Postinjury Exercise and Platelet-Rich Plasma Therapies Improve Skeletal Muscle Healing in Rats But Are Not Synergistic When Combined

2017 ◽  
Vol 45 (9) ◽  
pp. 2131-2141 ◽  
Author(s):  
Paola Contreras-Muñoz ◽  
Joan Ramon Torrella ◽  
Xavier Serres ◽  
David Rizo-Roca ◽  
Meritxell De la Varga ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Beneficial Effect ◽  
Muscle Injury ◽  
Platelet Rich Plasma ◽  
Healing Process ◽  
Scar Formation ◽  
Muscle Injuries ◽  
Daily Exercise ◽  
Active Rehabilitation

Background: Skeletal muscle injuries are the most common sports-related injury and a major concern in sports medicine. The effect of platelet-rich plasma (PRP) injections on muscle healing is still poorly understood, and current data are inconclusive. Purpose: To evaluate the effects of an ultrasound-guided intramuscular PRP injection, administered 24 hours after injury, and/or posttraumatic daily exercise training for 2 weeks on skeletal muscle healing in a recently established rat model of skeletal muscle injury that highly mimics the muscle trauma seen in human athletes. Study Design: Controlled laboratory study. Methods: A total of 40 rats were assigned to 5 groups. Injured rats (medial gastrocnemius injury) received a single PRP injection (PRP group), daily exercise training (Exer group), or a combination of a single PRP injection and daily exercise training (PRP-Exer group). Untreated and intramuscular saline–injected animals were used as controls. Muscle force was determined 2 weeks after muscle injury, and muscles were harvested and evaluated by means of histological assessment and immunofluorescence microscopy. Results: Both PRP (exhibiting 4.8-fold higher platelet concentration than whole blood) and exercise training improved muscle strength (maximum tetanus force, TetF) in approximately 18%, 20%, and 30% of rats in the PRP, PRP-Exer, and Exer groups, respectively. Specific markers of muscle regeneration (developmental myosin heavy chain, dMHC) and scar formation (collagen I) demonstrated the beneficial effect of the tested therapies in accelerating the muscle healing process in rats. PRP and exercise treatments stimulated the growth of newly formed regenerating muscle fibers (1.5-, 2-, and 2.5-fold increase in myofiber cross-sectional area in PRP, PRP-Exer, and Exer groups, respectively) and reduced scar formation in injured skeletal muscle (20%, 34%, and 41% of reduction in PRP, PRP-Exer, and Exer groups, respectively). Exercise-treated muscles (PRP-Exer and Exer groups) had significantly reduced percentage of dMHC-positive regenerating fibers (35% and 47% decrease in dMHC expression, respectively), indicating that exercise therapies accelerated the muscle healing process witnessed by the more rapid replacement of the embryonic-developmental myosin isoform by mature muscle myosin isoforms. Conclusion: Intramuscular PRP injection and, especially, treadmill exercise improve histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries in athletes. However, there was not a synergistic effect when both treatments were combined, suggesting that PRP does not add any beneficial effect to exercise-based therapy in the treatment of injured skeletal muscle. Clinical Relevance: This study demonstrates the efficacy of an early active rehabilitation protocol or single intramuscular PRP injection on muscle recovery. The data also reveal that the outcome of the early active rehabilitation is adversely affected by the PRP injection when the two therapies are combined, and this could explain why PRP therapies have failed in randomized clinical trials where the athletes have adhered to postinjection rehabilitation protocols based on the principle of early, active mobilization.

scholarly journals Tissue Engineered Strategies for Skeletal Muscle Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Umile Giuseppe Longo ◽  
Mattia Loppini ◽  
Alessandra Berton ◽  
Filippo Spiezia ◽  
Nicola Maffulli ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Muscle Injury ◽  
Platelet Rich Plasma ◽  
Residual Effects ◽  
Current Therapy ◽  
Muscle Injuries ◽  
Cell Based Therapy ◽  
Proliferation And Differentiation ◽  
Inflammatory Drugs

Skeletal muscle injuries are common in athletes, occurring with direct and indirect mechanisms and marked residual effects, such as severe long-term pain and physical disability. Current therapy consists of conservative management including RICE protocol (rest, ice, compression, and elevation), nonsteroidal anti-inflammatory drugs, and intramuscular corticosteroids. However, current management of muscle injuries often does not provide optimal restoration to preinjury status. New biological therapies, such as injection of platelet-rich plasma and stem-cell-based therapy, are appealing. Although some studies support PRP application in muscle-injury management, reasons for concern persist, and further research is required for a standardized and safe use of PRP in clinical practice. The role of stem cells needs to be confirmed, as studies are still limited and inconsistent. Further research is needed to identify mechanisms involved in muscle regeneration and in survival, proliferation, and differentiation of stem cells.

Muscle Precursor Cells Enhance Functional Muscle Recovery and Show Synergistic Effects With Postinjury Treadmill Exercise in a Muscle Injury Model in Rats

2021 ◽  
Vol 49 (4) ◽  
pp. 1073-1085
Author(s):  
Paola Contreras-Muñoz ◽  
Joan Ramón Torrella ◽  
Vanessa Venegas ◽  
Xavier Serres ◽  
Laura Vidal ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Therapy ◽  
Muscle Injury ◽  
Vehicle Group ◽  
Muscle Injuries ◽  
Muscle Recovery ◽  
Injury Model ◽  
Force Recovery ◽  
Active Rehabilitation ◽  
Muscle Precursor Cells

Background: Skeletal muscle injuries represent a major concern in sports medicine. Cell therapy has emerged as a promising therapeutic strategy for muscle injuries, although the preclinical data are still inconclusive and the potential clinical use of cell therapy has not yet been established. Purpose: To evaluate the effects of muscle precursor cells (MPCs) on muscle healing in a small animal model. Study Design: Controlled laboratory study. Methods: A total of 27 rats were used in the study. MPCs were isolated from rat (n = 3) medial gastrocnemius muscles and expanded in primary culture. Skeletal muscle injury was induced in 24 rats, and the animals were assigned to 3 groups. At 36 hours after injury, animals received treatment based on a single ultrasound-guided MPC (105 cells) injection (Cells group) or MPC injection in combination with 2 weeks of daily exercise training (Cells+Exercise group). Animals receiving intramuscular vehicle injection were used as controls (Vehicle group). Muscle force was determined 2 weeks after muscle injury, and muscles were collected for histological and immunofluorescence evaluation. Results: Red fluorescence–labeled MPCs were successfully transplanted in the site of the injury by ultrasound-guided injection and were localized in the injured area after 2 weeks. Transplanted MPCs participated in the formation of regenerating muscle fibers as corroborated by the co-localization of red fluorescence with developmental myosin heavy chain (dMHC)–positive myofibers by immunofluorescence analysis. A strong beneficial effect on muscle force recovery was detected in the Cells and Cells+Exercise groups (102.6% ± 4.0% and 101.5% ± 8.5% of maximum tetanus force of the injured vs healthy contralateral muscle, respectively) compared with the Vehicle group (78.2% ± 5.1%). Both Cells and Cells+Exercise treatments stimulated the growth of newly formed regenerating muscles fibers, as determined by the increase in myofiber cross-sectional area (612.3 ± 21.4 µm2 and 686.0 ± 11.6 µm2, respectively) compared with the Vehicle group (247.5 ± 10.7 µm2), which was accompanied by a significant reduction of intramuscular fibrosis in Cells and Cells+Exercise treated animals (24.2% ± 1.3% and 26.0% ± 1.9% of collagen type I deposition, respectively) with respect to control animals (40.9% ± 4.1% in the Vehicle group). MPC treatment induced a robust acceleration of the muscle healing process as demonstrated by the decreased number of dMHC-positive regenerating myofibers (enhanced replacement of developmental myosin isoform by mature myosin isoforms) (4.3% ± 2.6% and 4.1% ± 1.5% in the Cells and Cells+Exercise groups, respectively) compared with the Vehicle group (14.8% ± 13.9%). Conclusion: Single intramuscular administration of MPCs improved histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries. Cell therapy showed a synergistic effect when combined with an early active rehabilitation protocol in rats, which suggests that a combination of treatments can generate novel therapeutic strategies for the treatment of human skeletal muscle injuries. Clinical Relevance: Our study demonstrates the strong beneficial effect of MPC transplant and the synergistic effect when the cell therapy is combined with an early active rehabilitation protocol for muscle recovery in rats; this finding opens new avenues for the development of effective therapeutic strategies for muscle healing and clinical trials in athletes undergoing MPC transplant and rehabilitation protocols.

Platelet-Rich Plasma Releasate Promotes Regeneration and Decreases Inflammation and Apoptosis of Injured Skeletal Muscle

2018 ◽  
Vol 46 (8) ◽  
pp. 1980-1986 ◽  
Author(s):  
Wen-Chung Tsai ◽  
Tung-Yang Yu ◽  
Gwo-Jyh Chang ◽  
Li-Ping Lin ◽  
Miao-Sui Lin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Apoptosis ◽  
Muscle Injury ◽  
Animal Studies ◽  
Platelet Rich Plasma ◽  
Healing Process ◽  
Sprague Dawley ◽  
And Migration

Background: Platelet-rich plasma (PRP) contains various cytokines and growth factors that may be beneficial to the healing process of injured muscle. Based on the authors’ previous study, PRP releasate can promote proliferation and migration of skeletal muscle cells in vitro, so animal studies are performed to support the use of PRP to treat muscle injury in vivo. Purpose: To investigate the effect of PRP releasate on regeneration of injured muscle, as well as its effect on inflammatory reaction and cell apoptosis, in the early stages of the muscle-healing process. Study Design: Controlled laboratory study. Methods: The gastrocnemius muscles of Sprague-Dawley rats were injured by partial transverse incision and then treated with PRP releasate. Hematoxylin and eosin stain was used to evaluate the healing process of injured muscle at 2, 5, and 10 days after injury. TUNEL assay was used to evaluate the cell apoptosis of injured muscle after PRP releasate treatment. Immunohistochemistry was used to stain the CD68-positive cells during the healing process. Muscle contractile properties, including fast-twitch and tetanic strength, were evaluated by electric stimulation. Results: The results revealed that PRP releasate treatment could enhance the muscle-healing process and decrease CD68-positive cells and apoptotic cells. Furthermore, the tetanic strength was significantly higher in injured muscle treated with PRP releasate. Conclusion: In conclusion, PRP releasate could enhance the healing process of injured muscle and decrease inflammatory cell infiltration as well as cell apoptosis. Clinical Relevance: PRP promotes skeletal muscle healing in association with decreasing inflammation and apoptosis of injured skeletal muscle. These findings provide in vivo evidence to support the use of PRP to treat muscle injury.

scholarly journals Losartan no tratamento das lesões musculares

2021 ◽  
Vol 12 (2) ◽  
pp. 26-28
Author(s):  
Filipe Cabral ◽  
◽  
Pedro Barata ◽  
Keyword(s):  
Functional Capacity ◽  
Sports Medicine ◽  
Muscle Injury ◽  
Healing Process ◽  
Repair Process ◽  
Muscle Repair ◽  
Muscle Injuries ◽  
Fibrotic Scar ◽  
Tgf Β1 ◽  
Injury Recurrence

Muscle injuries are very common in sports medicine. Frequently the muscle repair process ends in the formation of a fibrotic scar, that not only limits the complete functional recovery, but also increases the likelihood of injury recurrence. TGF-β1 is the main profibrogenic factor involved in this healing process. By blocking its activity, Losartan has proven it efficacy in reducing fibrosis and increasing regenerative and functional capacity post muscle injury. Therefore, its use should be considered as an alternative therapeutic for this kind of injuries.

Antifibrotic effects of suramin in injured skeletal muscle after laceration

2003 ◽  
Vol 95 (2) ◽  
pp. 771-780 ◽  
Author(s):  
Yi-Sheng Chan ◽  
Yong Li ◽  
William Foster ◽  
Takashi Horaguchi ◽  
George Somogyi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Regeneration ◽  
Sports Medicine ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Healing Process ◽  
Muscle Injuries

Muscle injuries are very common in traumatology and sports medicine. Although muscle tissue can regenerate postinjury, the healing process is slow and often incomplete; complete recovery after skeletal muscle injury is hindered by fibrosis. Our studies have shown that decreased fibrosis could improve muscle healing. Suramin has been found to inhibit transforming growth factor (TGF)-β1 expression by competitively binding to the growth factor receptor. We conducted a series of tests to determine the antifibrotic effects of suramin on muscle laceration injuries. Our results demonstrate that suramin (50 μg/ml) can effectively decrease fibroblast proliferation and fibrotic-protein expression (α-smooth muscle actin) in vitro. In vivo, direct injection of suramin (2.5 mg) into injured murine muscle resulted in effective inhibition of muscle fibrosis and enhanced muscle regeneration, which led to efficient functional muscle recovery. These results support our hypothesis that prevention of fibrosis could enhance muscle regeneration, thereby facilitating more efficient muscle healing. This study could significantly contribute to the development of strategies to promote efficient muscle healing and functional recovery.

Platelet-Rich Plasma Enhances Equine Skeletal Muscle Regeneration in a Bupivacaine-Induced Muscle Injury Model

2021 ◽  
Author(s):  
Kentaro Fukuda ◽  
Taisuke Kuroda ◽  
Norihisa Tamura ◽  
Hiroshi Mita ◽  
Hirofumi Miyata ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Muscle Injury ◽  
Platelet Rich Plasma ◽  
Skeletal Muscle Regeneration ◽  
Injury Model

scholarly journals A Histoarchitectural Approach to Skeletal Muscle Injury: Searching for a Common Nomenclature

2020 ◽  
Vol 8 (3) ◽  
pp. 232596712090909 ◽  
Author(s):  
◽  
Ramon Balius ◽  
Marc Blasi ◽  
Carles Pedret ◽  
Xavier Alomar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Connective Tissue ◽  
Muscle Injury ◽  
Muscle Injuries ◽  
Macroscopic Anatomy ◽  
Skeletal Muscle Injury ◽  
Tissue Structures ◽  
Definition Of

In recent years, different classifications for muscle injuries have been proposed based on the topographic location of the injury within the bone-tendon-muscle chain. We hereby propose that in addition to the topographic classification of muscle injuries, a histoarchitectonic (description of the damage to connective tissue structures) definition of the injury be included within the nomenclature. Thus, the nomenclature should focus not only on the macroscopic anatomy but also on the histoarchitectonic features of the injury.

scholarly journals Influence of Platelet Rich Plasma on the Skeletal Muscle Fibrosis after Limb Lengthening in Mice

2020 ◽  
Vol 5 (4) ◽  
pp. 2473011420S0046
Author(s):  
Ichiro Tonogai ◽  
Ichiro Tonogai
Keyword(s):  
Skeletal Muscle ◽  
Gastrocnemius Muscle ◽  
Platelet Rich Plasma ◽  
Healing Process ◽  
Limb Lengthening ◽  
Major Constituent ◽  
Tibial Osteotomy ◽  
Muscle Fibrosis ◽  
Skeletal Muscle Fibrosis ◽  
Phosphate Buffered Saline

Category: Basic Sciences/Biologics Introduction/Purpose: Skeletal muscle fibrosis induced by the increase of collagen occurs after limb lengthening which is also called distraction osteogenesis. Although there are studies about influence of platelet rich plasma (PRP) on tissues healing process, its effectiveness is still controversial. The aim of this study was to examine whether PRP decreased the skeletal muscle fibrosis induced by limb lengthening. Methods: Tibial osteotomy was done to 8-week-old wild type mice. Tibia was lengthened at a rate of 0.42 mm/day during 2 weeks, launching 1 week after tibial osteotomy. Just after lengthening completed (3 weeks after tibial osteotomy), PRP was injected into the gastrocnemius muscle (PRP group). As a sham group, phosphate buffered saline (PBS) was injected into the gastrocnemius muscle (non-PRP group). The gastrocnemius (GC) muscles were taken and analyzed at 4, 6, 8 and 10 weeks after tibial osteotomy. Results: The fibrotic area of the GC muscles in the both groups increased at 4 weeks after tibial osteotomy in histological analysis (Figure). Then, it gradually decreased at 6, 8, and 10 weeks after tibial osteotomy. There were no significant differences between the both groups at 6, 8, and 10 weeks after tibial osteotomy. Hydroxyproline, which was a major constituent of collagen, increased in the non-PRP and PRP groups by limb lengthening as well. However, significant changes were not found between the both groups at all any points. Conclusion: At first, we anticipated that PRP should reduce the skeletal muscle fibrosis after limb lengthening significantly. But our results implied that PRP did not decrease the skeletal muscle fibrosis induced by limb lengthening.

Scar formation after skeletal muscle injury

1986 ◽  
Vol 104 (6) ◽  
pp. 366-370 ◽  
Author(s):  
M. Lehto ◽  
M. J�rvinen ◽  
O. Nelimarkka
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Scar Formation ◽  
Skeletal Muscle Injury
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