MMP1 gene expression enhances myoblast migration and engraftment following implanting into mdx/SCID mice

Pan, Haiying; Vojnits, Kinga; Liu, Thomas T.; Meng, Fanwei; Yang, Lei; Wang, Yigang; Huard, Johnny; Cox, Charles S.; Lally, Kevin P.; Li, Yong

doi:10.4161/19336918.2014.983799

Cited by 15 publications

(14 citation statements)

References 49 publications

(52 reference statements)

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“…This pretreatment made the subsequent systemic injection of myogenic capable mesoangioblasts able to engraft, leading to α-sarcoglycan positive muscle fibers. In a more concise manner, myoblasts themselves were transfected with an MMP-1 expression vector which permitted more robust engraftment and expression of dystrophin in an immunocompromised mdx mouse [117]. Together these studies emphasize the reality that fibrosis presents a barrier to donor cell delivery and engraftment into diseased muscle that in certain instances can be overcome by providing anti-fibrotic treatment in conjunction with cell therapy.…”

Section: Fibrosis and Cell Therapy In Muscular Dystrophymentioning

confidence: 99%

Regulation of fibrosis in muscular dystrophy

Smith

Barton

2018

Matrix Biology

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The production of force and power are inherent properties of skeletal muscle, and regulated by contractile proteins within muscle fibers. However, skeletal muscle integrity and function also require strong connections between muscle fibers and their extracellular matrix (ECM). A well-organized and pliant ECM is integral to muscle function and the ability for many different cell populations to efficiently migrate through ECM is critical during growth and regeneration. For many neuromuscular diseases, genetic mutations cause disruption of these cytoskeletal-ECM connections, resulting in muscle fragility and chronic injury. Ultimately, these changes shift the balance from myogenic pathways toward fibrogenic pathways, culminating in the loss of muscle fibers and their replacement with fatty-fibrotic matrix. Hence a common pathological hallmark of muscular dystrophy is prominent fibrosis. This review will cover the salient features of muscular dystrophy pathogenesis, highlight the signals and cells that are important for myogenic and fibrogenic actions, and discuss how fibrosis alters the ECM of skeletal muscle, and the consequences of fibrosis in developing therapies.

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Section: Fibrosis and Cell Therapy In Muscular Dystrophymentioning

confidence: 99%

Regulation of fibrosis in muscular dystrophy

Smith

Barton

2018

Matrix Biology

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“…Several substances that modulate p38-MAPK, NF-kB, NO-cGMP [116, 118, 200–203], inhibit TGF-β [204], reduce oxidative stress [205] or inflammation [206, 207] have had beneficial effects in muscular dystrophies and deserve to be tested, in preclinical settings, in combination with short-term, transitory MMP-9 inhibition. With the exception of MMP-9 that plays a dual role in skeletal muscle regeneration/dystrophy [110, 208, 209], the inhibition of other MMPs proved they are essential for efficient muscle regeneration -this review and [210]-, reduction of fibrosis [211] and amelioration of myoblast engraftment following implantation into dystrophic mice [212]. This confirms the necessity for questioning long-term inhibition of MMPs not only in cancer and inflammation [213] but also in muscular dystrophies and other muscle diseases.…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Inflammation and Fibrosis of Skeletal Muscles

Alameddine

Morgan

2016

JND

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In skeletal muscles, levels and activity of Matrix MetalloProteinases (MMPs) and Tissue Inhibitors of MetalloProteinases (TIMPs) have been involved in myoblast migration, fusion and various physiological and pathological remodeling situations including neuromuscular diseases. This has opened perspectives for the use of MMPs’ overexpression to improve the efficiency of cell therapy in muscular dystrophies and resolve fibrosis. Alternatively, inhibition of individual MMPs in animal models of muscular dystrophies has provided evidence of beneficial, dual or adverse effects on muscle morphology or function. We review here the role played by MMPs/TIMPs in skeletal muscle inflammation and fibrosis, two major hurdles that limit the success of cell and gene therapy. We report and analyze the consequences of genetic or pharmacological modulation of MMP levels on the inflammation of skeletal muscles and their repair in light of experimental findings. We further discuss how the interplay between MMPs/TIMPs levels, cytokines/chemokines, growth factors and permanent low-grade inflammation favor cellular and molecular modifications resulting in fibrosis.

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“…MMPs belong to the proteolytic enzyme family that participates in degradation of the basement membrane and extracellular matrix (ECM) (Ries et al, 2007). The matrix metalloproteinase-1 (MMP1), acting through the MMP1/PAR1 axis, causes decay of the interstitial collagen type I, II and III (Ho et al, 2009;Pan et al, 2014). It has been proven that upregulation of MMP1 expression leads to a high migration capacity of MSCs.…”

Section: Factors Involved In Mscs Migrationmentioning

confidence: 99%

“…It has been proven that upregulation of MMP1 expression leads to a high migration capacity of MSCs. In vitro studies have shown that knockdown of the MMP1 gene in MSCs results in inhibition of their migration capacity (Pan et al, 2014). Thus, cells with high MMP1 expression can be a valuable agent in clinical therapy affecting the possibility of cell engraftment at the target site.…”

Section: Factors Involved In Mscs Migrationmentioning

confidence: 99%

Secretion, migration and adhesion as key processes in the therapeutic activity of mesenchymal stem cells

et al. 2019

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The MSCs are immature cells that can be found in numerous different tissue types. In recent years, they have gained considerable attention, particularly with regard to their regenerative properties. Due to their paracrine activity, ability to migrate, adhesion and homing, MSCs currently appear to be the most relevant for therapeutic use. Numerous bioactive molecules secreted by MSCs exert paracrine effects and modulate many physiological processes, such as angiogenesis, immunomodulation and neuroprotection. Cell-cell communication may be also mediated by extracellular vesicles released from the cells. Due to these properties, MSCs have been widely studied for evaluation of their therapeutic benefits expected in the clinical applications. For effective tissue regeneration, transplanted MSCs have to exit the circulation and locate at the site of damage, which is possible because of their ability to migrate, adhere and engraft at the target site. Accumulating evidence suggests that MSCs recruitment from remote sites is similar to leukocytes’ migration. All of these biological features make MSCs highly investigated stem cells and the most commonly used cells in regenerative medicine. Since environmental factors affect the MSCs behavior, we discuss importance of oxygen concentration as a one of the key factors affecting MSCs properties.

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MMP1 gene expression enhances myoblast migration and engraftment following implanting into mdx/SCID mice

Cited by 15 publications

References 49 publications

Regulation of fibrosis in muscular dystrophy

Regulation of fibrosis in muscular dystrophy

Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Inflammation and Fibrosis of Skeletal Muscles

Secretion, migration and adhesion as key processes in the therapeutic activity of mesenchymal stem cells

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