requires a well-orchestrated processes mediated by periodontal ligament stem-cells. However, limited data are available on how SPMs can regulate the regenerative properties of human periodontal ligament stem cells (hPDLSCs) under inflammatory conditions. Thus, we measured the impact of MaR1 and RvE1 in an in vitro model of hPDLSCs after stimulation with IL-1β and TNF-α by evaluating pluripotency, migration, proliferation, cell death, periodontal ligament markers (α-smooth muscle actin, tenomodulin, and periostin), cementum-osteogenic differentiation and phosphoproteomic perturbations. The data showed that the inflammatory milieu suppresses pluripotency, proliferation and migration of hPDLSCs; MaR1 and RvE1 both restored regenerative capacity by increasing hPDLSC proliferation, accelerating wound healing/migration, and upregulating periodontal ligament markers and cementum-osteogenic differentiation. Protein phosphorylation perturbations were associated with the SPM-induced regenerative capacity of hPDLSCs. Together, these results demonstrate that MaR1 and RvE1 restore or improve the regenerative properties of highly specialized stem cells when inflammation is present and offer opportunities for direct pharmacologic treatment of lost tissue integrity.
2021-09-09 | PXD019546 | Pride
Project description:Gene Expression Profiling of Severed Rat Medial Collateral Ligament at 1, 2, 4, 7,1 0, and 14 days Following Injury with Control and Cultured Ligament Fibroblasts and Rat Universal Reference RNA The aim of this study was to assess the genes involved in the repair of the the dense connective tissue of the a rat ligament in order to provide targets for improvement in healing. Rat whole genome microarrays (Agilent) were used in this study and Cy3 and Cy5 labeled total RNA was extracted and labeled with Cy3 or Cy5 prior to fragmentation and hybridization. Keywords: Time course of changes in gene expression in the healing of the rat medial collateral ligament.
2008-03-05 | GSE10720 | GEO
Project description:Gene Expression Profiling of Severed Rat Medial Collateral Ligament at 1, 2, 4, 7,1 0, and 14 days Following Injury with Control and Cultured Ligament Fibroblasts and Rat Universal Reference RNA; The aim of this study was to assess the genes involved in the repair of the the dense connective tissue of the a rat ligament in order to provide targets for improvement in healing. Rat whole genome microarrays (Agilent) were used in this study and Cy3 and Cy5 labeled total RNA was extracted and labeled with Cy3 or Cy5 prior to fragmentation and hybridization. Experiment Overall Design: To conserve microarrays to allow maximum replicates, two samples either Cy3 or Cy5 labeled were hybridized to each microarry. Total RNA from each rat medial collateral ligament was labeled and hybrided to a microarray. The fluorescence intensity for each column minus the background was extracted from each microarray for submission to BRB Array tools for statistical analysis.
2008-04-05 | E-GEOD-10720 | biostudies-arrayexpress
Project description:Ligaments are prone to injury and degeneration in humans and animals, however the healing potential of ligament is poor and current treatment options lack effectiveness. Stem cell-based therapies hold potential for treatment of ligament injuries. This study aimed to characterise ligament-derived stem cell (LDSC) and ligament fibroblast populations as well as to identify specific niche components which could be used to promote the survival and function of LDSCs. LDSCs and ligament fibroblasts were isolated from canine cranial cruciate ligament and characterised for clonogenicity, multipotency and marker expression. The extracellular matrix (ECM) composition was characterised using a novel metabolic labelling and mass spectrometry approach. Both cell types demonstrated clonogenicity, with significant differences seen in colony size. Stem cell and tenogenic marker expression was increased in LDSCs compared with ligament fibroblasts, although this was only significant for the MSC marker CD73. Both cell types demonstrated multipotency, however this was more marked in LDSCs. A number of collagens, glycoproteins, proteoglycans and ECM regulators were identified in both the LDSC and ligament fibroblast niche using proteomics, with some differences between cell types, including collagens, decorin and fibronectin. Metabolic labelling of cells demonstrated unique turnover profiles for distinct ECM protein groups, with significant differences in new synthesis seen between cell types for a number of proteins, including collagen, decorin and elastin. In conclusion, different cell populations were observed in canine ligament with differences in niche composition and dynamics seen between the two cell types. These differences could be exploited to aid identification of LDSCs and to promote survival and function of LDSCs for potential therapeutic strategies.
2019-01-28 | PXD008602 | Pride
Project description:This study describes the discovery of the gene responsible for differentiation of stem cells into ligament tissue. This important finding may lead to the development of treatments for gonarthrosis, rupture of the cruciate ligament and periodontal ligament, and ossification of the posterior longitudinal ligament. This study describes the discovery of the gene (A) responsible for differentiation of stem cells into ligament tissue. The transfection of this gene into mouse mesenchymal stem cells resulted in the formation of ligament-like connective tissue composed of parallel fibres. We performed microarray analysis of four samples: stem cells (sample1), ligament-like tissue from stem cells transfected with A (sample 4), ligament tissue from A-transgenic mice (sample 2) , and ligament tissue from wild type mice (sample 3).
2013-03-31 | E-GEOD-35269 | biostudies-arrayexpress
Project description:Adult zebrafish have the capacity to regenerate craniofacial ligament tissue following a complete transection injury. How this robust skeletal regeneration is achieved remains undefined. Here, we use single cell RNA sequencing to profile RNA expression from FACS sorted cranial neural crest lineage and non-cranial neural crest lineage cells (including skin and immune populations) in the first 3 days after ligament injury.
2023-02-05 | GSE224197 | GEO