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Bozhokin MS, Bozhkova SA, Sopova JV, Leonova EI, Shubniakov MI, Rubel AA, Simental-Mendía M. Perspectives for using platelet-rich plasma in the treatment of knee osteoarthritis: Can it be improved through modifications of the protocol? Chin J Traumatol 2025:S1008-1275(25)00055-0. [PMID: 40382203 DOI: 10.1016/j.cjtee.2024.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/12/2024] [Accepted: 12/16/2024] [Indexed: 05/20/2025] Open
Abstract
PURPOSE Autologous platelet-rich plasma (PRP) injections are widely used in regenerative medicine, including the knee osteoarthritis (OA) therapy. This study reviews methods to enhance PRP therapy for knee OA, aiming to boost articular cartilage recovery. METHODS The search was conducted in the eLIBRARY, PubMed (MEDLINE), Ovid, ScienceDirect, and Google Scholar databases extracting publications available by the end of 2023. Studies were included if they simultaneously met the following criteria: (1) effect of using PRP in the recovery of hyaline cartilage damage after OA; (2) at least one way to modify the PRP protocol aimed to increase its efficiency; (3) data on the molecular mechanisms underlying the increase in efficiency of the modified PRP therapy in OA. RESULTS The findings of this study highlight the significant role that the composition and modification of PRP protocols play in enhancing chondrogenesis for cartilage repair. Beyond the activation or non-activation of platelets or the inclusion or removal of leukocytes, which are factors that could somehow affect the effectiveness of PRP formulations, the elimination of growth factors such as VEGF and EGF, which negatively influence cartilage regeneration, offers a promising approach to optimize PRP therapy. While growth factors like TGF-β3, PDGF, and IGF have been shown to promote chondrogenesis, the removal of detrimental factors that could contribute to chronic inflammation or OA progression could significantly improve treatment outcomes. Practices such as combining with hyaluronic acid, pre-injection PRP activation, and multiple administrations are clinically common, while other methods like adjusting growth factors concentration are still in development. CONCLUSION Various modifications of this technology allow to use molecular mechanisms involved in the restoration of hyaline cartilage and improve the effectiveness of PRP for the treatment of OA. However, significant challenges remain in standardizing PRP preparation and administration protocols. Variability in platelet concentration, growth factor composition, and activation methods complicate the assessment of efficacy and reproducibility.
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Affiliation(s)
- Mikhail S Bozhokin
- Treatment and Prevention of Wound Infection, Vreden National Medical Research Centre of Traumatology and Orthopedics, Saint Petersburg, 195427, Russia; Сenter of Cell Technologies, Institute of Cytology Russian Academy of Science, Saint Petersburg, 194064, Russia.
| | - Svetlana A Bozhkova
- Treatment and Prevention of Wound Infection, Vreden National Medical Research Centre of Traumatology and Orthopedics, Saint Petersburg, 195427, Russia
| | - Julia V Sopova
- Center of Transgenesis and Genome Editing, Saint Petersburg State University, Saint Petersburg, 198504, Russia; Laboratory of Plant Genetics and Biotechnology, Institute of General Genetics, St Petersburg Branch, Saint Petersburg, 198504, Russia
| | - Elena I Leonova
- Center of Transgenesis and Genome Editing, Saint Petersburg State University, Saint Petersburg, 198504, Russia
| | - Maxim I Shubniakov
- Treatment and Prevention of Wound Infection, Vreden National Medical Research Centre of Traumatology and Orthopedics, Saint Petersburg, 195427, Russia
| | - Aleksandr A Rubel
- Laboratory of Amyloid Biology, Saint Petersburg State University, Saint Petersburg, 198504, Russia
| | - Mario Simental-Mendía
- Orthopedic Trauma Service, "Dr. José Eleuterio González" University Hospital, School of Medicine, Autonomous University of Nuevo Leon, Monterrey, 66455, Mexico
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Paliaroutas OV, Evangelopoulos DS, Vasiliadis E, Stanitsa N, Zouris G, Vlamis J. Role of Platelet-Rich Plasma (PRP) in the Management of Stage III and IV Degenerative Disc Disease. Cureus 2025; 17:e79504. [PMID: 40144405 PMCID: PMC11937859 DOI: 10.7759/cureus.79504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/23/2025] [Indexed: 03/28/2025] Open
Abstract
Degenerative disc disease is a common disorder that can significantly impact patients' quality of life, leading to chronic pain and disability. Platelet-rich plasma (PRP) therapy is emerging as a potential treatment for degenerative disc disease. The purpose of this review is to summarize the role of PRP in the management of degenerative disc disease types III and IV. This is a scoping literature review. The online database PUBMED was used, and papers were searched using the keywords: ("PRP" OR "platelet-rich plasma") AND ("degenerative disk disease" OR "disk degeneration" OR "intradiscal injection" OR "discogenic pain" OR "intervertebral disc degeneration" OR "degenerative disk disease" OR "intervertebral disc disease"). Clinical studies evaluating the role of PRP in the management of stage III and IV degenerative disc disease were included in the study. Systematic reviews, animal studies, in vitro studies, case reports, study designs, case reports, and studies in languages other than English were excluded. The present study includes 14 studies. PRP has been found to promote tissue regeneration and modulate inflammatory response in degenerated discs. PRP can be administered mostly intradiscally but also epidurally. The benefits of PRP use include pain reduction, improvement of functionality, and low risk of adverse events. The effect of intradiscal PRP injections is similar to steroid injections. A higher concentration of platelets is associated with enhanced clinical outcomes. PRP therapy represents a promising avenue for tissue healing and regeneration across degenerative disc disease. While the evidence supporting its efficacy is encouraging, further research is needed to elucidate its mechanisms of action, optimize treatment protocols, and expand its clinical applications.
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Affiliation(s)
- Orestis V Paliaroutas
- First Orthopedic Department, National and Kapodistrian University of Athens School of Medicine, KAT Hospital, Athens, GRC
| | | | - Elias Vasiliadis
- Third Orthopedic Department, National and Kapodistrian University of Athens School of Medicine, KAT Hospital, Athens, GRC
| | - Nikoleta Stanitsa
- Cardiothoracic Surgery Department, Evangelismos Hospital, Athens, GRC
| | - Georgios Zouris
- Fifth Orthopedic Department, Asklepieion Voulas General Hospital, Athens, GRC
| | - John Vlamis
- Third Orthopedic Department, National and Kapodistrian University of Athens School of Medicine, KAT Hospital, Athens, GRC
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Abate M, Paganelli R, Pellegrino R, Di Iorio A, Salini V. Platelet Rich Plasma Therapy in Achilles and Patellar Tendinopathies: Outcomes in Subjects with Diabetes (A Retrospective Case-Control Study). J Clin Med 2024; 13:5443. [PMID: 39336930 PMCID: PMC11432448 DOI: 10.3390/jcm13185443] [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: 07/29/2024] [Revised: 09/06/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
Introduction: Diabetes mellitus (DM) is associated with a high risk of chronic degenerative Achilles (AT) and Patellar (PT) tendinopathies and ruptures. Growth factors (GFs) synthesis in diabetics is substantially decreased in human connective tissues, including in tendons. Platelet Rich Plasma (PRP), which is enriched in GFs, might prove of great help in tendon healing. The aim of the study was to assess whether pre-existent DM or Impaired Glucose Tolerance (IGT) could influence the clinical outcome in subjects undergoing PRP treatment. Methods: Sixty subjects with diabetes/pre-diabetes and sixty euglycemic controls, matched for sex and age, were enrolled. Patients suffering from proximal insertional PT and mid-portion AT, treated with PRP therapy, were included in the study. To assess the basal status and the efficacy of the therapy after 3 and 6 months, the Victorian Institute of Sport Assessment (VISA) questionnaire and the Ultrasound methodology study were used. Patient satisfaction was assessed by means of the Likert Scale. Results: In the population study at 6 months, the mean VISA-score increased (8.92 ± 0.67; p-value < 0.001). The improvement in the diabetic group was less evident compared to the controls (-2.76 ± 0.95; p-value = 0.003). Even though the improvement was poor, it was still significant. MCID analysis revealed that diabetics had higher risk of therapeutic unsuccess. Logistic regression analysis was applied to assess factors associated with unsatisfactory results (Likert-scale) of PRP treatment: AT (O.R.: 3.05; 95%CI: 1.40-6.64; p-value = 0.005), higher BMI values (O.R.: 1.02; 95%CI: 1.01-1.04; p-value = 0.01), and lower VISA score values at baseline (O.R.: 0.95; 95%CI: 0.90-0.99; p-value = 0.04). Conclusions: PRP treatment in AT and PT chronic tendinopathies resulted in less favorable results in subjects with diabetes compared with euglycemic subjects. Moreover, the subjects with PT showed better results than those with AT.
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Affiliation(s)
- Michele Abate
- IRCSS Ospedale San Raffaele, 20132 Milan, Italy; (M.A.); (V.S.)
| | - Roberto Paganelli
- Saint Camillus International University of Health and Medical Sciences, 00131 Rome, Italy;
| | | | - Angelo Di Iorio
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” Chieti-Pescara, Viale Abruzzo 322, 66100 Chieti, Italy
| | - Vincenzo Salini
- IRCSS Ospedale San Raffaele, 20132 Milan, Italy; (M.A.); (V.S.)
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Leonova EI, Chirinskaite AV, Sopova JV. A systematic review of the safety and efficacy of platelet-rich plasma for the treatment of posttraumatic knee osteoarthritis. KAZAN MEDICAL JOURNAL 2024; 105:637-647. [DOI: 10.17816/kmj568204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Injury of the knee joint can lead to a range of adverse outcomes and significantly contributes to the development of the knee osteoarthritis. Currently, autologous platelet-rich plasma is used as a promising and safe method of treating osteoarthritis. Such plasma contains various growth factors, some of which are secreted after platelet activation. These factors can trigger a regenerative response and improve the metabolic functions of damaged structures. However, there are different protocols for preparing platelet-rich plasma, which results in preparations with different amounts of bioactive substances. As a result, the data obtained on the effect of platelet-rich plasma on the restoration of hyaline cartilage of the knee joint are very contradictory. A search for publications on a given topic was performed in the eLIBRARY, PubMed (MEDLINE), Ovid, Science Direct, Google Scholar databases, and also a search was conducted for clinical trial data on the treatment of knee osteoarthritis with platelet-rich plasma over the past 20 years. Publications dealing with other aspects of the application of this technology were excluded from the search results. An analysis of published clinical trial results found that, in most cases, patients treated with platelet-rich plasma reported improved pain and joint function, with only three studies showing no difference between platelet-rich plasma and placebo. Thus, this technology is generally promising for use in the treatment of knee osteoarthritis, however, methods of obtaining and activating platelet-rich plasma, as well as the age and comorbidities of the patient, may affect the effectiveness of therapy.
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Affiliation(s)
- Elena I. Leonova
- Center for Transgenesis and Genome Editing, Institute of Translational Biomedicine, St. Petersburg State University
| | - Angelina V. Chirinskaite
- Center for Transgenesis and Genome Editing, Institute of Translational Biomedicine, St. Petersburg State University
| | - Julia V. Sopova
- Center for Transgenesis and Genome Editing, Institute of Translational Biomedicine, St. Petersburg State University
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Zhuo F, Jia X, Wang Z, Zhang Y, Yan X. Platelet-rich plasma alleviates knee arthritis in rats by inhibiting p65. Cell Tissue Bank 2024; 25:463-473. [PMID: 37501011 DOI: 10.1007/s10561-023-10102-3] [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: 06/29/2022] [Accepted: 07/06/2023] [Indexed: 07/29/2023]
Abstract
Knee osteoarthritis (KOA) is a chronic joint disease characterized by the degeneration of articular cartilage. In this study, we explored the potential therapeutic effects of platelet-rich plasma (PRP) and identified molecular targets for treating KOA. A rat model of KOA was established via the Hulth method and primary knee joint chondrocytes were isolated to evaluate the effects of PRP and shRNA targeting p65 (sh-p65). ELISA was used to detect inflammatory factors, including IL-6, IL-1β, and TNF-α. HE staining, Safranin O/Fast Green staining and Masson staining were performed to evaluate the morphology of articular cartilage, followed by detection of p65, COL2A1, ACAN, MMP13, and ADAMTS5 expression. The proliferation and apoptosis of primary knee chondrocytes were detected by the CCK-8 assay and TUNEL staining, respectively. Treatment with either PRP or sh-p65 decreased IL-6, IL-1β, and TNF-α levels in the peripheral blood of KOA rats and chondrocyte culture supernatants, increased COL2A1 and ACAN levels, and decreased MMP13 and ADAMTS5 expression. Furthermore, administration of PRP or sh-p65 exerted protective effects on articular cartilage, enhanced the vitality of knee joint chondrocytes, and inhibited apoptosis. Collectively, PRP inhibited inflammation, promoted chondrocyte proliferation and cartilage matrix secretion, and induced cartilage regeneration by suppressing p65 expression; these effects allow PRP to alleviate KOA progression. P65-based targeted therapy administered in combination with PRP might be a promising strategy for treating KOA.
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Affiliation(s)
- Feng Zhuo
- Department of Joint Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Lixia District, No. 16766, Jingshi Road, Jinan, 271000, Shandong, China
- Department of Joint Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Longtan Road, Taian, 271000, Shandong, China
| | - Xiaojing Jia
- Orthopedics Department, The Affiliated Taian City Central Hospital of Qingdao University, Longtan Road, Taian, 271000, Shandong, China
| | - Zongru Wang
- Department of Joint Surgery, Municipal Hospital of Taian, Tianpinghu Road, Taian, 271021, Shandong, China
| | - Yeyong Zhang
- Department of Joint Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Lixia District, No. 16766, Jingshi Road, Jinan, 271000, Shandong, China
| | - Xinfeng Yan
- Department of Joint Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Lixia District, No. 16766, Jingshi Road, Jinan, 271000, Shandong, China.
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Şeker Ş, Lalegül-Ülker Ö, Elçin AE, Elçin YM. Regeneration of Volumetric Muscle Loss Using MSCs Encapsulated in PRP-Derived Fibrin Microbeads. Methods Mol Biol 2024. [PMID: 38578577 DOI: 10.1007/7651_2024_533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
Volumetric muscle loss (VML) is one of the major types of soft tissue injury frequently encountered worldwide. In case of VML, the endogenous regenerative capacity of the skeletal muscle tissue is usually not sufficient for complete healing of the damaged area resulting in permanent functional musculoskeletal impairment. Therefore, the development of new tissue engineering approaches that will enable functional skeletal muscle regeneration by overcoming the limitations of current clinical treatments for VML injuries has become a critical goal. Platelet-rich plasma (PRP) is an inexpensive and relatively effective blood product with a high concentration of platelets containing various growth factors and cytokines involved in wound healing and tissue regeneration. Due to its autologous nature, PRP has been a safe and widely used treatment option for various wound types for many years. Recently, PRP-based biomaterials have emerged as a promising approach to promote muscle tissue regeneration upon injury. This chapter describes the use of PRP-derived fibrin microbeads as a versatile encapsulation matrix for the localized delivery of mesenchymal stem cells and growth factors to treat VML using tissue engineering strategies.
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Lai S, Wu T, Shi C, Wang X, Liu P, Wang L, Yu H. Triple-layered core-shell fiber dressings with enduring platelet conservation and sustained growth factor release abilities for chronic wound healing. Regen Biomater 2024; 11:rbae034. [PMID: 38601330 PMCID: PMC11004556 DOI: 10.1093/rb/rbae034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 03/08/2024] [Accepted: 03/12/2024] [Indexed: 04/12/2024] Open
Abstract
Platelet-rich plasma (PRP) is one of the most popular biomaterials in regenerative medicine. However, the difficulties encountered in its preservation, and the requirement for on-demand preparation severely limit its application. In addition, its rapid degradation in the wound microenvironment makes the sustained release of growth factors impossible and finally reduces the therapeutic effect on chronic wounds. Here, a multifunctional dressing based on triple-layered core-shell fibers for loading and enduring preservation of PRP was developed using a one-step coaxial bioprinting technique combined with freeze-drying. The platelets were effectively dispersed and immobilized in the core layer of the fiber, leading to a sustained release of growth factors from the PRP. The rate of release can be controlled by adjusting the triple-layered core-shell structure. Simultaneously, the triple-layered core-shell structure can reduce the deactivation of PRP during freezing and storage. The experimental findings suggest that PRP exhibits sustained activity, facilitating the process of wound healing even after a storage period of 180 days. Furthermore, the protective mechanism of PRP by the triple-layered core-shell fiber was investigated, and the conditions for freeze-drying and storage were optimized, further enhancing the long-term storability of PRP. As a result, the multifunctional core-shell fiber dressings developed in this study offer a novel approach for sustained growth factor release and the enduring preservation of active PRP.
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Affiliation(s)
- Simin Lai
- Guangdong–Hong Kong Joint Laboratory for New Textile Materials, School of Textile Science and Engineering, Wuyi University, Jiangmen 529020, China
| | - Tingbin Wu
- Guangdong–Hong Kong Joint Laboratory for New Textile Materials, School of Textile Science and Engineering, Wuyi University, Jiangmen 529020, China
| | - Chenxi Shi
- Guangdong–Hong Kong Joint Laboratory for New Textile Materials, School of Textile Science and Engineering, Wuyi University, Jiangmen 529020, China
| | | | - Pengbi Liu
- Guangdong–Hong Kong Joint Laboratory for New Textile Materials, School of Textile Science and Engineering, Wuyi University, Jiangmen 529020, China
| | - Lihuan Wang
- Guangdong–Hong Kong Joint Laboratory for New Textile Materials, School of Textile Science and Engineering, Wuyi University, Jiangmen 529020, China
| | - Hui Yu
- Guangdong–Hong Kong Joint Laboratory for New Textile Materials, School of Textile Science and Engineering, Wuyi University, Jiangmen 529020, China
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Huang M, Li Y, Liao C, Lai Q, Peng J, Guo N. Microfracture surgery combined with platelet-rich plasma injection in treating osteochondral lesions of talus: A system review and update meta analysis. Foot Ankle Surg 2024; 30:21-26. [PMID: 37730459 DOI: 10.1016/j.fas.2023.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Revised: 08/29/2023] [Accepted: 09/02/2023] [Indexed: 09/22/2023]
Abstract
BACKGROUND To systematically evaluate the efficacy of arthroscopic microfracture surgery combined with platelet-rich plasma (PRP) injection in treating osteochondral lesions of talus (OLT). METHOD A computer-based search of the PubMed, EMbase, Cochrane Library was developed. The search time was dated in December 2022. Randomized controlled trials and prospective case control studies comparing the treatment of OLT with microfracture surgery combined with PRP injection and microfracture surgery alone were included. The quality of the literatures were evaluated. Meta analysis was completed using the data of postoperative pain and function scores of the ankle joint reported in the literature. RESULTS Five randomized controlled trials with a total of 198 patients were included. Compared with microfracture surgery alone, meta-analysis showed that the postoperative visual analogue scale (VAS) score for ankle pain was significantly lower (P < 0.001), and the American Orthopaedic Foot and Ankle Society score (AOFAS) was significantly better ( P < 0.001) in the group of microfracture surgery combined with PRP injection. The change of VAS and AOFAS was also significantly better in the group of microfracture surgery combined with PRP injection (P < 0.001). CONCLUSION Arthroscopic microfracture surgery combined with PRP injection in treating OLT can significantly reduce pain and improve ankle function. More long-term follow-up, high-quality studies are needed. LEVEL OF EVIDENCE II.
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Affiliation(s)
- Mengquan Huang
- Department of Orthopaedics, Air Force Hospital of Southern Theater Command of PLA, Guangzhou 510602, Guangdong Province, China.
| | - Yubiao Li
- Department of Orthopaedics, Air Force Hospital of Southern Theater Command of PLA, Guangzhou 510602, Guangdong Province, China
| | - Chunlai Liao
- Department of Orthopaedics, Air Force Hospital of Southern Theater Command of PLA, Guangzhou 510602, Guangdong Province, China
| | - Qiulian Lai
- Department of Orthopaedics, Air Force Hospital of Southern Theater Command of PLA, Guangzhou 510602, Guangdong Province, China
| | - Jun Peng
- Department of Orthopaedics, Air Force Hospital of Southern Theater Command of PLA, Guangzhou 510602, Guangdong Province, China
| | - Naiming Guo
- Department of Orthopaedics, Air Force Hospital of Southern Theater Command of PLA, Guangzhou 510602, Guangdong Province, China
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Lu J, Li H, Zhang Z, Xu R, Wang J, Jin H. Platelet-rich plasma in the pathologic processes of tendinopathy: a review of basic science studies. Front Bioeng Biotechnol 2023; 11:1187974. [PMID: 37545895 PMCID: PMC10401606 DOI: 10.3389/fbioe.2023.1187974] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 07/10/2023] [Indexed: 08/08/2023] Open
Abstract
Tendinopathy is a medical condition that includes a spectrum of inflammatory and degenerative tendon changes caused by traumatic or overuse injuries. The pathological mechanism of tendinopathy has not been well defined, and no ideal treatment is currently available. Platelet-rich plasma (PRP) is an autologous whole blood derivative containing a variety of cytokines and other protein components. Various basic studies have found that PRP has the therapeutic potential to promote cell proliferation and differentiation, regulate angiogenesis, increase extracellular matrix synthesis, and modulate inflammation in degenerative tendons. Therefore, PRP has been widely used as a promising therapeutic agent for tendinopathy. However, controversies exist over the optimal treatment regimen and efficacy of PRP for tendinopathy. This review focuses on the specific molecular and cellular mechanisms by which PRP manipulates tendon healing to better understand how PRP affects tendinopathy and explore the reason for the differences in clinical trial outcomes. This article has also pointed out the future direction of basic research and clinical application of PRP in the treatment of tendinopathy, which will play a guiding role in the design of PRP treatment protocols for tendinopathy.
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Affiliation(s)
- Jialin Lu
- Department of Pain, The Second Hospital of Jilin University, Changchun, China
- Norman Bethune Health Science Center of Jilin University, Changchun, China
| | - Han Li
- Norman Bethune Health Science Center of Jilin University, Changchun, China
| | - Ziyu Zhang
- Norman Bethune Health Science Center of Jilin University, Changchun, China
| | - Rui Xu
- Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Jincheng Wang
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, China
| | - Hui Jin
- Department of Pain, The Second Hospital of Jilin University, Changchun, China
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, China
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Wani FA, Ibrahim MA, Ameen SH, Farage AE, Ali ZAE, Saleh K, Farag MM, Sayeed MU, Alruwaili MAY, Alruwaili AHF, Aljared AZA, Galhom RA. Platelet Rich Plasma and Adipose-Derived Mesenchymal Stem Cells Mitigate Methotrexate-Induced Nephrotoxicity in Rat via Nrf2/Pparγ/HO-1 and NF-Κb/Keap1/Caspase-3 Signaling Pathways: Oxidative Stress and Apoptosis Interplay. TOXICS 2023; 11:toxics11050398. [PMID: 37235213 DOI: 10.3390/toxics11050398] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/13/2023] [Accepted: 04/19/2023] [Indexed: 05/28/2023]
Abstract
BACKGROUND the nephrotoxicity of methotrexate (MTX) is observed in high-dose therapy. Moreover, low-dose MTX therapy for rheumatic diseases is debatable and claimed to cause renal impairment. This study aimed at studying the effect of methotrexate in repeated low doses on rat kidneys and assessing the efficacy of adipose-derived mesenchymal stem cells (AD-MSCs) and platelet rich plasma (PRP) for attenuating this effect. METHODS Forty-two male Wistar rats were used, 10 rats were donors of AD-MSCs and PRP, 8 rats served as control, and the remaining rats were subjected to induction of nephrotoxicity by MTX intraperitoneal injection once weekly for successive 8 weeks and then assigned into 3 groups of 8 animals each: Group II: received MTX only. Group III: received MTX + PRP. Group IV: received MTX + AD-MSCs. After one month, rats were anaesthetized, serum-sampled, and renal tissue removed for biochemical, histological, and ultrastructural evaluation. RESULTS there was significant tubular degeneration, glomerulosclerosis, fibrosis, decreased renal index, along with increased levels of urea and creatinine in the MTX group compared to the control group. Immunohistochemical expression of caspase-3 and iNOS in the renal tissue was significantly increased in group II compared to groups III and IV. Biochemical results revealed higher tissue malondialdehyde (MDA) concentration in the MTX-injected group which decreased significantly in co-treatment with either AD-MSC or PRP + MTX. MSC promoted the activation of the Nrf2/PPARγ/HO-1 and NF-κB/Keap1/caspase-3 pathways, increased antioxidant enzyme activities, reduced lipid peroxidation levels, and alleviated oxidative damage and apoptosis. PRP showed therapeutic effects and molecular mechanisms similar to MSC. Furthermore, MSC and PRP treatment significantly reduced MTX-induced upregulation of the pro-inflammatory (NF-κB, interleukin-1ß, and TNF-α), oxidative stress (Nrf-2, hemoxygenase-1, glutathione, and malondialdehyde), and nitrosative stress (iNOS) markers in the kidney. CONCLUSION repeated administration of low-dose MTX resulted in massive renal tissue toxicity and deterioration of renal function in rats which proved to be attenuated by PRP and AD-MSCs through their anti-inflammatory, anti-apoptotic and anti-fibrotic properties.
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Affiliation(s)
- Farooq A Wani
- Pathology Department, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia
| | - Mahrous A Ibrahim
- Forensic Medicine and Clinical Toxicology, College of Medicine, Jouf University, Sakaka 41412, Saudi Arabia
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Suez Canal University (SCU), Ismailia 41522, Egypt
| | - Shimaa H Ameen
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Zagazig University, Alsharqia 44519, Egypt
| | - Amira E Farage
- Department of Anatomy, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt
| | - Zinab Abd-Elhady Ali
- Vice Deanship for Academic Affairs, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
| | - Khaldoon Saleh
- Vice Deanship for Academic Affairs, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
| | - Medhat M Farag
- Medical Biochemistry Department, College of Medicine, Shaqra University, Shaqra 11961, Saudi Arabia
| | - Mohammed U Sayeed
- Pathology Department, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia
| | | | | | | | - Rania A Galhom
- Human Anatomy and Embryology Department, Faculty of Medicine, Suez Canal University (SCU), Ismailia 41522, Egypt
- Center of Excellence in Molecular and Cellular Medicine (CEMCM), Faculty of Medicine, Suez Canal University (SCU), Ismailia 41522, Egypt
- Human Anatomy and Embryology Department, Faculty of Medicine, Badr University in Cairo (BUC), Cairo 11829, Egypt
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Huseynov A, Reinhardt J, Chandra L, Dürschmied D, Langer HF. Novel Aspects Targeting Platelets in Atherosclerotic Cardiovascular Disease—A Translational Perspective. Int J Mol Sci 2023; 24:ijms24076280. [PMID: 37047253 PMCID: PMC10093962 DOI: 10.3390/ijms24076280] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/15/2023] [Accepted: 03/16/2023] [Indexed: 03/29/2023] Open
Abstract
Platelets are important cellular targets in cardiovascular disease. Based on insights from basic science, translational approaches and clinical studies, a distinguished anti-platelet drug treatment regimen for cardiovascular patients could be established. Furthermore, platelets are increasingly considered as cells mediating effects “beyond thrombosis”, including vascular inflammation, tissue remodeling and healing of vascular and tissue lesions. This review has its focus on the functions and interactions of platelets with potential translational and clinical relevance. The role of platelets for the development of atherosclerosis and therapeutic modalities for primary and secondary prevention of atherosclerotic disease are addressed. Furthermore, novel therapeutic options for inhibiting platelet function and the use of platelets in regenerative medicine are considered.
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Ranjan R, Kumar R, Jeyaraman M, Arora A, Kumar S, Nallakumarasamy A. Autologous platelet-rich plasma in the delayed union of long bone fractures - A quasi experimental study. J Orthop 2023; 36:76-81. [PMID: 36620095 PMCID: PMC9817092 DOI: 10.1016/j.jor.2022.12.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 12/15/2022] [Accepted: 12/28/2022] [Indexed: 01/01/2023] Open
Abstract
Introduction Fractures of long bones unite without any complication except for 2%-10% which may lead to delayed or non-union of the fracture. Management of delayed union of fractures poses a great challenge for orthopaedic surgeons. Platelet-rich plasma (PRP) is an autologous blood-derived biological agent, which delivers growth factors, cytokines, and bio-micro molecules at supraphysiologic concentrations at the site of tissue injury, thus potentiating the body's healing efforts. Various studies and research have proved the osteogenic activity of PRP. The growth factors present in the PRP induce the locally available resilient progenitor or stem cells and convert the atrophic environment into a trophic environment. Materials and methods We investigated the safety and efficacy of autologous PRP injection in the delayed union of long bone fractures. A total of 25 cases of delayed union of long bone fractures were augmented with 3 doses of autologous PRP at 3 weekly intervals and were followed up for 12 months. All the cases were documented with pre-and post-procedural and 12th -month visual analog score (VAS) and Warden's score. Results Out of 25 cases, 21 (84.00%) cases showed good union of fracture with adequate callus formation by 10-12 weeks with 3 doses of autologous PRP injections. The mean pre-procedural VAS and Warden's score at the final follow-up showed statistically significant results (p < 0.05). No other complications were noted due to autologous PRP application among the study participants during the study period except for 3 cases (2 cases of non-union, and 1 case of implant failure). Conclusion Results of the current study suggest that autologous injection of PRP might be a safe and effective therapeutic tool for the management of delayed union of long bone fractures.
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Affiliation(s)
- Rajni Ranjan
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India
| | - Rakesh Kumar
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai, Tamil Nadu, India
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh, India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, Uttar Pradesh, India
| | - Arunabh Arora
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India
| | - Sudhir Kumar
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India
| | - Arulkumar Nallakumarasamy
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, Uttar Pradesh, India
- Department of Orthopaedics, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
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COMPARISON OF THE RESULTS OF TREATMENT OF ADHESIVE CAPSULITIS OF THE SHOULDER JOINT WITH THE USE OF PRP AND POLYNUCLEOTIDES. TRAUMATOLOGY AND ORTHOPEDICS OF RUSSIA 2022. [DOI: 10.17816/2311-2905-1782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
Abstract
Conservative treatment is the basis for the treatment of adhesive capsulitis. Its effectiveness has been proven all over the world, and in 90% of cases leads to success. The main objective of adhesive capsulitis therapy is to relieve pain and inflammation in the capsule of the shoulder joint, which in turn allows you to increase the amplitude of movements and muscle strength, thereby improving the quality of life of the patient. Currently, with the development of cellular technologies, intra-articular injections of autologous platelet-rich plasma have been added to the arsenal of conservative therapy of adhesive capsulitis, which is a natural biological stimulant and affects various parts of the regenerative process due to a large number of growth factors secreted by platelets. Another direction in using the reparative potential of biopolymers was the use of polynucleotides (PN), which, due to their activity on fibroblasts, are able to stimulate regeneration processes during adhesive capsulitis.
The objective of this study was to compare these techniques in equivalent groups of patients with a reliably confirmed diagnosis of adhesive capsulitis.
Materials and methods: 42 patients aged 47-60 years with clinically established diagnosis of adhesive capsulitis and according to additional examination methods, who underwent outpatient treatment at the Traumatology Clinic. Orthopedics and Joint Pathology of the University Clinical Hospital No. 1 of the I.M. Sechenov First Moscow State Medical University, intra-articular injection of platelet-rich plasma and preparations containing polynucleotides were used in the complex therapy of adhesive capsulitis.
Results: the use of platelet-rich plasma in the treatment of adhesive capsulitis allowed to reduce the intensity of pain syndrome and increase the amplitude of active movements in the joint in patients treated at different stages of the disease. During treatment, PRP therapy makes it possible to reduce the intake of painkillers and anti-inflammatory drugs. Drugs based on PN also showed their effectiveness, which did not differ statistically from the use of PRP, but the effect was achieved faster. The results had statistically significant differences.
Conclusion: The use of PRP and PN in the complex treatment of adhesive capsulitis allows to stop the pain syndrome, restore the amplitude of movements, reduce the pharmacological load.
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Jaramillo-Chaustre X, Universidad de Pamplona, Fonseca-Matheus J, Delgado-Villamizar K, Gómez-Parra F, Mendoza-Ibarra J, Universidad de Pamplona, Universidad de Pamplona, Universidad de Pamplona, Universidad de Pamplona. Uso de plasma rico en plaquetas como coadyuvante en el tratamiento quirúrgico de la ruptura del tendón calcáneo común en gatos. REVISTA U.D.C.A ACTUALIDAD & DIVULGACIÓN CIENTÍFICA 2022. [DOI: 10.31910/rudca.v25.n1.2022.1878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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15
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Zhu Y, Peng N, Wang J, Jin Z, Zhu L, Wang Y, Chen S, Hu Y, Zhang T, Song Q, Xie F, Yan L, Li Y, Xiao J, Li X, Jiang B, Peng J, Wang Y, Luo Y. Peripheral nerve defects repaired with autogenous vein grafts filled with platelet-rich plasma and active nerve microtissues and evaluated by novel multimodal ultrasound techniques. Biomater Res 2022; 26:24. [PMID: 35690849 PMCID: PMC9188244 DOI: 10.1186/s40824-022-00264-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 04/28/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Developing biocompatible nerve conduits that accelerate peripheral nerve regeneration, lengthening and functional recovery remains a challenge. The combined application of nerve microtissues and platelet-rich plasma (PRP) provides abundant Schwann cells (SCs) and various natural growth factors and can compensate for the deficiency of SCs in the nerve bridge, as well as the limitations of applying a single type of growth factor. Multimodal ultrasound evaluation can provide additional information on the stiffness and microvascular flow perfusion of the tissue. This study was designed to investigate the effectiveness of a novel tissue-engineered nerve graft composed of an autogenous vein, nerve microtissues and PRP in reconstructing a 12-mm tibial nerve defect and to explore the value of multimodal ultrasound techniques in evaluating the prognosis of nerve repair. METHODS In vitro, nerve microtissue activity was first investigated, and the effects on SC proliferation, migration, factor secretion, and axonal regeneration of dorsal root ganglia (DRG) were evaluated by coculture with nerve microtissues and PRP. In vivo, seventy-five rabbits were equally and randomly divided into Hollow, PRP, Micro-T (Microtissues), Micro-T + PRP and Autograft groups. By analysing the neurological function, electrophysiological recovery, and the comparative results of multimodal ultrasound and histological evaluation, we investigated the effect of these new nerve grafts in repairing tibial nerve defects. RESULTS Our results showed that the combined application of nerve microtissues and PRP could significantly promote the proliferation, secretion and migration of SCs and the regeneration of axons in the early stage. The Micro-T + PRP group and Autograft groups exhibited the best nerve repair 12 weeks postoperatively. In addition, the changes in target tissue stiffness and microvascular perfusion on multimodal ultrasound (shear wave elastography; contrast-enhanced ultrasonography; Angio PlaneWave UltrasenSitive, AngioPLUS) were significantly correlated with the histological results, such as collagen area percentage and VEGF expression, respectively. CONCLUSION Our novel tissue-engineered nerve graft shows excellent efficacy in repairing 12-mm defects of the tibial nerve in rabbits. Moreover, multimodal ultrasound may provide a clinical reference for prognosis by quantitatively evaluating the stiffness and microvescular flow of nerve grafts and targeted muscles.
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Affiliation(s)
- Yaqiong Zhu
- Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China.,Beijing Key Lab of Regenerative Medicine in Orthopedics, Chinese PLA General Hospital, Beijing, China.,Key Lab of Musculoskeletal Trauma & War Injuries, Chinese PLA General Hospital, Beijing, China.,Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, Chinese PLA General Hospital, Beijing, China
| | - Nan Peng
- Department of Geriatric Rehabilitation, The Second Center of Chinese PLA General Hospital, Beijing, China
| | - Jing Wang
- Department of Orthopedic Surgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui Province, China
| | - Zhuang Jin
- General hospital of Northern Theater Command, Liaoning, China
| | - Lianhua Zhu
- Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China
| | - Yu Wang
- Beijing Key Lab of Regenerative Medicine in Orthopedics, Chinese PLA General Hospital, Beijing, China.,Key Lab of Musculoskeletal Trauma & War Injuries, Chinese PLA General Hospital, Beijing, China
| | - Siming Chen
- Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China
| | - Yongqiang Hu
- Department of Anesthesiology, JiangXi PingXiang People's Hospital, Jiangxi, China
| | - Tieyuan Zhang
- Beijing Key Lab of Regenerative Medicine in Orthopedics, Chinese PLA General Hospital, Beijing, China.,Key Lab of Musculoskeletal Trauma & War Injuries, Chinese PLA General Hospital, Beijing, China
| | - Qing Song
- Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China
| | - Fang Xie
- Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China
| | - Lin Yan
- Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China
| | - Yingying Li
- Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China
| | - Jing Xiao
- Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China
| | - Xinyang Li
- Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China
| | - Bo Jiang
- Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China
| | - Jiang Peng
- Beijing Key Lab of Regenerative Medicine in Orthopedics, Chinese PLA General Hospital, Beijing, China. .,Key Lab of Musculoskeletal Trauma & War Injuries, Chinese PLA General Hospital, Beijing, China.
| | - Yuexiang Wang
- Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China.
| | - Yukun Luo
- Departments of Ultrasound, The First Center of Chinese PLA General Hospital, Beijing, China.
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Medina-Porqueres I, Martin-Garcia P, Sanz-De-Diego S, Gomez-Caceres A, Moya-Torrecilla F, Reyes-Eldblom M, Rosado-Velazquez D. Clinical and Functional Outcome of Meniscal Injuries Treated with Platelet-Rich Plasma: A Single-Center Case Series. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19127118. [PMID: 35742366 PMCID: PMC9222768 DOI: 10.3390/ijerph19127118] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 06/02/2022] [Accepted: 06/07/2022] [Indexed: 11/16/2022]
Abstract
Meniscal injuries are among the most frequently encountered conditions in the knee joint. Therapeutic approaches are diverse and are largely dependent on the extent and location of the injury. The purpose of this study was to describe the clinical and functional outcomes of an intraarticular and percutaneous platelet-rich plasma (PRP) injection regime in patients with stable meniscal injuries. Demographics, the type of tear, affected knee, surgical procedure, type of intervention, follow-up period, and outcomes were recorded in all cases. Patient-reported outcome measures included the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Tegner activity level scale. Overall patient satisfaction, quality of life, and pain intensity were also assessed. A total of 38 cases (8 females) had sustained a stable meniscal lesion (32 medial, 6 lateral) and met the inclusion criteria. All of them received three intraarticular and percutaneous PRP injections. Patients receiving the PRP injection regime reported clinically (p = 0.000) and functionally (p = 0.000 and p = 0.001) significant improvement in all outcome measures during this interval. All patients reported they were very satisfied or satisfied with the outcome. The results of this study suggest that the treatment of stable meniscal injuries with percutaneous-intraarticular PRP injections can achieve a significant clinical and functional improvement.
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Affiliation(s)
- Ivan Medina-Porqueres
- Department of Physical Therapy, Faculty of Health Sciences, University of Malaga, 29071 Malaga, Spain
- Malaga Football Club, Medical Services, 29011 Malaga, Spain; (A.G.-C.); (D.R.-V.)
- Correspondence:
| | - Pablo Martin-Garcia
- Onco-Hematology Unit, University Hospital Virgen de la Victoria, 29010 Malaga, Spain;
| | | | - Abel Gomez-Caceres
- Malaga Football Club, Medical Services, 29011 Malaga, Spain; (A.G.-C.); (D.R.-V.)
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17
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Öztürk GT, Erden E, Erden E, Ulašlı AM. Effects of ultrasound-guided platelet rich plasma injection in patients with piriformis syndrome. J Back Musculoskelet Rehabil 2022; 35:633-639. [PMID: 34397402 DOI: 10.3233/bmr-210032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Piriformis syndrome (PS) is the common entrapment neuropathy causing buttock pain. Patients are conventionally treated with lifestyle modification, exercise, non-steroidal anti-inflammatory drugs, corticosteroid or botulinum toxin injections. However, some patients may not respond to these conventional treatment methods. Platelet rich plasma (PRP) injection has been shown to be beneficial in various muscular injuries, but its effects have not yet been investigated in PS. OBJECTIVE The aim of this study was to explore the effect of PRP on pain and functional status in patients with PS, and to identify any correlations between clinical changes and demographic features. METHODS A total of 60 patients with PS were randomly separated into two groups (PRP and control groups). All patients received one session of either PRP or saline injection performed under ultrasound guidance. The pain was measured with a visual analog scale (VAS) and Oswestry Disability Index (ODI) scores were noted at three intervals in both groups: before treatment, 1 week after treatment and 1 month after treatment. RESULTS The VAS and ODI scores were improved in both groups. The improvement was more obvious in the PRP group in the first week, and the results were similar for both groups when measured 1 month after the treatment. CONCLUSION Ultrasound-guided PRP injection provided greater improvements in both pain and functional status in patients with PS, starting in the early period after treatment. A repeat injection might be needed for a long-term effect.
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Affiliation(s)
- Gökhan Tuna Öztürk
- Ankara Physical Medicine and Rehabilitation Training and Research Hospital, Ankara, Turkey
| | - Ender Erden
- Ankara Physical Medicine and Rehabilitation Training and Research Hospital, Ankara, Turkey
| | - Ebru Erden
- Ankara Physical Medicine and Rehabilitation Training and Research Hospital, Ankara, Turkey
| | - Alper Murat Ulašlı
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Lokman Hekim University, Ankara, Turkey
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Cognasse F, Hamzeh-Cognasse H, Mismetti P, Thomas T, Eglin D, Marotte H. The Non-Haemostatic Response of Platelets to Stress: An Actor of the Inflammatory Environment on Regenerative Medicine? Front Immunol 2021; 12:741988. [PMID: 34589090 PMCID: PMC8473800 DOI: 10.3389/fimmu.2021.741988] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 08/27/2021] [Indexed: 12/12/2022] Open
Affiliation(s)
- Fabrice Cognasse
- Etablissement Français du Sang Auvergne-Rhône-Alpes, Saint-Etienne, France.,SAINBIOSE, INSERM, U1059, University of Lyon, Saint-Etienne, France
| | | | - Patrick Mismetti
- SAINBIOSE, INSERM, U1059, University of Lyon, Saint-Etienne, France.,Vascular and Therapeutic Medicine Department, Saint-Etienne University Hospital Center, Saint-Etienne, France
| | - Thierry Thomas
- SAINBIOSE, INSERM, U1059, University of Lyon, Saint-Etienne, France.,Department of Rheumatology, University Hospital of Saint-Etienne, Saint-Etienne, France
| | - David Eglin
- Mines Saint-Étienne, Univ Lyon, Univ Jean Monnet, INSERM, U1059 Sainbiose, Saint-Étienne, France
| | - Hubert Marotte
- SAINBIOSE, INSERM, U1059, University of Lyon, Saint-Etienne, France.,Department of Rheumatology, University Hospital of Saint-Etienne, Saint-Etienne, France
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Ma Y, Xuan M, Dong Y, Wang H, Huang J, Cheng B, Cui X. Platelet-rich plasma protects human melanocytes from oxidative stress and ameliorates melanogenesis induced by UVB irradiation. Biosci Biotechnol Biochem 2021; 85:1686-1696. [PMID: 33974003 DOI: 10.1093/bbb/zbab085] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 05/05/2021] [Indexed: 01/23/2023]
Abstract
To investigate the role of platelet-rich plasma (PRP) from different sources in alleviating oxidative stress and ameliorating melanogenesis in UVB-irradiated PIG1 cells, PIG1 cells were irradiated with 80 mJ/cm2 UVB prior to 1% PRP application and the following experiments were taken: the viability of UVB-irradiated PIG1 cells, cellular malondialdehyde (MDA) and reactive oxygen species (ROS) content, and activities of antioxidant enzymes. Western blotting was utilized to detect the expression level of proteins associated with melanin synthesis, apoptosis, and DNA lesions. We found that PRP intervention promoted cell proliferation, reduced MDA and ROS content, increased the activities of series of antioxidant enzymes, and alleviated DNA damages in UVB-damaged PIG1 cells. It is important to note that PRP treatment inhibited UVB-induced melanogenesis via the PI3K/Akt/GSK3β signal pathway. Therefore, we suppose PRP treatment exerts a protective role through their antioxidation effect on UVB-damaged PIG1 cells and hinders melanogenesis induced by UVB irradiation.
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Affiliation(s)
- Yongshi Ma
- Guangdong Province Engineering Research Center for Antibody Drug and Immunoassay, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China
| | - Min Xuan
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, PLA, Guangzhou, Guangdong, China.,The Key Laboratory of Trauma Treatment and Tissue Repair of Tropical Area of Chinese PLA, Guangzhou, Guangdong, China
| | - Yunqing Dong
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, PLA, Guangzhou, Guangdong, China
| | - Hong Wang
- Guangdong Province Engineering Research Center for Antibody Drug and Immunoassay, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China
| | - Jianfang Huang
- Guangdong Province Engineering Research Center for Antibody Drug and Immunoassay, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China
| | - Biao Cheng
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, PLA, Guangzhou, Guangdong, China.,The Key Laboratory of Trauma Treatment and Tissue Repair of Tropical Area of Chinese PLA, Guangzhou, Guangdong, China
| | - Xiao Cui
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, PLA, Guangzhou, Guangdong, China.,The Key Laboratory of Trauma Treatment and Tissue Repair of Tropical Area of Chinese PLA, Guangzhou, Guangdong, China.,Department of Physiotherapy, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, China
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20
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Lana JFSD, da Fonseca LF, Macedo RDR, Mosaner T, Murrell W, Kumar A, Purita J, de Andrade MAP. Platelet-rich plasma vs bone marrow aspirate concentrate: An overview of mechanisms of action and orthobiologic synergistic effects. World J Stem Cells 2021; 13:155-167. [PMID: 33708344 PMCID: PMC7933989 DOI: 10.4252/wjsc.v13.i2.155] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 12/15/2020] [Accepted: 01/15/2021] [Indexed: 02/06/2023] Open
Abstract
The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade. Currently, there are multiple alternatives available as suitable treatments; however, the use of autologous blood-derived products such as platelet-rich plasma (PRP), bone marrow aspirate (BMA) and BMA concentrate (BMAC), specifically, is expanding. Although many investigations attempted to demonstrate the effectiveness of these therapies, even with positive results, the literature lacks standardized protocols and overall accuracy in study designs, which leads to variance and difficulty in reproducibility of protocols. The efficacy of PRP for the treatment of cartilage, bone and muscle tissues is well known. Although BMAC has generated optimistic results for the same purposes, its applicability in clinical trials is still relatively recent when compared to PRP. Both products demonstrate the potential to set forth reparative processes, each in their own distinct mechanism. The combination of these biological products has been previously proposed, yet little is known about their synergism. Evidence indicates that growth factor, cytokine, and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing. BMAC products seem to work well without PRP; however, the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself. Nevertheless, additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.
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Affiliation(s)
| | | | - Rafael da Rocha Macedo
- Department of Orthopedics, Rede D’Or Unit IFOR Hospital, São Bernardo do Campo 09715-021, SP, Brazil
| | - Tomas Mosaner
- Department of Orthopedics, The Bone and Cartilage Institute, Indaiatuba 13334-170, SP, Brazil
| | - William Murrell
- Department of Orthopaedics, Healthpoint UAE, Abu Dhabi 00000, United Arab Emirates
| | - Ashok Kumar
- Department of Orthopaedics, My Doc Specialist Medical Centre, Dubai 00000, United Arab Emirates
| | - Joseph Purita
- Department of Orthopedics, Institute of Regenerative Medicine, Boca Raton, FL 33432, United States
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Cui X, Ma Y, Wang H, Huang J, Li L, Tang J, Cheng B. The Anti-photoaging Effects of Pre- and Post-treatment of Platelet-rich Plasma on UVB-damaged HaCaT Keratinocytes. Photochem Photobiol 2020; 97:589-599. [PMID: 33174201 DOI: 10.1111/php.13354] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 11/06/2020] [Accepted: 11/06/2020] [Indexed: 02/03/2023]
Abstract
Platelet-rich plasma (PRP) has seen wide clinical use owing to its regenerative and repair abilities. OBJECTIVE To investigate the anti-photoaging effects of pre- and post-treatment of PRP on UVB-damaged HaCaT cells. METHODS HaCaT cells were irradiated with 80 mJ/cm2 UVB, before or after PRP treatment (1000 × 107 /L), and following measurements were taken: survival rate of UVB-irradiated HaCaT cells, malondialdehyde (MDA) content and activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT). Western blot was used to determine the effect of different PRP intervention on the expression of PI3K, AKT, ERK, MMP-1, MMP-9, TIMP-1 and γ-H2AX in the UVB-irradiated HaCaT cells. RESULTS pre- and post-PRP treatment reduced MDA content and increased the activities of GSH-Px, SOD and CAT in photoaged HaCaT cells. These changes resulted in reduced cytotoxic effects. Besides, different PRP intervention promoted cell proliferation via PI3K/AKT pathway. Furthermore, PRP application suppressed the expression of γ-H2AX. Also, PRP intervention alleviated photoaging effects by upregulating the expression level of tissue inhibitor of metalloproteinases-1 (TIMP-1) while downregulating matrix metalloproteinase (MMP) expression level in photoaged HaCaT cells. CONCLUSION pre- and post-PRP treatment play anti-photoaging role through strengthening cellular oxidative defense capacity, mitigating MMP expression, alleviating DNA damages and promoting proliferation of UVB-irradiated HaCaT cells.
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Affiliation(s)
- Xiao Cui
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.,Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, PLA, Guangzhou, China.,The Key Laboratory of Trauma Treatment & Tissue Repair of Tropical Area of Chinese PLA, Guangzhou, China
| | - Yongshi Ma
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Hong Wang
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Jianfang Huang
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Linlin Li
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, PLA, Guangzhou, China.,The Key Laboratory of Trauma Treatment & Tissue Repair of Tropical Area of Chinese PLA, Guangzhou, China
| | - Jianbing Tang
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, PLA, Guangzhou, China.,The Key Laboratory of Trauma Treatment & Tissue Repair of Tropical Area of Chinese PLA, Guangzhou, China
| | - Biao Cheng
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, PLA, Guangzhou, China.,The Key Laboratory of Trauma Treatment & Tissue Repair of Tropical Area of Chinese PLA, Guangzhou, China
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Guevara JA, Entezari V, Ho JC, Derwin KA, Iannotti JP, Ricchetti ET. An Update on Surgical Management of the Repairable Large-to-Massive Rotator Cuff Tear. J Bone Joint Surg Am 2020; 102:1742-1754. [PMID: 32740266 DOI: 10.2106/jbjs.20.00177] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Affiliation(s)
- Jonathan A Guevara
- Department of Orthopaedic Surgery, Orthopaedic and Rheumatologic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Vahid Entezari
- Department of Orthopaedic Surgery, Orthopaedic and Rheumatologic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Jason C Ho
- Department of Orthopaedic Surgery, Orthopaedic and Rheumatologic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Kathleen A Derwin
- Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Joseph P Iannotti
- Department of Orthopaedic Surgery, Orthopaedic and Rheumatologic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Eric T Ricchetti
- Department of Orthopaedic Surgery, Orthopaedic and Rheumatologic Institute, Cleveland Clinic, Cleveland, Ohio
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Seong H, Kim RK, Shin Y, Lee HW, Koh JC. Application of purified porcine collagen in patients with chronic refractory musculoskeletal pain. Korean J Pain 2020; 33:395-399. [PMID: 32989204 PMCID: PMC7532294 DOI: 10.3344/kjp.2020.33.4.395] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 08/07/2020] [Accepted: 08/17/2020] [Indexed: 11/17/2022] Open
Abstract
Background This study aimed to assess the potential efficacy of purified porcine atelocollagen (PAC) for the management of refractory chronic pain due to suspected connective tissue damage. Methods Patients treated with PAC were retrospectively evaluated. Patients with chronic refractory pain, suspected to have originated from musculoskeletal damage or defects with the evidence of imaging studies were included. Pain intensity, using the 11-point numerical rating scale (NRS), was assessed before the procedure, and 1 month after the last procedure. Results Eighty-eight patients were finally included for investigation. The mean NRS score was decreased from 5.8 to 4.1 after 1 month of PAC injection (P < 0.001). No independent factor was reported to be directly related to the decrease in NRS score by more than half. Conclusions Application of PAC may have potential as a treatment option for refractory chronic musculoskeletal pain. PAC might promote tissue recovery, act as a scaffold for repair, or directly reduce inflammation.
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Affiliation(s)
- Hyunyoung Seong
- Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital, Seoul, Korea
| | - Raing Kyu Kim
- Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital, Seoul, Korea
| | - Youngjae Shin
- Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital, Seoul, Korea
| | - Hye Won Lee
- Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital, Seoul, Korea
| | - Jae Chul Koh
- Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital, Seoul, Korea
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Mariani E, Pulsatelli L. Platelet Concentrates in Musculoskeletal Medicine. Int J Mol Sci 2020; 21:ijms21041328. [PMID: 32079117 PMCID: PMC7072911 DOI: 10.3390/ijms21041328] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 01/29/2020] [Accepted: 02/06/2020] [Indexed: 12/02/2022] Open
Abstract
Platelet concentrates (PCs), mostly represented by platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are autologous biological blood-derived products that may combine plasma/platelet-derived bioactive components, together with fibrin-forming protein able to create a natural three-dimensional scaffold. These types of products are safely used in clinical applications due to the autologous-derived source and the minimally invasive application procedure. In this narrative review, we focus on three main topics concerning the use of platelet concentrate for treating musculoskeletal conditions: (a) the different procedures to prepare PCs, (b) the composition of PCs that is related to the type of methodological procedure adopted and (c) the clinical application in musculoskeletal medicine, efficacy and main limits of the different studies.
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Affiliation(s)
- Erminia Mariani
- Laboratorio di Immunoreumatologia e rigenerazione tissutale, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy;
- Dipartimento di Scienze Mediche e Chirurgiche, Alma Mater Studiorum-University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
- Correspondence: ; Tel.: +39-051-6366803
| | - Lia Pulsatelli
- Laboratorio di Immunoreumatologia e rigenerazione tissutale, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy;
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Nardini M, Perteghella S, Mastracci L, Grillo F, Marrubini G, Bari E, Formica M, Gentili C, Cancedda R, Torre ML, Mastrogiacomo M. Growth Factors Delivery System for Skin Regeneration: An Advanced Wound Dressing. Pharmaceutics 2020; 12:120. [PMID: 32028579 PMCID: PMC7076531 DOI: 10.3390/pharmaceutics12020120] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 01/17/2020] [Accepted: 01/21/2020] [Indexed: 12/20/2022] Open
Abstract
Standard treatments of chronic skin ulcers based on the direct application of dressings still present several limits with regard to a complete tissue regeneration. Innovative strategies in tissue engineering offer materials that can tune cell behavior and promote growth tissue favoring cell recruitment in the early stages of wound healing. A combination of Alginate (Alg), Sericin (SS) with Platelet Lysate (PL), as a freeze-dried sponge, is proposed to generate a bioactive wound dressing to care skin lesions. Biomembranes at different composition were tested for the release of platelet growth factors, cytotoxicity, protective effects against oxidative stress and cell proliferation induction. The highest level of the growth factors release occurred within 48 h, an optimized time to burst a healing process in vivo; the presence of SS differently modulated the release of the factors by interaction with the proteins composing the biomembranes. Any cytotoxicity was registered, whereas a capability to protect cells against oxidative stress and induce proliferation was observed when PL was included in the biomembrane. In a mouse skin lesion model, the biomembranes with PL promoted the healing process, inducing an accelerated and more pronounced burst of inflammation, formation of granulation tissue and new collagen deposition, leading to a more rapid skin regeneration.
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Affiliation(s)
- Marta Nardini
- Department of Internal Medicine (DIMI), University of Genova, viale Benedetto XV 10, 16132 Genova, Italy;
- Biotherapy Unit, Ospedale Policlinico San Martino IRCCS, largo Rosanna Benzi 10, 16132 Genova, Italy
| | - Sara Perteghella
- Department of Drug Sciences, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy; (S.P.); (G.M.); (E.B.); (M.L.T.)
| | - Luca Mastracci
- Ospedale Policlinico San Martino IRCCS, largo Rosanna Benzi 10, 16132 Genova, Italy; (L.M.); (F.G.); (M.F.)
- Anatomic Pathology, Department of Integrated Surgical and Diagnostic Sciences (DISC), University of Genova, viale Benedetto XV 6, 16132 Genova, Italy
| | - Federica Grillo
- Ospedale Policlinico San Martino IRCCS, largo Rosanna Benzi 10, 16132 Genova, Italy; (L.M.); (F.G.); (M.F.)
- Anatomic Pathology, Department of Integrated Surgical and Diagnostic Sciences (DISC), University of Genova, viale Benedetto XV 6, 16132 Genova, Italy
| | - Giorgio Marrubini
- Department of Drug Sciences, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy; (S.P.); (G.M.); (E.B.); (M.L.T.)
| | - Elia Bari
- Department of Drug Sciences, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy; (S.P.); (G.M.); (E.B.); (M.L.T.)
| | - Matteo Formica
- Ospedale Policlinico San Martino IRCCS, largo Rosanna Benzi 10, 16132 Genova, Italy; (L.M.); (F.G.); (M.F.)
- Orthopedic Clinic, Department of Integrated Surgical and Diagnostic Sciences (DISC), University of Genova viale Benedetto XV 6, 16132 Genova, Italy
| | - Chiara Gentili
- Regenerative Medicine Laboratory, Department of Experimental Medicine (DIMES), University of Genova, via Leon Battista Alberti 2, 16132 Genova, Italy;
- Center for Biomedical Research (CEBR), University of Genova, viale Benedetto XV 9, 16132 Genova, Italy
| | - Ranieri Cancedda
- Endolife S.r.l., Piazza della Vittoria 15/23, 16121 Genova, Italy;
| | - Maria Luisa Torre
- Department of Drug Sciences, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy; (S.P.); (G.M.); (E.B.); (M.L.T.)
| | - Maddalena Mastrogiacomo
- Department of Internal Medicine (DIMI), University of Genova, viale Benedetto XV 10, 16132 Genova, Italy;
- Biotherapy Unit, Ospedale Policlinico San Martino IRCCS, largo Rosanna Benzi 10, 16132 Genova, Italy
- Center for Biomedical Research (CEBR), University of Genova, viale Benedetto XV 9, 16132 Genova, Italy
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Zaki SM, Algaleel WA, Imam RA, Abdelmoaty MM. Mesenchymal stem cells pretreated with platelet-rich plasma modulate doxorubicin-induced cardiotoxicity. Hum Exp Toxicol 2019; 38:857-874. [PMID: 30991846 DOI: 10.1177/0960327119842613] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The cardiotoxic adverse effect of doxorubicin (DOX) is the major factor limiting its use. Recently, mesenchymal stem cells (MSCs) have been implicated in the preclinical studies of treatment of DOX-induced cardiotoxicity. The question is MSCs pretreated with platelet-rich plasma (PRP) have a better influence on DOX-induced cardiotoxicity compared to the influence of MSCs alone. Twenty-four Wistar rats were categorized into control, DOX-treated, MSC-treated, and PRP/MSC-treated groups. DOX was injected for two consecutive weeks. Light microscopic, biochemical markers (interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α), and creatine kinase-MB (CK-MB)), immunohistochemical (Bax, Bcl2, vascular endothelial growth factor (VEGF), and cardiac troponin-I (CT-I)), and oxidative/antioxidative markers (malondialdehyde (MDA)/superoxide dismutase (SOD)) were measured. Degenerative cardiac changes were detected in the DOX-treated group with complete loss of the architecture and coagulative necrosis. These changes were accompanied with the elevation of the serum level of CK-MB and loss of CT-I immunoreactivity. The major factors in the DOX-induced cardiotoxicity were the oxidative stress (elevated MDA/decreased SOD), inflammation (elevated TNF-α/decreased IL-10), and cardiac apoptosis (lower Bcl2, higher Bax, and lower Bcl2/Bax ratio). MSCs and PRP/MSCs attenuate DOX-induced cardiotoxicity. Better attenuation was observed in the PRP/MSC-treated group. PRP/MSC combination reduced greatly the MDA and TNF-α and increased IL-10, Bcl2/Bax ratio, and VEGF. PRP had no significant influence over the Bcl2, Bax, and SOD. In conclusion, DOX in its toxic dose induced myocardial injury. This destructive effect is related to oxidative stress, inflammation, and cardiac apoptosis. PRP/MSC possesses a better attenuation over the DOX-induced toxicity compared to MSC alone.
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Affiliation(s)
- S M Zaki
- 1 Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt.,2 Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia
| | - Wa Abd Algaleel
- 1 Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt.,2 Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia
| | - R A Imam
- 1 Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - M M Abdelmoaty
- 1 Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt
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Scully D, Sfyri P, Verpoorten S, Papadopoulos P, Muñoz‐Turrillas MC, Mitchell R, Aburima A, Patel K, Gutiérrez L, Naseem KM, Matsakas A. Platelet releasate promotes skeletal myogenesis by increasing muscle stem cell commitment to differentiation and accelerates muscle regeneration following acute injury. Acta Physiol (Oxf) 2019; 225:e13207. [PMID: 30339324 DOI: 10.1111/apha.13207] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 09/27/2018] [Accepted: 10/14/2018] [Indexed: 12/11/2022]
Abstract
AIM The use of platelets as biomaterials has gained intense research interest. However, the mechanisms regarding platelet-mediated skeletal myogenesis remain to be established. The aim of this study was to determine the role of platelet releasate in skeletal myogenesis and muscle stem cell fate in vitro and ex vivo respectively. METHODS We analysed the effect of platelet releasate on proliferation and differentiation of C2C12 myoblasts by means of cell proliferation assays, immunohistochemistry, gene expression and cell bioenergetics. We expanded in vitro findings on single muscle fibres by determining the effect of platelet releasate on murine skeletal muscle stem cells using protein expression profiles for key myogenic regulatory factors. RESULTS TRAP6 and collagen used for releasate preparation had a more pronounced effect on myoblast proliferation vs thrombin and sonicated platelets (P < 0.05). In addition, platelet concentration positively correlated with myoblast proliferation. Platelet releasate increased myoblast and muscle stem cell proliferation in a dose-dependent manner, which was mitigated by VEGFR and PDGFR inhibition. Inhibition of VEGFR and PDGFR ablated MyoD expression on proliferating muscle stem cells, compromising their commitment to differentiation in muscle fibres (P < 0.001). Platelet releasate was detrimental to myoblast fusion and affected differentiation of myoblasts in a temporal manner. Most importantly, we show that platelet releasate promotes skeletal myogenesis through the PDGF/VEGF-Cyclin D1-MyoD-Scrib-Myogenin axis and accelerates skeletal muscle regeneration after acute injury. CONCLUSION This study provides novel mechanistic insights on the role of platelet releasate in skeletal myogenesis and set the physiological basis for exploiting platelets as biomaterials in regenerative medicine.
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Affiliation(s)
- David Scully
- Molecular Physiology Laboratory, Centre for Atherothrombotic and Metabolic Disease, Hull York Medical School University of Hull Hull UK
| | - Peggy Sfyri
- Molecular Physiology Laboratory, Centre for Atherothrombotic and Metabolic Disease, Hull York Medical School University of Hull Hull UK
| | - Sandrine Verpoorten
- Molecular Physiology Laboratory, Centre for Atherothrombotic and Metabolic Disease, Hull York Medical School University of Hull Hull UK
| | - Petros Papadopoulos
- Department of Hematology, Instituto de Investigación Sanitaria San Carlos (IdISSC) Hospital Clínico San Carlos Madrid Spain
| | - María Carmen Muñoz‐Turrillas
- Centro Comunitario de Sangre y Tejidos de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Oviedo Spain
| | - Robert Mitchell
- School of Biological Sciences University of Reading Reading UK
| | - Ahmed Aburima
- Molecular Physiology Laboratory, Centre for Atherothrombotic and Metabolic Disease, Hull York Medical School University of Hull Hull UK
| | - Ketan Patel
- School of Biological Sciences University of Reading Reading UK
| | - Laura Gutiérrez
- Department of Medicine Universidad de Oviedo and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Oviedo Spain
| | - Khalid M. Naseem
- Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds Leeds UK
| | - Antonios Matsakas
- Molecular Physiology Laboratory, Centre for Atherothrombotic and Metabolic Disease, Hull York Medical School University of Hull Hull UK
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Akeda K, Yamada J, Linn ET, Sudo A, Masuda K. Platelet-rich plasma in the management of chronic low back pain: a critical review. J Pain Res 2019; 12:753-767. [PMID: 30881089 PMCID: PMC6394242 DOI: 10.2147/jpr.s153085] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Low back pain (LBP) is now regarded as the first cause of disability worldwide and should be a priority for future research on prevention and therapy. Intervertebral disc (IVD) degeneration is an important pathogenesis of LBP. Platelet-rich plasma (PRP) is an autologous blood concentrate that contains a natural concentration of autologous growth factors and cytokines and is currently widely used in the clinical setting for tissue regeneration and repair. PRP has great potential to stimulate cell proliferation and metabolic activity of IVD cells in vitro. Several animal studies have shown that the injection of PRP into degenerated IVDs is effective in restoring structural changes (IVD height) and improving the matrix integrity of degenerated IVDs as evaluated by magnetic resonance imaging (MRI) and histology. The results of this basic research have shown the great possibility that PRP has significant biological effects for tissue repair to counteract IVD degeneration. Clinical studies for evaluating the effects of the injection of PRP into degenerated IVDs for patients with discogenic LBP have been reviewed. Although there was only one double-blind randomized controlled trial, all the studies reported that PRP was safe and effective in reducing back pain. While the clinical evidence of tissue repair of IVDs by PRP treatment is currently lacking, there is a great possibility that the application of PRP has the potential to lead to a feasible intradiscal therapy for the treatment of degenerative disc diseases. Further large-scale studies may be required to confirm the clinical evidence of PRP for the treatment of discogenic LBP.
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Affiliation(s)
- Koji Akeda
- Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu City, Mie 514-8507, Japan,
| | - Junichi Yamada
- Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu City, Mie 514-8507, Japan,
| | - Erikka T Linn
- Department of Orthopaedic Surgery, University of California, San Diego, La Jolla, CA 92093-0863, USA
| | - Akihiro Sudo
- Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu City, Mie 514-8507, Japan,
| | - Koichi Masuda
- Department of Orthopaedic Surgery, University of California, San Diego, La Jolla, CA 92093-0863, USA
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29
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Influence of Platelet-Rich and Platelet-Poor Plasma on Endogenous Mechanisms of Skeletal Muscle Repair/Regeneration. Int J Mol Sci 2019; 20:ijms20030683. [PMID: 30764506 PMCID: PMC6387315 DOI: 10.3390/ijms20030683] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 01/29/2019] [Accepted: 02/01/2019] [Indexed: 12/11/2022] Open
Abstract
The morpho-functional recovery of injured skeletal muscle still represents an unmet need. None of the therapeutic options so far adopted have proved to be resolutive. A current scientific challenge remains the identification of effective strategies improving the endogenous skeletal muscle regenerative program. Indeed, skeletal muscle tissue possesses an intrinsic remarkable regenerative capacity in response to injury, mainly thanks to the activity of a population of resident muscle progenitors called satellite cells, largely influenced by the dynamic interplay established with different molecular and cellular components of the surrounding niche/microenvironment. Other myogenic non-satellite cells, residing within muscle or recruited via circulation may contribute to post-natal muscle regeneration. Unfortunately, in the case of extended damage the tissue repair may become aberrant, giving rise to a maladaptive fibrotic scar or adipose tissue infiltration, mainly due to dysregulated activity of different muscle interstitial cells. In this context, plasma preparations, including Platelet-Rich Plasma (PRP) and more recently Platelet-Poor Plasma (PPP), have shown advantages and promising therapeutic perspectives. This review focuses on the contribution of these blood-derived products on repair/regeneration of damaged skeletal muscle, paying particular attention to the potential cellular targets and molecular mechanisms through which these products may exert their beneficial effects.
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30
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Harrison P. The use of platelets in regenerative medicine and proposal for a new classification system: guidance from the SSC of the ISTH. J Thromb Haemost 2018; 16:1895-1900. [PMID: 30099839 DOI: 10.1111/jth.14223] [Citation(s) in RCA: 173] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Indexed: 11/26/2022]
Abstract
Autologous and single-donor allogenic platelet preparations are increasingly being used in many areas of regenerative medicine. However, there are few properly controlled randomized clinical trials, and the preparation, content and characteristics of platelet preparations are generally poorly defined and controlled. The Platelet Physiology Subcommittee of the Scientific and Standardization Committee (SSC) of the ISTH formed a working party of experts with the aim of producing consensus recommendations for guidance on the use of platelets in regenerative medicine. Owing to a lack of investigations that provide definitive evidence for the efficacy, definition and use of different platelet preparations in regenerative medicine, there were insufficient data to develop evidence-based guidelines. Therefore, the RAND method was used, which obtains a formal consensus among experts particularly when scientific evidence is absent, scarce and/or heterogeneous. Using this approach, each expert scored as 'appropriate', 'uncertain' or 'inappropriate' a series of 45 statements about the practice of regenerative medicine with platelets, which included different sections on general aspects, platelet preparations, clinical trial design, and potential utility in different clinical scenarios. After presentation and public discussion at SSC meetings, the assessments were further refined to produce final consensus recommendations, which constitute the subject of the present report.
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Affiliation(s)
- P Harrison
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
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31
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Scully D, Naseem KM, Matsakas A. Platelet biology in regenerative medicine of skeletal muscle. Acta Physiol (Oxf) 2018; 223:e13071. [PMID: 29633517 DOI: 10.1111/apha.13071] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 03/07/2018] [Accepted: 04/01/2018] [Indexed: 12/13/2022]
Abstract
Platelet-based applications such as platelet-rich plasma (PRP) and platelet releasate have gained unprecedented attention in regenerative medicine across a variety of tissues as of late. The rationale behind utilizing PRP originates in the delivery of key cytokines and growth factors from α-granules to the targeted area, which in turn act as cell cycle regulators and promote the healing process across a variety of tissues. The aim of the present review is to assimilate current experimental evidence on the role of platelets as biomaterials in tissue regeneration, particularly in skeletal muscle, by integrating findings from human, animal and cell studies. This review is composed of 3 parts: firstly, we review key aspects of platelet biology that precede the preparation and use of platelet-related applications for tissue regeneration. Secondly, we critically discuss relevant evidence on platelet-mediated regeneration in skeletal muscle focusing on findings from (i) clinical trials, (ii) experimental animal studies and (iii) cell culture studies; and thirdly, we discuss the application of platelets in the regeneration of several other tissues including tendon, bone, liver, vessels and nerve. Finally, we review key technical variations in platelet preparation that may account for the large discrepancy in outcomes from different studies. This review provides an up-to-date reference tool for biomedical and clinical scientists involved in platelet-mediated tissue regenerative applications.
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Affiliation(s)
- D. Scully
- Molecular Physiology Laboratory; Centre for Atherothrombotic & Metabolic Disease; Hull York Medical School; University of Hull; Hull UK
| | - K. M. Naseem
- Leeds Institute of Cardiovascular and Metabolic Medicine; University of Leeds; Leeds UK
| | - A. Matsakas
- Molecular Physiology Laboratory; Centre for Atherothrombotic & Metabolic Disease; Hull York Medical School; University of Hull; Hull UK
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Andia I, Martin JI, Maffulli N. Advances with platelet rich plasma therapies for tendon regeneration. Expert Opin Biol Ther 2018; 18:389-398. [DOI: 10.1080/14712598.2018.1424626] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Isabel Andia
- Regenerative Medicine Laboratory, BioCruces Health Research Institute, Cruces University Hospital, Barakaldo, Spain
| | - Jose Ignacio Martin
- Regenerative Medicine Laboratory, BioCruces Health Research Institute, Cruces University Hospital, Barakaldo, Spain
- Interventional Imaging. Department of Radiology, Cruces University Hospital, Barakaldo, Spain
| | - Nicola Maffulli
- Department of Musculoskeletal Disorders, University of Salerno School of Medicine and Dentristry, Salerno, Italy
- Barts and the London School of Medicine and Dentistry Centre for Sports and Exercise Medicine, Queen Mary University of London, London, England
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Abstract
UNLABELLED Osteochondral lesions remain as a clinical challenge despite the advances in orthopedic regenerative strategies. Biologics, in particular, platelet-rich plasma, has been applied for the reparative and regenerative effect in many tissues, and osteochondral tissue is not an exception. Platelet-rich plasma is an autologous concentrate prepared from the collected blood; thus, this safe application is free of immune response or risk of transmission of disease. It has a high potential to promote regeneration, thanks to its content, and can be applied alone or can reinforce a tissue engineering strategy. The relevant works making use of platelet-rich plasma in osteochondral lesions are overviewed herein. The practical success of platelet-rich plasma is uncertain since there are many factors involved including but not limited to its preparation and administration method. Nevertheless, today, the issues and challenges of platelet-rich plasma have been well acknowledged by researchers and clinicians. Thus, it is believed that a consensus will be built it, and then with high-quality randomized controlled trials and standardized protocols, the efficacy of platelet-rich plasma therapy can be better evaluated. HIGHLIGHTS The need of treating the osteochondral lesions has not been yet met in the clinics. Thanks to being an autologous source of growth factors, interleukins, and other cytokines and relative ease of clinical application, i.e., during a single-step surgical procedure, the use of platelet-rich plasma is of great interest. The high theoretical potential of the role of platelet-rich plasma in the regeneration process of osteochondral lesions is known, and the efficiency needs to be confirmed by high-quality randomized controlled trials for a robust position in the treatments of osteochondral lesions in the clinics.
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Adjuvant Biological Therapies in Chronic Leg Ulcers. Int J Mol Sci 2017; 18:ijms18122561. [PMID: 29182584 PMCID: PMC5751164 DOI: 10.3390/ijms18122561] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2017] [Revised: 11/22/2017] [Accepted: 11/28/2017] [Indexed: 02/06/2023] Open
Abstract
Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced synthesis of extracellular matrix. In this context, regenerative medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell products, may form part of adjuvant interventions in an integral patient management. We synthesized the clinical experience on ulcer management using these two categories of biological adjuvants. The results of ten controlled trials that are included in this systematic review favor the use of mesenchymal stromal cell based-adjuvants for impaired wound healing, but the number and quality of studies is moderate-low and are complicated by the diversity of biological products. Regarding platelet-derived products, 18 controlled studies investigated their efficacy in chronic wounds in the lower limb, but the heterogeneity of products and protocols hinders clinically meaningful quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical need in this condition. Overall, there is not sufficient evidence to inform routine care, and further clinical research is necessary to realize the full potential of adjuvant regenerative medicine strategies in the management of chronic leg ulcers.
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