Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture

Anitua, Eduardo; Andí, Isabel; Sánchez, Mikel; Azofra, Juan; Zalduendo, Ma del Mar; Fuente, María de la; Nurden, Paquita; Nurden, Alan T.

doi:10.1016/j.orthres.2004.08.015

Cited by 446 publications

(374 citation statements)

References 25 publications

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“…In vitro studies have shown that PRP may increase proteincoding gene expression of the extracellular matrix, collagen production and tenocyte proliferation [39e41]. Tendon tissue is known to heal slower than connective tissues because of a poor intrinsic vascularization [42]. No inflammatory response is observed in histological samples taken from chronic tendon injuries, but rather an abnormal response to fibroblast and vascular degeneration, known as angiofibroblastic hyperplasia [43].…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-guided injection of platelet-rich plasma in chronic Achilles and patellar tendinopathy

Ferrero

Fabbro

Orlandi

et al. 2012

Journal of Ultrasound

117

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KEYWORDSPlatelet-rich plasma; Achilles tendon; Patellar tendon; Jumper's knee; Achilles tendinopathy.Abstract Purpose: The efficacy of platelet-rich plasma (PRP) in the treatment and healing of chronic tendinopathy through stimulation of cell proliferation and total collagen production has been demonstrated by both in vitro and in vivo studies. The aim of this study is to evaluate the effectiveness of ultrasound (US)-guided autologous PRP injections in patellar and Achilles tendinopathy. Materials and methods: Autologous PRP was injected under US-guidance into the Achilles and patellar tendons (30 Achilles tendons, 28 patellar tendons) in 48 prospectively selected patients (30 males, 18 females, mean age 38 AE 16 years, range 20e61 years). All patients were previously evaluated according to the Victoria Institute of Sport Assessment (VISA) scale, which assessed pain and activity level, and they all underwent US of the tendon before treatment and at follow-up after 20 days and 6 months. Statistical analysis was performed with Chi-square and Wilcoxon tests. Results: 20 days after PRP injection the patients presented a non-significant improvement of clinical symptoms. At the 6-month follow-up VISA score increased from a mean value of 57 e75.5 (p < .01). US evaluation revealed a reduction of hypoechoic areas in 26 tendons (p < .01) associated with a widespread improvement of fibrillar echotexture of the tendon and reduced hypervascularity at power Doppler. Conclusion: PRP injection in patellar and Achilles tendinopathy results in a significant and lasting improvement of clinical symptoms and leads to recovery of the tendon matrix potentially helping to prevent degenerative lesions. US-guidance allows PRP injection into the tendon with great accuracy. Sommario Scopo: Il plasma ricco di piastrine (PRP), provocando un iperafflusso di citochine nel sito di iniezione si è dimostrato efficace, sia in vitro che in studi clinici in vivo, come promotore della rigenerazione tissutale. Lo scopo di questo studio è quello di valutare l'efficacia dell'iniezione ecoguidata di PRP autologo nel trattamento delle tendinopatie croniche del rotuleo e dell'achilleo. Materiali e metodi: Il PRP autologo è stato iniettato sotto guida ecografica in tendini rotulei e achillei (30 tendini di Achille, 28 tendini rotulei) di 48 pazienti selezionati in modo prospettico (30 maschi, 18 femmine, età media 38 AE 16 anni, range 20e61 anni). Tutti i pazienti erano stati precedentemente valutati mediante questionario Victoria Institute of Sport di valutazione (VISA) in cui si analizza il punteggio del dolore e il livello di attività. È stata poi eseguita una valutazione ecografica dei tendini mirata a valutarne l'ecostruttura e vascolarizzazione. La valutazione statistica dei dati ottenuti è stata eseguita mediante i test del Chi-quadrato e di Wilcoxon. Risultati: Venti giorni dopo l'iniezione di PRP è stato rilevato un miglioramento dei sintomi clinici non significativo. Il punteggio VISA è migliorato da una base di 57 a 75,5 a 6 mesi (p < .01). La v...

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Section: Discussionmentioning

confidence: 99%

Ultrasound-guided injection of platelet-rich plasma in chronic Achilles and patellar tendinopathy

Ferrero

Fabbro

Orlandi

et al. 2012

Journal of Ultrasound

117

View full text Add to dashboard Cite

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“…The clinical application of PLG with bone marrow-derived MSC also was reported by Kito et al [53] in the course of distraction osteogenesis. In soft tissue engineering, Anitua et al [54] identified the role of PLG releasate on cultured tendon cells. These authors state that the treatment of tendon injuries may be of benefit because cell proliferation is induced with the promotion of endogenous angiogenic growth factor synthesis.…”

Section: Tissue Engineeringmentioning

confidence: 99%

The use of autologous platelet–leukocyte gels to enhance the healing process in surgery, a review

et al. 2007

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Background: The therapeutic use of autologously prepared, platelet-leukocyte-enriched gel (PLG) is a relatively new technology for the stimulation and acceleration of soft tissue and bone healing. The effectiveness of this procedure lies in the delivery of a wide range of platelet growth factors mimicking the physiologic wound healing and reparative tissue processes. Despite an increase in PLG applications, the structures and kinetics of this autogenously derived biologic material have not been observed. Methods: A review of the most recent literature was performed to evaluate the use of PLG in various surgical disciplines. Results: The review showed that the application of PLG has been extended to various surgical disciplines including orthopedics, cardiac surgery, plastic and maxillofacial surgery, and recently also endoscopic surgery. Conclusion: This review demonstrates the usefulness of PLG in a wide range of clinical applications for improvement of healing after surgical procedures.Key words: Growth factors -Leukocytes -Platelet gel -Wound healing Soft tissue wound healing and bone growth involve physiologic cascades in which cellular and hormonal factors play pivotal roles [1,2]. Some of these cascade components can be isolated from autologously drawn whole blood. Point-of-care devices can intraoperatively fractionate the autologous blood into platelet-poor plasma, platelet-leukocyte-rich plasma (P-LRP), and red blood cells [3,4]. The P-LRP fraction, a mixture of concentrated platelets and leukocytes, can be activated by (autologous) thrombin to create a viscous solution known as platelet-leukocyte gel (PLG). This platelet coagulum can be exogenously applied to soft wound tissues, bone, or synthetic bone as a spray or as a solid, clotted, gelatinous mass. The rationale for applying platelet gel is based on the delivery of platelet growth factors to tissues and on the fact that platelet a-granules, found inside the platelets, contain a variety of growth factors [5]. Platelet gel growth factors are peptides that promote cell proliferation, differentiation, chemotaxis, and the migration of various cells involved in both wound healing and bone growth [6,7].Recently, numerous P-LRP devices have become available for therapeutic use to stimulate and accelerate soft tissue and bone healing and to control postoperative wound bleeding. The rationale for applying PLG lies in the mimicking and accelerating of physiologic wound healing and reparative tissue processes.This article provides information on the results of electron microscopic imaging used to evaluate the content of PLG. Furthermore, because the use of PLG is a relatively new per-and/or perioperative biotechnological application, new and additional indications for the use of PLG are defined. New PLG applications are reviewed for different applications including cardiac surgery, general surgery, orthopedics and traumatology, cosmetic surgery, maxillofacial surgery, sports medicine, and endoscopic surgical procedures. Defining platelet-leukocyte-rich...

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“…These chemokines participate not only in inflammation and pain modulation, but also in angiogenesis. Understanding their mechanisms of action will allow us to extend previous knowledge reporting on MCP-1/CCL2, RANTES/CCL5, vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) production by tendon cells after PRP treatment [11,12].…”

Section: Introductionmentioning

confidence: 99%

Platelet-rich Plasma Modulates the Secretion of Inflammatory/Angiogenic Proteins by Inflamed Tenocytes

Andı́a

Rubio‐Azpeitia

Maffulli

2015

Clinical Orthopaedics &Amp; Related Research

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Background Platelet-rich plasma therapies for tendinopathy appear to provide moderate pain reduction. However, the biological mechanisms behind the observed clinical effects remain poorly characterized. Questions/purposes The purpose of this study was to explore whether platelet-rich plasma modifies the inflammatory/angiogenic status of already inflamed tenocytes by examining (1) gene expression; (2) modulation of chemokine and interleukin secretion; and (3) differences between healthy and tendinopathic tenocytes. Methods Cells from both healthy and tendinopathic tendons were exposed to interleukin (IL)-1ß and after treated with platelet-rich plasma. Modifications in the expression of selected genes were assessed by real-time reverse transcription-polymerase chain reaction and changes in secretion of angiogenic/inflammatory molecules by enzyme-linked immunosorbent assay. Platelet-rich plasmainduced changes in tendinopathic cells were compared with normal after normalizing platelet-rich plasma data against IL-1ß status in each specific sample. Results In IL-1ß-exposed cells, platelet-rich plasma downregulates expression of IL-6/CXCL-6 (mean, 0.015; 95% confidence interval [CI], 0.005-0.025; p = 0.026), IL-6R (mean, 0.61; 95% CI, 0.27-0.95; p = 0.029), and IL-8/CXCL-8 (mean, 0.02; 95% CI, 0.007-0.023; p = 0.026). Secretion of IL-6/CXCL6, 0.35 (95% CI, 0.3-0.4; p = 0.002), IL-8/CXCL8, 0.55 (95% CI, 0.5-0.7; p = 0.01), and monocyte chemoattractant protein-1/CCL2, 0.40 (95% CI, 0.2-0.6; p = 0.001) was reduced by platelet-rich plasma, whereas vascular endothelial growth factor increased by twofold, (95% CI, 1.7-2.3; p \ 0.001). RANTES/CCL5 increased by10-fold (95% CI, 4-17) and hepatocyte growth factor by 21-fold (95% CI, 0.2-42) in tendinopathic and by 2.3-fold (95% CI, 2-3) and threefold (95% CI, 1-5) in normal cells (p = 0.005 for both). Conclusions Platelet-rich plasma induces an immunomodulatory and proangiogenic phenotype consistent with healing mechanisms with few differences between tendinopathic and normal cells. Clinical Relevance Platelet-rich plasma injections in pathological and nearby tissue might help to recover tendon homeostasis.

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Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture

Cited by 446 publications

References 25 publications

Ultrasound-guided injection of platelet-rich plasma in chronic Achilles and patellar tendinopathy

Ultrasound-guided injection of platelet-rich plasma in chronic Achilles and patellar tendinopathy

The use of autologous platelet–leukocyte gels to enhance the healing process in surgery, a review

Platelet-rich Plasma Modulates the Secretion of Inflammatory/Angiogenic Proteins by Inflamed Tenocytes

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