Treatment Of Skeletal Muscle Injury Research Articles

Development of a local controlled release system for therapeutic proteins in the treatment of skeletal muscle injuries and diseases

The present study aims to develop and characterize a controlled-release delivery system for protein therapeutics in skeletal muscle regeneration following an acute injury. The therapeutic protein, a membrane-GPI anchored protein called Cripto, was immobilized in an injectable hydrogel delivery vehicle for local administration and sustained release. The hydrogel was made of poly(ethylene glycol)-fibrinogen (PEG-Fibrinogen, PF), in the form of injectable microspheres. The PF microspheres exhibited a spherical morphology with an average diameter of approximately 100 micrometers, and the Cripto protein was uniformly entrapped within them. The release rate of Cripto from the PF microspheres was controlled by tuning the crosslinking density of the hydrogel, which was varied by changing the concentration of poly(ethylene glycol) diacrylate (PEG-DA) crosslinker. In vitro experiments confirmed a sustained-release profile of Cripto from the PF microspheres for up to 27 days. The released Cripto was biologically active and promoted the in vitro proliferation of mouse myoblasts. The therapeutic effect of PF-mediated delivery of Cripto in vivo was tested in a cardiotoxin (CTX)-induced muscle injury model in mice. The Cripto caused an increase in the in vivo expression of the myogenic markers Pax7, the differentiation makers eMHC and Desmin, higher numbers of centro-nucleated myofibers and greater areas of regenerated muscle tissue. Collectively, these results establish the PF microspheres as a potential delivery system for the localized, sustained release of therapeutic proteins toward the accelerated repair of damaged muscle tissue following acute injuries.

Traditional Chinese Medicine for Topical Treatment of Skeletal Muscle Injury.

Muscle injuries are common musculoskeletal problems, but the pharmaceutical agent for muscle repair and healing is insufficient. Traditional Chinese Medicine (TCM) frequently uses topical treatments to treat muscle injuries, although scientific evidence supporting their efficacy is scarce. In this study, an in vitro assay was used to test the cytotoxicity of a topical TCM formula containing Carthami Flos, Dipsaci Radix, and Rhei Rhizoma (CDR). Then, a muscle contusion rat model was developed to investigate the in vivo effect and basic mechanisms underlying CDR on muscle regeneration. The in vitro assay illustrated that CDR was non-cytotoxic to immortalized rat myoblast culture and increased cell viability. Histological results demonstrated that the CDR treatment facilitated muscle repair by increasing the number of new muscle fibers and promoting muscle integrity. The CDR treatment also upregulated the expression of Pax7, MyoD and myogenin, as evidenced by an immunohistochemical study. A gene expression analysis indicated that the CDR treatment accelerated the regeneration and remodeling phases during muscle repair. This study demonstrated that topical CDR treatment was effective at facilitating muscle injury repair.

Retracted: Application of Low-Intensity Laser in the Treatment of Skeletal Muscle Injury in Runners.

[This retracts the article DOI: 10.1155/2022/1211602.].

Application of Low-Intensity Laser in the Treatment of Skeletal Muscle Injury in Runners.

With the continuous improvement of people's economic level, running, as the most common sports, is not limited by sports venues and sports levels and deeply loved by people. However, during running, soft tissue resonates with the impact force, increasing the load on joints and tendons and potentially leading to sports injuries. The purpose of this article is to study the application of low-intensity laser in the treatment of muscle strain. This article analyzes running, muscle adjustment, and lower limb stiffness. On the basis of theory, 20 healthy male college students were selected as research objects in the experimental part. The subjects were allowed to run at three speeds: slow, medium, and fast. The kinematics, dynamics, and surface EMG signals of the subjects during running were collected to analyze the effect of low-intensity laser therapy on exercise muscle strain. The experimental results showed that a low-intensity laser can effectively alleviate muscle inflammation, reduce the number of cell damage, bring the mean and integral optical density of protein to the normal level significantly, and reduce the strain degree of exercise muscle. In this article, a statistical method was used to obtain the gait cycle time (P & LT; 0.01) and support cycle time (slow P < 0.01).

A Histological Study on the Effect of Dextrose Prolotherapy on Skeletal Muscle Injury in Adult Male Albino Rats

Abstract Background Skeletal muscle injuries are one of the most common injuries occurring in sport medicine varies from 10% to 55% of all injuries. Phases of muscle injuries includes a series of complex stages including inflammation, regeneration and remodeling. Treatment of the injuries is based on conservative measures as rest, elevation, physical therapy and non steroidal anti-inflammatory medications. Many injection protocols have been proposed for the treatment of muscle lesions as corticosteroid injection. Recently prolotherapy appears to have a safety profile comparable with other injection procedures. Aim of the work The aim of the present work is to determine the efficacy of dextrose prolotherapy in treatment of skeletal muscle injury in adult male albino rats. Material and methods Sixty six adult male albino rats were used in the study. They were divided into control (group I) and experimental groups. Control group: rats were left without any intervention. The experimental group was group II that was divided into sham operated group in which skin incision was done in the left hindlimb without injury to gastrocnemius (group II`) and muscle injury group in which transverse cut injury across the midbelly of the gastrocnemius muscle of right hindlimb was done (group II``) and group III that was divided into lidocaine injected group in which skin incision in lefthindlimb was done without injury to gastrocnemius followed by injection of 0.3 ml 1% lidocaine was injected across the muscle (group III`) and muscle injury treated with dextrose prolotherapy group in which a transverse cut injury across the midbelly of gastrocnemius of right hindlimb was done followed by injection of 0.1 ml of dextrose prolotherapy of mixture of 0.1ml of 12.5% dextrose and 0.3 ml of 1% lidocaine (group III``). The animals were received 6 injections of lidocaine and dextrose prolotherapy at 5 days interval (starting from day 0 to day 25). In group II and III, muscle specimens were taken at 5,12 and 28 days and processed for light microscope Results Examination of Group II``A (5 days untreated group) showed intense infiltration of mononucleated inflammatory cells intermingling with dispersed myoblasts and macrophages. Group II`` B (12 days untreated group) showed regenerating myotubes intermingling with mononuclear inflammatory infiltrate and macrophages. Group II``C (28 days untreated group) showed some muscle fibers with peripherally elongated nuclei while others showed centrally vesicular ones. Examination of group III``A (5 day treated group with prolotherapy) showed longitudinal regenerating myofibers with multiple rows of internal vesiculated nuclei. Group III``B (12 days treated group) showed newly formed myofibers with incomplete striations together with well developed newly formed striated longitudinal muscle bundles with peripheral flattened nuclei, group III``C (28 days treated group) showed cross striated muscle fibers with the appearance of elongated vesicular nuclei. Conclusions dextrose prolotherapy was effective in soft tissue healing as it accelerated myoblast proliferation and differentiation

Adipogenic Differentiation Alters Properties of Vascularized Tissue-Engineered Skeletal Muscle.

Advances in the engineering of comprehensive skeletal muscle models in vitro will improve drug screening platforms and can lead to better therapeutic approaches for the treatment of skeletal muscle injuries. To this end, a vascularized tissue-engineered skeletal muscle (TE-SkM) model that includes adipocytes was developed to better emulate the intramuscular adipose tissue that is observed in skeletal muscles of patients with diseases such as diabetes. Muscle precursor cells cultured with and without microvessels derived from adipose tissue (microvascular fragments) were used to generate TE-SkM constructs, with and without a microvasculature, respectively. TE-SkM constructs were treated with adipogenic induction media to induce varying levels of adipogenesis. With a delayed addition of induction media to allow for angiogenesis, a robust microvasculature in conjunction with an increased content of adipocytes was achieved. The augmentation of vascularized TE-SkM constructs with adipocytes caused a reduction in maturation (compaction), mechanical integrity (Young's modulus), and myotube and vessel alignment. An increase in basal glucose uptake was observed in both levels of adipogenic induction, and a diminished insulin-stimulated glucose uptake was associated with the higher level of adipogenic differentiation and the greater number of adipocytes.

In Vivo Printing of Nanoenabled Scaffolds for the Treatment of Skeletal Muscle Injuries.

Extremity skeletal muscle injuries result in substantial disability. Current treatments fail to recoup muscle function, but properly designed and implemented tissue engineering and regenerative medicine techniques can overcome this challenge. In this study, a nanoengineered, growth factor-eluting bioink that utilizes Laponite nanoclay for the controlled release of vascular endothelial growth factor (VEGF) and a GelMA hydrogel for a supportive and adhesive scaffold that can be crosslinked in vivo is presented. The bioink is delivered with a partially automated handheld printer for the in vivo formation of an adhesive and 3D scaffold. The effect of the controlled delivery of VEGF alone or paired with adhesive, supportive, and fibrilar architecture has not been studied in volumetric muscle loss (VML) injuries. Upon direct in vivo printing, the constructs are adherent to skeletal muscle and sustained release of VEGF. The in vivo printing of muscle ink in a murine model of VML injury promotes functional muscle recovery, reduced fibrosis, and increased anabolic response compared to untreated mice. The in vivo construction of a therapeutic-eluting 3D scaffold paves the way for the immediate treatment of a variety of soft tissue traumas.

A Histological Study on the Effect of Dextrose Prolotherapy on Skeletal Muscle Injury in Adult Male Albino Rats.

Background: Skeletal muscle injuries are one of the most common injuries in sport medicine. Many injection protocols have been proposed for the treatment as corticosteroid injection. Recently prolotherapy appears to have a safety profile comparable with other injection procedures. Aim of the work: was to determine the efficacy of dextrose prolotherapy in treatment of skeletal muscle injury in adult male albino rats.Material and methods: Sixty three adult male albino rats were used in the study. They were divided into control (group I). Group II was divided into sham operated group (group IIA) and muscle injury group (group IIB) and group III was divided into lidocaine injected group (group IIIA ) and muscle injury treated with dextrose prolotherapy group (group IIIB). Muscle specimens were taken at 5,12 and 28 days and processed for light microscopeResults: Examination of Group IIB1 (5 days) showed intense infiltration of mononucleated inflammatory cells intermingling with dispersed myoblasts and macrophages. Group IIB2 (12 days) showed regenerating myotubes intermingling with mononuclear inflammatory infiltrate and macrophages. Group IIB3 (28 days) showed some muscle fibers with peripherally elongated nuclei while others showed centrally vesicular ones. Examination of group IIIB1 (5 day treated) showed longitudinal regenerating myofibers with multiple rows of internal vesiculated nuclei. Group IIIB2 (12 days treated) showed newly formed myofibers with incomplete striations together with well developed newly formed striated longitudinal muscle bundles with peripheral flattened nuclei ,group IIIB3 (28 days treated) showed cross striated muscle fibers with the appearance of elongated vesicular nuclei.Conclusion: dextrose prolotherapy was effective in soft tissue healing as it accelerated myoblast proliferation and differentiation.

Biomaterial and stem cell-based strategies for skeletal muscle regeneration.

Adult skeletal muscle can regenerate effectively after mild physical or chemical insult. Muscle trauma or disease can overwhelm this innate capacity for regeneration and result in heightened inflammation and fibrotic tissue deposition resulting in loss of structure and function. Recent studies have focused on biomaterial and stem cell-based therapies to promote skeletal muscle regeneration following injury and disease. Many stem cell populations besides satellite cells are implicated in muscle regeneration. These stem cells include but are not limited to mesenchymal stem cells, adipose-derived stem cells, hematopoietic stem cells, pericytes, fibroadipogenic progenitors, side population cells, and CD133+ stem cells. However, several challenges associated with their isolation, availability, delivery, survival, engraftment, and differentiation have been reported in recent studies. While acellular scaffolds offer a relatively safe and potentially off-the-shelf solution to cell-based therapies, they are often unable to stimulate host cell migration and activity to a level that would result in clinically meaningful regeneration of traumatized muscle. Combining stem cells and biomaterials may offer a viable therapeutic strategy that may overcome the limitations associated with these therapies when they are used in isolation. In this article, we review the stem cell populations that can stimulate muscle regeneration in vitro and in vivo. We also discuss the regenerative potential of combination therapies that utilize both stem cell and biomaterials for the treatment of skeletal muscle injury and disease. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1246-1262, 2019.

Regeneration of injured skeletal muscle after the injury

Muscle injuries are one of the most common traumas occurring in sports. Despite their clinical importance, few clinical studies exist on the treatment of these traumas. Thus, the current treatment recommendations for muscle injuries have either been derived from experimental studies or been tested only empirically. Although non operative treatment should almost always be the 1(st) choice as it results in good functional outcomes in the majority of athletes with muscle injuries, the consequences of failed treatment can be very dramatic, possibly postponing an athlete's return to sports for weeks or even months. Moreover, the recognition of some basic principles of skeletal muscle regeneration and healing processes can considerably help in both avoiding the imminent dangers and accelerating the return to competition. Accordingly, in this review, the authors have summarized the prevailing understanding on the biology of muscle regeneration in hopes of extending these findings to clinical practice in an attempt to propose an evidence-based approach for the diagnosis and optimal treatment of skeletal muscle injuries.

Local cryotherapy minimally impacts the metabolome and transcriptome of human skeletal muscle

Cryotherapy is commonly used in the treatment of skeletal muscle injuries. However, the data to support the use of cryotherapy is inconclusive, and the biochemical etiology of cryotherapy in human skeletal muscle remains largely unknown. We therefore sought to determine how a clinically-relevant dose of cryotherapy would impact the transcriptome and metabolome of skeletal muscle. Eight healthy male subjects (age 24.7 ± 4.5 years, BMI 22.2 ± 1.6) received a 15 minute bout of local cryotherapy, delivered via ice cup massage over the anterolateral thigh. This resulted in an 85% decrease in skin temperature and a predicted 27% reduction in intramuscular temperature. The contralateral side served as a non-treated control. Two hours after cryotherapy, muscle biopsies were obtained to analyze changes in the transcriptome, metabolome, and activation of p38 MAPK, ERK1/2, Akt, and p70S6K proteins. No changes were detected in the transcriptome between control and cooled muscles. Cryotherapy reduced levels of hexose sugars and hypoxanthine by 1.3%, but no statistically different changes were observed in 60 additional metabolites. Overall, no differences in phosphorylated p38 MAPK, ERK1/2, Akt, and p70S6K were observed. A clinically relevant dose of cryotherapy produced negligible acute biochemical and molecular changes in the skeletal muscle of human subjects.

Myoprotective effects of bFGF on skeletal muscle injury in pressure-related deep tissue injury in rats.

BackgroundPressure ulcers (PUs) are a major clinical problem that constitutes a tremendous economic burden on healthcare systems. Deep tissue injury (DTI) is a unique serious type of pressure ulcer that arises in skeletal muscle tissue. DTI arises in part because skeletal muscle tissues are more susceptible than skin to external compression. Unfortunately, few effective therapies are currently available for muscle injury. Basic fibroblast growth factor (bFGF), a potent mitogen and survival factor for various cells, plays a crucial role in the regulation of muscle development and homeostasis. The main purpose of this study was to test whether local administration of bFGF could accelerate muscle regeneration in a rat DTI model.MethodsMale Sprague Dawley (SD) rats (age 12 weeks) were individually housed in plastic cages and a DTI PU model was induced according to methods described before. Animals were randomly divided into three groups: a normal group, a PU group treated with saline, and a PU group treated with bFGF (10 μg/0.1 ml) subcutaneously near the wound.ResultsWe found that application of bFGF accelerated the rate of wound closure and promoted cell proliferation and tissue angiogenesis. In addition, compared to saline administration, bFGF treatment prevented collagen deposition, a measure of fibrosis, and up-regulated the myogenic marker proteins MyHC and myogenin, suggesting bFGF promoted injured muscle regeneration. Moreover, bFGF treatment increased levels of myogenesis-related proteins p-Akt and p-mTOR.ConclusionsOur findings show that bFGF accelerated injured skeletal muscle regeneration through activation of the PI3K/Akt/mTOR signaling pathway and suggest that administration of bFGF is a potential therapeutic strategy for the treatment of skeletal muscle injury in PUs.Electronic supplementary materialThe online version of this article (doi:10.1186/s41038-016-0051-y) contains supplementary material, which is available to authorized users.

Effect of low-level phototherapy on delayed onset muscle soreness: a systematic review and meta-analysis.

To determine the effectiveness of low-level phototherapy (i.e. light-emitting diode therapy [LEDtherapy] or light amplification by stimulated emission of radiation therapy [LASERtherapy]) on pain, skeletal muscle injury (creatine kinase [CK] levels and edema) and skeletal muscle function (range of movement and strength) in people undergoing an exercise protocol. (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PEDro, SciELO and LILACS up to May 2014), we included randomized controlled trials, quasi-randomized controlled trials and crossover studies in which study participants were allocated to receive either low-level phototherapy or placebo treatment. Phototherapy should have been applied in a single treatment session, either before or after an exercise protocol. We identified 15 studies involving 317 participants. Meta-analyses were limited by substantial heterogeneity. Compared to the placebo group, reduction in CK levels was only observed when LASERtherapy was applied before an exercise protocol (standardized mean difference = -0.66; 95% CI = -1.30, -0.02). No between-group difference in edema, range of movement and strength were detected when phototherapy was applied before or after exercise. Evidence from this review suggests that low-level phototherapy may not have substantial effect in the treatment of skeletal muscle injury and pain caused by exercise. Definitive conclusions are limited due to the small number of included studies in each meta-analysis, disparities across the included studies and small sample sizes.

Effects of low-level laser therapy on skeletal muscle repair: a systematic review.

A review of the literature was performed to demonstrate the most current applicability of low-level laser therapy (LLLT) for the treatment of skeletal muscle injuries, addressing different lasers, irradiation parameters, and treatment results in animal models. Searches were performed in the PubMed/MEDLINE, SCOPUS, and SPIE Digital Library databases for studies published from January 2006 to August 2013 on the use of LLLT for the repair of skeletal muscle in any animal model. All selected articles were critically appraised by two independent raters. Seventeen of the 36 original articles on LLLT and muscle injuries met the inclusion criteria and were critically evaluated. The main effects of LLLT were a reduction in the inflammatory process, the modulation of growth factors and myogenic regulatory factors, and increased angiogenesis. The studies analyzed demonstrate the positive effects of LLLT on the muscle repair process, which are dependent on irradiation and treatment parameters. The findings suggest that LLLT is an excellent therapeutic resource for the treatment of skeletal muscle injuries in the short-term.

Effect of Low Power Laser Irradiation on the Ability of Cell Growth and Myogenic Differentiation of Myoblasts CulturedIn Vitro

As a therapeutic modality, low power laser irradiation (LPLI) has been used clinically in the treatment of skeletal muscle injuries and other myopathic conditions, but the cellular and molecular mechanisms attributed to this therapy were still unclear. Myoblasts are a type of myogenic stem cells quiescence in mature skeletal muscle fibers and are considered as the source cells during the regenerating process. The purpose of this paper was to investigate the effects of LPLI on the proliferation and myogenic differentiation of the cultured myoblasts and to find out the major candidates responsible for LPLI-induced muscle regenerationin vivo. In this study, primary rat myoblasts were exposed to helium-neon (He-Ne) laser. Cell proliferation, differentiation, and the cellular responses to LPLI were monitored by using morphological observation and molecular biological methods. It was found that LPLI at a certain fluence could increase the cell growth potential for myoblasts and further induce more cells entering into S phase of the mitotic cycle as indicated by high levels of bromodeoxyuridine (BrdU) incorporation, while at the same time inhibiting theirin vitrodifferentiation and decreasing the expression of myogenic regulatory genes to a certain extent. Taken together, these results provide experimental evidence for the clinical applications of LPLI in regenerating skeletal muscle.

Improvement of Contraction Force in Injured Skeletal Muscle after Autologous Mesenchymal Stroma Cell Transplantation Is Accompanied by Slow to Fast Fiber Type Shift

SummaryBackground: Skeletal muscle trauma leads to severe functional deficits, which cannot be addressed by current treatment options. Previous investigation could show the efficacy of a local transplantation (TX) of mesenchymal stroma cells (MSCs) for the therapy of muscle injury. Underlying mechanisms remain to be elucidated. The aim of the present work was to characterize the fiber composition changes following MSC-TX after open crush injury. Methods: 20 male SD rats received an open crush trauma of the left soleus muscle. 2.5 × 10⁶ autologous MSCs were transplanted into the crushed soleus muscle of 10 animals 7 days after trauma (group 1, n = 10). Control animals received an injection of saline solution (group 2, n = 10). Histologic analysis of fibrosis, fiber type composition, and muscle force measurements were performed 28 days after trauma. Results: MSC-TX improved muscle force significantly (fast-twitch, treated: 0.76 (0.51-1.15), untreated: 0.45 (0.32-0.73); p = 0.01). Tetanic stimulation resulted in a significant increase of force development (treated: 0.63 (0.4-1.21), untreated: 0.34 (0.16-0.48); p = 0.04). Histological analyses showed no differences in the amount of fibrotic tissue (treated vs. untreated, p = 0.42). A shift towards fastMHC-positive fibers was observed following MSC-TX (treated vs. untreated; p = 0.01 (mm²) or 0.007 (%)). Conclusion: This study demonstrated an effect of locally administered MSCs in the treatment of skeletal muscle injuries on a structural level. For the first time a fiber type shift towards fastMHC following MSC-TX after crush injury could be demonstrated and related to MSC-TX. These results might open the discussion of an alternative mode of action of MSCs in tissue regeneration.

Chondroitin Sulfate Is a Crucial Determinant for Skeletal Muscle Development/Regeneration and Improvement of Muscular Dystrophies

Skeletal muscle formation and regeneration require myoblast fusion to form multinucleated myotubes or myofibers, yet their molecular regulation remains incompletely understood. We show here that the levels of extra- and/or pericellular chondroitin sulfate (CS) chains in differentiating C2C12 myoblast culture are dramatically diminished at the stage of extensive syncytial myotube formation. Forced down-regulation of CS, but not of hyaluronan, levels enhanced myogenic differentiation in vitro. This characteristic CS reduction seems to occur through a cell-autonomous mechanism that involves HYAL1, a known catabolic enzyme for hyaluronan and CS. In vivo injection of a bacterial CS-degrading enzyme boosted myofiber regeneration in a mouse cardiotoxin-induced injury model and ameliorated dystrophic pathology in mdx muscles. Our data suggest that the control of CS abundance is a promising new therapeutic approach for the treatment of skeletal muscle injury and progressive muscular dystrophies.

Low-level laser therapy (808 nm) contributes to muscle regeneration and prevents fibrosis in rat tibialis anterior muscle after cryolesion

Muscle regeneration is a complex phenomenon, involving replacement of damaged fibers by new muscle fibers. During this process, there is a tendency to form scar tissue or fibrosis by deposition of collagen that could be detrimental to muscle function. New therapies that could regulate fibrosis and favor muscle regeneration would be important for physical therapy. Low-level laser therapy (LLLT) has been studied for clinical treatment of skeletal muscle injuries and disorders, even though the molecular and cellular mechanisms have not yet been clarified. The aim of this study was to evaluate the effects of LLLT on molecular markers involved in muscle fibrosis and regeneration after cryolesion of the tibialis anterior (TA) muscle in rats. Sixty Wistar rats were randomly divided into three groups: control, injured TA muscle without LLLT, injured TA muscle treated with LLLT. The injured region was irradiated daily for four consecutive days, starting immediately after the lesion using an AlGaAs laser (808 nm, 30 mW, 180 J/cm(2); 3.8 W/cm(2), 1.4 J). The animals were sacrificed on the fourth day after injury. LLLT significantly reduced the lesion percentage area in the injured muscle (p<0.05), increased mRNA levels of the transcription factors MyoD and myogenin (p<0.01) and the pro-angiogenic vascular endothelial growth factor (p<0.01). Moreover, LLLT decreased the expression of the profibrotic transforming growth factor TGF-β mRNA (p<0.01) and reduced type I collagen deposition (p<0.01). These results suggest that LLLT could be an effective therapeutic approach for promoting skeletal muscle regeneration while preventing tissue fibrosis after muscle injury.

Intra-Arterial MSC Transplantation Restores Functional Capacity After Skeletal Muscle Trauma

Introduction:Skeletal muscle trauma leads to severe functional deficits, which cannot be addressed by current treatment options. Our group could show the efficacy of local transplantation of mesenchymal stroma cells (MSCs) for the treatment of injured muscles. While local application of MSCs has proven to be effective, we hypothesized that a selective intra-arterial transplantation would lead to a better distribution of the cells and so improved physiological recovery of muscle function.Materials and Methodology:18 female Sprague Dawley rats received an open crush trauma of the left soleus muscle. Autologous MSC were transduced using dsCOP-GFP and 2.5 x 106cells were transplanted into the femoral artery of 9 animals one week after trauma. Control animals (n=9) received a saline injection. Cell tracking, analysis of tissue fibrosis and muscle force measurements were performed after 3 weeks.Results:Systemic MSC-therapy improved the muscle force significantly compared to control (fast twitch: 82.4%, tetany: 61.6%, p = 0.02). The histological analysis showed no differences in the quantity of fibrotic tissue. Histological examination revealed no cells in the traumatized muscle tissue 21 days after transplantation.Conclusions:The present study demonstrated an effect of systemically administered MSCs in the treatment of skeletal muscle injuries. For possible future therapeutic approaches a systemic application of MSCs seems to present an alternative to a local administration. Such systemic treatment would be preferable since it allows functional improvement and possible cellular concentration at injury sites that are not easily accessible

Treatment of skeletal muscle injury: a review.

Skeletal muscle injuries are the most common sports-related injuries and present a challenge in primary care and sports medicine. Most types of muscle injuries would follow three stages: the acute inflammatory and degenerative phase, the repair phase and the remodeling phase. Present conservative treatment includes RICE (rest, ice, compression, elevation), nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy. However, if use improper, NSAIDs may suppress an essential inflammatory phase in the healing of injured skeletal muscle. Furthermore, it remains controversial whether or not they have adverse effects on the healing process or on the tensile strength. However, several growth factors might promote the regeneration of injured skeletal muscle, many novel treatments have involved on enhancing complete functional recovery. Exogenous growth factors have been shown to regulate satellite cell proliferation, differentiation and fusion in myotubes in vivo and in vitro, TGF-β1 antagonists behave as inhibitors of TGF-β1. They prevent collagen deposition and block formation of muscle fibrosis, so that a complete functional recovery can be achieved.