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1.
J Am Acad Dermatol ; 84(5): 1321-1328, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33359595

RESUMO

BACKGROUND: Platelet-rich plasma has shown some promise in the treatment of alopecia areata. OBJECTIVE: To evaluate the effect of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata. METHODS: This was a randomized, placebo-controlled, split-head study involving 27 patients with alopecia areata (Severity of Alopecia Tool score ≥25%). Alopecia patches on either side of the scalp were randomized to receive 3 intradermal injections of platelet-rich plasma or normal saline at monthly intervals and evaluated 3 months after the last session. Lesional T-cell cytokine messenger RNA expression was compared pre- and posttreatment in the platelet-rich plasma-treated sites. RESULTS: The mean Severity of Alopecia Tool score did not change significantly compared with baseline with either platelet-rich plasma or placebo injections at any visit; however, the mean percentage reduction in the score in the platelet-rich plasma arm was more than in the placebo arm (9.05% ± 36.48% vs 4.99% ± 33.88%; P = .049) at final assessment. The mean interferon gamma (P = .001) and interleukin 17 cytokine (P = .009) messenger RNA expression decreased, whereas the mean interleukin 10 (P = .049) and FOXP3 (P = .011) messenger RNA expression increased significantly after platelet-rich plasma treatment. LIMITATIONS: Small sample size and a relatively short follow-up. CONCLUSION: Platelet-rich plasma was found to have limited efficacy in alopecia areata. However, it may play a role in restoring immune balance in the alopecic patches.


Assuntos
Alopecia em Áreas/terapia , Citocinas/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Plasma Rico em Plaquetas/imunologia , Adolescente , Adulto , Alopecia em Áreas/imunologia , Alopecia em Áreas/patologia , Transfusão de Sangue Autóloga/métodos , Método Duplo-Cego , Seguimentos , Folículo Piloso/citologia , Folículo Piloso/imunologia , Folículo Piloso/patologia , Humanos , Injeções Intradérmicas , Masculino , Projetos Piloto , Placebos/administração & dosagem , Placebos/efeitos adversos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do Tratamento , Adulto Jovem
2.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652994

RESUMO

Osteoarthritis of the knee (OAK) is a chronic degenerative disease and progresses with an imbalance of cytokines and macrophages in the joint. Studies regarding the use of platelet-rich plasma (PRP) as a point-of-care treatment for OAK have reported on its effect on tissue repair and suppression of inflammation but few have reported on its effect on macrophages and macrophage polarization. Based on our clinical experience with two types of PRP kits Cellaid Serum Collection Set P type kit (leukocyte-poor-PRP) and an Autologous Protein Solution kit (APS leukocyte-rich-PRP), we investigated the concentrations of humoral factors in PRPs prepared from the two kits and the effect of humoral factors on macrophage phenotypes. We found that the concentrations of cell components and humoral factors differed between PRPs purified using the two kits; APS had a higher concentration of M1 and M2 macrophage related factors. The addition of PRP supernatants to the culture media of monocyte-derived macrophages and M1 polarized macrophages revealed that PRPs suppressed M1 macrophage polarization and promoted M2 macrophage polarization. This research is the first to report the effect of PRPs purified using commercial kits on macrophage polarization.


Assuntos
Ativação de Macrófagos , Macrófagos/imunologia , Plasma Rico em Plaquetas/imunologia , Adulto , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Int J Mol Sci ; 22(4)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33572157

RESUMO

Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor's health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65‒85 and 20‒25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.


Assuntos
Córtex Cerebral/imunologia , Mediadores da Inflamação/metabolismo , Microglia/imunologia , Plasma Rico em Plaquetas/imunologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Animais , Apoptose/imunologia , Linhagem Celular Tumoral , Proliferação de Células , Córtex Cerebral/citologia , Quimiocina CCL11/metabolismo , Feminino , Humanos , Masculino , Camundongos , Microglia/citologia , Células-Tronco Neurais/imunologia , Neurogênese/imunologia , Neurônios/imunologia , Plasma Rico em Plaquetas/citologia , Plasma Rico em Plaquetas/metabolismo , Cultura Primária de Células , Ratos , Sinapses/imunologia , Adulto Jovem
4.
Int J Mol Sci ; 22(4)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673372

RESUMO

One of the most severe effects of coronavirus disease 2019 (COVID-19) is lung disorders such as acute respiratory distress syndrome. In the absence of effective treatments, it is necessary to search for new therapies and therapeutic targets. Platelets play a fundamental role in respiratory disorders resulting from viral infections, being the first line of defense against viruses and essential in maintaining lung function. The direct application of platelet lysate (PL) obtained from the platelet-rich plasma of healthy donors could help in the improvement of the patient due its anti-inflammatory, immunomodulatory, antifibrotic, and repairing effects. This work evaluates PL nebulization by analyzing its levels of growth factors and its biological activity on lung fibroblast cell cultures, besides describing a scientific basis for its use in this kind of pathology. The data of the work suggest that the molecular levels and biological activity of the PL are maintained after nebulization. Airway administration would allow acting directly on the lung tissue modulating inflammation and stimulating reparative processes on key structures such as the alveolocapillary barrier, improving the disease and sequels. The protocol developed in this work is a first step for the study of nebulized PL both in animal experimentation and in clinical trials.


Assuntos
Anti-Inflamatórios/farmacologia , COVID-19/terapia , Fatores Imunológicos/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Plasma Rico em Plaquetas , Adulto , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/imunologia , Plaquetas/imunologia , COVID-19/imunologia , Linhagem Celular , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Masculino , Nebulizadores e Vaporizadores , Plasma Rico em Plaquetas/imunologia , SARS-CoV-2/imunologia , Resultado do Tratamento
5.
Plast Surg Nurs ; 40(2): 68-72, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32459753

RESUMO

Platelet-rich plasma (PRP) therapy is a new approach in dermatology and there is evidence to suggest that it provides excellent adjuvant treatment for nonscarring alopecia cases. There is evidence supporting the hypothesis that PRP therapy increases hair growth and thickness in patients with nonscarring alopecia. Studies including participants with scarring alopecia are limited and larger scale studies with tighter controls in PRP preparation, administration, and follow-up are needed to determine whether this is a clinically sound approach. Further symptom control analysis is also warranted as in both single and combination PRP therapy trials there are little data to support treatment effect on symptoms such as burning and itching. In this article, the author explains PRP preparation processes and PRP types and compares stand-alone PRP therapy with combination PRP study results. The author also makes recommendations for treatment and discusses the future of PRP research.


Assuntos
Alopecia/tratamento farmacológico , Cabelo/efeitos dos fármacos , Plasma Rico em Plaquetas/metabolismo , Alopecia/fisiopatologia , Cabelo/crescimento & desenvolvimento , Humanos , Plasma Rico em Plaquetas/imunologia
6.
Transfusion ; 59(11): 3501-3510, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31599981

RESUMO

BACKGROUND: Alloimmunization to platelet-rich plasma (PRP) transfusions can cause adverse reactions such as platelet refractoriness or transplant rejection. Pathogen reduction treatment with ultraviolet light and riboflavin (UV + R) of allogeneic PRP was shown to reduce allogeneic antibody responses and confer partial antigen-specific immune tolerance to subsequent transfusions in mice. Studies have shown that UV + R was effective at both rapidly killing donor white blood cells (WBCs) and reducing their ability to stimulate an allogeneic response in vitro. However, the manner in which UV + R induces WBC death and its associated role in the immune response to treated PRP is unknown. METHODS AND MATERIALS: This study evaluates whether UV + R causes WBC apoptosis by examining phosphatidylserine exposure on the plasma membrane, membrane asymmetry, caspase activity, and chromatin condensation by flow cytometry. The immunogenicity of WBCs killed with UV + R versus apoptotic or necrotic pathways was also examined in vivo. RESULTS: WBCs after UV + R exhibited early apoptotic-like characteristics including phosphatidylserine exposure on the outer leaflet of the plasma membrane and loss of membrane asymmetry, but unlike canonical apoptotic cells, caspase activity and chromatin condensation were not apparent. However, in vivo studies demonstrated, unlike untreated or necrotic WBCs, both apoptotic WBCs and UV + R-treated WBCs failed to prime alloantibody responses to subsequent untreated transfusions. CONCLUSION: Overall, the mechanism of WBC death following UV + R treatment shares some membrane characteristics of early apoptosis but is distinct from classic apoptosis. Despite these differences, UV + R-treated and apoptotic WBCs both offer some protection from alloimmunization.


Assuntos
Apoptose/efeitos dos fármacos , Segurança do Sangue/métodos , Leucócitos/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Riboflavina/farmacologia , Reação Transfusional/prevenção & controle , Raios Ultravioleta , Animais , Biomarcadores/metabolismo , Feminino , Citometria de Fluxo , Humanos , Tolerância Imunológica , Leucócitos/imunologia , Leucócitos/metabolismo , Leucócitos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fármacos Fotossensibilizantes/administração & dosagem , Transfusão de Plaquetas/métodos , Plasma Rico em Plaquetas/citologia , Plasma Rico em Plaquetas/imunologia , Riboflavina/administração & dosagem
7.
Platelets ; 29(1): 9-20, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28681651

RESUMO

The infection of a wound is one of the major contributors to delays in healing and tissue regeneration. As multi-drug resistance to antibiotics is becoming a serious threat, research in this field has focused on finding new agents and strategies to fight infection and additionally to reduce healing times. The topical use of autologous Platelet Rich Plasma (PRP) as a biological accelerator of the healing process, has been safely used as a form of treatment for wounds since the 1990s. Although the presence or absence of leucocytes in PRP preparation was previously neglected, in the last decade more attention has been paid to their role and several studies have been conducted to explore both their immuno-metabolic effects and their antimicrobial properties. In this review, we aim to summarise the literature on the contribution of leucocytes included in PRP preparations in terms of their antimicrobial properties. This should help to inform clinical practice and additional research in this promising field.


Assuntos
Anti-Infecciosos , Leucócitos/imunologia , Leucócitos/microbiologia , Plasma Rico em Plaquetas/citologia , Plasma Rico em Plaquetas/imunologia , Anti-Infecciosos/uso terapêutico , Antissepsia , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/terapia , Biomarcadores , Plaquetas/metabolismo , Humanos , Leucócitos/metabolismo , Ativação Plaquetária , Resultado do Tratamento
9.
Clin Orthop Relat Res ; 473(5): 1624-34, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25670657

RESUMO

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 plasma-induced 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.


Assuntos
Proteínas Angiogênicas/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Plasma Rico em Plaquetas/metabolismo , Tendinopatia/terapia , Tendões/metabolismo , Cicatrização , Proteínas Angiogênicas/genética , Estudos de Casos e Controles , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/farmacologia , Fenótipo , Plasma Rico em Plaquetas/imunologia , RNA Mensageiro/metabolismo , Transdução de Sinais , Tendinopatia/sangue , Tendinopatia/genética , Tendinopatia/imunologia , Tendinopatia/patologia , Tendões/efeitos dos fármacos , Tendões/imunologia , Tendões/patologia , Fatores de Tempo , Cicatrização/efeitos dos fármacos
10.
BMC Musculoskelet Disord ; 16: 153, 2015 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-26092588

RESUMO

BACKGROUND: Platelet-rich plasma (PRP) preparations are a common treatment in osteoarthritis (OA) and inflammatory synovitis. However, there is ambiguity regarding the ideal concentration of leukocytes and platelets in these preparations necessary to induce an adequate anti-inflammatory and anabolic response in joint tissues, such as the synovial membrane. This research aimed to study, in normal synovial membrane explants (SME) challenged with lipopolysaccharide (LPS), the temporal effects (at 48 and 96h) of leukocyte- and platelet-rich gel (L-PRG) and pure platelet-rich gel (P-PRG) supernatants on the production and degradation of platelet associated growth factors (GF) (platelet derived GF isoform BB (PDGF-BB) and transforming growth factor beta-1 (TGF-ß1)), pro-inflammatory (tumour necrosis factor alpha (TNF-α)) and anti-inflammatory cytokines (interleukin 4 (IL-4) and IL-1 receptor antagonists (IL-1ra)) and hyaluronan (HA). METHODS: Synovial membrane explants (SMEs) from 6 horses were challenged with LPS and cultured for 96h with L-PRG and P-PRG supernatants at concentrations of 25 and 50 %, respectively. The SME culture medium was changed every 48h and used for determination by ELISA of PDGF-BB, TGF-ß1, TNF-α, IL-4, IL-1ra and HA. These molecules were also determined in synovial fluid from the horses. RESULTS: Both the 25 and 50 % PRG supernatants produced a molecular profile in the culture media unlike that of the SME challenged with LPS only. They presented GF, cytokine and HA concentrations very near to the concentrations of these molecules in normal synovial fluid when compared with the SME control groups (either with LPS or without LPS). However, in comparison with the rest of the SME treated groups, the 25 % L-PRG produced the most IL-1ra, and the 50 % P-PRG induced the sustained production of IL-4 and HA. CONCLUSIONS: These in vitro findings suggest that anabolic and anti-inflammatory joint responses depend on the leukocyte and platelet concentration of the PRP preparation and on the volume of this substance injected. Moreover, it is possible, that leukoreduced PRP preparations are more effective for the medical treatment of patients with OA and inflammatory synovitis.


Assuntos
Plaquetas/metabolismo , Citocinas/metabolismo , Ácido Hialurônico/metabolismo , Mediadores da Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Lipopolissacarídeos/farmacologia , Plasma Rico em Plaquetas/metabolismo , Membrana Sinovial/efeitos dos fármacos , Animais , Plaquetas/imunologia , Fracionamento Celular , Meios de Cultura/metabolismo , Géis , Cavalos , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Leucócitos/metabolismo , Plasma Rico em Plaquetas/imunologia , Líquido Sinovial/imunologia , Líquido Sinovial/metabolismo , Membrana Sinovial/imunologia , Membrana Sinovial/metabolismo , Fatores de Tempo , Técnicas de Cultura de Tecidos
11.
Knee Surg Sports Traumatol Arthrosc ; 23(9): 2690-703, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24942296

RESUMO

PURPOSE: To analyse the modifications induced by two different platelet-rich plasma (PRP) preparations on osteoarthritis (OA) synoviocytes, by documenting changes in gene expression of factors involved in joint physiopathology. METHODS: OA synoviocytes were cultured for 7 days in medium with different concentrations of either P-PRP (a pure platelet concentrate without leucocytes but with a limited number of platelets), L-PRP (a higher platelet concentrate containing leucocytes) or platelet-poor plasma (PPP). Gene expression of interleukin (IL)-1beta, IL-6, IL-8/CXCL8, tumour necrosis factor alpha, IL-10, IL-4, IL-13, metalloproteinase-13, tissue inhibitor of metalloproteinase (TIMP)-1, (TIMP)-3, (TIMP)-4, vascular endothelial growth factor, transforming growth factor beta1, fibroblast growth factor (FGF)-2, hepatocyte growth factor (HGF), hyaluronic acid (HA) synthases (HAS)-1, (HAS)-2, and (HAS)-3 was analysed by RT-PCR. HA production was determined in culture supernatants by ELISA. RESULTS: IL-1ß, IL-8 and FGF-2 were significantly induced by L-PRP compared to both P-PRP and PPP; HGF was down-modulated by L-PRP versus both P-PRP and PPP, and an inverse dose-response influence was shown for all preparations. Expression level of TIMP-4 was lower in the presence of L-PRP compared with P-PRP. HA production and HAS gene expression did not seem to be modulated by PRP. CONCLUSIONS: L-PRP is able to sustain the up-regulation of proinflammatory factors, (IL-1beta, IL-8 and FGF-2), together with a down-modulation of HGF and TIMP-4 expression, two factors that have been recognized as anti-catabolic mediators in cartilage, thus supporting the need to further optimize the PRP preparations to be applied in clinical practice.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Osteoartrite do Joelho/imunologia , Plasma Rico em Plaquetas/imunologia , Membrana Sinovial/imunologia , Adulto , Plaquetas/imunologia , Células Cultivadas , Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Leucócitos/imunologia , Masculino , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/patologia , Membrana Sinovial/patologia , Regulação para Cima
12.
Arthroscopy ; 29(4): 675-83, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23395471

RESUMO

PURPOSE: The purpose of this study was to quantify the extent of the anti-inflammatory effect of platelet-rich plasma (PRP) in a controlled in vitro environment. METHODS: Through the stimulation of human umbilical vein endothelial cells with inflammatory cytokines (tumor necrosis factor α and interferon γ), cell adhesion molecule expression (E-selectin, vascular cell adhesion molecule, and human leukocyte antigen DR) and PRP's anti-inflammatory effect can be measured. PRP was produced from 3 individuals using a single-spin (PRPLP) process. Treatment groups include negative (unstimulated) controls, positive (stimulated) controls, ketorolac tromethamine, methylprednisolone, PRP, ketorolac-PRP, and methylprednisolone-PRP. A fluorescence assay of the cellular inflammation markers was measured by the BioTek Synergy HT plate reader (BioTek Instruments, Winooski, VT) at 0, 1, 2, and 5 days. RESULTS: At days 2 and 5, methylprednisolone treatment showed a 2.1- to 5.8-fold reduction (P < .05) in inflammation markers over PRP. In addition, PRP and ketorolac showed a 1.4- to 2.5-fold reduction (P < .05) in cellular inflammation markers over the control. There was no statistically significant difference between ketorolac and PRP. CONCLUSIONS: Although PRP and ketorolac reduced cellular inflammation markers (E-selectin, vascular cell adhesion molecule, and human leukocyte antigen DR) compared with control, neither caused as great a reduction as methylprednisolone. CLINICAL RELEVANCE: Although PRP and ketorolac did not produce as significant a reduction in cellular inflammation markers as methylprednisolone, they reduced cellular inflammation compared with the control. These agents may have clinical application as injectable anti-inflammatory medications.


Assuntos
Anti-Inflamatórios/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Cetorolaco/farmacologia , Metilprednisolona/farmacologia , Plasma Rico em Plaquetas/imunologia , Adulto , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/imunologia , Humanos , Inflamação , Masculino , Adulto Jovem
13.
J Tissue Eng Regen Med ; 15(1): 3-13, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33197147

RESUMO

The recurrence of ventral hernias continues to be a problem faced by surgeons, in spite of efforts toward implementing novel repair techniques and utilizing different materials to promote healing. Cadaveric acellular dermal matrices (Alloderm) have shown some promise in numerous surgical subspecialties, but these meshes still suffer from subsequent failure and necessitation of re-intervention. Here, it is demonstrated that the addition of platelet rich plasma to Alloderm meshes temporally modulates both the innate and cytotoxic inflammatory responses to the implanted material. This results in decreased inflammatory cytokine production at early time points, decreased matrix metalloproteinase expression, and decreased CD8+ T cell infiltration. Collectively, these immune effects result in a healing phenotype that is free from mesh thinning and characterized by increased material stiffness.


Assuntos
Derme Acelular , Materiais Biocompatíveis , Colágeno , Plasma Rico em Plaquetas , Ratos Endogâmicos Lew , Telas Cirúrgicas , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Colágeno/química , Colágeno/imunologia , Hérnia Ventral/imunologia , Hérnia Ventral/cirurgia , Masculino , Plasma Rico em Plaquetas/química , Plasma Rico em Plaquetas/imunologia , Ratos
14.
Front Immunol ; 11: 942, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32536916

RESUMO

Cord blood platelet rich plasma (CB-PRP) derivatives have been investigated as potential therapeutic agents for the treatment of diverse conditions including ocular surface disease and skin ulcers. We have developed processes for the formulation of several CB-PRP preparations, which have different composition and attributes. Here we describe the molecular characteristics of these preparations and we make recommendations as to their most appropriate clinical application based on functional and immunomodulatory profiles. We show that incubation of adult peripheral blood mononuclear cells (PBMCs) with all three preparations dramatically reduced the production of INFγ and the expression of NKG2D and CD107a in NK, NKT, and T cells thus diminishing their activation, we propose that the likely mechanism is the high levels of soluble NKG2D ligands present in plasma. Of the three preparations we investigated, CB platelet lysate (PL) and platelet releaseate (PR) have higher concentrations of trophic and pro-angiogenic factors, CB platelet poor plasma (PPP) has the lowest concentration of all analytes measured. Based on these finding we propose that CB-PR is the most suitable raw material for skin wound patches, while CB-PL and PPP can be used to prepare eye drops for severe ocular surface pathologies and inflammatory conditions such as corneal ulcers or severe dry eye disease, respectively.


Assuntos
Comunicação Celular , Sangue Fetal/metabolismo , Linfócitos/metabolismo , Plasma Rico em Plaquetas/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Células Cultivadas , Citocinas/metabolismo , Sangue Fetal/citologia , Sangue Fetal/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interferon gama/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Ativação Linfocitária , Linfócitos/imunologia , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Soluções Oftálmicas , Plasma Rico em Plaquetas/citologia , Plasma Rico em Plaquetas/imunologia , Polimorfismo Genético , Cicatrização
15.
J Cardiovasc Pharmacol ; 54(1): 57-62, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19528814

RESUMO

Bacterial infection may increase risk for thrombosis and atherosclerosis. Human platelets express toll-like receptor 4 (TLR4), the receptor for gram-negative bacterial lipopolysaccharide (LPS). Experiments were designed to evaluate direct, acute effects of TLR4 activation on aggregation, secretion, and generation of prothrombogenic microparticles in vitro on platelets derived from healthy women at risk for development of cardiovascular disease because of their hormonal status. Platelet-rich plasma from recently menopausal women was incubated with ultrapure Escherichia coli LPS in the absence or presence of antibodies that neutralize the human TLR4. Incubating platelets with LPS (100 ng/mL) for 5 minutes decreased aggregation and dense granule adenosine triphosphate secretion induced by thrombin receptor agonist peptide (TRAP) but not by adenosine diphosphate or collagen. The antibody to TLR4 blocked this effect of LPS. TLR4 activation increased phosphorylation of p38 mitogen-activated protein kinase and decreased production of prothrombotic phosphatidylserine and P-selectin-positive microparticles in response to TRAP. Therefore, acute, direct activation of TLR4 reduces platelet reactivity to TRAP stimulation in vitro. Increased thrombotic and cardiovascular risk with bacterial infection most likely reflects the sum of TLR4 activation on other blood and vascular cells to release proinflammatory cytokines/chemokines, which indirectly affect platelet reactivity.


Assuntos
Plaquetas/metabolismo , Agregação Plaquetária/imunologia , Receptor 4 Toll-Like/metabolismo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Adulto , Plaquetas/imunologia , Feminino , Humanos , Lipopolissacarídeos/farmacologia , Menopausa/imunologia , Menopausa/metabolismo , Pessoa de Meia-Idade , Nanopartículas , Tamanho da Partícula , Fragmentos de Peptídeos/farmacologia , Ativação Plaquetária , Plasma Rico em Plaquetas/imunologia , Plasma Rico em Plaquetas/metabolismo , Receptor 4 Toll-Like/imunologia
16.
Clin Hemorheol Microcirc ; 73(1): 43-51, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31561346

RESUMO

BACKGROUND: To overcome the compromised wound healing in radiation induced chronic wounds platelet-rich plasma (PRP), as therapeutic agent, is current subject of studies. PRP is associated with pro-angiogenic effects. Nevertheless, effects of platelet-rich plasma in cutaneous wound healing processes are poorly understood so far. METHODS: In this study, the migration of endothelial cells, fibroblasts and keratinocytes in conjunction with platelet-rich plasma treatment is investigated in the context of radiation effects. Additionally, cell proliferation and viability after external radiation was analyzed regarding treatment by platelet-rich plasma. RESULTS: All cell cultures showed a trend towards decreasing proliferation and viability after irradiation irrespective of PRP. Upon PRP treatment, irradiated fibroblasts as well as endothelial cells showed an enhanced proliferation whereas proliferation and viability of keratinocytes was reduced after PRP treatment. Scratch assays support the positive effect of PRP on fibroblast and endothelial cell migration, whereas a negative effect on keratinocytes was observed after PRP treatment. CONCLUSIONS: The present study documents both deleterious effects of external radiation as well as the protective effect of PRP. In summary, increased viability, proliferation and migration are indeed a consequence of the pro-proliferative effect exerted by PRP. Therefore, treatment with PRP products might be useful in the management of chronic radiogenic wounds.


Assuntos
Movimento Celular/imunologia , Células Endoteliais/efeitos da radiação , Plasma Rico em Plaquetas/imunologia , Humanos
17.
J Neuroimmunol ; 333: 476958, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31103935

RESUMO

The use of growth factors is considered to be one of the promising therapeutic strategies for multiple sclerosis (MS). Various studies have shown that platelet-rich plasma (PRP), a bioproduct of concentrated platelets, contains a variety of growth factors such as insulin-like growth factor 1 (IGF-1), platelet-derived growth factor (PDGF), epithelial growth factor (EGF), and transforming growth factor ß (TGF-ß). The therapeutic roles of PRP, with regard to a wide range of growth factors, on the nervous system have been shown in a limited number of studies. This study aimed to investigate the therapeutic effect of PRP in experimental autoimmune encephalomyelitis (EAE) mouse model of MS. PRP was prepared and intrathecally injected into the EAE mice. The EAE scoring test, the modified neurological severity score (mNSS) test, luxol fast blue and hematoxylin and eosin staining, real-time PCR, and western blotting were used for studying the effect of PRP on the motosensory function, remyelination, inflammatory cell infiltration, gliosis, and inflammatory cytokines expression. PRP administration in treated animals improved the functional abilities, remyelination, and oligodendrogenesis compared to the EAE mice. Furthermore, high numbers of microglia, astrocytes and infiltrating inflammatory cells and also the expression of proinflammatory cytokines were reversed after PRP therapy. In conclusion, these data suggest the PRP as a potential candidate for MS treatment.


Assuntos
Encefalomielite Autoimune Experimental/terapia , Plasma Rico em Plaquetas , Animais , Encefalomielite Autoimune Experimental/patologia , Feminino , Gliose/patologia , Gliose/prevenção & controle , Inflamação , Injeções Espinhais , Interleucina-1beta/biossíntese , Interleucina-1beta/genética , Interleucina-6/biossíntese , Interleucina-6/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteína Básica da Mielina/biossíntese , Proteína Básica da Mielina/genética , Plasma Rico em Plaquetas/imunologia , Medula Espinal/patologia , Regulação para Cima
18.
Artigo em Inglês | MEDLINE | ID: mdl-30481239

RESUMO

In this study, we determine the in vivo effects of injecting sub-populations of leukocytes into normal rat Achilles tendons via a controlled laboratory study. Allogenic monocytes, granulocytes, or plasma were injected into 24 healthy rat Achilles tendons. Treated and contralateral un-treated control tendons then assessed for cellularity, histologic morphology, and vascularity after 7 and 14 days. Significant increases of 221% and 249% in cellularity (P = 0.014) were seen on day 14 within Achilles tendons injected with granulocytes as compared to plasma and monocytes, respectively. Also, significant improvement in morphology (P = 0.029) between days 7 and 14 was seen for the granulocyte injected Achilles tendons. Significant increases in cellularity after an injection of granulocytes, compared to monocytes and plasma, corresponds to a significant increase in inflammation within the tissue, suggesting that leukocyte-rich platelet-rich plasma (PRP) preparations are proinflammatory and potentially catabolic when injected into tendon tissue. The concentration and composition of white blood cells within PRP preparations is variable and needs to be better understood in order to optimize clinical utility of PRP injections.


Assuntos
Tendão do Calcâneo/imunologia , Tendão do Calcâneo/patologia , Granulócitos/imunologia , Inflamação/imunologia , Monócitos/imunologia , Plasma Rico em Plaquetas/imunologia , Animais , Granulócitos/patologia , Injeções , Transfusão de Leucócitos/efeitos adversos , Masculino , Modelos Animais , Monócitos/patologia , Estudos Prospectivos , Ratos , Transplante Homólogo , Cicatrização/imunologia
19.
Mol Med Rep ; 16(4): 4082-4088, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28765945

RESUMO

Platelet-rich plasma (PRP) is a multifunctional blood product containing highly concentrated platelets, and various cell growth factors which promote cell proliferation and differentiation. PRP exhibited benefits in injurious articular cartilage repair and the removal of inflammatory factors in clinical studies. Rheumatoid arthritis (RA) is an autoimmune disease manifesting primarily as inflammatory arthritis, which is associated with notable morbidity in humans. In the present study, the therapeutic effects and primary mechanism of PRP on a type II collagen­induced arthritis (CIA) mouse model was investigated. Inflammatory factors interleukin (IL)­6, IL­8, IL­17, IL­1ß, tumor necrosis factor (TNF)­α and interferon (IFN)­Î³ were analyzed in PRP and PBS­treated groups. Vascular endothelial growth factor (VEGF), platelet­derived growth factor (PDGF), insulin­like growth factor (IGF)­1 and transforming growth factor (TGF)­ß expression in peripheral whole blood was additionally analyzed. The therapeutic efficacy of PRP for RA mice was evaluated using clinical arthritis scores. The results of the present study demonstrated that treatment with PRP alleviated arthritis, and reduced humoral and cellular immune responses, leading to beneficial effects on histological parameters as observed using joint tissue histological staining. CIA mice treated with PRP exhibited downregulated expression of IL­6, IL­8, IL­17A, IL­1ß, TNF­α, receptor activator for nuclear factor­κB and IFN­Î³ in inflammatory tissue. In addition, VEGF, PDGF, IGF­1 and TGF­ß expression in peripheral whole blood was increased following treatment with PRP. The serum concentration of anti­collagen antibody was decreased in PRP­treated CIA mice. In conclusion, CIA mice treated with PRP exhibited beneficial effects, including decreased joint inflammation, cartilage destruction and bone damage, and increased repair of joint tissue. The results of the present study suggested that PRP may be an effective therapeutic agent for RA.


Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Plasma Rico em Plaquetas/imunologia , Animais , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Artrite Experimental , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Biomarcadores , Proteínas do Sistema Complemento/imunologia , Citocinas/genética , Modelos Animais de Doenças , Expressão Gênica , Células HeLa , Humanos , Masculino , Camundongos , Plasma Rico em Plaquetas/metabolismo
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