Laminin therapy for the promotion of muscle regeneration

Riederer, Ingo; Bonomo, Adriana; Mouly, Vincent; Savino, Wilson

doi:10.1016/j.febslet.2015.10.004

Cited by 25 publications

(19 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The main component of matrigel is laminin, which can mediate the adhesion of myogenic cells through the muscle specific integrin, α7β1 (Yao et al, 1996; Riederer et al, 2015). Laminin is known to be essential for migration and proliferation of murine myoblasts (Fig.…”

Section: Discussionmentioning

confidence: 99%

Efficient and high yield isolation of myoblasts from skeletal muscle

et al. 2018

View full text Add to dashboard Cite

Skeletal muscle (SkM) regeneration relies on the activity of myogenic progenitors that reside beneath the basal lamina of myofibers. Here, we describe a protocol for the isolation of the SkM progenitors from young and old mice by exploiting their outgrowth potential from SkM explants on matrigel coated dishes in the presence of high serum, chicken embryo extract and basic fibroblast growth factor. Compared to other protocols, this method yields a higher number of myoblasts (10–20 million) by enabling the outgrowth of these cells from tissue fragments. The majority of outgrowth cells (~90%) were positive for myogenic markers such as α7-integrin, MyoD, and Desmin. The myogenic cell population could be purified to 98% with one round of pre-plating on collagen coated dishes, where differential attachment of fibroblasts and other non-myogenic progenitors separates them from myoblasts. Moreover, the combination of high serum medium and matrigel coating provided a proliferation advantage to myogenic cells, which expanded rapidly (~24 h population doubling), while non-myogenic cells diminished over time, thereby eliminating the need for further purification steps such as FACS sorting. Finally, myogenic progenitors gave rise to multinucleated myotubes that exhibited sarcomeres and spontaneous beating in the culture dish.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficient and high yield isolation of myoblasts from skeletal muscle

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Mutations in the LN α2 chain, which is part of the α2β1γ1 trimer (LN-211), the major LN isoform on muscle, cause severe muscular dystrophy [ 66 ]. Although LN-111 is not present in the normal adult muscle, it is the most studied LN isoform, also applied as a therapeutic agent in different animal models for muscular dystrophies, such as Duchenne muscular dystrophy (DMD) and merosin-deficient congenital muscular dystrophy type 1A (MDC1A) [ 22 , 67 – 69 ]. Different LN isoforms can have differential effects on myoblast proliferation or differentiation, as shown recently for LN-211 or LN-521 [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Laminin (LN) and fibronectin (FN) are ECM glycoproteins able to stimulate the migration of different cell types [ 14 – 18 ], including myoblasts [ 19 – 21 ]. LN is the major glycoprotein of the basal membrane in different tissues, and the isoforms 211 and 221 surrounds the muscle fibers and the SCs [ 22 ]. Although the SC niche does not contain FN, after muscle injury, the expression of this molecule is transiently enhanced, peaking on day 5 [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…Considering myoblast injection as a potential treatment for at least, some muscular disorders, substantial dispersion inside the muscle will be necessary to improve this approach. LN isoforms could be instrumental in this context, and LN-111 has already been used as a therapeutic agent in different animal models, despite its absence in normal adult muscles [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

HGF potentiates extracellular matrix-driven migration of human myoblasts: involvement of matrix metalloproteinases and MAPK/ERK pathway

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundThe hepatocyte growth factor (HGF) is required for the activation of muscle progenitor cells called satellite cells (SC), plays a role in the migration of proliferating SC (myoblasts), and is present as a soluble factor during muscle regeneration, along with extracellular matrix (ECM) molecules. In this study, we aimed at determining whether HGF is able to interact with ECM proteins, particularly laminin 111 and fibronectin, and to modulate human myoblast migration.MethodsWe evaluated the expression of the HGF-receptor c-Met, laminin, and fibronectin receptors by immunoblotting, flow cytometry, or immunofluorescence and used Transwell assays to analyze myoblast migration on laminin 111 and fibronectin in the absence or presence of HGF. Zymography was used to check whether HGF could modulate the production of matrix metalloproteinases by human myoblasts, and the activation of MAPK/ERK pathways was evaluated by immunoblotting.ResultsWe demonstrated that human myoblasts express c-Met, together with laminin and fibronectin receptors. We observed that human laminin 111 and fibronectin have a chemotactic effect on myoblast migration, and this was synergistically increased when low doses of HGF were added. We detected an increase in MMP-2 activity in myoblasts treated with HGF. Conversely, MMP-2 inhibition decreased the HGF-associated stimulation of cell migration triggered by laminin or fibronectin. HGF treatment also induced in human myoblasts activation of MAPK/ERK pathways, whose specific inhibition decreased the HGF-associated stimulus of cell migration triggered by laminin 111 or fibronectin.ConclusionsWe demonstrate that HGF induces ERK phosphorylation and MMP production, thus stimulating human myoblast migration on ECM molecules. Conceptually, these data state that the mechanisms involved in the migration of human myoblasts comprise both soluble and insoluble moieties. This should be taken into account to optimize the design of therapeutic cell transplantation strategies by improving the migration of donor cells within the host tissue, a main issue regarding this approach.Electronic supplementary materialThe online version of this article (10.1186/s13395-017-0138-6) contains supplementary material, which is available to authorized users.

show abstract

“…Previous research has shown that treatment with natural Englebreth-Holm-Swam (EHS) murine sarcoma derived Laminin-111 enhances muscle regeneration and prevents myopathy of mouse models of LAMA2-CMD and Duchenne Muscular Dystrophy (DMD) [10,11,16,[21][22][23]. To test whether human Laminin-111 has the same effect, we treated NODScid dy W mice with HsLAM-111.…”

Section: Human Laminin-111 and Laminin-211 Protein Therapy Increase Mmentioning

confidence: 99%

Human Laminin-111 and Laminin-211 protein therapy prevents muscle disease progression in an immune deficient mouse model of LAMA2-CMD

Barraza-Flores

Hermann

Bates

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Laminin-α2 related Congenital Muscular dystrophy (LAMA2-CMD) is a devastating genetic disease caused by mutations in the LAMA2 gene. These mutations result in progressive muscle wasting and inflammation leading to delayed milestones, and reduced lifespan in affected patients. There is currently no cure or treatment for LAMA2-CMD. Preclinical studies have demonstrated that mouse Laminin-111 can serve as an effective protein replacement therapy in a mouse model of LAMA2-CMD. Methods In this study, we generated a novel immunocompromised dy W mouse model of LAMA2-CMD to study the role the immune system plays in muscle disease progression. We used this immune deficient dy W mouse model to test the therapeutic benefits of recombinant human laminin-111 and laminin-211 protein therapy on Laminin-α2 deficient muscle disease progression. Results We show that immune deficient Laminin-α2 null mice demonstrate subtle differences in muscle regeneration compared to immune competent animals during early disease stages, but overall exhibit a comparable muscle disease progression. We found human laminin-111 and laminin-211 could serve as effective protein replacement strategies with mice showing improvements in muscle pathology and function. We observed that human laminin-111 and laminin-211 exhibit differences on satellite and myoblast cell populations and differentially affect muscle repair. Conclusions This study describes the generation of a novel immune deficient mouse model that allows investigation of the role the immune system plays in LAMA2-CMD. This model can be used to assess the therapeutic potential of heterologous therapies that would illicit an immune response. Using this model, we show that recombinant human Laminin-111 can serve as effective protein replacement therapy for the treatment of LAMA2-CMD.

show abstract

Laminin therapy for the promotion of muscle regeneration

Cited by 25 publications

References 54 publications

Efficient and high yield isolation of myoblasts from skeletal muscle

Efficient and high yield isolation of myoblasts from skeletal muscle

HGF potentiates extracellular matrix-driven migration of human myoblasts: involvement of matrix metalloproteinases and MAPK/ERK pathway

Human Laminin-111 and Laminin-211 protein therapy prevents muscle disease progression in an immune deficient mouse model of LAMA2-CMD

Contact Info

Product

Resources

About