Local IL-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA852258 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19805737.fastq.gz | Fastqsanger.gz | |||
| SRR19805738.fastq.gz | Fastqsanger.gz | |||
| SRR19805741.fastq.gz | Fastqsanger.gz | |||
| SRR19805742.fastq.gz | Fastqsanger.gz | |||
| SRR19805743.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 7 |
Similar Datasets
Project description:To explore the impact of targeting IL-10 signaling, tibialis anterior (TA) VML injuries were created and then treated in Sprague Dawley rats using an autologous minced muscle regenerative medicine repair strategy in combination with delayed exogenous IL-10 delivery. We then performed gene expression profiling analysis using data obtained from RNA-seq from rat muscles (n=4 for IL-10 treatment, n=4 for PBS control , and n=4 for uninjured control) at day 14 post injury
2022-06-26 | GSE206823 | GEO
Project description:Mice with either a cranial bone defect, skin biopsy punch injury, quadriceps volumetric muscle loss defect or myocardial infarction (MI) were treated with Tregs, either via local hydrogel-mediated delivery (for bone, muscle and skin), or with systemic (intravenous) delivery (for heart). Control mice were treated with hydrogel alone (for bone, muscle and skin) or PBS (for heart). On day 4 and 7 post-MI, the injured tissues were harvested and the endogenous monocytes/macrophages were sorted and used for mini-bulk RNA sequencing, to compare the transcriptomic profiles of injured tissue monocytes/macrophages in Treg-treated and untreated mice post-injury.
2024-05-31 | GSE230173 | GEO
Project description:Unwavering Pathobiology of Volumetric Muscle Loss Injury
| PRJNA472640 | ENA
Project description:Volumetric muscle loss (VML) resulting from extremity trauma presents chronic and persistent functional deficits which ultimately manifest disability. Acellular biological scaffolds, or decellularized extracellular matrices (ECMs), embody an ideal treatment platform due to their current clinical use for soft tissue repair, off-the-shelf availability, and zero autogenous donor tissue burden. ECMs have been reported to promote functional skeletal muscle tissue remodeling in small and large animal models of VML injury, and this conclusion was reached in a recent clinical trial that enrolled 13 patients. However, numerous other pre-clinical reports have not observed ECM-mediated skeletal muscle regeneration. The current study was designed to reconcile these discrepancies. The capacity of ECMs to orchestrate functional muscle tissue remodeling was interrogated in a porcine VML injury model using unbiased assessments of muscle tissue regeneration and functional recovery. Here, we show that VML injury incites an overwhelming inflammatory and fibrotic response that leads to expansive fibrous tissue deposition and chronic functional deficits, which ECM repair does not augment.
2018-05-23 | GSE114798 | GEO
Project description:Volumetric muscle loss (VML) is an acute loss of a critical volume of skeletal muscle that results in inflammation, fibrotic scarring in muscle tissue, and permanent muscle defects. The cellular and molecular processes that underlie fibrosis induced from VML injury need to be evaluated in larger animal models. Therefore, we used a canine model of VML alongisde treatment with an extracellular matrix (ECM) hydrogel. Treatment with the ECM hydrogel improved muscle regenerative responses and decreased proportions and spatial signatures of fibrotic and inflammatory cell populations.
2024-06-01 | GSE266585 | GEO
Project description:The acute traumatic or surgical loss of skeletal muscle, known as volumetric muscle loss (VML), is a devastating type of injury that results in exacerbated and persistent inflammation followed by fibrosis. The mechanisms that mediate the magnitude and duration of the inflammatory response and ensuing fibrosis after VML remain understudied, and as such, the development of regenerative therapies has been limited. To address this need, we profiled how lipid mediators, which are potent regulators of the immune response after injury, varied with VML injuries that heal or result in fibrosis. We observed that non-healing VML injuries displayed increased pro-inflammatory eicosanoids and a lack of pro-resolving lipid mediators. Treatment of VML with a pro-resolving lipid mediator synthesized from docosahexaenoic acid, called Maresin 1, ameliorated fibrosis through reduction of neutrophils and macrophages and enhanced recovery of muscle strength. These results expand our knowledge of the dysregulated immune response that develops after VML and identify a novel immuno-regenerative therapeutic modality in Maresin 1.
2024-01-18 | GSE215808 | GEO
Project description:Volumetric muscle loss (VML) is an acute trauma that results in persistent inflammation, supplantation of muscle tissue with fibrotic scarring, and decreased muscle function. The cell types, nature of cellular communication, and tissue locations that drive the aberrant VML response have remained elusive. Herein, we used spatial transcriptomics on mouse and canine models of VML and observed VML engenders a unique spatial pro-fibrotic pattern driven by crosstalk between fibrotic and inflammatory macrophages and mesenchymal derived cells. The dysregulated response was conserved between murine and canine VML models, albeit with varying kinetics, and impinged on muscle stem cell mediated repair. Targeting this circuit in a murine model resulted in increased regeneration and reductions in inflammation and fibrosis. Collectively, these results enhance our understanding of the cellular crosstalk that drives aberrant regeneration and provides further insight into possible avenues for fibrotic therapy exploration.
2023-02-23 | GSE205707 | GEO
Project description:Exosomes are nanosized extracellular vesicles which have been recently demonstrated as promising agents for tissue repair/regeneration by inducing and guiding appropriate immune responses in dystrophic pathologies. Unfortunately, the accurate manipulation of exosomes by controlling their biodistribution still poses significant challenges. Here we overcome this limitation by developing an externally controlled delivery system for primed ANXA1 myo-exosomes (Exomyo). Effective nanocarriers are realized by immobilizing the Exomyo onto ferromagnetic nanotubes (NT-MAG) to achieve a controlled delivery and localization of Exomyo into skeletal muscles by an applied external magnetic field. Quantitative muscle-level analyses revealed that macrophages dominate the uptake of Exomyo from NT-MAG in vivo, to synergistically promote beneficial muscle responses in a murine animal model of Duchenne Muscular Dystrophy (DMD) thanks to the successful localization of therapeutic Exomyo upon systemic injection. These findings provide valuable insights into the development of exosome-based therapies for muscle diseases and in general highlight the formulation of effective functional nanocarriers aimed at optimizing exosome biodistribution.
2024-07-23 | GSE263456 | GEO
Project description:Exosomes are nanosized extracellular vesicles which have been recently demonstrated as promising agents for tissue repair/regeneration by inducing and guiding appropriate immune responses in dystrophic pathologies. Unfortunately, the accurate manipulation of exosomes by controlling their biodistribution still poses significant challenges. Here we overcome this limitation by developing an externally controlled delivery system for primed ANXA1 myo-exosomes (Exomyo). Effective nanocarriers are realized by immobilizing the Exomyo onto ferromagnetic nanotubes (NT-MAG) to achieve a controlled delivery and localization of Exomyo into skeletal muscles by an applied external magnetic field. Quantitative muscle-level analyses revealed that macrophages dominate the uptake of Exomyo from NT-MAG in vivo, to synergistically promote beneficial muscle responses in a murine animal model of Duchenne Muscular Dystrophy (DMD) thanks to the successful localization of therapeutic Exomyo upon systemic injection. These findings provide valuable insights into the development of exosome-based therapies for muscle diseases and in general highlight the formulation of effective functional nanocarriers aimed at optimizing exosome biodistribution.
2024-07-23 | GSE263142 | GEO
Project description:Skeletal muscle possesses a remarkable capacity to regenerate when injured, but when confronted with major traumatic injury resulting in volumetric muscle loss (VML), the regenerative process consistently fails. The loss of muscle tissue and function from VML injury has prompted development of a suite of therapeutic approaches but these strategies have proceeded without a comprehensive understanding of the molecular landscape that drives the injury response. Herein, we administered a VML injury in an established rodent model and monitored the evolution of the healing phenomenology over multiple time points using muscle function testing, histology, and expression profiling by RNA sequencing. The injury response was then compared to a regenerative medicine treatment using orthotopic transplantation of autologous minced muscle grafts (~1 mm3 tissue fragments). A chronic inflammatory and fibrotic response was observed at all time points following VML. These results suggest that the pathological response to VML injury during the acute stage of the healing response overwhelms endogenous and therapeutic regenerative processes. Overall, the data presented delineate key molecular characteristics of the pathobiological response to VML injury that are critical effectors of effective regenerative treatment paradigms.
2018-05-23 | GSE114799 | GEO