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De Castro Pochini A, Bueno AC, Mattos RAC, Ejnisman B, Cohen M. Case series: effects of platelet-rich plasma (PRP) on the recovery of bilateral muscle injuries after removal of semitendinosus and gracilis grafts in bilateral anterior cruciate ligament (ACL) reconstruction. J Surg Case Rep 2025; 2025:rjae641. [PMID: 39931035 PMCID: PMC11808801 DOI: 10.1093/jscr/rjae641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Accepted: 11/27/2024] [Indexed: 02/13/2025] Open
Abstract
To assess the healing of acute bilateral muscle injury in cases of bilateral anterior cruciate ligament reconstruction using platelet-rich plasma (PRP) after tendon graft removal. The study included 12 cases of bilateral anterior cruciate ligament reconstruction using semitendinosus and gracilis (STG) grafts. In the right knee, the STG graft was removed, and saline solution was applied; in the left knee, the graft was removed, and PRP was applied. Patients were evaluated using the visual analog scale, pre and postoperative isokinetic tests (5 months), and muscle area analysis. A slight difference in results was observed at 15 and 30 days on the PRP-treated side, but there was no variation in circumference and muscle strength. Due to the small sample size, the study will be continued to increase the number of cases, aiming for the publication of results.
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Affiliation(s)
- Alberto De Castro Pochini
- Department of Orthopedics and Traumatology, UNIFESP, RUA BOTUCATU, 740-1o. ANDARVILA CLEMENTINO – SP, CEP 04023-900, Sao Paulo, Brazil
- Sports Medicine and Physical Activity Discipline, EPM/UNIFESP, R. Estado de Israel, 713 - Vila Clementino, São Paulo - SP, 04022-002, Brazil
- Knee Group, SBCJ (Hospital Novo Atibaia), R. Pedro Cunha, 145 - Vila Santista, Atibaia - SP, 12941-020, Sao Paulo, Brazil
| | - Anna Carolina Bueno
- Knee Surgery, Hospital Novo Atibaia, R. Pedro Cunha, 145 - Vila Santista, Atibaia - SP, 12941-020, Brazil
- Center for Sports Traumatology - CETE, Federal University of São Paulo - UNIFESP, R. Estado de Israel, 713 - Vila Clementino, São Paulo - SP, 04022-002, Brazil
- Medical Residency in Orthopedics and Traumatology, Santa Casa de Misericórdia de São Paulo, R. Dr. Cesário Mota Júnior, 112 - Vila Buarque, São Paulo - SP, 01221-010, Brazil
| | - Roque Antonio Cury Mattos
- Orthopedic and Traumatology, Hospital São Francisco de Assis, R. 9-A, 110 - St. Aeroporto, Goiânia - GO, 74075-250, Brazil
- Knee Surgery, Orthopedics, and Traumatology, Hospital Novo Atibaia, R. Pedro Cunha, 145 - Vila Santista, Atibaia - SP, 12941-020, Brazil
| | - Benno Ejnisman
- Sports Traumatology Section of the Department of Orthopedics and Traumatology, UNIFESP/EPM, R. Estado de Israel, 713 - Vila Clementino, São Paulo - SP, 04022-002, Brazil
- Sports Medicine and Physical Activity Discipline of the Department of Orthopedics and Traumatology, UNIFESP/EPM, R. Estado de Israel, 713 - Vila Clementino, São Paulo - SP, 04022-002, Brazil
| | - Moises Cohen
- Department of Orthopedics and Traumatology, Paulista School of Medicine, Translational Surgery Postgraduate Program at UNIFESP (Medicine III, Capes grade 6), Postgraduate Program in Health Sciences at Hospital Israelita Albert Einstein, Rua Pedro de Toledo, 650 - Vila Clementino, São Paulo - SP, 04039-002, Brazil
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Rajkovic CJ, Merckling ML, Lee AW, Subah G, Malhotra A, Thomas ZD, Zeller SL, Wainwright JV, Kinon MD. Conservative management of spinal pathology with autologous conditioned serum: A systematic review of the literature. World J Orthop 2024; 15:870-881. [PMID: 39318497 PMCID: PMC11417626 DOI: 10.5312/wjo.v15.i9.870] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 08/22/2024] [Accepted: 08/28/2024] [Indexed: 09/12/2024] Open
Abstract
BACKGROUND Chronic inflammatory pain is associated with increased expression of interleukin (IL)-1, an inflammatory cytokine, and activity on its receptor (IL-1R). In response, the body produces IL-1R antagonist (IL-1Ra) to reduce this signaling. Autologous conditioned serum (ACS) is the only biologic therapy for spinal pathologies that enhances the action of endogenous IL-1Ra reserves to improve symptoms. This systematic review investigates the effectiveness of ACS in treating pain and disability caused by spinal pathologies.
AIM To evaluate the use of ACS as a conservative management option for spinal pathology.
METHODS A systematic review of PubMed/Medline was performed to identify studies investigating administration of ACS for treatment of any spinal pathology.
RESULTS Six articles were included, comprising 684 patients treated with epidural (n = 133) or transforaminal (n = 551) ACS injections. Patients had an average age of 54.0 years with slight female predominance (53.2%). The lumbar spine was most commonly treated, with 567 patients (82.9%) receiving injections for lumbar radiculopathy (n = 67), degenerative disc disease (DDD) (n = 372), or spinal stenosis (n = 128); cervical injections were performed in 109 patients (15.9%). Mean (SD) follow-up was 21.7 (4.8) weeks from first ACS injection. All studies investigating mechanical lumbar and lumbar or cervical radicular pain reported significant pain reduction at final follow-up compared to baseline. ACS achieved comparable or superior results to lumbar epidural steroid injections. Adverse events were reported in 21 patients (3.1%), with no serious adverse events.
CONCLUSION ACS injection is a safe and effective intervention for pain reduction in many spinal pathologies, including cervical and lumbar radiculopathies.
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Affiliation(s)
- Christian J Rajkovic
- Department of Neurosurgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Matthew L Merckling
- Department of Neurosurgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Alyssa W Lee
- Department of Neurosurgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Galadu Subah
- Department of Neurosurgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Aryan Malhotra
- Department of Neurosurgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Zachary D Thomas
- Department of Neurosurgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Sabrina L Zeller
- Department of Neurosurgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - John V Wainwright
- Department of Neurosurgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Merritt D Kinon
- Department of Neurosurgery, Westchester Medical Center, Valhalla, NY 10595, United States
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Ravikumar C, Sasikala B, Krishnakumar Raja VB, Elavenil P. Evaluation of the efficacy of autologous conditioned serum versus dextrose prolotherapy in internal derangement of the TMJ - A pilot study. J Craniomaxillofac Surg 2024; 52:477-483. [PMID: 38368212 DOI: 10.1016/j.jcms.2024.01.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 11/19/2023] [Accepted: 01/16/2024] [Indexed: 02/19/2024] Open
Abstract
It was the aim of the study to compare the effectiveness of autologous conditioned serum (ACS) and dextrose prolotherapy (DP) solutions, in treating patients with TMJ internal derangement (ID). 24 participants with TMJ ID (Wilkes II-V) were recruited and randomized into study and control groups, with 12 patients each, treated with IA injection of ACS and DP, respectively. Pain, mouth opening, joint sounds, and jaw deviation were evaluated, with patients reviewed at 2 weeks, 1 month, and 2 months intervals. Based on the nature of the variables, appropriate descriptive statistics and statistical tests were applied. The pain score was zero in the study group after 2 months of treatment, which was statistically significant (p = 0.006). Deviation was also significantly reduced (p < 0.001) and mouth opening significantly improved (p = 0.004) in the ACS-treated patients. ACS demonstrated superiority over DP in the management of TMJ dysfunction. Therefore, ACS can be considered an ideal, minimally invasive treatment option for TMJ ID. Clinical trial registry number: (CTRI/2021/10/037043).
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Affiliation(s)
- C Ravikumar
- Department of Oral and Maxillofacial Surgery, SRM Dental College and Hospital, Ramapuram, Chennai, India
| | - B Sasikala
- Department of Oral and Maxillofacial Surgery, SRM Dental College and Hospital, Ramapuram, Chennai, India.
| | - V B Krishnakumar Raja
- Department of Oral and Maxillofacial Surgery, SRM Dental College and Hospital, Ramapuram, Chennai, India
| | - P Elavenil
- Department of Oral and Maxillofacial Surgery, SRM Dental College and Hospital, Ramapuram, Chennai, India
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Damjanov N, Zekovic A. Intra-articular autologous conditioned serum and triamcinolone injections in patients with knee osteoarthritis: a controlled, randomized, double-blind study. J Int Med Res 2023; 51:3000605231203851. [PMID: 37818751 PMCID: PMC10566289 DOI: 10.1177/03000605231203851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 09/11/2023] [Indexed: 10/13/2023] Open
Abstract
OBJECTIVE This study was performed to assess the impact of autologous conditioned serum (ACS) when added to preceding intra-articular glucocorticoid therapy on pain, function, and quality of life outcomes over 24 weeks. METHODS In this single-center, randomized controlled trial involving 40 patients with advanced knee osteoarthritis (Kellgren-Lawrence grades III and IV), ACS or saline placebo was injected after 40 mg triamcinolone acetonide (TA) intra-articular injection. Numerical rating scale (NRS) pain scores and Knee Injury and Osteoarthritis Outcome Score (KOOS) assessments were conducted at baseline and at weeks 3, 6, 12, and 24. The primary endpoint was the change in KOOS Pain at 24 weeks. Patient safety events were also monitored. RESULTS At week 24, TA + ACS significantly improved KOOS Pain, Symptoms, Activities of Daily Living, Quality of Life, and KOOS Sport scores. TA + ACS also outperformed TA + placebo in NRS pain scores (average and maximum intensity) at week 24 and NRS pain score (at rest) at weeks 12 and 24. The TA injection followed by ACS or placebo was well-tolerated. CONCLUSION ACS adds long-term pain relief and functional improvement to the short-term pain relief provided by glucocorticoids.
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Affiliation(s)
- Nemanja Damjanov
- University of Belgrade School of Medicine, Institute of Rheumatology, Belgrade, Serbia
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Godek P, Szczepanowska-Wolowiec B, Golicki D. Comparison of Analgesic Efficacy between Epidural and Perineural Administration of Autologous Conditioned Serum in the Conservative Treatment of Low Back Pain Due to Lumbar Degenerative Disc Disease: A Randomized, Open-Label, Controlled Clinical Trial. Brain Sci 2023; 13:brainsci13050749. [PMID: 37239221 DOI: 10.3390/brainsci13050749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 04/24/2023] [Accepted: 04/28/2023] [Indexed: 05/28/2023] Open
Abstract
Lumbar degenerative disc disease (LDDD) is widely acknowledged as a significant contributor to low back pain (LBP), which is a prevalent and debilitating health condition affecting millions of individuals worldwide. The pathogenesis of LDDD and associated pain mechanisms are thought to be mediated by inflammatory mediators. Autologous conditioned serum (ACS, Orthokine) may be used for symptomatic treatment of LBP due to LDDD. This study aimed to compare the analgesic efficacy and safety of two routes of ACS administration, perineural (periarticular) and epidural (interlaminar), in the conservative treatment of LBP. This study used an open-label, randomized, controlled trial protocol. A group of 100 patients were enrolled in the study and randomly allocated into two comparative groups. Group A (n = 50) received the epidural (interlaminar) approach-2 ultrasound-guided injections as control intervention (each containing two doses of ACS-8 mL). Group B (n = 50) received the perineural (periarticular) approach-2 ultrasound-guided injections as experimental intervention at 7-day intervals (the same volume of ACS). Assessments consisted of an initial assessment (IA) and control assessments at 4 (T1), 12 (T2), and 24 (T3) weeks after the last intervention. Primary outcomes comprised Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), Roland Morris Questionnaire (RMQ), and Euro Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L): Index, Visual Analogue Scale (VAS), and Level Sum Score (LSS). Secondary outcomes included differences between groups in specific endpoints for the above-mentioned questionnaires. In conclusion, this study revealed that both perineural (periarticular) and epidural ACS injections tended to perform in a very similar way. Both routes of Orthokine application show significant improvement in the primary clinical parameters, such as pain and disability, and therefore, both methods can be considered equally effective in managing LBP due to LDDD.
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Affiliation(s)
- Piotr Godek
- Sutherland Medical Center, 04-036 Warsaw, Poland
| | | | - Dominik Golicki
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, 02-091 Warsaw, Poland
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Gholian S, Pishgahi A, Shakouri SK, Eslamian F, Yousefi M, Kheiraddin BP, Dareshiri S, Yarani R, Dolatkhah N. Use of autologous conditioned serum dressings in hard-to-heal wounds: a randomised prospective clinical trial. J Wound Care 2022; 31:68-77. [PMID: 35077207 DOI: 10.12968/jowc.2022.31.1.68] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE In this study, we aimed to assess both the efficacy and tolerability of autologous conditioned serum (ACS) as an innovative wound dressing in the local management of hard-to-heal wounds. METHOD In this single-blinded randomised controlled trial, patients with hard-to-heal wounds were randomly assigned to receive either ACS treatment or normal saline (NS) dressings. The treatment was applied once a week for three weeks with a final assessment at three weeks from the first ACS application. RESULTS A total of 30 patients took part in the study. Analysis of wound assessment data demonstrated statistically significant differences for wound surface area and Pressure Ulcer Scale for Healing scores (area score, exudate and tissue) from baseline to the end of the study in patients who received the ACS dressing, but not in patients who received the normal saline dressing. There were statistically significant differences in changes in: the wound surface area at week three (-6.4±2.69cm2 versus +0.4±2.52cm2); area score at week three (-2.2±1.08 versus +0.2±0.86); exudate at week two (-1.2±0.70 versus +0.0±0.45) and at week 3 (-1.3±0.72 versus -0.1±0.63); tissue at week two (-1.1±0.35 versus +0.0±0.53) and at week three (-1.8±0.65 versus -0.1±0.63); and the PUSH total score at week one (-1.6±0.98 versus +0.4±1.22), week two (-3.2±0.86 versus +0.4±0.98) and week three (-5.3±1.17 versus -0.0±1.33) between the ACS and NS groups, respectively. CONCLUSION This trial revealed a significant decrease in wound surface area as well as a considerable improvement in wound healing in the ACS dressing group.
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Affiliation(s)
- Shakiba Gholian
- Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Pishgahi
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Kazem Shakouri
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fariba Eslamian
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Yousefi
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Shahla Dareshiri
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Yarani
- Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of Medicine, US.,Translational Type 1 Diabetes Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - Neda Dolatkhah
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
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Repair of Large Hiatal Hernias With the Use of Mesh and Autologous Platelet-Rich Plasma. SURGICAL LAPAROSCOPY, ENDOSCOPY & PERCUTANEOUS TECHNIQUES 2021; 32:9-13. [PMID: 34545035 DOI: 10.1097/sle.0000000000001004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 08/24/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND According to recent studies, large hiatal hernias (HH) can be associated with a lower content of type-I and type-III collagen in the phrenoesophageal ligament (POL). We therefore hypothesize that the use of a mesh implant with autologous platelet-rich plasma (PRP) for repair of large HH would have a positive effect on long-term outcome.The purpose of our study was to determine the level of type-I and type-III collagens in the POL of patients with large HH with the aim of improving the technique of HH repair. MATERIALS AND METHODS During the first phase of the study, the collagen content within the POL was assessed in 18 patients with HH and 14 cadaveric specimens without HH. During the second phase, 54 patients with large HH (defined as 10 to 20 cm2), that required surgery were recruited. Laparoscopic repair involved use of a nonabsorbable self-fixating ProGrip mesh infiltrated with 2 to 4 mL of autologous PRP was used for reinforcement of crural repair. Results were assessed using endoscopy, barium swallow, 24-hour impedance-pH monitoring and a quality of life gastroesophageal reflux disease-health related quality of life questionnaire. RESULTS The content of collagen within POL in patients with HH was significantly lower than in the cadaveric specimens without HH. Of the 54 patients undergoing HH repair, all procedures were performed laparoscopically and there were no mortalities in this group. At 48 months, only 2 HH recurrences (3.7%) were detected. During this period, the mean gastroesophageal reflux disease-health related quality of life score decreased from 15.7±5.5 to 5.9±0.6 (P<0.05). CONCLUSION Our study has shown that the collagen content is reduced in patients with large HH; thus, it is advisable to use mesh for HH repair in such patients. Use of mesh infiltrated in PRP is safe and can have positive impact on results of HH repair.
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Tsai WC, Yu TY, Chang GJ, Chang HN, Lin LP, Lin MS, Pang JHS. Use of Platelet-Rich Plasma Plus Suramin, an Antifibrotic Agent, to Improve Muscle Healing After Injuries. Am J Sports Med 2021; 49:3102-3112. [PMID: 34351815 DOI: 10.1177/03635465211030295] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND The increasing use of platelet-rich plasma (PRP) to treat muscle injuries raises concerns because transforming growth factor-beta (TGF-β) in PRP may promote fibrosis in the injured muscle and thus impair muscle regeneration. PURPOSE To investigate whether suramin (a TGF-β inhibitor) can reduce muscle fibrosis to improve healing of the injured muscle after PRP treatment and identify the underlying molecular mechanism. STUDY DESIGN Controlled laboratory study. METHODS Myoblasts isolated from the gastrocnemius muscle of Sprague Dawley rats were treated with PRP or PRP plus suramin. MTT assays were performed to evaluate cell viability. The expression of fibrosis-associated proteins (such as type I collagen and fibronectin), Smad2, and phosphorylated Smad2 was determined using Western blot analysis and immunofluorescent staining. An anti-TGF-β antibody was employed to verify the role of TGF-β in fibronectin expression. Gastrocnemius muscles were injured through a partial transverse incision and then treated using PRP or PRP plus suramin. Hematoxylin and eosin staining was conducted to evaluate the healing process 7 days after the injury. Immunofluorescent staining was performed to evaluate fibronectin expression. Muscle contractile properties-fast-twitch and tetanic strength-were evaluated through electric stimulation. RESULTS PRP plus 25 μg/mL of suramin promoted myoblast proliferation. PRP induced fibronectin expression in myoblasts, but suramin reduced this upregulation. The anti-TGF-β antibody also reduced the upregulation of fibronectin expression in the presence of PRP. The upregulation of phosphorylated Smad2 by PRP was reduced by either the anti-TGF-β antibody or suramin. In the animal study, no significant difference was discovered in muscle healing between the PRP versus PRP plus suramin groups. However, the PRP plus suramin group had reduced fibronectin expression at the injury site. Fast-twitch strength and tetanic strength were significantly higher in the injured muscle treated using PRP or PRP plus suramin. CONCLUSION Simultaneous PRP and suramin use reduced fibrosis in the injured muscle and promoted healing without negatively affecting the muscle's contractile properties. The underlying molecular mechanism may be associated with the phosphorylated Smad2 pathway. CLINICAL RELEVANCE Simultaneous PRP and suramin use may reduce muscle fibrosis without compromising muscle contractile properties and thus improve muscle healing.
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Affiliation(s)
- Wen-Chung Tsai
- Department of Physical Medicine and Rehabilitation, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan.,College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Tung-Yang Yu
- Department of Physical Medicine and Rehabilitation, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan.,Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan City, Taiwan
| | - Gwo-Jyh Chang
- Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan City, Taiwan
| | - Hsiang-Ning Chang
- Department of Physical Medicine and Rehabilitation, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan
| | - Li-Ping Lin
- Department of Physical Medicine and Rehabilitation, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan.,Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan City, Taiwan
| | - Miao-Sui Lin
- Department of Physical Medicine and Rehabilitation, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan
| | - Jong-Hwei S Pang
- Department of Physical Medicine and Rehabilitation, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan.,Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan City, Taiwan
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Ozer K. COVID-19-associated Cytokine Release Syndrome and Autologous Conditioned Serum: A Hypothesis. EXPLORATORY RESEARCH AND HYPOTHESIS IN MEDICINE 2021; 000:000-000. [DOI: 10.14218/erhm.2021.00006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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de Melo UP, Ferreira C. Multimodal therapy for treatment of equine back pain: a report of 15 cases. BRAZILIAN JOURNAL OF VETERINARY MEDICINE 2021; 43:e003321. [PMID: 35749060 PMCID: PMC9179183 DOI: 10.29374/2527-2179.bjvm003321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/05/2021] [Indexed: 11/17/2022] Open
Abstract
Back pain and diseases of the spine are considered significant problems in equine sports and veterinary medicine. This article reports a multimodal approach to the treatment of equine back pain using ozonized platelet rich plasma (PRP), dynamic mobilization exercises, and therapeutic shoeing in 15 horses involved in the vaquejada discipline. Fifteen American Quarter Horses of both sexes engaged in vaquejada in the state of Rio Grande do Norte, Brazil, with a mean age of 8.61 ? 1.73 years were examined at a training center for lower performance diagnostics or back pain. A complete clinical examination was performed on all horses at rest to determine the general conformation and alterations in posture, symmetry, and curvature of the spine. The horses were examined while walking and trotting in straight lines and circles to determine the presence of lameness and/or gait asymmetry. Spinal abnormalities on clinical examination were classified on a scale of 0 to 5 based on the following parameters: degree of response to pain from back palpation, hypertonicity of the back muscles, stiffness of the thoracolumbar joint, and physical dysfunction. After physical examination, ultrasound was performed to identify the cause of the thoracolumbar pain. The therapeutic protocol consisted of the intralesional application of ozonized PRP combined with therapeutic ultrasound, dynamic mobilization exercises, and therapeutic shoeing. All treated animals returned to sports activities at a higher level of performance than at the beginning of the treatment. Six months after treatment, telephone contact was made with the owner or trainer to determine if the back pain had relapsed. None of the animals relapsed during this period, and they participated in vaquejada normally.
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Affiliation(s)
| | - Cintia Ferreira
- Veterinarian, DSc. Faculdade Maurício de Nassau (Uninassau). Campus Natal, RN, Brazil.
- Correspondence Ubiratan Pereira de Melo Faculdade Maurício de Nassau - Uninassau, Campus Natal Rua Engenheiro Roberto Freire, 1514, Capim Macio CEP 59080-400 - Natal (RN), Brasil E-mail:
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Zhao L, Liu X, Zhang J, Dong G, Xiao W, Xu X. Hydrogen Sulfide Alleviates Skeletal Muscle Fibrosis via Attenuating Inflammation and Oxidative Stress. Front Physiol 2020; 11:533690. [PMID: 33071808 PMCID: PMC7530892 DOI: 10.3389/fphys.2020.533690] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Accepted: 08/12/2020] [Indexed: 12/11/2022] Open
Abstract
The purpose of this study was to investigate the effect of exogenous hydrogen sulfide (H2S) treatment on skeletal muscle contusion. We established a skeletal muscle contusion model (S group) and an H2S treated of skeletal muscle contusion model (H2S group). Gastrocnemius muscles (GMs) were collected at day 1, day 5, day 10, and day 15 after injury, and comprehensive morphological and genetic analyses was conducted. H2S treatment reduced M1 macrophage (CD68), profibrotic cytokines (TGF-β), pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6), chemokines (CCL2, CCR2, CCL3, CCL5, CXCL12, and CXCR4), matrix metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-14) and oxidative stress factor (gp91phox) expression levels, improved M2 macrophage (CD206) level. Thus, exogenous H2S treatment reduced inflammation and oxidative stress, attenuated skeletal muscle fibrosis, and partly improved skeletal muscle injury.
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Affiliation(s)
- Linlin Zhao
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Xiaoguang Liu
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Jing Zhang
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Gaoyang Dong
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Weihua Xiao
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Xin Xu
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
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12
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Improvement of Skeletal Muscle Regeneration by Platelet-Rich Plasma in Rats with Experimental Chronic Hyperglycemia. BIOMED RESEARCH INTERNATIONAL 2020; 2020:6980607. [PMID: 32766312 PMCID: PMC7374220 DOI: 10.1155/2020/6980607] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 06/05/2020] [Accepted: 07/02/2020] [Indexed: 02/07/2023]
Abstract
Herein, the structural effect of autologous platelet-rich plasma (PRP) on posttraumatic skeletal muscle regeneration in rats with chronic hyperglycemia (CH) was tested. 130 white laboratory male rats divided into four groups (I—control; II—rats with CH; III—rats with CH and PRP treatment; and IV—rats for CH confirmation) were used for the experiment. CH was simulated by streptozotocin and nicotinic acid administration. Triceps surae muscle injury was reproduced by transverse linear incision. Autologous PRP was used in order to correct the possible negative CH effect on skeletal muscle recovery. On the 28th day after the injury, the regenerating muscle fiber and blood vessel number in the CH+PRP group were higher than those in the CH rats. However, the connective tissue area in the CH group was larger than that in the CH+PRP animals. The amount of agranulocytes in the regenerating muscle of the CH rats was lower compared to that of the CH+PRP group. The histological analysis of skeletal muscle recovery in CH+PRP animals revealed more intensive neoangiogenesis compared to that in the CH group. Herewith, the massive connective tissue development and inflammation signs were observed within the skeletal muscle of CH rats. Obtained results suggest that streptozotocin-induced CH has a negative effect on posttraumatic skeletal muscle regeneration, contributing to massive connective tissue development. The autologous PRP injection promotes muscle recovery process in rats with CH, shifting it away from fibrosis toward the complete muscular organ repair.
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Shirokova L, Noskov S, Gorokhova V, Reinecke J, Shirokova K. Intra-Articular Injections of a Whole Blood Clot Secretome, Autologous Conditioned Serum, Have Superior Clinical and Biochemical Efficacy Over Platelet-Rich Plasma and Induce Rejuvenation-Associated Changes of Joint Metabolism: A Prospective, Controlled Open-Label Clinical Study in Chronic Knee Osteoarthritis. Rejuvenation Res 2020; 23:401-410. [PMID: 31847701 DOI: 10.1089/rej.2019.2263] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Osteoarthritis is a frequent, age-associated disease affecting >10% of world's population over 60 years of age. This study intended to compare intra-articular whole blood clot secretome (autologous conditioned serum [ACS], recently re-named blood clot secretome [BCS]) to platelet-rich plasma (PRP) in knee osteoarthritis (OA). A clinical, nonrandomized open-label comparison of ACS versus PRP in knee OA with subclinical or moderate synovitis symptomology was performed. One hundred and twenty-three patients with knee OA, Kellgren and Lawrence grade II-III, were each treated with six i.a. injections of ACS or PRP. The clinical efficacy was measured by visual analog scale and Western Ontario and McMaster Universities Arthritis Index (WOMAC) score. The biochemical effects measured include synovial fluid (SF) viscosity, cytokines interleukin (IL)-1Ra and IL-1b, radical footprint NO3, and conjugated dienes (CDs). At the 3-month follow-up, clinical efficacy of ACS was significant in all groups, versus PRP. PRP had significant versus baseline efficacy in subclinical, but not in moderate, synovitis cases. ACS was more effective than PRP regarding all analytical parameters. It induced endogenous IL-1Ra expression, downregulated IL-1b, and improved SF viscosity. ACS reduced-significantly stronger than PRP-the concentration of CDs-interpreted as reactive oxygen species footprints-and NO3-interpreted as nitric oxide footprint-in SF. ACS displayed significant efficacy in all groups, which was clinically and biochemically superior to PRP. ACS appears to improve i.a. homeostasis. Strength of this open clinical study is the combination of clinical and biochemical data.
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Affiliation(s)
- Larisa Shirokova
- Department of Hospital Therapy, Yaroslavl State Medical University of MoH of RF, Yaroslavl, Russia
| | - Sergey Noskov
- Department of Hospital Therapy, Yaroslavl State Medical University of MoH of RF, Yaroslavl, Russia
| | - Victoria Gorokhova
- Department of Hospital Therapy, Yaroslavl State Medical University of MoH of RF, Yaroslavl, Russia
| | | | - Ksenia Shirokova
- Department of Hospital Therapy, Yaroslavl State Medical University of MoH of RF, Yaroslavl, Russia
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Kılınç BE, Öç Y. Evaluation of the autologous conditioned serum in the treatment of osteoarthritis. ARCHIVES OF CLINICAL AND EXPERIMENTAL MEDICINE 2019. [DOI: 10.25000/acem.569936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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15
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Blázquez R, Sánchez-Margallo FM, Reinecke J, Álvarez V, López E, Marinaro F, Casado JG. Conditioned Serum Enhances the Chondrogenic and Immunomodulatory Behavior of Mesenchymal Stem Cells. Front Pharmacol 2019; 10:699. [PMID: 31316380 PMCID: PMC6609570 DOI: 10.3389/fphar.2019.00699] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 05/29/2019] [Indexed: 12/31/2022] Open
Abstract
Osteoarthritis is one of the most common chronic health conditions associated with pain and disability. Advanced therapies based on mesenchymal stem cells have become valuable options for the treatment of these pathologies. Conditioned serum (CS, “Orthokine”) has been used intra-articularly for osteoarthritic patients. In this work, we hypothesized that the rich content on anti-inflammatory proteins and growth factors of CS may exert a beneficial effect on the biological activity of human adipose-derived mesenchymal stem cells (hAdMSCs). In vitro studies were designed using hAdMSCs cocultured with CS at different concentrations (2.5, 5, and 10%). Chondrogenic differentiation assays and immunomodulatory experiments using in vitro-stimulated lymphocytes were performed. Our results demonstrated that CS significantly enhanced the differentiation of hAdMSCs toward chondrocytes. Moreover, hAdMSCs pre-sensitized with CS reduced the lymphocyte proliferation as well as their differentiation toward activated lymphocytes. These results suggest that in vivo coadministration of CS and hAdMSCs may have a beneficial effect on the therapeutic potential of hAdMSCs. Moreover, these results indicate that intra-articular administration of CS might influence the biological behavior of resident stem cells increasing their chondrogenic differentiation and inherent immunomodulatory activity. To our knowledge, this is the first in vitro study reporting this combination.
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Affiliation(s)
- Rebeca Blázquez
- Stem Cell Therapy Unit, "Jesús Usón" Minimally Invasive Surgery Centre, Cáceres, Spain.,CIBER de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain
| | - Francisco Miguel Sánchez-Margallo
- Stem Cell Therapy Unit, "Jesús Usón" Minimally Invasive Surgery Centre, Cáceres, Spain.,CIBER de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain
| | - Julio Reinecke
- Research and Development Department, ORTHOGEN AG, Düsseldorf, Germany
| | - Verónica Álvarez
- Stem Cell Therapy Unit, "Jesús Usón" Minimally Invasive Surgery Centre, Cáceres, Spain
| | - Esther López
- Stem Cell Therapy Unit, "Jesús Usón" Minimally Invasive Surgery Centre, Cáceres, Spain
| | - Federica Marinaro
- Stem Cell Therapy Unit, "Jesús Usón" Minimally Invasive Surgery Centre, Cáceres, Spain
| | - Javier G Casado
- Stem Cell Therapy Unit, "Jesús Usón" Minimally Invasive Surgery Centre, Cáceres, Spain.,CIBER de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain
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Cox BA, Kindle BJ, Goyeneche N, Hackel JG, Andrews JR, Saper MG. Ultrasound-guided platelet-rich plasma injection for a high-grade sternocleidomastoid tear in a professional football player. CURRENT ORTHOPAEDIC PRACTICE 2019. [DOI: 10.1097/bco.0000000000000731] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Abstract
PURPOSE OF REVIEW This review discusses the current literature regarding the use of platelet-rich plasma (PRP) in the treatment of muscle strain injuries. Case series as well as experimental trials for both human and animal models are covered. RECENT FINDINGS Multiple studies have examined outcomes for the use of PRP in the treatment of muscle strain injuries. PRP has been shown to promote muscle recovery via anabolic growth factors released from activated platelets, and in doing so, potentially reduces pain, swelling, and time for return to play. In vitro studies support the regenerative potential of PRP for acute soft tissue injuries. Multiple clinical case series for PRP injections in the setting of muscle strains demonstrate imaging evidence for faster healing, less swelling, which can decrease time for return to play. These studies, however, are retrospective in nature, and few randomized controlled studies exist to demonstrate a clear clinical benefit. Additionally, there is tremendous heterogeneity regarding the injectant preparation, optimum platelet concentration, presence of leukocytes, and volume of PRP which should be administered as well as number of and timing of treatments.
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Borrione P, Fossati C, Pereira MT, Giannini S, Davico M, Minganti C, Pigozzi F. The use of platelet-rich plasma (PRP) in the treatment of gastrocnemius strains: a retrospective observational study. Platelets 2018; 29:596-601. [PMID: 28895770 DOI: 10.1080/09537104.2017.1349307] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 06/01/2017] [Accepted: 06/22/2017] [Indexed: 12/13/2022]
Abstract
The aim of the present retrospective observational study was to evaluate the time of functional recovery following a specific combined therapeutic approach characterized by an active exercise therapy carried out immediately after Platelet-rich plasma (PRP) injections for the treatment of the muscular lesion of the distal musculotendinous junction of the gastrocnemius medial head.Medical records of 31 subjects treated with three PRP intra-lesional ultrasound guided injections and 30 patients treated with the standard therapeutic approach (control group) were analyzed. Both groups followed the same rehabilitation therapy. Patients in the control group were able to start active exercise with a significant delay when compared to the PRP treated subjects: 17 ± 7.2 days and 9 ± 3.8 days (p = 0.0001), respectively. This delay was mainly due to the persistence of pain in the subjects in the control group. The time necessary to return to walk without pain was significantly shorter in the PRP treated group: 24.27 ± 12.36 days versus 52.4 ± 20.03 days in the control group (p < 0.001) as well as the time needed to fully return to practice the previous sport activity: 53.33 ± 27.74 days versus 119.3 ± 43.87 days in the control group (p < 0.001).The present study showed that ultrasound guided delivery of PRP into the site of muscle injury has to be considered a valid therapeutic approach with the potentiality of significantly reduce time and costs for reaching a complete functional recovery.
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Affiliation(s)
- Paolo Borrione
- a Department of Movement, Human and Health Sciences , University of Rome "Foro Italico" , Rome , Italy
- b Villa Stuart Sport Clinic-FIFA Centre of Excellence , Rome , Italy
- c Department for Health and Performance , Regional Antidoping and Toxicology Center , Orbassano , TO, Italy
| | - Chiara Fossati
- a Department of Movement, Human and Health Sciences , University of Rome "Foro Italico" , Rome , Italy
| | | | - Silvana Giannini
- b Villa Stuart Sport Clinic-FIFA Centre of Excellence , Rome , Italy
| | - Marco Davico
- c Department for Health and Performance , Regional Antidoping and Toxicology Center , Orbassano , TO, Italy
| | - Carlo Minganti
- a Department of Movement, Human and Health Sciences , University of Rome "Foro Italico" , Rome , Italy
| | - Fabio Pigozzi
- a Department of Movement, Human and Health Sciences , University of Rome "Foro Italico" , Rome , Italy
- b Villa Stuart Sport Clinic-FIFA Centre of Excellence , Rome , Italy
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19
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Tonogai I, Hayashi F, Iwame T, Takasago T, Matsuura T, Sairyo K. Platelet-rich plasma does not reduce skeletal muscle fibrosis after distraction osteogenesis. J Exp Orthop 2018; 5:26. [PMID: 30006750 PMCID: PMC6045562 DOI: 10.1186/s40634-018-0143-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Accepted: 07/09/2018] [Indexed: 12/22/2022] Open
Abstract
Background Skeletal muscle fibrosis caused by an increase in collagen deposition often occurs after distraction osteogenesis. Although studies are available reporting the effects of platelet-rich plasma (PRP) on tissue healing following injury, current findings remain controversial. This study focused on determining whether PRP reduces skeletal muscle fibrosis caused by distraction osteogenesis. Methods Tibial osteotomies were performed on 8-week-old wild type mice, and tibiae were distracted at a rate of 0.42 mm/day for 2 weeks, starting 1 week after osteotomy. Immediately after distraction was completed (3 weeks after osteotomy), PRP or phosphate buffered saline (as a sham) was injected into the gastrocnemius (GC) muscle. The GC muscles were harvested and analyzed. Results The amount and area of collagenous tissue increased in both the PRP and control groups following distraction osteogenesis, but the changes were not significantly different between both groups at all time points (p = 0.89, 0.45, 0.33 and 0.52 at 4, 6, 8 and 10 weeks). Conclusion From this study, our results suggest that PRP did not significantly reduce skeletal muscle fibrosis due to distraction osteogenesis.
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Affiliation(s)
- Ichiro Tonogai
- Department of Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
| | - Fumio Hayashi
- Department of Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan
| | - Toshiyuki Iwame
- Department of Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan
| | - Tomoya Takasago
- Department of Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan
| | - Tetsuya Matsuura
- Department of Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan
| | - Koichi Sairyo
- Department of Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan
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20
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Tsai WC, Yu TY, Chang GJ, Lin LP, Lin MS, Pang JHS. Platelet-Rich Plasma Releasate Promotes Regeneration and Decreases Inflammation and Apoptosis of Injured Skeletal Muscle. Am J Sports Med 2018; 46:1980-1986. [PMID: 29772187 DOI: 10.1177/0363546518771076] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
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.
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Affiliation(s)
- Wen-Chung Tsai
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan.,College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Tung-Yang Yu
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan.,Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan City, Taiwan
| | - Gwo-Jyh Chang
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan.,Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan City, Taiwan
| | - Li-Ping Lin
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan.,Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan City, Taiwan
| | - Miao-Sui Lin
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan
| | - Jong-Hwei S Pang
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan.,Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan City, Taiwan
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21
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Bisciotti GN, Volpi P, Amato M, Alberti G, Allegra F, Aprato A, Artina M, Auci A, Bait C, Bastieri GM, Balzarini L, Belli A, Bellini G, Bettinsoli P, Bisciotti A, Bisciotti A, Bona S, Brambilla L, Bresciani M, Buffoli M, Calanna F, Canata GL, Cardinali D, Carimati G, Cassaghi G, Cautero E, Cena E, Corradini B, Corsini A, D'Agostino C, De Donato M, Delle Rose G, Di Marzo F, Di Pietto F, Enrica D, Eirale C, Febbrari L, Ferrua P, Foglia A, Galbiati A, Gheza A, Giammattei C, Masia F, Melegati G, Moretti B, Moretti L, Niccolai R, Orgiani A, Orizio C, Pantalone A, Parra F, Patroni P, Pereira Ruiz MT, Perri M, Petrillo S, Pulici L, Quaglia A, Ricciotti L, Rosa F, Sasso N, Sprenger C, Tarantola C, Tenconi FG, Tosi F, Trainini M, Tucciarone A, Yekdah A, Vuckovic Z, Zini R, Chamari K. Italian consensus conference on guidelines for conservative treatment on lower limb muscle injuries in athlete. BMJ Open Sport Exerc Med 2018; 4:e000323. [PMID: 29862040 PMCID: PMC5976114 DOI: 10.1136/bmjsem-2017-000323] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Revised: 02/14/2018] [Accepted: 03/02/2018] [Indexed: 02/07/2023] Open
Abstract
Provide the state of the art concerning (1) biology and aetiology, (2) classification, (3) clinical assessment and (4) conservative treatment of lower limb muscle injuries (MI) in athletes. Seventy international experts with different medical backgrounds participated in the consensus conference. They discussed and approved a consensus composed of four sections which are presented in these documents. This paper represents a synthesis of the consensus conference, the following four sections are discussed: (i) The biology and aetiology of MIs. A definition of MI was formulated and some key points concerning physiology and pathogenesis of MIs were discussed. (ii) The MI classification. A classification of MIs was proposed. (iii) The MI clinical assessment, in which were discussed anamnesis, inspection and clinical examination and are provided the relative guidelines. (iv) The MI conservative treatment, in which are provided the guidelines for conservative treatment based on the severity of the lesion. Furthermore, instrumental therapy and pharmacological treatment were discussed. Knowledge of the aetiology and biology of MIs is an essential prerequisite in order to plan and conduct a rehabilitation plan. Another important aspect is the use of a rational MI classification on prognostic values. We propose a classification based on radiological investigations performed by ultrasonography and MRI strongly linked to prognostic factors. Furthermore, the consensus conference results will able to provide fundamental guidelines for diagnostic and rehabilitation practice, also considering instrumental therapy and pharmacological treatment of MI. Expert opinion, level IV.
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Affiliation(s)
- Gian Nicola Bisciotti
- Qatar Orthopaedic and Sport Medicine Hospital, Doha, Qatar
- Centro Studi Kinemove Rehabilitation Centers, Pontremoli, Italy
| | - Piero Volpi
- Istituto Clinico Humanitas, Milano, Italy
- FC Internazionale, Milano, Italy
| | | | | | | | | | | | - Alessio Auci
- UOS Angiografia e Radiologia Interventistica, Ospedale delle Apuane, Massa-Carrara, Italy
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Emanuele Cena
- Qatar Orthopaedic and Sport Medicine Hospital, Doha, Qatar
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Biagio Moretti
- Azienda Ospedaliero-Universitaria “Policlinico”, Bari, Italy
| | - Lorenzo Moretti
- Azienda Ospedaliero-Universitaria “Policlinico”, Bari, Italy
| | | | | | | | | | - Federica Parra
- Centro Studi Kinemove Rehabilitation Centers, Pontremoli, Italy
| | | | | | | | | | - Luca Pulici
- Istituto Ortopedico Gaetano Pini, Milano, Italy
| | | | - Luca Ricciotti
- Centro Studi Kinemove Rehabilitation Centers, Pontremoli, Italy
| | | | | | | | | | | | - Fabio Tosi
- Centro Studi Kinemove Rehabilitation Centers, Pontremoli, Italy
| | | | | | - Ali Yekdah
- FAF Jenia Centre Med Sport, Algeri, Algeria
| | - Zarko Vuckovic
- Qatar Orthopaedic and Sport Medicine Hospital, Doha, Qatar
| | - Raul Zini
- Maria Cecilia Hospital, Cotignola, Italy
| | - Karim Chamari
- Qatar Orthopaedic and Sport Medicine Hospital, Doha, Qatar
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22
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Implantation of platelet rich fibrin and allogenic mesenchymal stem cells facilitate the healing of muscle injury: An experimental study on animal. INTERNATIONAL JOURNAL OF SURGERY OPEN 2018. [DOI: 10.1016/j.ijso.2018.03.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Liu X, Zeng Z, Zhao L, Xiao W, Chen P. Changes in inflammatory and oxidative stress factors and the protein synthesis pathway in injured skeletal muscle after contusion. Exp Ther Med 2017; 15:2196-2202. [PMID: 29434825 DOI: 10.3892/etm.2017.5625] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Accepted: 11/20/2017] [Indexed: 12/13/2022] Open
Abstract
Injury of skeletal muscle, and particularly mechanically-induced damage, including contusion injury, frequently occurs in contact sports as well as in sports with accidental contact. Although the mechanisms of skeletal muscle regeneration are well understood, those involved in muscle contusion are not. A total of 40 male mice were randomly divided into control (n=8) and muscle contusion (n=32) groups. A muscle contusion model was established by weight-drop injury. Subsequently, the gastrocnemius muscles in the two groups were harvested at different times (1, 3, 7 and 14 days) post-injury. The changes in skeletal muscle morphology were assessed by hematoxylin and eosin (H&E) stains. Furthermore, quantitative polymerase chain reaction and western blotting were used to analyze inflammatory cytokines, oxidative stress factors and the Akt/mechanistic target of rapamycin (mTOR) pathway. The results revealed that pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interferon-γ (IFN-γ)] increased significantly at day 1 and 3 and still exhibited high levels of expression at days 7 and 14 (except IL-6) post-injury. Additionally, the anti-inflammatory cytokine IL-10 increased significantly at 1, 3 and 7 days and reached its peak levels at 7 days post-injury. It was revealed that gp91phox mRNA increased significantly at all time points and gp91phox protein increased significantly at day 3 post-injury. Furthermore, it was observed that p-Akt/Akt increased significantly at 1 day post-injury. P-mTOR/mTOR increased significantly at day 1 and 7, and p-p70s6k/p70s6k and P-4EBP1/4EBP1 increased significantly at 1, 3, 7 and 14 days post-injury. These results indicate that inflammatory and oxidative stress factors and the Akt/mTOR pathway may serve important roles in the regeneration of muscle contusion. In addition, certain inflammatory factors and oxidative stress factors maintained high levels of expression at 14 days after injury, indicating that the healing process of muscle was still not fully achieved at this time.
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Affiliation(s)
- Xiaoguang Liu
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, P.R. China
| | - Zhigang Zeng
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, P.R. China.,College of Physical Education, Jinggangshan University, Ji'an, Jiangxi 343009, P.R. China
| | - Linlin Zhao
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, P.R. China
| | - Weihua Xiao
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, P.R. China
| | - Peijie Chen
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, P.R. China
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Tsai WC, Yu TY, Lin LP, Lin MS, Tsai TT, Pang JHS. Platelet rich plasma promotes skeletal muscle cell migration in association with up-regulation of FAK, paxillin, and F-Actin formation. J Orthop Res 2017; 35:2506-2512. [PMID: 28233384 DOI: 10.1002/jor.23547] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 02/10/2017] [Indexed: 02/04/2023]
Abstract
Platelet rich plasma (PRP) contains various cytokines and growth factors which may be beneficial to the healing process of injured muscle. The aim of this study was to investigate the effect and molecular mechanism of PRP on migration of skeletal muscle cells. Skeletal muscle cells intrinsic to Sprague-Dawley rats were treated with PRP. The cell migration was evaluated by transwell filter migration assay and electric cell-substrate impedance sensing. The spreading of cells was evaluated microscopically. The formation of filamentous actin (F-actin) cytoskeleton was assessed by immunofluorescence staining. The protein expressions of paxillin and focal adhesion kinase (FAK) were assessed by Western blot analysis. Transfection of paxillin small-interfering RNA (siRNAs) to muscle cells was performed to validate the role of paxillin in PRP-mediated promotion of cell migration. Dose-dependently PRP promotes migration of and spreading and muscle cells. Protein expressions of paxillin and FAK were up-regulated dose-dependently. F-actin formation was also enhanced by PRP treatment. Furthermore, the knockdown of paxillin expression impaired the effect of PRP to promote cell migration. It was concluded that PRP promoting migration of muscle cells is associated with up-regulation of proteins expression of paxillin and FAK as well as increasing F-actin formation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2506-2512, 2017.
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Affiliation(s)
- Wen-Chung Tsai
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan.,College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Tung-Yang Yu
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan
| | - Li-Ping Lin
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan.,Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan City, Taiwan
| | - Mioa-Sui Lin
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan
| | - Ting-Ta Tsai
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan
| | - Jong-Hwei S Pang
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan.,Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan City, Taiwan
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Changes in haematological indices following local application of interleukin-1 receptor antagonist protein after tenotomy in rabbits. ACTA VET BRNO 2017. [DOI: 10.2754/avb201786020183] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Interleukin-1 (IL-1) is the most important cytokine in the inflammation cascade activation in all tissues and is present in acute and chronic phases of inflammation. By blocking IL-1 binding to target cells, numerous inflammation processes are prevented. The use of autologous conditioned serum rich with IL-1 receptor antagonist protein (IL-1Ra) is a novel treatment method of tendon inflammation in domestic animals and humans. Injections of autologous conditioned serum (ACS) have demonstrated clinical efficacy and safety in animal models and humans in the treatment of osteoarthritis, disc prolapse and muscles and tendons injuries with low side effect. Neutropaenia, reduced white blood cell count, and infections or local irritations are described as side effects of IL-1 antagonist use in humans. Therefore, a study of blood changes in rabbits after local administration of IL-1Ra in the Achilles tendon tissue after iatrogenic inflammation was conducted. Interleukin-1 receptor antagonist protein was used to prevent and reduce tendon inflammation after longitudinal tenotomy. The study was done on 26 white Californian rabbits, divided into two equal groups consisting of 13 animals each; the experimental interleukin-1 receptor antagonist protein (irap) group, and the control group. In the irap group, autologous serum rich with IL-1Ra was used (Orthokine®vet irap, Alfa-Arthro, Croatia). Differences between two groups were considered significant as changes in the blood for certain blood elements atP< 0.01. ThePvalue wasP= 0.0153 for the white blood cells,P= 0.00153 for neutrophils,P= 0.00017 and for platelets. In the control group, an increased platelet count was noticed in 70% of blood samples and a decreased neutrophil count was found in all of the irap group samples at the end of the study in comparison to the initial blood count prior to application.
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Macrophage Depletion Impairs Skeletal Muscle Regeneration: the Roles of Pro-fibrotic Factors, Inflammation, and Oxidative Stress. Inflammation 2017; 39:2016-2028. [PMID: 27605219 DOI: 10.1007/s10753-016-0438-8] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Muscle contusion is one of the most common muscle injuries in sports medicine. Macrophages play complex roles in the regeneration of skeletal muscle. However, the roles of macrophages, especially the mechanisms involved, in the regeneration of muscle contusion are still not fully understood. We hypothesize that the depletion of macrophages impairs skeletal muscle regeneration and that pro-fibrotic factors, inflammation, and oxidative stress may be involved in the process. To test these hypotheses, we constructed a muscle contusion injury and a macrophage depletion model and followed it up with morphological and gene expression analyses. The data showed that fibrotic scars were formed in the muscle of contusion injury, and they deteriorated in the mice of macrophage depletion. Furthermore, the sizes of regenerating myofibers were significantly reduced by macrophage depletion. Pro-fibrotic factors, inflammatory cytokines, chemokines, and oxidative stress-related enzymes increased significantly after muscle injury. Moreover, the expression of these factors was delayed by macrophage depletion. Most of them were still significantly higher in the later stage of regeneration. These results suggest that macrophage depletion impairs skeletal muscle regeneration and that pro-fibrotic factors, inflammation, and oxidative stress may play important roles in the process.
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Liu X, Liu Y, Zhao L, Zeng Z, Xiao W, Chen P. Macrophage depletion impairs skeletal muscle regeneration: The roles of regulatory factors for muscle regeneration. Cell Biol Int 2017; 41:228-238. [PMID: 27888539 DOI: 10.1002/cbin.10705] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 11/18/2016] [Indexed: 01/28/2023]
Abstract
Though macrophages are essential for skeletal muscle regeneration, which is a complex process, the roles and mechanisms of the macrophages in the process of muscle regeneration are still not fully understood. The objective of this study is to explore the roles of macrophages and the mechanisms involved in the regeneration of injured skeletal muscle. One hundred and twelve C57BL/6 mice were randomly divided into muscle contusion and macrophages depleted groups. Their gastrocnemius muscles were harvested at the time points of 12 h, 1, 3, 5, 7, 14 d post-injury. The changes in skeletal muscle morphology were assessed by hematoxylin and eosin (HE) stain. The gene expression was analyzed by real-time polymerase chain reaction. The data showed that CL-liposomes treatment did affect the expression of myogenic regulatory factors (MyoD, myogenin) after injury. In addition, CL-liposomes treatment decreased the expression of regulatory factors of muscle regeneration (HGF, uPA, COX-2, IGF-1, MGF, FGF6) and increased the expression of inflammatory cytokines (TGF-β1, TNF-α, IL-1β, RANTES) in the late stage of regeneration. Moreover, there were significant correlations between macrophages and some regulatory factors (such as HGF, uPA) for muscle regeneration. These results suggested that macrophages depletion impairs skeletal muscle regeneration and that the regulatory factors for muscle regeneration may play important roles in this process.
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Affiliation(s)
- Xiaoguang Liu
- School of Kinesiology, Shanghai University of Sport, Shanghai, 200438, China
| | - Yu Liu
- School of Kinesiology, Shanghai University of Sport, Shanghai, 200438, China.,Department of Exercise Science, Shenyang Sport University, Shenyang, 110001, China
| | - Linlin Zhao
- School of Kinesiology, Shanghai University of Sport, Shanghai, 200438, China
| | - Zhigang Zeng
- School of Kinesiology, Shanghai University of Sport, Shanghai, 200438, China
| | - Weihua Xiao
- School of Kinesiology, Shanghai University of Sport, Shanghai, 200438, China
| | - Peijie Chen
- School of Kinesiology, Shanghai University of Sport, Shanghai, 200438, China
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Borrione P, Fagnani F, Di Gianfrancesco A, Mancini A, Pigozzi F, Pitsiladis Y. The Role of Platelet-Rich Plasma in Muscle Healing. Curr Sports Med Rep 2017; 16:459-463. [DOI: 10.1249/jsr.0000000000000432] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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van der Made AD, Reurink G, Tol JL, Marotta M, Rodas G, Kerkhoffs GM. Emerging Biological Approaches to Muscle Injuries. BIO-ORTHOPAEDICS 2017:227-238. [DOI: 10.1007/978-3-662-54181-4_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Pinheiro CL, Peixinho CC, Esposito CC, Manso JEF, Machado JC. Ultrasound biomicroscopy and claudication test for in vivo follow-up of muscle repair enhancement based on platelet-rich plasma therapy in a rat model of gastrocnemius laceration. Acta Cir Bras 2016; 31:103-10. [PMID: 26959619 DOI: 10.1590/s0102-865020160020000004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 01/15/2016] [Indexed: 01/15/2023] Open
Abstract
PURPOSE To track the regeneration process of lateral gastrocnemius due to a muscle laceration in rats, and to treatment with plateletrich plasma (PRP). METHODS Ultrasound (40 MHz) images were used for measuring pennation angle (PA), muscle thickness (MT) and mean pixel intensity, along with claudication scores, of treated (PRPG) and non-treated (NTG) groups of rats. RESULTS NTG showed a PA increase for the non-injured leg (p<0.05) and a tendency of MT to increase, whereas for PRPG there were no differences. There was a progressive reduction of the claudication score for the PRPG group throughout the entire period, with an immediate difference after seven days (p<0.05), whereas the NTG had a significant reduction only at day 28 (p<0.05). CONCLUSION It was observed a compensatory hypertrophic response due to the overload condition imposed to healthy leg for NTG that did not occur in PRPG, suggesting an accelerated repair process of the injured leg due to treatment, anticipating its use.
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Affiliation(s)
| | | | | | | | - João Carlos Machado
- School of Medicine and Biomedical Engineering Program, UFRJ, Rio de Janeiro, RJ, Brazil
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Tsai WC, Yu TY, Lin LP, Lin MS, Wu YC, Liao CH, Pang JHS. Platelet rich plasma releasate promotes proliferation of skeletal muscle cells in association with upregulation of PCNA, cyclins and cyclin dependent kinases. Platelets 2016; 28:491-497. [PMID: 27780401 DOI: 10.1080/09537104.2016.1227061] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Platelet rich plasma (PRP) contains various cytokines and growth factors which may be beneficial to the healing process of injured muscle. The purpose of this study is to investigate the effect and molecular mechanism of PRP releasate on proliferation of skeletal muscle cells. Skeletal muscle cells intrinsic to Sprague-Dawley rats were treated with PRP releasate. Cell proliferation was evaluated by 3-[4,5-Dimethylthiazol- 2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and immunocytochemistry with Ki-67 stain. Flow cytometric analysis was used to evaluate the cell cycle progression. Western blot analysis was used to evaluate the protein expressions of PCNA, cyclin E1, cyclin A2, cyclin B1, cyclin dependent kinase (cdk)1 and cdk2. The results revealed that PRP releasate enhanced proliferation of skeletal muscle cells by shifting cells from G1 phase to S phase and G2/M phases. Ki-67 stain revealed the increase of proliferative capability after PRP releasate treatment. Protein expressions including cyclin A2, cyclin B1, cdk1, cdk2 and PCNA were up-regulated by PRP releasate in a dose-dependent manner. It was concluded that PRP releasate promoted proliferation of skeletal muscle cells in association with the up-regulated protein expressions of PCNA, cyclin A2, cyclin B1, cdk1 and cdk2.
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Affiliation(s)
- Wen-Chung Tsai
- a Department of Physical Medicine and Rehabilitation , Chang Gung Memorial Hospital at Linkou , Taoyuan City , Taiwan.,b College of Medicine , Chang Gung University , Taoyuan City , Taiwan
| | - Tung-Yang Yu
- a Department of Physical Medicine and Rehabilitation , Chang Gung Memorial Hospital at Linkou , Taoyuan City , Taiwan
| | - Li-Ping Lin
- a Department of Physical Medicine and Rehabilitation , Chang Gung Memorial Hospital at Linkou , Taoyuan City , Taiwan.,c Graduate Institute of Clinical Medical Sciences, Chang Gung University , Taoyuan City , Taiwan
| | - Miao-Sui Lin
- a Department of Physical Medicine and Rehabilitation , Chang Gung Memorial Hospital at Linkou , Taoyuan City , Taiwan
| | - Yi-Cheng Wu
- a Department of Physical Medicine and Rehabilitation , Chang Gung Memorial Hospital at Linkou , Taoyuan City , Taiwan
| | - Chih-Hao Liao
- a Department of Physical Medicine and Rehabilitation , Chang Gung Memorial Hospital at Linkou , Taoyuan City , Taiwan.,b College of Medicine , Chang Gung University , Taoyuan City , Taiwan
| | - Jong-Hwei S Pang
- a Department of Physical Medicine and Rehabilitation , Chang Gung Memorial Hospital at Linkou , Taoyuan City , Taiwan.,c Graduate Institute of Clinical Medical Sciences, Chang Gung University , Taoyuan City , Taiwan
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RETRACTED ARTICLE: Comparison of double-bundle anterior cruciate ligament reconstruction with and without autologous conditioned serum application. Knee Surg Sports Traumatol Arthrosc 2016; 24:3377. [PMID: 25448137 DOI: 10.1007/s00167-014-3457-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Accepted: 11/19/2014] [Indexed: 01/15/2023]
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Denapoli PMA, Stilhano RS, Ingham SJM, Han SW, Abdalla RJ. Platelet-Rich Plasma in a Murine Model: Leukocytes, Growth Factors, Flt-1, and Muscle Healing. Am J Sports Med 2016; 44:1962-71. [PMID: 27217525 DOI: 10.1177/0363546516646100] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND It is well known that platelet-rich plasma (PRP) preparations are not the same and that not all preparations include white blood cells, but the part that leukocytes play on the healing role of PRP is still unknown. PURPOSE The primary aim of this study was to evaluate the influence of leukocytes in different PRP preparations with a special emphasis on growth factor concentrations. The secondary aim was to evaluate the influence of PRP on muscle healing. STUDY DESIGN Controlled laboratory study. METHODS Two PRP preparation procedures were evaluated. Blood fractions were stained with Rapid Panoptic, and growth factors (transforming growth factor beta 1 [TGF-β1], vascular endothelial growth factor [VEGF], insulin-like growth factor [IGF], epidermal growth factor [EGF], hepatocyte growth factor [HGF], and platelet-derived growth factor [PDGF]) were quantified by enzyme-linked immunosorbent assay. Western blotting analysis was performed for Fms-related tyrosine kinase 1 (Flt-1). A muscle contusion injury was created and treated with PRP at different time points. RESULTS Leukocytes were the main source of VEGF, and all other growth factors measured had a higher concentration in the preparations that included the buffy coat and consequently had a higher concentration of white blood cells. Flt-1 was also found in platelet-poor plasma (PPP). There were higher concentrations of PDGF and HGF in the preparations that encompassed the buffy coat. A PRP injection 7 days after the injury provided significantly increased exercise performance and decreased the fibrotic area when compared with other PRP-treated groups. CONCLUSION VEGF is only present in PRP's buffy coat, while Flt-1 is present in PPP. A PRP injection 7 days after an injury resulted in improved exercise performance. CLINICAL RELEVANCE The presence of Flt-1 in PRP provides yet another explanation for results described in the literature after a PRP injection. This information is relevant for selecting the best PRP for each type of injury.
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Affiliation(s)
| | - Roberta Sessa Stilhano
- Center for Cell and Molecular Therapy, Federal University of São Paulo, São Paulo, Brazil
| | - Sheila Jean McNeill Ingham
- Department of Orthopedic Surgery, School of Medicine, Federal University of São Paulo, São Paulo, Brazil Knee Institute, Heart Hospital, São Paulo, Brazil
| | - Sang Won Han
- Center for Cell and Molecular Therapy, Federal University of São Paulo, São Paulo, Brazil
| | - Rene Jorge Abdalla
- Department of Orthopedic Surgery, School of Medicine, Federal University of São Paulo, São Paulo, Brazil Knee Institute, Heart Hospital, São Paulo, Brazil
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Punduk Z, Oral O, Ozkayin N, Rahman K, Varol R. Single dose of intra-muscular platelet rich plasma reverses the increase in plasma iron levels in exercise-induced muscle damage: A pilot study. JOURNAL OF SPORT AND HEALTH SCIENCE 2016; 5:109-114. [PMID: 30356475 PMCID: PMC6188580 DOI: 10.1016/j.jshs.2014.11.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/26/2014] [Revised: 10/02/2014] [Accepted: 11/17/2014] [Indexed: 06/08/2023]
Abstract
BACKGROUND Platelet rich plasma (PRP) therapy is widely used in enhancing the recovery of skeletal muscle from injury. However, the impact of intramuscular delivery of PRP on hematologic and biochemical responses has not been fully elucidated in exercise-induced muscle damage. The purpose of this investigation the effects of intramuscular delivery of PRP on hematologic and biochemical responses and recovery strategy muscle damage induced by high intensity muscle exercise (exercise-induced muscle damage, EIMD). METHODS Moderately active male volunteers participated in this study and were assigned to a control group (control, n = 6) and PRP administration group (PRP, n = 6). The subjects performed exercise with a load of 80% one repetition maximum (1RM) maximal voluntary contraction of the elbow flexors until point of exhaustion of the non-dominant arm was reached. The arms were treated with saline or autologous PRP post-24 h EIMD. Venous blood samples were obtained in the morning to establish a baseline value and 1-4 days post-exercise and were analyzed for serum ferritin, iron, iron binding capacity (IBC), creatinine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). RESULTS The baseline levels of plasma iron, ferritin, IBC, CK, LDH, AST, and ALT were similar in both the control and PRP groups. However, 24-h following exercise a significant increase in these parameters was observed in both groups between 1 and 4 days during the recovery period. Interestingly, PRP administration decreased plasma iron levels compared to the control on the second day post-exercise. Plasma IBC increased in PRP group from Days 2 to 4 post-exercise compared to the control group whilst PRP administration had no effect on plasma ferritin, CK, AST, ALT, or LDH. CONCLUSION Acute exhaustive exercise increased muscle damage markers, including plasma iron, IBC, and ferritin levels, indicating muscle damage induced by exercise. PRP administration improves inflammation by reversing the increase in the iron levels post-exercise without displaying any myotoxicity and may have a role to play in the recovery of exercise-induced muscle damage.
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Affiliation(s)
- Zekine Punduk
- Department of Physical Education and Sports, University of Balikesir, Balikesir 10100, Turkey
| | - Onur Oral
- Department of Physical Education and Sports, University of Ege, Izmir 35040, Turkey
| | - Nadir Ozkayin
- Medical Faculty, Department of Orthopaedics and Traumatology, University of Ege, Izmir 35100, Turkey
| | - Khalid Rahman
- Faculty of Science, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK
| | - Rana Varol
- Department of Physical Education and Sports, University of Ege, Izmir 35040, Turkey
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Xiao W, Liu Y, Luo B, Zhao L, Liu X, Zeng Z, Chen P. Time-dependent gene expression analysis after mouse skeletal muscle contusion. JOURNAL OF SPORT AND HEALTH SCIENCE 2016; 5:101-108. [PMID: 30356928 PMCID: PMC6191981 DOI: 10.1016/j.jshs.2016.01.017] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Revised: 09/06/2015] [Accepted: 10/16/2015] [Indexed: 06/08/2023]
Abstract
BACKGROUND Though the mechanisms of skeletal muscle regeneration are deeply understood, those involved in muscle contusion, one of the most common muscle injuries in sports medicine clinics, are not. The objective of this study is to explore the mechanisms involved in muscle regeneration after contusion injury. METHODS In this study, a total of 72 mice were used. Eight of them were randomly chosen for the control group, while the rest were subjected to muscle contusion. Subsequently, their gastrocnemius muscles were harvested at different time points. The changes in muscle morphology were assessed by hematoxylin and eosin (HE) stain. In addition, the gene expression was analyzed by real-time polymerase chain reaction. RESULTS The data showed that the expression of many genes, i.e., specific markers of immune cells and satellite cells, regulatory factors for muscle regeneration, cytokines, and chemokines, increased in the early stages of recovery, especially in the first 3 days. Furthermore, there were strict rules in the expression of these genes. However, almost all the genes returned to normal at 14 days post-injury. CONCLUSION The sequence of immune cells invaded after muscle contusion was neutrophils, M1 macrophages and M2 macrophages. Some CC (CCL2, CCL3, and CCL4) and CXC (CXCL10) chemokines may be involved in the chemotaxis of these immune cells. HGF may be the primary factor to activate the satellite cells after muscle contusion. Moreover, 2 weeks are needed to recover when acute contusion happens as used in this study.
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Affiliation(s)
- Weihua Xiao
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China
| | - Yu Liu
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China
- Department of Exercise Science, Shenyang Sport University, Shenyang 110001, China
| | - Beibei Luo
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China
| | - Linlin Zhao
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China
| | - Xiaoguang Liu
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China
| | - Zhigang Zeng
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China
| | - Peijie Chen
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China
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Baselga García-Escudero J, Miguel Hernández Trillos P. Treatment of Osteoarthritis of the Knee with a Combination of Autologous Conditioned Serum and Physiotherapy: A Two-Year Observational Study. PLoS One 2015; 10:e0145551. [PMID: 26709697 PMCID: PMC4692499 DOI: 10.1371/journal.pone.0145551] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Accepted: 12/04/2015] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Autologous conditioned serum (ACS) is an autologous blood product that has shown efficacy against knee osteoarthritis (OA) in randomized controlled trials. However, there are few reports of its effectiveness in everyday practice. Here, we report clinical efficacy results from a two-year prospective observational study of patients with highly symptomatic knee OA who received ACS in conjunction with physiotherapy. METHODS 118 patients with unilateral knee OA (Kellgren-Lawrence grades I-IV), who were candidates for surgery but instead chose conservative treatment, were treated with a combination of four intra-articular injections of ACS (2 mL each) once weekly over four weeks and subsequent physiotherapy applied 4 weeks after ACS injection. Main endpoints of the study were pain (Numeric Rating Scale [NRS]) assessed at 0, 3, 6, 12 and 24 months, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, assessed at 0 and 24 months. The effect size (Cohen's d) was calculated for pain and WOMAC outcomes, with effect sizes >0.8 considered large. RESULTS By 3 months, there were significant improvements in pain (NRS) from baseline (-63.0%, p<0.001), which were maintained over 24 months. Mean WOMAC global score was reduced at 24 months compared to baseline (-56.9%, p<0.001), as were WOMAC subscores of pain (-86.0%, p<0.001) and function (-51.3%, p<0.001). Effect sizes for pain (>5) and WOMAC improvement (8.0-13.6) were very large. Only one patient received total knee joint replacement during the study. Clinical improvement did not correlate with gender, age, Kellgren-Lawrence grade, or body mass index. CONCLUSIONS Treatment with ACS and physiotherapy produced a rapid decline in pain, which was sustained for the entire two years of the study. This was accompanied by a large improvement in WOMAC scores at two years. These results confirm that ACS combined with physiotherapy is an effective treatment for OA of the knee.
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Elevated CRP level could herald less efficient autologous conditioned serum (ACS) treatment. Med Hypotheses 2015; 86:135-7. [PMID: 26559885 DOI: 10.1016/j.mehy.2015.11.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 11/01/2015] [Indexed: 01/12/2023]
Abstract
Autologous conditioned serum (ACS) is a biologically based local treatment aiming to influence the cytokine imbalance and is used in a variety of orthopedic diseases and conditions. The ACS contains elevated levels of various anti-inflammatory cytokines, such as IL-1 RA (receptor antagonist), IL-4 and IL-10 and several growth factors. It contains a combination of cytokines and growth factors, and their specific contribution to clinical effects have yet to be determined. Serum conditioned in that specific way does not always have the same content and concentration of the anti-inflammatory cytokines and growth factors. We hypothesize that ACS should not be prepared and administered if elevated C-reactive protein (CRP) levels are present at the moment of obtaining the patient's blood because of the potential detrimental effect of elevated pro-inflammatory cytokines in the same blood, namely IL-1 and TNF. We propose introduction of CRP measuring before any ACS treatment. The cut off value would be set at 5mg/dL as an usual value suggesting inflammation. Avoidance of collecting and administering ACS if elevated CRP is present would potentially eliminate low quality ACS.
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Quarteiro ML, Tognini JRF, de Oliveira ELF, Silveira I. O efeito do plasma rico em plaquetas no reparo de lesões musculares em ratos. Rev Bras Ortop 2015. [DOI: 10.1016/j.rbo.2014.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Quarteiro ML, Tognini JRF, de Oliveira ELF, Silveira I. The effect of platelet-rich plasma on the repair of muscle injuries in rats. Rev Bras Ortop 2015; 50:586-95. [PMID: 26535207 PMCID: PMC4610980 DOI: 10.1016/j.rboe.2015.08.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Accepted: 09/12/2014] [Indexed: 12/19/2022] Open
Abstract
Objective The need for therapeutic options for muscle injuries, which are increasingly frequent among sports practitioners, was the motivation for this experimental study, which had the aim of evaluating the histological effects of platelet-rich plasma (PRP) on repairs to muscle tissues of rats. Methods PRP was obtained by means of double centrifugation of blood from five animals. In 30 rats, an injury was produced in the middle third of the belly of the gastrocnemius muscle of each hind limb. These injuries did not receive any treatment in six rats (12 legs). In 24 rats, 0.9% physiological serum was injected into the injury in the left leg and PRP into the injury in the right leg. Samples from the treated and untreated tissue were evaluated histologically 7 and 21 days after the procedures. Results The quantity of collagen in the injuries treated with PRP was significantly lower than that in the other injuries, in the evaluation made 7 days after the procedure, but it became equal to the other groups in the evaluation done on the 21st day. There was a significant increase (p < 0.001) in the quantity of collagen from the 7th to the 21st day in the injuries treated with PRP, but this was not seen in the injuries treated using other methods. The inflammatory process was shown to be more intense in the injuries treated with PRP than in the injuries of the other treatment groups, in the evaluation done 7 days after the procedure. However, the morphological aspects of these injuries were seen to be similar to those of the untreated injuries, 21 days after the procedure. Conclusion PRP promoted complete tissue restitution between the 7th and 21st days in experimental muscle injuries.
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Affiliation(s)
| | | | | | - Izabelli Silveira
- Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil
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Padilla S, Sánchez M, Orive G, Anitua E. Towards a correct timing and dosage in PRP applications. Injury 2015; 46:1697-8. [PMID: 25920374 DOI: 10.1016/j.injury.2015.03.022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Accepted: 03/05/2015] [Indexed: 02/02/2023]
Affiliation(s)
- S Padilla
- Foundation Eduardo Anitua, Vitoria, Spain
| | - M Sánchez
- Arthroscopy Surgery Unit, Hospital Vithas San José, Vitoria, Spain
| | - G Orive
- Foundation Eduardo Anitua, Vitoria, Spain.
| | - E Anitua
- Foundation Eduardo Anitua, Vitoria, Spain; Biotechnology Institute (BTI), Vitoria, Spain
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Hamilton B, Tol JL, Almusa E, Boukarroum S, Eirale C, Farooq A, Whiteley R, Chalabi H. Platelet-rich plasma does not enhance return to play in hamstring injuries: a randomised controlled trial. Br J Sports Med 2015; 49:943-50. [DOI: 10.1136/bjsports-2015-094603] [Citation(s) in RCA: 104] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Geburek F, Lietzau M, Beineke A, Rohn K, Stadler PM. Effect of a single injection of autologous conditioned serum (ACS) on tendon healing in equine naturally occurring tendinopathies. Stem Cell Res Ther 2015; 6:126. [PMID: 26113022 PMCID: PMC4513386 DOI: 10.1186/s13287-015-0115-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2014] [Revised: 02/27/2015] [Accepted: 06/11/2015] [Indexed: 11/29/2022] Open
Abstract
Introduction Autologous blood-derived biologicals, including autologous conditioned serum (ACS), are frequently used to treat tendinopathies in horses despite limited evidence for their efficacy. The purpose of this study was to describe the effect of a single intralesional injection of ACS in naturally occurring tendinopathies of the equine superficial digital flexor tendon (SDFT) on clinical, ultrasonographic, and histological parameters. Methods Fifteen horses with 17 naturally occurring tendinopathies of forelimb SDFTs were examined clinically and ultrasonographically (day 0). Injured tendons were randomly assigned to the ACS-treated group (n = 10) receiving a single intralesional ACS injection or included as controls (n = 7) which were either untreated or injected with saline on day 1. All horses participated in a gradually increasing exercise programme and were re-examined nine times at regular intervals until day 190. Needle biopsies were taken from the SDFTs on days 0, 36 and 190 and examined histologically and for the expression of collagen types I and III by immunohistochemistry. Results In ACS-treated limbs lameness decreased significantly until day 10 after treatment. Swelling (scores) of the SDFT region decreased within the ACS group between 50 and 78 days after treatment. Ultrasonographically, the percentage of the lesion in the tendon was significantly lower and the echogenicity of the lesion (total echo score) was significantly higher 78 and 106 days after intralesional ACS injection compared to controls. Histology revealed that, compared to controls, tenocyte nuclei were more spindle-shaped 36 days after ACS injection. Immunohistochemistry showed that collagen type I expression significantly increased between days 36 and 190 after ACS injection. Conclusions Single intralesional ACS injection of equine SDFTs with clinical signs of acute tendinopathy contributes to an early significant reduction of lameness and leads to temporary improvement of ultrasonographic parameters of repair tissue. Intralesional ACS treatment might decrease proliferation of tenocytes 5 weeks after treatment and increase their differentiation as demonstrated by elevated collagen type I expression in the remodelling phase. Potential enhancement of these effects by repeated injections should be tested in future controlled clinical investigations.
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Affiliation(s)
- Florian Geburek
- Equine Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany.
| | - Maren Lietzau
- Equine Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany.
| | - Andreas Beineke
- Institute for Pathology, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559, Hannover, Germany.
| | - Karl Rohn
- Institute for Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Foundation, Bünteweg 2, 30559, Hannover, Germany.
| | - Peter M Stadler
- Equine Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany.
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Abstract
Muscle injuries are common and may be associated with impaired functional capacity, especially among athletes. The results of healing with conventional therapy including rest, ice, compression, and elevation (RICE) are often inadequate, generating substantial interest in the potential for emerging technologies such as platelet-rich plasma (PRP) to enhance the process of soft-tissue healing and to decrease time to recovery. In vitro studies and animal research have suggested that PRP may have benefits associated with the increased release of cytokines and growth factors resulting from supraphysiological concentrations of platelets that facilitate muscle repair, regeneration, and remodeling. Despite the promise of basic science, there is a paucity of clinical data to support the theoretical benefits of PRP. The only double-blind controlled clinical trial was recently reported and showed no benefit of PRP in the time to resume sports activity among athletes with hamstring muscle injury. This review examines the current evidence and the theoretical framework for PRP and muscle healing. Scientific gaps and technological barriers are discussed that must be addressed if the potential promise of PRP as a therapeutic modality for muscle injury is to be realized.
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Affiliation(s)
- Michael J. Mosca
- />Harvard College, 372 Lowell Mail Center, Cambridge, MA 02138 USA
| | - Scott A. Rodeo
- />Sports Medicine and Shoulder Service Orthopedic Surgery, 535 East 70th St., New York, NY USA
- />The Hospital for Special Surgery, Weill Medical College of Cornell, New York, NY 10021 USA
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Abstract
Skeletal muscle injuries are among the most common sports-related injuries that result in time lost from practice and competition. The cellular response to muscle injury can often result in changes made to the muscle fibers as well as the surrounding extracellular matrix during repair. This can negatively affect the force and range of the injured muscle even after the patient's return to play. Diagnosis of skeletal muscle injury involves both history and physical examinations; imaging modalities including ultrasound and magnetic resonance imaging (MRI) can also be used to assess the extent of injury. Current research is investigating potential methods, including clinical factors and MRI, by which to predict a patient's return to sports. Overall, function of acutely injured muscles seems to improve with time. Current treatment methods for skeletal muscle injuries include injections of steroids, anesthetics, and platelet-rich plasma (PRP). Other proposed methods involve inhibitors of key players in fibrotic pathways, such as transforming growth factor (TGF)-ß and angiotensin II, as well as muscle-derived stem cells.
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Affiliation(s)
- Stephanie Wong
- Department of Orthopaedic Surgery, University of California, 1500 Owens Ave, Box 3004, San Francisco, CA, 94127, USA
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Reurink G, Goudswaard GJ, Moen MH, Weir A, Verhaar JAN, Bierma-Zeinstra SMA, Maas M, Tol JL. Rationale, secondary outcome scores and 1-year follow-up of a randomised trial of platelet-rich plasma injections in acute hamstring muscle injury: the Dutch Hamstring Injection Therapy study. Br J Sports Med 2015; 49:1206-12. [DOI: 10.1136/bjsports-2014-094250] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/11/2015] [Indexed: 12/19/2022]
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Abstract
INTRODUCTION Every year recreational and professional sports cause thousands of lesions to muscle, ligament and tendon. Critical progress in biological interventions could meet a pressing health need to help athletes resume their activity levels. AREAS COVERED We perform a narrative review on platelet-rich plasma (PRP) therapies and muscle injuries. The field is eminently translational, thus besides clinical data we summarize experimental studies that bring meaningful biological insights on PRP effects. Some concepts regarding healing mechanisms are reviewed including innate immune response, myogenesis and fibrosis. It is commonly thought that PRPs are not uniform and cannot be assessed against each other, thus current PRP classifications are addressed. PRP effects also depend on the characteristics of the host tissue; therefore we focus on clinical muscle injury classifications. Controversial clinical findings are attributed to both the variability in PRP formulations and variability in the application protocols, so we discuss current clinical data in this basis. EXPERT OPINION Currently, there is little clinical evidence to support the use of PRP in skeletal muscle injuries. The future of PRP therapies relies not only in finding the best products, most appropriate indications and application protocols, but also in conceiving combination products. Moreover, as our understanding of healing mechanisms progresses, off-the-shelf allogenic PRP products could be part of the solution for sport injuries.
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Affiliation(s)
- Isabel Andia
- Cruces University Hospital, BioCruces Health Research Institute, Regenerative Medicine Laboratory , Barakaldo 48903 , Spain
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Dimauro I, Grasso L, Fittipaldi S, Fantini C, Mercatelli N, Racca S, Geuna S, Di Gianfrancesco A, Caporossi D, Pigozzi F, Borrione P. Platelet-rich plasma and skeletal muscle healing: a molecular analysis of the early phases of the regeneration process in an experimental animal model. PLoS One 2014; 9:e102993. [PMID: 25054279 PMCID: PMC4108405 DOI: 10.1371/journal.pone.0102993] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Accepted: 06/24/2014] [Indexed: 12/27/2022] Open
Abstract
Platelet-rich plasma (PRP) has received increasing interest in applied medicine, being widely used in clinical practice with the aim of stimulating tissue healing. Despite the reported clinical success, there is still a lack of knowledge when considering the biological mechanisms at the base of the activity of PRP during the process of muscle healing. The aim of the present study was to verify whether the local delivery of PRP modulates specific molecular events involved in the early stages of the muscle regeneration process. The right flexor sublimis muscle of anesthetized Wistar rats was mechanically injured and either treated with PRP or received no treatment. At day 2 and 5 after surgery, the animals were sacrificed and the muscle samples evaluated at molecular levels. PRP treatment increased significantly the mRNA level of the pro-inflammatory cytokines IL-1β, and TGF-β1. This phenomenon induced an increased expression at mRNA and/or protein levels of several myogenic regulatory factors such as MyoD1, Myf5 and Pax7, as well as the muscular isoform of insulin-like growth factor1 (IGF-1Eb). No effect was detected with respect to VEGF-A expression. In addition, PRP application modulated the expression of miR-133a together with its known target serum response factor (SRF); increased the phosphorylation of αB-cristallin, with a significant improvement in several apoptotic parameters (NF-κB-p65 and caspase 3), indexes of augmented cell survival. The results of the present study indicates that the effect of PRP in skeletal muscle injury repair is due both to the modulation of the molecular mediators of the inflammatory and myogenic pathways, and to the control of secondary pathways such as those regulated by myomiRNAs and heat shock proteins, which contribute to proper and effective tissue regeneration.
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Affiliation(s)
- Ivan Dimauro
- Unit of Biology, Genetics and Biochemistry, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italy
| | - Loredana Grasso
- Unit of Internal Medicine, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italy
| | - Simona Fittipaldi
- Unit of Biology, Genetics and Biochemistry, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italy
| | - Cristina Fantini
- Unit of Biology, Genetics and Biochemistry, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italy
| | - Neri Mercatelli
- Unit of Biology, Genetics and Biochemistry, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italy
| | - Silvia Racca
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Stefano Geuna
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Alessia Di Gianfrancesco
- Unit of Internal Medicine, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italy
| | - Daniela Caporossi
- Unit of Biology, Genetics and Biochemistry, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italy
- * E-mail:
| | - Fabio Pigozzi
- Unit of Internal Medicine, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italy
| | - Paolo Borrione
- Unit of Internal Medicine, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italy
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