MÉTODOS E APLICAÇÕES DO PLASMA RICO EM PLAQUETAS: Uma Revisão Bibliográfica

RESUMO
O plasma rico em plaquetas (PRP) é um produto derivado de sangue autólogo, cujo preparado visa obter uma alta concentração de plaquetas em um pequeno volume de plasma. Desde meados da década de 90, o gel de PRP, tem sido usado nas áreas de cirurgia oral, reconstrutiva oral, bucomaxilofacial e procedimentos de reconstrução para implantodontia, medicina estética, entre outros ramos da medicina, visando acelerar o reparo da ferida cirúrgica e a regeneração óssea. As plaquetas atuam no processo de hemostasia, cicatrização de feridas e reepitelização. Elas liberam diversos fatores de crescimento que estimulam a angiogênese, a mitose celular, a quimiotaxia dos neutrófilos, macrófagos e fibroblastos, que por sua vez proporcionam um aumento na síntese de colágenos e a produção de linfócitos com a produção de interleucina, promovendo aceleração da reparação tecidual. O propósito deste trabalho é avaliar o PRP, quanto aos seus métodos de obtenção, suas vantagens e desvantagens e suas aplicações clínicas através de um estudo descritivo de revisão literatura, realizada por meio de base de dados de artigos da literatura científica. Com base nas bibliografias estudadas, pode-se concluir que o PRP é uma ferramenta veio para somar na prática de consultório e também cirúrgica e entre estudos positivos e negativos, são esperadas conclusões mais certeiras na expectativa de se poder contar com mais uma opção no tratamento das patologias.


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Contributions for classification of
platelet rich plasma – proposal of a new
classification: MARSPILL

Platelet-rich plasma (PRP) has emerged as a significant therapy used in medical conditions with heterogeneous results. There are some important classifications to try to standardize the PRP procedure. The aim of this report is to describe PRP contents studying celular and molecular components, and also propose a new classification for PRP. The main focus is on mononuclear cells, which comprise progenitor cells and monocytes. In addition, there are important variables related to PRP application incorporated in this study, which are the harvest method, activation, red blood cells, number of spins, image guidance, leukocytes number and light activation. The other focus is the discussion about progenitor cells presence on peripherial blood which are interesting due to neovasculogenesis and proliferation. The function of monocytes (in tissue-macrophages) are discussed here and also its plasticity, a potential property for regenerative medicine treatments.

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Platelet Rich Plasma Treatment
of Androgenetic Alopecia in Men
and Women

Introduction
Androgenic Alopecia (AGA) is one of the most common hair loss complaints in men and women. The population frequency of AGA varies with ethnicity but as a rough generalization up to 70% of men and 40% of women will experience some degree of AGA in their life time. In most men AGA develops with a distinctive “patterned” hair line recession. In women the presentation may be less clear typically women will develop a diffuse thinning over the top of the scalp yielding a “Christmas tree” pattern with more thinning towards the front though the frontal hairline is maintained [1]. The long-term treatment of AGA with the FDA approved topical minoxidil and oral finasteride therapy reported several side effects including scalp irritation facial hypertrichosis and loss of libido.
So the use of a newer modality of Platelet-Rich Plasma (PRP) has attracted attention in the treatment of AGA because of its beneficial effect with minimal or even no side effects [2,3]. Platelet-Rich Plasma (PRP) can be defined as an autologous concentration of human platelets in a small volume of plasma. This concentrate contains various Growth Factors (GFs) that stimulate cell proliferation and differentiation including PDGF, fibroblast FGF, HGF, TGF and VEGF [4]. These growth factors are released once the platelets therein are activated either by calcium chloride, thrombin or fibrinogen. All seem equally effective in activating the platelets ex vivo [5]. Activated autologous PRP has been reported to induce the proliferation of dermal papilla cells by up-regulating Fibroblast Growth Factor 7 (FGF-7) and β-catenin as well as Extracellular Signal-related Kinase (ERK) and Akt signaling. Anagen associated angiogenesis has been suggested as one of the important factors in active hair growth. In addition the angiogenic factor of Vascular Endothelial Growth Factor (VEGF) also originated from the keratinocytes in the outer root sheath and fibroblasts in dermal papilla [6]. Therefore injection of PRP has been demonstrated to improve cutaneous ischemic conditions and to increase vascular structures around hair follicles [7]. The use of PRP has attracted attention in many fields of medicine as in bone grafts, teeth osteosynthesis, wound healing, tendinopathy, ligament sprain, muscle strain, osteoarthrosis, fracture non union and face rejuvenation [8]. In 2006 Uebel and colleagues reported the application of PRP for male pattern baldness surgery. Implanting follicular units with PRP raised the hair yield rate probably because of the partial effects of GFs in PRP [9]. The aim of this study was to assess the efficacy and safety of autologous platelet-rich plasma injection for treatment of AGA.

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To evaluate the effect of combining photo-activation therapy with platelet-rich plasma injections for the novel treatment of osteoarthritis

BACKGROUND
Arthritis is a major cause of disability and chronic pain and has a significant economical impact. Osteoarthritis (OA) is a progressive and degenerative form of arthritis that does not discriminate against age. Osteoarthritis is difficult to treat, with most current medical treatment strategies aimed at pain reduction and/or symptom control rather than biochemical disease modification. Available pharmacological treatments are limited and often bear unwanted side effects. Viscosupplement/hyaluronic acid (HA) intraarticular injections have been used for many years as an adjunctive treatment in conservative management of osteoarthritis. However, the mechanism of action of HA is uncertain, with some studies suggesting little improvement beyond that achieved with placebo injections. Recent research has focused on the catabolic cytokines involved in destruction of hyaline cartilage
and joint degeneration. Interleukin-1 (IL-1) has been identified as a potent mediator of cartilage loss and reciprocally IL-1 receptor antagonist (IL-1RA) has been shown to limit the intra-articular actions of IL-1. Autologous conditioned serum (ACS) is an injectable IL-1RA medium that has been used in Europe for the treatment of osteoarthritis. Research has indicated significant improvement in symptoms of OA post ACS therapy, however, further research is required to determine whether ACS is actually disease modifying. Use of
ACS is limited due to cost and logistical hurdles such as incubating the autolgous blood overnight prior to reinjection. Owing to the limitations of ACS, the research focus has shifted towards platelet-rich plasma (PRP) injections, where reports have demonstrated improved cartilage matrix expression in animal and in-vitro studies, along with the synthesis of hylauronic acid. Platelets, once originally thought to act solely in haemostasis at sites of vascular injury, are now known to contain an abundance of growth factors and cytokines, crucial to soft-tissue healing. In fact, a retrospective cohort study has indicated significant reduction in pain postintrarticular injection of PRP compared with hyaluroinc acid supplements. 16 Similarly, a recent study of patients with grades I–III OA, demonstrated significantly improved pain and function following PRP, when compared with the hyaluronic acid injection control group.  Beside PRP, photo-activation therapy has been shown to increase expression of leucocyte-derived anti-inflammatory cytokines (IL-1RA) and also to cause reduction in proinflammatory cytokines (IL-2 and 6). Thus, a combined photo-activated PRP (PAPRP) preparation may offer a novel method for treatment of osteoarthritis that combines the proven benefits of ACS with potentially diseasemodifying properties of PRP.


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Inflammatory Interaction Between LIGHT and
Proteinase-Activated Receptor-2 in Endothelial Cells

Abstract

The interaction between inflammatory cytokines and endothelial cells is a critical step in atherogenesis leading to endothelial dysfunction and inflammation. We have previously reported that the tumor necrosis factor superfamily member LIGHT could be involved in atherogenesis through its ability to promote vascular inflammation. In the present study we identified proteinase-activated receptor (PAR)-2 as an inflammatory mediator that was markedly enhanced by LIGHT in endothelial cells. We also found that LIGHT acted synergistically with PAR-2 activation to promote enhanced release of the proatherogenic chemokines interleukin-8 and monocyte chemoattractant protein-1, underscoring that the interaction between LIGHT and PAR-2 is biologically active, promoting potent inflammatory effects. We showed that the LIGHT-mediated upregulation of PAR-2 in endothelial cells is mediated through the HVEM receptor, involving Jun N-terminal kinase signaling pathways. A LIGHT-mediated upregulation of PAR-2 mRNA levels was also found in human monocytes when these cells were preactivated by tumor necrosis factor . We have previously demonstrated increased plasma levels of LIGHT in unstable angina patients, and here we show a similar pattern for PAR-2 expression in peripheral blood monocytes. We also found that LIGHT, LIGHT receptors, and PAR-2 showed enhanced expression, and, to some degree, colocalization in endothelial cells and macrophages, in the atherosclerotic plaques of ApoE/ mice, suggesting that the inflammatory interaction between LIGHT and PAR-2 also may be operating in vivo within an atherosclerotic lesion. Our findings suggest that LIGHT/PAR-2–driven inflammation could be a pathogenic loop in atherogenesis potentially representing a target for therapy in this disorder.

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AVALIAÇÃO DO EFEITO DO PLASMA RICO EM PLAQUETAS NA REPARAÇÃO TENDÍNEA UTILIZANDO MODELO EXPERIMENTAL EM OVINOS

RESUMO

PINHEIRO, J. C. M. N. Avaliação do efeito do plasma rico em plaquetas na reparação tendinea utilizando modelo experimental em ovinos. 2015. 44 f. Dissertação (Mestrado em Biociência Animal) - Faculdade de Medicina Veterinária, Universidade de Cuiabá, Cuiabá, 2015.

A terapia de lesões tendíneas é reconhecida como um desafio na medicina humana e veterinária em parte devido à dificuldade do completo restabelecimento da morfologia tendínea e de sua resistência biomecânica. Diversas biotecnologias terapêuticas têm sido empregadas com resultados promissores na terapia da tendinite sendo o plasma rico em plaquetas (PRP) muito popular, no entanto, ainda faltam dados para a comprovação de sua real eficácia. Este estudo teve como objetivo avaliar os efeitos do PRP na cicatrização de lesão experimentalmente induzida no tendão flexor digital superficial (TFDS). Foi realizada tenotomia parcial da face palmar do TFDS com o auxílio de um punch dermatológico em 10 ovinos machos, estes foram divididos em
dois grupos: grupo tratado (GT) com PRP autólogo; e grupo controle (GC) tratado com placebo. Foram realizadas avaliações clínicas, ultrassonográficas e termográficas. Na avaliação termográfica foi observado aumento de temperatura sobre a lesão tendínea do GC comparado ao GT. Na avaliação ultrassonográfica foi possível observar menor edema no GT em diferentes momentos, sugerindo uma possível ação antiinflamatória do PRP. Conclui-se que a administração de PRP apresentou efeitos benéficos no tratamento de lesões tendíneas experimentais de ovinos.

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REVISÃO SISTEMÁTICA DA LITERATURA SOBRE A EFETIVIDADE CLÍNICA DO PLASMA RICO EM PLAQUETAS PARA O TRATAMENTO DERMATOLÓGICO ESTÉTICO

RESUMO

Objetivo: Avaliar o conjunto das evidências sobre a eficácia clínica do plasma rico em plaquetas (PRP) para o tratamento dermatológico estético.

Material e Métodos: Na fundamentação da presente tese, foi realizada uma revisão narrativa sobre envelhecimento cutâneo, opções para o tratamento dermatológico estético das alterações relacionadas ao envelhecimento cutâneo, fatores de crescimento teciduais encontrados nas plaquetas e uso do plasma rico em plaquetas para regeneração tecidual no contexto experimental. Para responder à questão de pesquisa, foi conduzida uma abrangente revisão sistemática da literatura médica visando avaliar a eficácia clínica do PRP para o tratamento dermatológico estético, compreendendo as bases de dados MEDLINE, Cochrane CENTRAL e Embase. Estudos clínicos em humanos avaliando o efeito do PRP como estimulador dérmico no tratamento estético da pele foram incluídos. A busca da literatura, a seleção de artigos e a extração de dados foram realizadas por dois revisores independentes.
Resultados: Somente 7 de 2.132 artigos identificados encontraram os critérios de inclusão da revisão sistemática. Desses, 5 avaliaram o efeito da aplicação do PRP na pele da face para tratamento de cicatrizes de acne, revitalização da pele, sulcos nasolabiais proeminentes ou como adjuvante à cirurgia plástica facial. Outros 2 estudos avaliaram alterações histológicas decorrentes da aplicação do PRP na pele dos braços. Todos estudos avaliados demonstraram resultados benéficos relacionados à aplicação do PRP. Entretanto os estudos apresentam limitações relevantes, como pequeno tamanho amostral, critérios não uniformes na aferição dos desfechos e ausência de grupo controle em sua maioria.
Conclusão: O atual conjunto de evidência científica identificado através de revisão sistemática sugere que o PRP seja um método promissor para o tratamento cosmético da pele. Entretanto, ainda são necessários estudos clínicos de maior porte e com melhores critérios de aferição de desfechos para definir o papel do PRP na prática clínica.

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AVALIAÇÃO DO EFEITO DO PLASMA RICO EM PLAQUETAS FOTOESTIMULADO PELO LASER DE BAIXA POTÊNCIA NO PROCESSO DE REGENERAÇÃO ÓSSEA

Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series

Abstract

Introduction: This is a series of clinical case reports demonstrating that a combination of percutaneously injected
autologous adipose-tissue-derived stem cells, hyaluronic acid, platelet rich plasma and calcium chloride may be
able to regenerate bones in human osteonecrosis, and with addition of a very low dose of dexamethasone, cartilage in human knee osteoarthritis.

Case reports: Stem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. These stem cells, along with hyaluronic acid, platelet rich plasma and calcium chloride, were injected into the right hip of a 29-year-old Korean woman and a 47-year-old Korean man. They both had a history
of right hip osteonecrosis of the femoral head. For cartilage regeneration, a 70-year-old Korean woman and a 79-year-old Korean woman, both with a long history of knee pain due to osteoarthritis, were injected with stem cells along with hyaluronic acid, platelet rich plasma, calcium chloride and a nanogram dose of dexamethasone. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed. Conclusions: The MRI data for all the patients in this series showed significant positive changes. Probable bone
formation was clear in the patients with osteonecrosis, and cartilage regeneration in the patients with osteoarthritis. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional
status all improved. Autologous mesenchymal stem cell injection, in conjunction with hyaluronic acid, platelet rich
plasma and calcium chloride, is a promising minimally invasive therapy for osteonecrosis of femoral head and, with low-dose dexamethasone, for osteoarthritis of human knees.


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Stem cell therapy for idiopathic pulmonary
fibrosis: a protocol proposal

Abstract

Background: Idiopathic pulmonary fibrosis represents a lethal form of progressive fibrotic lung disorder with gradually increasing incidence worldwide. Despite intense research efforts its pathogenesis is still elusive and controversial reflecting in the current disappointing status regarding its treatment. Patients and Methods: We report the first protocol proposal of a prospective, unicentric, non-randomized, phase Ib clinical trial to study the safety and tolerability of the adipose-derived stem cells (ADSCs) stromal vascular fraction (SVF) as a therapeutic agent in IPF. After careful patient selection based on functional criteria (forced vital capacity-FVC > 50%, diffuse lung capacity for carbon monoxide-DLCO > 35% of the predicted values) all eligible subjects will be subjected to lipoaspiration resulting in the isolation of approximately 100- 500 gr of adipose tissue. After preparation, isolation
and labelling ADSCs-SVF will be endobronchially infused to both lower lobes of the fibrotic lungs. Procedure will be repeated thrice at monthly intervals. Primary end-point represent safety and tolerability data, while exploratory
secondary end-points include assessment of clinical functional and radiological status. Results: Preliminary results recently presented in the form of an abstract seem promising and tantalizing since there were no cases of
clinically significant allergic reactions, infections, disease acute exacerbations or ectopic tissue formation. In addition 6 months follow-up data revealed a marginal improvement at 6-minute walking distance and forced vital capacity.

Conclusions: Adipose tissue represents an abundant, safe, ethically uncontested and potentially beneficial source of stem cells for patients with IPF. Larger multicenter phase II and III placebo-controlled clinical trials are sorely needed in order to prove efficacy. However, pilot safety studies are of major importance and represent the first hamper that should be overcome to establish a rigid basis for larger clinical trials.


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