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Perfusable adipose decellularized extracellular matrix biological scaffoldco-recellularizedwith adipose-derived stem cellsand L6 promotes functional skeletal muscle regeneration following volumetric muscle loss

ABSTRACT: Perfusable adipose decellularized extracellular matrix biological scaffoldco-recellularizedwith adipose-derived stem cellsand L6 promotes functional skeletal muscle regeneration following volumetric muscle loss

PROVIDER: PRJNA1040263 | ENA |

REPOSITORIES: ENA

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Perfusable adipose decellularized extracellular matrix biological scaffoldco-recellularizedwith adipose-derived stem cellsand L6 promotes functional skeletal muscle regeneration following volumetric muscle loss

Project description:In this study, we used a recellularization method of perfusing cells into biological scaffolds through vascular pedicles. ASCs and L6 cells were co-seeded into adipose decellularized extracellular matrix (adECM) biological scaffolds. On one hand, this strategy ensures uniform distribution of seeded cells in the scaffold and avoids the formation of non-functional "muscle islands" later. On the other hand, co-seeding of L6 cells and ASCs addresses the issue of low myogenic differentiation potential of ASCs. Subsequently, the recellularized biological scaffold treatment of VML animal experiments showed that the combined recellularization strategy had significantly better muscle regeneration and angiogenesis than the single ASCs recellularization strategy, and the former had better functional recovery of tibialis anterior muscle (TA). Further single cell sequencing analysis found that compared to singly seeded ASCs in biological scaffolds, L6 cells in the combined recellularization induced ASCs to transform into a new subpopulation of cells highly expressing Mki67, CD34 and CDK1 genes, which had stronger ability of oriented myogenic differentiation and formed more mature and larger muscle fibers, significantly restoring TA muscle function.

2024-03-26 | GSE247751 | GEO

Unwavering Pathobiology of Volumetric Muscle Loss Injury

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

Unwavering Pathobiology of Volumetric Muscle Loss Injury

Project description:Unwavering Pathobiology of Volumetric Muscle Loss Injury

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Maresin 1 Repletion Improves Muscle Regeneration After Volumetric Muscle Loss

Project description:Maresin 1 Repletion Improves Muscle Regeneration After Volumetric Muscle Loss

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Plant-derived compounds strigolactone GR24 and pinosylvin modulate gene expression in rat L6 skeletal muscle cells

Project description:We investigated the effects of novel SIRT1 activating plant-derived compounds strigolactone GR24 and pinosylvin on gene expression in rat L6 skeletal muscle myotubes. Resveratrol was included in analyses as a reference compound.

2017-12-18 | GSE90833 | GEO

Deconstruction of cellular dynamics after treatment of volumetric muscle loss injury with extracellular matrix

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.

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Maresin 1 Repletion Improves Muscle Regeneration After Volumetric Muscle Loss

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

Spatiotemporal mapping of immune and stem cell dysregulation after volumetric muscle loss

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

Lentimicrobium sp. L6 strain:L6

Project description:Lentimicrobium sp. L6 strain:L6 Genome sequencing and assembly

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Multiscale analysis of a regenerative therapy for treatment of volumetric muscle loss injury

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

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