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Tanzadehpanah H, Nobari S, Hoseini AJ, Ghotbani F, Mehrabzadeh M, Jalili shahri J, Alipour A, Sheykhhasan M, Manoochehri H, Darroudi S, Mahaki H. Effect of platelet-rich plasma on angiogenic and regenerative properties in patients with critical limb ischemia. Regen Ther 2025; 28:517-526. [PMID: 39995496 PMCID: PMC11848493 DOI: 10.1016/j.reth.2025.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 01/01/2025] [Accepted: 01/10/2025] [Indexed: 02/26/2025] Open
Abstract
Platelet-rich plasma (PRP) is a promising regenerative therapy due to its simplicity, clinical application, safety, and ability to promote angiogenesis. It utilizes various angiogenic growth factors in platelets, including platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF), which are integral to the tissue repair. Critical limb ischemia (CLI) is a major symptom of peripheral arterial disease (PAD), and PRP therapy aims to improve blood circulation to the distal limb through the development of blood vessels. This review focuses on the extensive research on the molecular mechanisms of PRPs in treating CLI. A comprehensive search was conducted on Web of Science, PubMed, Google Scholar, and Scopus to find studies published during PRP therapy in critical limb ischemia up to June 2024. Current studies reveal that PRP composition varies by case, affecting preparation methods, storage duration, storage methods, and interaction with other materials. PRP-derived growth factors have shown promising results in treating CLI, but well-controlled human research is scarce despite positive animal studies.
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Affiliation(s)
- Hamid Tanzadehpanah
- Antimicrobial Resistance Research Center, Basic Science Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sima Nobari
- Deputy of Health, Iran University of Medical Science, Tehran, Iran
| | | | - Farzaneh Ghotbani
- Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Mehrabzadeh
- Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Jamal Jalili shahri
- Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirreza Alipour
- Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Sheykhhasan
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Hamed Manoochehri
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Susan Darroudi
- Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hanie Mahaki
- Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Malcangi G, Inchingolo AM, Inchingolo AD, Ferrante L, Latini G, Trilli I, Nardelli P, Longo M, Palermo A, Inchingolo F, Dipalma G. The Role of Platelet Concentrates and Growth Factors in Facial Rejuvenation: A Systematic Review with Case Series. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:84. [PMID: 39859067 PMCID: PMC11767021 DOI: 10.3390/medicina61010084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 12/29/2024] [Accepted: 12/30/2024] [Indexed: 01/27/2025]
Abstract
Background and objectives: Due to the regeneration potential of growth factors (GFs) and platelet concentrates (PCs), facial rejuvenation has been a major area of attention in esthetic medicine. The effectiveness and safety of PCs and GFs in promoting face rejuvenation are examined in this systematic review, which is complemented by a case series. GFs are essential for collagen production and dermal matrix remodeling, while PCs, like Platelet-Rich Plasma (PRP), are abundant in bioactive chemicals that promote tissue healing and cellular regeneration. Materials and Methods: A comprehensive literature search was performed on PubMed, Web of Science, and Scopus, focusing on human clinical trials published between February 2019 and February 2024 related to PRP and facial esthetics. Results: Thirteen studies met the inclusion criteria and were analyzed. Conclusions: The review summarizes the most recent data on patient outcomes, treatment regimens, and possible hazards. The case series that goes with it shows real-world examples of how to improve skin elasticity, texture, and general facial appearance with little negative side effects. These results highlight the potential use of PCs and GFs as minimally invasive procedures.
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Affiliation(s)
- Giuseppina Malcangi
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.M.); (A.D.I.); (L.F.); (G.L.); (I.T.); (P.N.); (M.L.); (G.D.)
| | - Angelo Michele Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.M.); (A.D.I.); (L.F.); (G.L.); (I.T.); (P.N.); (M.L.); (G.D.)
| | - Alessio Danilo Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.M.); (A.D.I.); (L.F.); (G.L.); (I.T.); (P.N.); (M.L.); (G.D.)
| | - Laura Ferrante
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.M.); (A.D.I.); (L.F.); (G.L.); (I.T.); (P.N.); (M.L.); (G.D.)
| | - Giulia Latini
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.M.); (A.D.I.); (L.F.); (G.L.); (I.T.); (P.N.); (M.L.); (G.D.)
| | - Irma Trilli
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.M.); (A.D.I.); (L.F.); (G.L.); (I.T.); (P.N.); (M.L.); (G.D.)
| | - Paola Nardelli
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.M.); (A.D.I.); (L.F.); (G.L.); (I.T.); (P.N.); (M.L.); (G.D.)
| | - Marialuisa Longo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.M.); (A.D.I.); (L.F.); (G.L.); (I.T.); (P.N.); (M.L.); (G.D.)
| | - Andrea Palermo
- Department of Experimental Medicine, University of Salento, 73100 Lecce, Italy;
| | - Francesco Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.M.); (A.D.I.); (L.F.); (G.L.); (I.T.); (P.N.); (M.L.); (G.D.)
| | - Gianna Dipalma
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.M.); (A.D.I.); (L.F.); (G.L.); (I.T.); (P.N.); (M.L.); (G.D.)
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Yogiswara N, Rizaldi F, Soebadi MA. The potential role of intracavernosal injection of platelet-rich plasma for treating patients with mild to moderate erectile dysfunction: A GRADE-Assessed systematic review and meta-analysis of randomized controlled trials. Arch Ital Urol Androl 2024; 96:12687. [PMID: 39356015 DOI: 10.4081/aiua.2024.12687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 06/07/2024] [Indexed: 10/03/2024] Open
Abstract
INTRODUCTION Platelet-rich plasma (PRP) has shown positive effects on enhancing erectile function in animal studies. Human clinical trials are limited and provide contradictory results. This review aims to conduct a meta-analysis of the available Randomized controlled trials (RCT) to assess the efficacy of PRP in males with ED. METHODS A systematic review was carried out following the Cochrane Handbook of Intervention and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and registered in PROSPERO (CRD42023441655). RESULTS A total of three RCTs were included in the analysis for a total of 221 patients with mild to moderate ED. The patients receiving PRP reported significantly better improvement of IIEFEF score during 1,3- and 6-months follow-up compared to the placebo group (mean difference [MD] 2.66, 95% confidence interval [CI] 1.48 to 3.83, p < 0.01; MD 2.11, 95%CI 0.13 to 4.09, p = 0.04; MD 2.99, 95%CI 1.79 to 4.19, p < 0.01). The pooled analysis indicated that attainment of minimally clinical important difference (MCID) was significantly higher in patients receiving PRP compared to the placebo group during one and 6-month follow-up (odds ratio [OR] 5.51, 95%CI 1.2 to 254, p = 0.03; OR 5.64, 95%CI 2.05 to 15.55, p < 0.01; respectively). Encouragingly, no major AEs were reported in all three trials in the PRP and placebo groups (p = 0.99). CONCLUSIONS This review highlights the potential role of PRP in providing short-term improvement of erectile function parameters for up to 6 months in mild to moderate ED patients. Future RCTs with longer-duration follow-ups and more standardized treatment protocols are necessary to gain sufficient details on PRP's long-term effectiveness and safety.
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Affiliation(s)
- Niwanda Yogiswara
- Department of Urology, Faculty of Medicine, Universitas Airlangga, Surabaya; Dr. Soetomo General-Academic Hospital, Surabaya.
| | - Fikri Rizaldi
- Department of Urology, Faculty of Medicine, Universitas Airlangga, Surabaya; Universitas Airlangga Teaching Hospital, Surabaya.
| | - Mohammad Ayodhia Soebadi
- Department of Urology, Faculty of Medicine, Universitas Airlangga, Surabaya; Universitas Airlangga Teaching Hospital, Surabaya.
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Wei W, Xu D, Hu F, Jiang T, Liu H. Platelet-rich plasma promotes wound repair in diabetic foot ulcer mice via the VEGFA/VEGFR2/ERK pathway. Growth Factors 2024; 42:161-170. [PMID: 39543829 DOI: 10.1080/08977194.2024.2422014] [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: 03/05/2024] [Accepted: 09/18/2024] [Indexed: 11/17/2024]
Abstract
Diabetic foot ulcers (DFUs) are a severe microvascular complication. Platelet-rich plasma (PRP) pitches in DFU treatment. This study explored the mechanism of PRP facilitating wound repair in DFU mice via vascular endothelial growth factor A (VEGFA)/VEGF receptor 2 (VEGFR2)/extracellular signal-regulated kinase (ERK) pathway. The DFU mouse model was established, with wound skin injected with PRP, followed by the detections of wound area, histopathological changes, and CD31-positive cells. IL-6/TNF-α/VEGFA/VEGFR2/p-VEGFR2/(ERK1/2)/(p-ERK1/2) levels in wound tissue homogenates were assessed. VEGFA-VEGFR2 interaction was evaluated. PRP-treated DFU mice were simultaneously treated with fruquintinib/PD98059. PRP reduced wound area, IL-6 and TNF-α levels, elevated epidermal dermal thickness, CD31-positive cell number, and aligned tissue structure, which were mitigated by fruquintinib/PD98059. PRP promoted VEGFR2 phosphorylation. PRP and fruquintinib/PD98059 abated p-VEGFR2/VEGFR2 or p-ERK1/2/ERK1/2 levels in DFU mice. PRP activated the ERK pathway through VEGFA/VEGFR2. Collectively, PRP promoted VEGFR2 phosphorylation and activated the ERK pathway, thereby facilitating wound repair in DFU mice.
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Affiliation(s)
- Weiqiang Wei
- Department of Orthopaedics, The Fourth Hospital of Changsha, Changsha, China
| | - Di Xu
- Department of Orthopaedics, The Fourth Hospital of Changsha, Changsha, China
| | - Fan Hu
- Department of Orthopaedics, The Fourth Hospital of Changsha, Changsha, China
| | - Tenglong Jiang
- Department of Orthopaedics, The Fourth Hospital of Changsha, Changsha, China
| | - Hong Liu
- Department of Orthopaedics, The Fourth Hospital of Changsha, Changsha, China
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Serdarogullari M, Raad G, Makieva S, Liperis G, Fraire-Zamora JJ, Celik-Ozenci C. Revitalizing female fertility: platelet-rich plasma - hype or hope? Reprod Biomed Online 2024; 49:103813. [PMID: 38852205 DOI: 10.1016/j.rbmo.2024.103813] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 12/30/2023] [Accepted: 01/03/2024] [Indexed: 06/11/2024]
Abstract
Platelet-rich plasma (PRP) has gained popularity as an experimental tool in regenerative medicine, with potential applications in reproductive medicine. This review will assess the existing literature on the role of PRP in female fertility enhancement, focusing on ovarian rejuvenation and increased endometrial thickness. PRP is being explored as a treatment for recurrent implantation failure, primary ovarian insufficiency and poor ovarian response. While the influence of PRP on endometrial thickness and implantation success is postulated, its effectiveness remains the subject of debate due to protocol variability and unclear patient selection criteria. This narrative review includes 36 articles published before December 2022, and highlights the lack of comprehensive molecular studies examining the impact of PRP on reproductive capacity. This review underscores the importance of standardizing PRP preparation protocols in reproductive medicine. However, challenges persist, and there is a need for well-planned randomized controlled trials and a deeper understanding of the patient population that would gain the greatest benefit from PRP treatment. Clarifying these aspects is crucial to improve outcomes for low-prognosis patients undergoing assisted reproductive technology.
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Affiliation(s)
- Munevver Serdarogullari
- Department of Histology and Embryology, Faculty of Medicine, Cyprus International University, Northern Cyprus via Mersin 10, Turkey
| | - Georges Raad
- Faculty of Medicine and Medical Sciences, Holy Spirit University of Kaslik, Jounieh, Lebanon; Al Hadi Laboratory and Medical Centre, Beirut, Lebanon
| | - Sofia Makieva
- Kinderwunschzentrum, Klinik für Reproduktions-Endokrinologie, Universitätsspital Zürich, Zurich, Switzerland
| | - Georgios Liperis
- Westmead Fertility Centre, Institute of Reproductive Medicine, University of Sydney, Westmead, NSW, Australia
| | | | - Ciler Celik-Ozenci
- Department of Histology and Embryology, School of Medicine, Koc University, Istanbul, Turkey; Koç University Research Centre for Translational Medicine, Istanbul, Turkey.
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Vladulescu D, Scurtu LG, Simionescu AA, Scurtu F, Popescu MI, Simionescu O. Platelet-Rich Plasma (PRP) in Dermatology: Cellular and Molecular Mechanisms of Action. Biomedicines 2023; 12:7. [PMID: 38275368 PMCID: PMC10813350 DOI: 10.3390/biomedicines12010007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 12/10/2023] [Accepted: 12/18/2023] [Indexed: 01/27/2024] Open
Abstract
Platelet-rich plasma (PRP) therapy has gained attention in the scientific field due to its potential regenerative effects and great benefit-risk ratio. This review extensively explores the most studied mechanisms of this therapy according to the etiopathogenesis of skin diseases: cellular proliferation, matrix formation, regulation of inflammation, angiogenesis, collagen synthesis, and the remodeling of new tissue. Moreover, it draws on newly reported and lesser-known effects of PRP: its anti-apoptotic effects, immunological suppression, decrease in melanin synthesis, anti-microbial effects, overexpression of miR-155, antioxidant effects, and their involved pathways. This work aims to provide a complete update for understanding PRP's benefits and clinical relevance in wound healing, alopecia, pigmentary disorders, scars, rejuvenation, lichen sclerosus, and other inflammatory dermatoses, based on the current evidence. Furthermore, recent reports with novel indications for PRP therapy are highlighted, and new potential pathways correlated with the pathogenesis of skin diseases are explored.
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Affiliation(s)
- Denisa Vladulescu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Dermatology I, Colentina Hospital, 020125 Bucharest, Romania
| | - Lucian G. Scurtu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Dermatology I, Colentina Hospital, 020125 Bucharest, Romania
| | - Anca Angela Simionescu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Obstetrics and Gynecology, Filantropia Clinical Hospital, 011132 Bucharest, Romania
| | - Francesca Scurtu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Obstetrics and Gynecology, Filantropia Clinical Hospital, 011132 Bucharest, Romania
| | - Marco I. Popescu
- Faculty of Medicine, “Titu Maiorescu” University, 040441 Bucharest, Romania
| | - Olga Simionescu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Dermatology I, Colentina Hospital, 020125 Bucharest, Romania
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Li X, Liu H, Lin G, Xu L. The effect of ovarian injection of autologous platelet rich plasma in patients with poor ovarian responder: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2023; 14:1292168. [PMID: 38155954 PMCID: PMC10754527 DOI: 10.3389/fendo.2023.1292168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 11/27/2023] [Indexed: 12/30/2023] Open
Abstract
Objective To evaluate the effects of ovarian injection of autologous platelet rich plasma (aPRP) on patients with poor ovarian responder (POR) based on the existing clinical evidence. Methods According to systematic review and meta-analysis, we comprehensively searched nine databases established as of September 6, 2023, and evaluated the impact of ovarian PRP infusion on poor ovarian responder. The research results include serum follicle-stimulating hormone(FSH) and anti-Mullerian hormone(AMH) levels, antral Follicle Count(AFC), oocyte number, and embryo number. The Newcastle Ottawa Scale (NOS) was used to evaluate the quality of inclusion in trials. Results Add up to 10 studies consisting of 793 participants were included in the meta-analysis. A review of existing evidence showed that intraovarian injection of PRP has significant therapeutic effects in increasing levels of anti-Müllerian hormone (AMH) (SMD=0.44,95% CI [0.07,0.81], p=0.02), antral follicle count (AFC) (MD=1.15,95% CI [0.4,1.90], p=0.003), oocyte count (MD=0.91, 95% CI [0.40, 1.41], p=0.0004), and embryo number (MD=0.78, 95% CI [0.5,1.07], p<0.0001). We compared the relevant data of patients before and after treatment after 2 months of intervention. It can be seen that ovarian injection of PRP treatment for 2 months has better effects in reducing FSH levels, increasing AMH levels, increasing antral follicle count, and increasing the number of oocytes and embryos (p<0.05). When the dose of PRP injected into each ovary was ≥ 4ml, there was also a significant correlation (p<0.05) with improving the number of AFC, oocytes and embryos. Significant heterogeneity existed among the studies. Conclusion The pooled results suggest that intra-ovarian injection of PRP can promote ovarian regeneration and improve the reproductive outcomes of patients with ovarian dysfunction. This therapy may have significant clinical potential in improving sex hormone levels, increasing AFC, oocyte count, and embryo count. However, this findings still requires more rigorous and extensive trials worldwide to determine the value of intra-ovarian injection of PRP in POR patients. Systematic review registration https://www.crd.york.ac.uk, Identifier CRD42023451232.
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Affiliation(s)
| | | | | | - Lianwei Xu
- Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Pellicer N, Cozzolino M, Diaz-García C, Galliano D, Cobo A, Pellicer A, Herraiz S. Ovarian rescue in women with premature ovarian insufficiency: facts and fiction. Reprod Biomed Online 2023; 46:543-565. [PMID: 36710157 DOI: 10.1016/j.rbmo.2022.12.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 11/16/2022] [Accepted: 12/02/2022] [Indexed: 12/24/2022]
Abstract
The ovary has a comparatively short functional lifespan compared with other organs, and genetic and pathological injuries can further shorten its functional life. Thus, preserving ovarian function should be considered in the context of women with threats to ovarian reserve, such as ageing, premature ovarian insufficiency (POI) and diminished ovarian reserve (DOR). Indeed, one-third of women with POI retain resting follicles that can be reactivated to produce competent oocytes, as proved by the in-vitro activation of dormant follicles. This paper discusses mechanisms and clinical data relating to new therapeutic strategies using ovarian fragmentation, stem cells or platelet-rich plasma to regain ovarian function in women of older age (>38 years) or with POI or DOR. Follicle reactivation techniques show promising experimental outcomes and have been successful in some cases, when POI is established or DOR diagnosed; however, there is scarce clinical evidence to warrant their widespread clinical use. Beyond these contexts, also discussed is how new insights into the biological mechanisms governing follicular dynamics and oocyte competence may play a role in reversing ovarian damage, as no technique modifies oocyte quality. Additional studies should focus on increasing follicle number and quality. Finally, there is a small but important subgroup of women lacking residual follicles and requiring oocyte generation from stem cells.
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Affiliation(s)
| | | | - César Diaz-García
- IVI London, EGA Institute for Women's Health, UCL, London, UK; IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
| | | | - Ana Cobo
- IVI RMA Valencia, Valencia, Spain
| | - Antonio Pellicer
- IVI RMA Rome, Rome, Italy; IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
| | - Sonia Herraiz
- IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain.
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Platelet-Derived Mitochondria Attenuate 5-FU-Induced Injury to Bone-Associated Mesenchymal Stem Cells. Stem Cells Int 2023; 2023:7482546. [PMID: 36756493 PMCID: PMC9902133 DOI: 10.1155/2023/7482546] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 10/27/2022] [Accepted: 11/25/2022] [Indexed: 02/03/2023] Open
Abstract
Background Myelosuppression is a common condition during chemotherapy. Bone-associated mesenchymal stem cells (BA-MSCs) play an essential role in the composition of the hematopoietic microenvironment and support hematopoietic activity. However, chemotherapy-induced damage to BA-MSCs is rarely studied. Recent studies have shown that platelets promote the wound-healing capability of MSCs by mitochondrial transfer. Therefore, this study is aimed at investigating the chemotherapy-induced damage to BA-MSCs and the therapeutic effect of platelet-derived mitochondria. Material/Methods. We established in vivo and in vitro BA-MSC chemotherapy injury models using the chemotherapy agent 5-fluorouracil (5-FU). Changes in the mitochondrial dynamics were detected by transmission electron microscopy, and the expression of mitochondrial fusion and fission genes was analyzed by qRT-PCR. In addition, mitochondrial functions were also explored by flow cytometry and luminometer. Platelet-derived mitochondria were incubated with 5-FU-damaged BA-MSCs to repair the injury, and BA-MSC functional changes were examined to assess the therapy efficacy. The mechanism of treatment was explored by studying the expression of mitochondrial fission and fusion genes and hematopoietic regulatory factor genes in BA-MSCs. Results Stimulation with 5-FU increased the apoptosis and suppressed cell cycle progression of BA-MSCs both in vivo and in vitro. In addition, 5-FU chemotherapy inhibited the hematopoietic regulatory ability and disrupted the mitochondrial dynamics and functions of BA-MSCs. The mitochondrial membrane potential and ATP content of 5-FU-injured BA-MSCs were decreased. Interestingly, when platelet-derived mitochondria were transferred to BA-MSCs, the 5-FU-induced apoptosis was alleviated, and the hematopoietic regulatory ability of 5-FU-injured BA-MSCs was effectively improved by upregulating the expression of mitochondrial fusion genes and hematopoietic regulatory factor genes. Conclusion BA-MSCs were severely damaged by 5-FU chemotherapy both in vivo and in vitro. Meanwhile, platelet-derived mitochondria could attenuate the 5-FU-induced injury to BA-MSCs, which provides future research directions for exploring the treatment strategies for chemotherapy-injured BA-MSCs and establishes a research basis for related fields.
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Visweswaran M, Cunningham CW, Sidhu KS. Isolation and Characterisation of an Adipose-derived human mesenchymal stem cell line - ' CKC-Endeavour-1'. J Stem Cells Regen Med 2022; 18:2-10. [PMID: 36003657 DOI: 10.46582/jsrm.1801002] [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: 10/01/2021] [Accepted: 12/19/2021] [Indexed: 11/19/2022]
Abstract
Mesenchymal stem cells derived from adipose tissue (ADMSCs) are being increasingly considered in regenerative medicine-based clinical applications. Apart from possessing therapeutic applications themselves, ADMSCs also secrete a myriad of soluble factors which are promising candidates for treating several degenerative diseases such as osteoarthritis and neurodegenerative diseases, wound repair as well as for cosmeceutical purposes. In our research study, we successfully isolated ADMSCs in-house, now called CKC-Endeavour-1 from the lipoaspirate sample of a patient who underwent liposuction. The subsequent expansion of cells was performed in xeno-free and serum-free conditions and their characterisation was performed using tri-lineage differentiation studies. The levels of differentiation were assessed by staining and gene expression which was observed to be comparable between the in-house developed ADMSC cell line and the commercially purchased ADMSCs. Following characterisation, the secretory components from these MSCs, namely, conditioned media (ADMSC-CM) and exosomes (ADMSC-EXO) were harvested from CKC-Endeavour-1 under xeno-free, serum-free, and supplement-free conditions followed by lyophilisation in order to attempt to prolong its shelf-life. The comprehensive analysis of the secretome profile of ADMSC-CM using carried out using cytokine array and demonstrated the presence of 105 cytokines and growth factors. Also, clinical grade Izon columns were used to isolate the exosomes from ADMSC-CM obtaining exosomes in the size range of <200nm, analysed using nanoparticle tracking analysis. Overall, our study developed an ADMSC cell line, CKC-Endeavour-1, along with their CM and exosome (EXO) products under clinically safe conditions. Additionally, we have obtained a comprehensive understanding of the secreted factors present in the ADMSC-CM which could be further explored in detail to tap the best therapeutic benefits from them.
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Singh G, Borah D, Khanna G, Jain S. Efficacy of Local Autologous Platelet-Rich Plasma in the Treatment of Pressure Ulcer in Spinal Cord Injury Patients. Cureus 2021; 13:e18668. [PMID: 34790446 PMCID: PMC8583427 DOI: 10.7759/cureus.18668] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/11/2021] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND Pressure ulcer is one of the common complications occurring in spinal cord injury (SCI) patients. Platelet-rich plasma (PRP) has been found useful in the treatment of pressure ulcers in few studies. The purpose of this study was to evaluate the role of PRP in pressure ulcer healing in comparison to hydrogel dressing in SCI patients. METHODS In this randomized interventional study, 52 patients of SCI having pressure ulcers of grade III/IV were randomized into two groups of 26 each. In group A patients, hydrogel dressing was done while freshly prepared PRP was used in patients of group B. Pressure ulcers were evaluated at baseline and after three weeks and six weeks in terms of ulcer surface area, volume, Pressure Ulcer Scale for Healing (PUSH) score, histopathology, and ulcer healing parameters. Data were collected and quantitative variables were compared using unpaired t-test or Mann-Whitney test between the two groups and qualitative variables were compared using the chi-square test or Fisher's exact test. A p-value of <0.05 was considered statistically significant. RESULTS Baseline characteristics were comparable in both groups. There was a significant improvement in ulcers in terms of surface area, volume, and PUSH score in both the groups but it was comparable (p-value >0.05). There was a significant improvement in the PRP group as compared to the other group in terms of epithelization, granulation, and neovascularization at three and six-week follow-up. CONCLUSIONS This study suggests that PRP is a possible and better alternative to conventional dressing methods for the treatment of pressure ulcers.
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Affiliation(s)
- Gurpreet Singh
- Physical Medicine and Rehabilitation, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
| | - Diganta Borah
- Physical Medicine and Rehabilitation, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
| | - Geetika Khanna
- Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, IND
| | - Sakshi Jain
- Physical Medicine and Rehabilitation, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, New Delhi, IND
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12
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Atkinson L, Martin F, Sturmey RG. Intraovarian injection of platelet-rich plasma in assisted reproduction: too much too soon? Hum Reprod 2021; 36:1737-1750. [PMID: 33963408 PMCID: PMC8366566 DOI: 10.1093/humrep/deab106] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 04/09/2021] [Indexed: 12/13/2022] Open
Abstract
The prospect of ovarian rejuvenation offers the tantalising prospect of treating age-related declines in fertility or in pathological conditions such as premature ovarian failure. The concept of ovarian rejuvenation was invigorated by the indication of the existence of oogonial stem cells (OSCs), which have been shown experimentally to have the ability to differentiate into functional follicles and generate oocytes; however, their clinical potential remains unknown. Furthermore, there is now growing interest in performing ovarian rejuvenation in situ. One proposed approach involves injecting the ovary with platelet rich plasma (PRP). PRP is a component of blood that remains after the in vitro removal of red and white blood cells. It contains blood platelets, tiny anucleate cells of the blood, which are responsible for forming athrombus to prevent bleeding. In addition, PRP contains an array of cytokines and growth factors, as well as a number of small molecules.The utility ofPRP has been investigatedin a range of regenerative medicine approaches and has been shown to induce differentiation of a range of cell types, presumably through the action of cytokines. A handful ofcasereports have described the use of PRP injections into the ovaryin the human, and while these clinical data report promising results, knowledge on the mechanisms and safety of PRP injections into the ovary remain limited.In this article, we summarise some of the physiological detail of platelets and PRP, before reviewing the existing emerging literature in this area. We then propose potential mechanisms by which PRP may be eliciting any effects before reflecting on some considerations for future studies in the area. Importantly, on the basis of our existing knowledge, we suggest that immediate use of PRP in clinical applications is perhaps premature and further fundamental and clinical research on the nature of ovarian insufficiency, as well as the mechanism by which PRP may act on the ovary, is needed to fully understand this promising development.
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Affiliation(s)
- Lloyd Atkinson
- Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, University of Hull, Hull, UK
| | - Francesca Martin
- Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, University of Hull, Hull, UK
| | - Roger G Sturmey
- Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, University of Hull, Hull, UK.,Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, St Mary's Hospital, Manchester, UK
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13
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Time-dependent effects of platelet-rich plasma on the memory and hippocampal synaptic plasticity impairment in vascular dementia induced by chronic cerebral hypoperfusion. Brain Res Bull 2020; 164:299-306. [DOI: 10.1016/j.brainresbull.2020.08.033] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 08/19/2020] [Accepted: 08/30/2020] [Indexed: 12/19/2022]
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14
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He R, Li Q, Shen W, Wang T, Lu H, Lu J, Lu F, Luo M, Zhang J, Gao H, Wang D, Xing W, Jia W, Liu F. The efficacy and safety of cold atmospheric plasma as a novel therapy for diabetic wound in vitro and in vivo. Int Wound J 2020; 17:851-863. [PMID: 32168435 DOI: 10.1111/iwj.13341] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 02/21/2020] [Accepted: 03/04/2020] [Indexed: 12/30/2022] Open
Abstract
Cold atmospheric plasma (CAP) is a group of various chemical active species, such as ozone and nitric oxide, generated by working gas. CAP was demonstrated to have an effect on tissue regeneration and wound healing. We conducted this study to evaluate the efficacy and safety of CAP as a novel therapy for diabetic wounds in vitro and in vivo. The plasma consists of ionised helium gas that is produced by a high-voltage and high-frequency power supply. Eight-week-old male db/db mice and C57BL mice were treated with helium gas (control group), 90s' CAP (low-dose group), and 180s' CAP (high-dose group). Mice were treated and observed for 2 weeks. Skin samples from around the wound and blood samples were collected. Our in vitro analysis included scratch wound-healing assays by using human HaCaT immortalised human epidermal cells. After 14 days of treatment, CAP could obviously promote diabetic wound healing. Wound closure rates were significantly higher in the low-dose group and high-dose groups compared with the control group. Meanwhile, compared with the control group, the protein expression of IL-6, tumour necrosis factor-α, inducible nitric oxide synthase, and superoxide dismutase in two CAP groups significantly decreased, while the protein expression of vascular endothelial growth factor and transforming growth factor-β in two CAP groups significantly increased (all P < .05); these data show good agreement with the change in mRNA level (all P < .05). In vitro, scratch wound-healing assays showed that plasma treatment could effectively ensure healing within 3 minutes of exposure (all P < .05). In addition, no difference was found in histological observations of normal skin and the level of serum alanine transaminase, aspartate aminotransferase, blood urea nitrogen, creatinine, and white blood cells among the CAP groups and control group. CAP treatment for 3 minutes every day improves wound healing in diabetic mice by suppressing inflammation, reducing oxidative stress, and enhancing angiogenesis, involving several proteins signalling, and it is safe for the liver and kidney.
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Affiliation(s)
- Rui He
- Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Qin Li
- Capital Bio Corporation, National Engineering Research Center for Beijing Biochip Technology, Beijing, China
| | - Wenqi Shen
- Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Tao Wang
- Department of Vascular Surgery, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Huijuan Lu
- Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Junxi Lu
- Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Fendi Lu
- Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Ming Luo
- Capital Bio Corporation, National Engineering Research Center for Beijing Biochip Technology, Beijing, China
| | - Jiankang Zhang
- Capital Bio Corporation, National Engineering Research Center for Beijing Biochip Technology, Beijing, China
| | - Haiwei Gao
- Capital Bio Corporation, National Engineering Research Center for Beijing Biochip Technology, Beijing, China
| | - Dong Wang
- Capital Bio Corporation, National Engineering Research Center for Beijing Biochip Technology, Beijing, China
| | - Wanli Xing
- Capital Bio Corporation, National Engineering Research Center for Beijing Biochip Technology, Beijing, China
| | - Weiping Jia
- Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Fang Liu
- Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China
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Bretschneider H, Quade M, Lode A, Gelinsky M, Rammelt S, Zwingenberger S, Schaser KD, Vater C. Characterization of Naturally Occurring Bioactive Factor Mixtures for Bone Regeneration. Int J Mol Sci 2020; 21:ijms21041412. [PMID: 32093051 PMCID: PMC7073126 DOI: 10.3390/ijms21041412] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 02/11/2020] [Accepted: 02/13/2020] [Indexed: 12/13/2022] Open
Abstract
In this study, the bone-regenerative potential of bioactive factors derived from adipose tissue, platelet-rich plasma (PRP) and conditioned medium from hypoxia-treated human telomerase immortalized bone-marrow-derived mesenchymal stem cells (hTERT-MSC) was investigated in vitro with the aim to develop cost-effective and efficient bone substitutes for optimized regeneration of bone defects. Adipose tissue was harvested from human donors undergoing reconstructive surgery, and adipose tissue extract (ATE) was prepared. Platelet lysates (PL) were produced by repeated freeze-thaw cycles of PRP, and hypoxia-conditioned medium (HCM) was obtained by culturing human telomerase immortalized bone-marrow-derived mesenchymal stromal cells for 5 days with 1% O2. Besides analysis by cytokine and angiogenesis arrays, ELISA was performed. Angiogenic potential was investigated in cocultures of bone-marrow-derived (BM)-MSC and human umbilical vein endothelial cells. Multiple angiogenic proteins and cytokines were detected in all growth factor mixtures. HCM and ATE contained high amounts of angiogenin and CCL2/MCP-1, whereas PL contained high amounts of IGFBP-1. Culturing cells with HCM and ATE significantly increased specific ALP activity of BM-MSC as well as tubule length and junctions of endothelial networks, indicating osteogenic and angiogenic stimulation. To achieve a synergism between chemoattractive potential and osteogenic and angiogenic differentiation capacity, a combination of different growth factors appears promising for potential clinical applications.
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Affiliation(s)
- Henriette Bretschneider
- University Center of Orthopaedics and Traumatology, University Hospital Carl Gustav Carus of Technische, Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische, Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
| | - Mandy Quade
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische, Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
| | - Anja Lode
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische, Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
| | - Michael Gelinsky
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische, Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
| | - Stefan Rammelt
- University Center of Orthopaedics and Traumatology, University Hospital Carl Gustav Carus of Technische, Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
| | - Stefan Zwingenberger
- University Center of Orthopaedics and Traumatology, University Hospital Carl Gustav Carus of Technische, Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische, Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
| | - Klaus-Dieter Schaser
- University Center of Orthopaedics and Traumatology, University Hospital Carl Gustav Carus of Technische, Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
| | - Corina Vater
- University Center of Orthopaedics and Traumatology, University Hospital Carl Gustav Carus of Technische, Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische, Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
- Correspondence:
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16
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do Amaral RJFC, Zayed NMA, Pascu EI, Cavanagh B, Hobbs C, Santarella F, Simpson CR, Murphy CM, Sridharan R, González-Vázquez A, O'Sullivan B, O'Brien FJ, Kearney CJ. Functionalising Collagen-Based Scaffolds With Platelet-Rich Plasma for Enhanced Skin Wound Healing Potential. Front Bioeng Biotechnol 2019; 7:371. [PMID: 31921799 PMCID: PMC6915093 DOI: 10.3389/fbioe.2019.00371] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Accepted: 11/13/2019] [Indexed: 12/21/2022] Open
Abstract
Porous collagen-glycosaminoglycan (collagen-GAG) scaffolds have shown promising clinical results for wound healing; however, these scaffolds do not replace the dermal and epidermal layer simultaneously and rely on local endogenous signaling to direct healing. Functionalizing collagen-GAG scaffolds with signaling factors, and/or additional matrix molecules, could help overcome these challenges. An ideal candidate for this is platelet-rich plasma (PRP) as it is a natural reservoir of growth factors, can be activated to form a fibrin gel, and is available intraoperatively. We tested the factors released from PRP (PRPr) and found that at specific concentrations, PRPr enhanced cell proliferation and migration and induced angiogenesis to a greater extent than fetal bovine serum (FBS) controls. This motivated us to develop a strategy to successfully incorporate PRP homogeneously within the pores of the collagen-GAG scaffolds. The composite scaffold released key growth factors for wound healing (FGF, TGFβ) and vascularization (VEGF, PDGF) for up to 14 days. In addition, the composite scaffold had enhanced mechanical properties (when compared to PRP gel alone), while providing a continuous upper surface of extracellular matrix (ECM) for keratinocyte seeding. The levels of the factors released from the composite scaffold were sufficient to sustain proliferation of key cells involved in wound healing, including human endothelial cells, mesenchymal stromal cells, fibroblasts, and keratinocytes; even in the absence of FBS supplementation. In functional in vitro and in vivo vascularization assays, our composite scaffold demonstrated increased angiogenic and vascularization potential, which is known to lead to enhanced wound healing. Upon pro-inflammatory induction, macrophages released lower levels of the pro-inflammatory marker MIP-1α when treated with PRPr; and released higher levels of the anti-inflammatory marker IL1-ra upon both pro- and anti-inflammatory induction when treated with the composite scaffold. Finally, our composite scaffold supported a co-culture system of human fibroblasts and keratinocytes that resulted in an epidermal-like layer, with keratinocytes constrained to the surface of the scaffold; by contrast, keratinocytes were observed infiltrating the PRP-free scaffold. This novel composite scaffold has the potential for rapid translation to the clinic by isolating PRP from a patient intraoperatively and combining it with regulatory approved scaffolds to enhance wound repair.
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Affiliation(s)
- Ronaldo J. F. C. do Amaral
- Kearney Lab, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
- Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
- Centre for Research in Medical Devices (CURAM), National University of Ireland Galway, Galway, Ireland
| | - Noora M. A. Zayed
- Kearney Lab, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
- Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
- Department of Biomedical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates
| | - Elena I. Pascu
- Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | - Brenton Cavanagh
- Cellular and Molecular Imaging Core, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | - Chris Hobbs
- Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland
- Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin (TCD), Dublin, Ireland
| | - Francesco Santarella
- Kearney Lab, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
- Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | - Christopher R. Simpson
- Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | - Ciara M. Murphy
- Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
- Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland
| | - Rukmani Sridharan
- Kearney Lab, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
- Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | - Arlyng González-Vázquez
- Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
- Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland
| | - Barry O'Sullivan
- Beaumont Hospital, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | - Fergal J. O'Brien
- Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
- Centre for Research in Medical Devices (CURAM), National University of Ireland Galway, Galway, Ireland
- Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland
- Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland
| | - Cathal J. Kearney
- Kearney Lab, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
- Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
- Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland
- Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland
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Karimi A, Shahrooz R, Hobbenagh R, Delirezh N, Amani S, Garssen J, Mortaz E, M Adcock I. Histological Evidence for Therapeutic Induction of Angiogenesis Using Mast Cells and Platelet-Rich Plasma within A Bioengineered Scaffold following Rat Hindlimb Ischemia. CELL JOURNAL 2019; 21:391-400. [PMID: 31376320 PMCID: PMC6722454 DOI: 10.22074/cellj.2020.6287] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Accepted: 11/26/2018] [Indexed: 11/29/2022]
Abstract
Objective Peripheral arterial disease results from obstructed blood flow in arteries and increases the risk of amputation
in acute cases. Therapeutic angiogenesis using bioengineered tissues composed of a chitosan scaffold that was
enriched with mast cells (MCs) and/or platelet-rich plasma (PRP) was used to assess the formation of vascular networks
and subsequently improved the functional recovery following hindlimb ischemia. This study aimed to find an optimal
approach for restoring local vascularization.
Materials and Methods In this experimental study, thirty rats were randomly divided into six experimental groups: a.
Ischemic control group with right femoral artery transection, b. Ischemia with phosphate-buffered saline (PBS) control
group, c. Ischemia with chitosan scaffold, d. Ischemia with chitosan and MCs, e. Ischemia with chitosan and PRP, and
f. Ischemia with chitosan, PRP, and MCs. The left hind limbs served as non-ischemic controls. The analysis of capillary
density, arterial diameter, histomorphometric analysis and immunohistochemistry at the transected locations and in
gastrocnemius muscles was performed.
Results The group treated with chitosan/MC significantly increased capillary density and the mean number of
large blood vessels at the site of femoral artery transection compared with other experimental groups (P<0.05). The
treatment with chitosan/MC also significantly increased the muscle fiber diameter and the capillary-to-muscle fiber ratio
in gastrocnemius muscles compared with all other ischemic groups (P<0.05).
Conclusion These findings suggested that chitosan and MCs together could offer a new approach for the therapeutic
induction of angiogenesis in cases of peripheral arterial diseases.
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Affiliation(s)
- Ali Karimi
- Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Rasoul Shahrooz
- Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.Electronic Address:
| | - Rahim Hobbenagh
- Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Nowruz Delirezh
- Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Saeede Amani
- Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.,Nutricia Research Centre for Specialized Nutrition, Utrecht, Netherlands
| | - Esmaeil Mortaz
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.,Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Clinical Tuberculosis and Epidemiology Research Center, National Research Institute for Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.Electronic Address:
| | - Ian M Adcock
- Cell and Molecular Biology Group, Airways Disease Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom.,Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
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18
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Gaspar D, Peixoto R, De Pieri A, Striegl B, Zeugolis DI, Raghunath M. Local pharmacological induction of angiogenesis: Drugs for cells and cells as drugs. Adv Drug Deliv Rev 2019; 146:126-154. [PMID: 31226398 DOI: 10.1016/j.addr.2019.06.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 05/12/2019] [Accepted: 06/16/2019] [Indexed: 12/12/2022]
Abstract
The past decades have seen significant advances in pro-angiogenic strategies based on delivery of molecules and cells for conditions such as coronary artery disease, critical limb ischemia and stroke. Currently, three major strategies are evolving. Firstly, various pharmacological agents (growth factors, interleukins, small molecules, DNA/RNA) are locally applied at the ischemic region. Secondly, preparations of living cells with considerable bandwidth of tissue origin, differentiation state and preconditioning are delivered locally, rarely systemically. Thirdly, based on the notion, that cellular effects can be attributed mostly to factors secreted in situ, the cellular secretome (conditioned media, exosomes) has come into the spotlight. We review these three strategies to achieve (neo)angiogenesis in ischemic tissue with focus on the angiogenic mechanisms they tackle, such as transcription cascades, specific signalling steps and cellular gases. We also include cancer-therapy relevant lymphangiogenesis, and shall seek to explain why there are often conflicting data between in vitro and in vivo. The lion's share of data encompassing all three approaches comes from experimental animal work and we shall highlight common technical obstacles in the delivery of therapeutic molecules, cells, and secretome. This plethora of preclinical data contrasts with a dearth of clinical studies. A lack of adequate delivery vehicles and standardised assessment of clinical outcomes might play a role here, as well as regulatory, IP, and manufacturing constraints of candidate compounds; in addition, completed clinical trials have yet to reveal a successful and efficacious strategy. As the biology of angiogenesis is understood well enough for clinical purposes, it will be a matter of time to achieve success for well-stratified patients, and most probably with a combination of compounds.
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Affiliation(s)
- Diana Gaspar
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland; Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland
| | - Rita Peixoto
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland; Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland
| | - Andrea De Pieri
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland; Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland; Proxy Biomedical Ltd., Coilleach, Spiddal, Galway, Ireland
| | - Britta Striegl
- Competence Centre Tissue Engineering for Drug Development (TEDD), Centre for Cell Biology & Tissue Engineering, Institute for Chemistry and Biotechnology, Zurich University of Applied Sciences, Zurich, Switzerland
| | - Dimitrios I Zeugolis
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland; Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland
| | - Michael Raghunath
- Competence Centre Tissue Engineering for Drug Development (TEDD), Centre for Cell Biology & Tissue Engineering, Institute for Chemistry and Biotechnology, Zurich University of Applied Sciences, Zurich, Switzerland.
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19
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Notodihardjo SC, Morimoto N, Kakudo N, Mitsui T, Le TM, Tabata Y, Kusumoto K. Comparison of the efficacy of cryopreserved human platelet lysate and refrigerated lyophilized human platelet lysate for wound healing. Regen Ther 2019; 10:1-9. [PMID: 30525065 PMCID: PMC6260428 DOI: 10.1016/j.reth.2018.10.003] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 10/08/2018] [Accepted: 10/23/2018] [Indexed: 11/16/2022] Open
Abstract
INTRODUCTION Human platelet lysate (hPL) part of the growth factor cocktail derived from human platelets, which has been applied as a cell growth supplement. The production process is easier in comparison to platelet-rich plasma; thus, hPL is now considered for use in wound healing therapy. However, methods for preserving hPL for more than several months that maintain its bioactivity must be considered, especially for chronic wound treatment. The present study compared the effects of preservation for 9 months using a refrigerator or deep freezer. METHODS We investigated three preservation conditions. In the C-hPL group, hPL was stored at -80 °C in a deep freezer for 9 months; in the CL-hPL group, hPL was cryopreserved for 9 months at -80 °C in a deep freezer then lyophilized; in the L-hPL group, lyophilized hPL was refrigerated at 4 °C for 9 months. The quantity and quality of growth factors in these three groups were measured by an ELISA and in fibroblast cell cultures. Then, gelatin hydrogel discs were impregnated with hPL and its effects with regard to the promotion of wound healing in mice were evaluated by histologic examinations. RESULTS The PDGF-BB concentration in C-hPL, CL-hPL and L-hPL was 18,363 ± 370 pg/ml, 11,325 ± 171 pg/ml, and 12,307 ± 348 pg/ml, respectively; the VEGF concentration was 655 ± 23 pg/ml, 454 ± 27 pg/ml, and 499 ± 23 pg/ml, respectively; and the TGF-β1 concentration was 97,363 ± 5418 pg/ml, 73,198 ± 2442 pg/ml, and 78,034 ± 3885 pg/ml, respectively. In cell culture medium, fibroblast cell cultures were better supported in the hPL groups than in the fetal bovine serum group. In the histologic examination of the wound healing process, no differences were observed among the three preserved hPL groups with regard to epithelialization, or granulation tissue or capillary formation. The wounds in all groups had almost healed by day 14. CONCLUSIONS The stability of growth factors contained in lyophilized hPL is maintained at 4 °C for up to 9 months. This was a versatile preservation method that can be applied in clinical practice.
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Affiliation(s)
- Sharon Claudia Notodihardjo
- Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
| | - Naoki Morimoto
- Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
| | - Natsuko Kakudo
- Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
| | - Toshihito Mitsui
- Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
| | - Tien Minh Le
- Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
| | - Yasuhiko Tabata
- Laboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawahara-cho Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Kenji Kusumoto
- Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata City, Osaka, 573-1010, Japan
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Platelet-Rich Plasma and Platelet-Rich Fibrin Enhance the Outcomes of Fat Grafting. Plast Reconstr Surg 2019; 143:1201e-1212e. [DOI: 10.1097/prs.0000000000005624] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Sasaki GH. A Preliminary Clinical Trial Comparing Split Treatments to the Face and Hand With Autologous Fat Grafting and Platelet-Rich Plasma (PRP): A 3D, IRB-Approved Study. Aesthet Surg J 2019; 39:675-686. [PMID: 30534955 DOI: 10.1093/asj/sjy254] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Numerous methodologies have been suggested to enhance fat graft survival, but few long-term studies are available. OBJECTIVES The authors of this institutional review board-approved study investigated the safety and efficacy of utilizing platelet-rich plasma (PRP). METHODS Each of 10 patients received equal volumes of syringe-harvested, centrifuged fat to opposing midfaces with a lateral submuscular aponeurotic system-plication or no face lift and hands that were combined with equal volumes of either concentrated PRP or normal saline. Comparable assessments of fat retention/baseline values by 3D Vectra Analysis, VISIA, and Cortex facial skin analyses were performed. Clinical results were judged on a visual analogue scale. RESULTS The average percent change in mean volume assessments at the fat/PRP sites from baseline values, as profiled by 3D Vectra Analysis, demonstrated a higher, but statistically nonsignificant value over 1 year than the percent value changes at the fat/normal saline sites in the opposing face or hand. Three independent evaluators were able to assess volume restorations to the malar fat pad, naso-jugal groove, and nasolabial fold as well as to intermetacarpal hollowness with reduction of visible veins and tendons in the anterior midface and hands with both treatments. No adverse events were observed over the year-long study. Perioperative edema, erythema, bruising, and tenderness lasted up to 1 to 2 weeks at most. CONCLUSIONS Autologous fat grafting continues to be a safe and effective adjunct in facial and hand aesthetic surgery. This study will require more patients and longer follow-up periods to determine whether PRP has a potential role to increase fat graft retention in aesthetic patients. LEVEL OF EVIDENCE: 3
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Affiliation(s)
- Gordon H Sasaki
- Department of Plastic Surgery, Loma Linda Medical University, Loma Linda, CA
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22
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Zhang W, Guo Y, Kuss M, Shi W, Aldrich AL, Untrauer J, Kielian T, Duan B. Platelet-Rich Plasma for the Treatment of Tissue Infection: Preparation and Clinical Evaluation. TISSUE ENGINEERING PART B-REVIEWS 2019; 25:225-236. [PMID: 30712506 DOI: 10.1089/ten.teb.2018.0309] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
IMPACT STATEMENT The clinical application of platelet-rich plasma (PRP) has been widely studied for its effects on trauma or injury repair/regeneration, however the antibacterial property of PRP has been overlooked. Increasing evidence suggests PRP as a good antibacterial agent and that it could help prevent/treat tissue infection. This review emphasizes the importance of PRP's antibacterial property and summarizes the preclinical and clinical findings regarding the application of PRP in the prevention and treatment of wound and bone infection. The use of biocompatible PRP may be advantageous for tissue infection treatment due to its inherent antibacterial and healing promoting properties.
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Affiliation(s)
- Wenhai Zhang
- 1 Department of Orthopedics, Tianjin Hospital, Tianjin, People's Republic of China.,2 Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, Nebraska
| | - Yue Guo
- 3 Tissue Engineering Labs of Orthopedics Institute, Tianjin Hospital, Tianjin, People's Republic of China
| | - Mitchell Kuss
- 2 Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, Nebraska.,4 Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska
| | - Wen Shi
- 2 Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, Nebraska.,4 Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska
| | - Amy L Aldrich
- 5 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska
| | - Jason Untrauer
- 6 Division of Oral and Maxillofacial Surgery, Department of Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska
| | - Tammy Kielian
- 5 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska
| | - Bin Duan
- 2 Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, Nebraska.,4 Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska.,7 Department of Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska.,8 Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska
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Platelet Lysate Inhibits NF-κB Activation and Induces Proliferation and an Alert State in Quiescent Human Umbilical Vein Endothelial Cells Retaining Their Differentiation Capability. Cells 2019; 8:cells8040331. [PMID: 30970613 PMCID: PMC6523925 DOI: 10.3390/cells8040331] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 04/02/2019] [Accepted: 04/08/2019] [Indexed: 12/24/2022] Open
Abstract
Injured blood vessel repair and blood circulation re-establishment are crucial events for tissue repair. We investigated in primary cultures of human umbilical vein endothelial cells (HUVEC), the effects of platelet lysate (PL), a cocktail of factors released by activated platelets following blood vessel disruption and involved in the wound-healing process triggering. PL exerted a protective effect on HUVEC in an inflammatory milieu by inhibiting IL-1α-activated NF-κB pathway and by inducing the secretion of PGE2, a pro-resolving molecule in the wound microenvironment. Moreover, PL enhanced HUVEC proliferation, without affecting their capability of forming tube-like structures on matrigel, and activated resting quiescent cells to re-enter cell cycle. In agreement with these findings, proliferation-related pathways Akt and ERK1/2 were activated. The expression of the cell-cycle activator Cyclin D1 was also enhanced, as well as the expression of the High Mobility Group Box-1 (HMGB1), a protein of the alarmin group involved in tissue homeostasis, repair, and remodeling. These in vitro data suggest a possible in vivo contribution of PL to new vessel formation after a wound by activation of cells resident in vessel walls. Our biochemical study provides a rationale for the clinical use of PL in the treatment of wound healing-related pathologies.
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Lei X, Xu P, Cheng B. Problems and Solutions for Platelet-Rich Plasma in Facial Rejuvenation: A Systematic Review. Aesthetic Plast Surg 2019; 43:457-469. [PMID: 30327852 DOI: 10.1007/s00266-018-1256-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 10/02/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND In recent years, platelet-rich plasma (PRP) has been widely applied in orthopedics, maxillofacial surgery, burns, and plastic surgery, especially in facial rejuvenation. Research is ongoing into new indications and mechanisms of PRP to promote its wider, safer, and more effective use in the clinic. This article reviews the possible mechanisms of PRP in facial rejuvenation and related research. It is expected that the application of PRP in this field will increase. METHODS The use of PRP in facial rejuvenation was screened using inclusion and exclusion criteria. The relevant articles were searched through Pubmed digest database, SCI full-text database, ScienceDirect full-text database, and the CNKI full-text database. The different effects and limitations of PRP were extracted. RESULTS A total of 108 articles were obtained, including 18 articles researching PRP in cells, 10 articles on animal research using PRP, 16 articles on the clinical study of PRP, 24 articles involving signs of skin aging, and four articles on the limitations of PRP. The remaining articles were related to the preparation of PRP, the introduction of PRP, and other aspects. CONCLUSION Based on in vitro and in vivo research, PRP may play a role in promoting tissue regeneration, oxidative stress and revascularization, which form the theoretical basis for the use of PRP in the clinical treatment of facial rejuvenation. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Affiliation(s)
- Xiaoxuan Lei
- The Graduate School of Southern Medical University, Guangzhou, 510515, China
- Center of Wound Treatment, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, 510010, China
| | - Pengcheng Xu
- Center of Wound Treatment, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, 510010, China
| | - Biao Cheng
- The Graduate School of Southern Medical University, Guangzhou, 510515, China.
- Center of Wound Treatment, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, 510010, China.
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25
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Ali M, Mohamed A, Ahmed HE, Malviya A, Atchia I. The use of ultrasound-guided platelet-rich plasma injections in the treatment of hip osteoarthritis: a systematic review of the literature. J Ultrason 2019; 18:332-337. [PMID: 30763018 PMCID: PMC6444309 DOI: 10.15557/jou.2018.0048] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/12/2018] [Indexed: 11/29/2022] Open
Abstract
Purpose: This review aims to determine whether ultrasound-guided platelet-rich plasma injection has any role in improving clinical outcomes in patients with hip osteoarthritis. Methods: A search of the National Institute for Health and Care Excellence database using the Healthcare Databases Advanced Search tool was conducted. The PubMed database was also utilised to search the Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index of Nursing and Allied Health and Allied and Complimentary Medicine databases. The Preferred Reporting Items for Systematic Review and Meta-Analysis methodology guidance was employed and a quality assessment was performed using the Jadad score. Results: Three randomised clinical trials met the inclusion criteria and were included for analysis. All three trials were of good quality based on the Jadad score. A total of 115 patients out of 254 received platelet-rich plasma injections under ultrasound guidance. The platelet-rich plasma recipient group included 61 males and 54 females with an age range from 53 to 71 years. Outcome scores show an improvement of symptoms and function maintained up to 12 months following platelet-rich plasma injection. Conclusions: Literature to date concludes that intra-articular platelet-rich plasma injections of the hip, performed under ultrasound guidance to treat hip osteoarthritis, are well tolerated and potentially efficacious in delivering long-term and clinically significant pain reduction and functional improvement in patients with hip osteoarthritis. Larger future trials including a placebo group are required to further evaluate these promising results. Level of evidence: Level I, a systematic review of level I studies.
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Affiliation(s)
- Mohammed Ali
- Northumbria Healthcare NHS Foundation Trust , North Shields , United Kingdom
| | - Ahmed Mohamed
- Health Education North East , Newcastle , United Kingdom
| | | | - Ajay Malviya
- Northumbria Healthcare NHS Foundation Trust , North Shields , United Kingdom
| | - Ismael Atchia
- Northumbria Healthcare NHS Foundation Trust , North Shields , United Kingdom
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26
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Gomez TW, Gopal RV, Gaffoor FMA, Kumar STR, Girish CS, Prakash R. Comparative evaluation of angiogenesis using a novel platelet-rich product: An in vitro study. J Conserv Dent 2019; 22:23-27. [PMID: 30820078 PMCID: PMC6385567 DOI: 10.4103/jcd.jcd_216_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Background: In vivo angiogenesis is normal and vital process in growth and development, wound healing, and formation of granulation tissue wherein new blood vessels form from preexisting vessels as part of revascularization. Platelet-rich products promote wound healing associated with angiogenesis. Biomaterials such as titanium were found to be angiogenic. Unlike in vivo situations, in vitro angiogenesis, study cells, within a controlled environment. Aims: The aim of this study is to evaluate the angiogenic potential of a novel platelet-rich product. Materials and Methods: Blood was drawn from volunteers with informed consent. Blood samples were centrifuged to obtain platelet-rich products. Platelet concentrates prepared were platelet-rich plasma (PRP), platelet-rich fibrin, and a novel platelet-rich product which is titanium-prepared PRP (TPRP), obtained using titanium. The study which compared platelet concentrate was divided into four groups subjected to tissue culture. Phase-contrast microscope was used to determine the rate of growth by cell counting. Statistical Analysis: ANOVA was used for comparison within groups and post hoc for multiple comparisons. Results: TPRP group showed granular ground substance. Group with platelet-rich fibrin (PRF) shows a high rate of growth whereas those with TPRP showed better growth rate when compared to its counterpart, PRP. Conclusions: This is the first study which introduces TPRP. Previous studies have proved that titanium-prepared PRF has better structural quality than its counterpart platelet-rich fibrin. This study concludes that TPRP has better angiogenic potential than its counterpart PRP. Further in vivo studies are needed to promote TPRP as a new generation of platelet products.
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Affiliation(s)
- Treesa William Gomez
- Department of Conservative and Endodontics, Noorul Islam College of Dental Science, Kerala University of Health Sciences, Thiruvananthapuram, Kerala, India
| | - Rajesh V Gopal
- Department of Conservative and Endodontics, Noorul Islam College of Dental Science, Kerala University of Health Sciences, Thiruvananthapuram, Kerala, India
| | - Faisal M A Gaffoor
- Department of Conservative and Endodontics, Noorul Islam College of Dental Science, Kerala University of Health Sciences, Thiruvananthapuram, Kerala, India
| | - Santhosh T R Kumar
- Department of Biotechnology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India
| | - C Sabari Girish
- Department of Conservative and Endodontics, Noorul Islam College of Dental Science, Kerala University of Health Sciences, Thiruvananthapuram, Kerala, India
| | - R Prakash
- Department of Biotechnology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India
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27
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Chen CF, Liao HT. Platelet-rich plasma enhances adipose-derived stem cell-mediated angiogenesis in a mouse ischemic hindlimb model. World J Stem Cells 2018; 10:212-227. [PMID: 30613314 PMCID: PMC6306556 DOI: 10.4252/wjsc.v10.i12.212] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 10/18/2018] [Accepted: 11/07/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the angiogenic effect of platelet-rich plasma (PRP)-preconditioned adipose-derived stem cells (ADSCs) both in vitro and in a mouse ischemic hindlimb model.
METHODS ADSCs were divided based on culture medium: 2.5% PRP, 5% PRP, 7.5% PRP, and 10% PRP. Cell proliferation rate was analyzed using the MTS assay. The gene expression of CD31, vascular endothelial growth factor, hypoxia-inducible factors, and endothelial cell nitric oxide synthase was analyzed using reverse transcription polymerase chain reaction. Cell markers and structural changes were assessed through immunofluorescence staining and the tube formation assay. Subsequently, we studied the in vivo angiogenic capabilities of ADSCs by a mouse ischemic hindlimb model.
RESULTS The proliferation rate of ADSCs was higher in the 2.5%, 5%, and 7.5% PRP groups. The expression of hypoxia-inducible factor, CD31, vascular endothelial growth factor, and endothelial cell nitric oxide synthase in the 5% and 7.5% PRP groups increased. The 5%, 7.5%, and 10% PRP groups showed higher abilities to promote both CD31 and vascular endothelial growth factor production and tubular structure formation in ADSCs. According to laser Doppler perfusion scan, the perfusion ratios of ischemic limb to normal limb were significantly higher in 5% PRP, 7.5% PRP, and human umbilical vein endothelial cells groups compared with the negative control and fetal bovine serum (FBS) groups (0.88 ± 0.08, 0.85 ± 0.07 and 0.81 ± 0.06 for 5%, 7.5% PRP and human umbilical vein endothelial cells compared with 0.42 ± 0.17 and 0.54 ± 0.14 for the negative control and FBS, P < 0.01).
CONCLUSION PRP-preconditioned ADSCs presented endothelial cell characteristics in vitro and significantly improved neovascularization in ischemic hindlimbs. The optimal angiogenic effect occurred in 5% PRP- and 7.5% PRP-preconditioned ADSCs.
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Affiliation(s)
- Chia-Fang Chen
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Han-Tsung Liao
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
- Craniofacial Research Center, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
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Ratajczak J, Vangansewinkel T, Gervois P, Merckx G, Hilkens P, Quirynen M, Lambrichts I, Bronckaers A. Angiogenic Properties of 'Leukocyte- and Platelet-Rich Fibrin'. Sci Rep 2018; 8:14632. [PMID: 30279483 PMCID: PMC6168453 DOI: 10.1038/s41598-018-32936-8] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 09/13/2018] [Indexed: 01/07/2023] Open
Abstract
Leukocyte- and Platelet-Rich Fibrin (L-PRF) is an autologous platelet concentrate, consisting of a fibrin matrix enriched with platelets, leukocytes and a plethora of cytokines and growth factors. Since L-PRF is produced bedside from whole blood without the use of an anti-coagulant, it is becoming a popular adjuvant in regenerative medicine. While other types of platelet concentrates have been described to stimulate blood vessel formation, little is known about the angiogenic capacities of L-PRF. Therefore, this study aimed to fully characterize the angiogenic potential of L-PRF. With an antibody array, the growth factors released by L-PRF were determined and high levels of CXC chemokine receptor 2 (CXCR-2) ligands and epidermal growth factor (EGF) were found. L-PRF induced in vitro key steps of the angiogenic process: endothelial proliferation, migration and tube formation. In addition, we could clearly demonstrate that L-PRF is able to induce blood vessel formation in vivo, the chorioallantoic membrane assay. In conclusion, we could demonstrate the angiogenic capacity of L-PRF both in vitro and in vivo, underlying the clinical potential of this easy-to-use platelet concentrate.
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Affiliation(s)
- Jessica Ratajczak
- Department of Morphology, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
| | - Tim Vangansewinkel
- Department of Morphology, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
| | - Pascal Gervois
- Department of Morphology, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
| | - Greet Merckx
- Department of Morphology, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
| | - Petra Hilkens
- Department of Morphology, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
| | - Marc Quirynen
- Department of Oral Health Sciences, Katholieke Universiteit Leuven (KUL) & Periodontology, University Hospitals Leuven, Leuven, Belgium
| | - Ivo Lambrichts
- Department of Morphology, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
| | - Annelies Bronckaers
- Department of Morphology, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
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Cho EB, Park GS, Park SS, Jang YJ, Kim KH, Kim KJ, Park EJ. Effect of platelet-rich plasma on proliferation and migration in human dermal fibroblasts. J Cosmet Dermatol 2018; 18:1105-1112. [PMID: 30280483 DOI: 10.1111/jocd.12780] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 07/27/2018] [Accepted: 08/10/2018] [Indexed: 01/15/2023]
Abstract
BACKGROUND Platelet-rich plasma (PRP) is a blood fraction that contains high concentrations of several growth factors. PRP has been recently used in skin wound healing and rejuvenation. However, the precise molecular mechanisms underlying PRP-induced wound healing are unknown. AIMS This study aimed to evaluate the effects of PRP on extracellular matrix remodeling, which requires the activation of dermal fibroblasts. METHODS Cell proliferation and migration assay, enzyme-linked immunosorbent analysis, and Western blotting were performed on PRP-treated human skin fibroblasts. RESULTS Platelet numbers were enhanced by 4.6-fold in PRP compared to that in whole blood. PRP stimulated the proliferation and migration of human dermal fibroblasts and increased the expression of human procollagen I alpha 1, elastin, MMP-1, and MMP-2 in human dermal fibroblasts. PRP-treated human dermal fibroblasts also showed a dramatic reduction in the phosphorylation of c-Jun N-terminal kinase (JNK), whereas total JNK levels were not significantly reduced. CONCLUSIONS Collectively, PRP induced increased expression of type I collagen, elastin, MMP-1, and MMP-2, thereby accelerating wound healing. Our findings reveal basic mechanisms underlying PRP-mediated tissue remodeling. Thus, these results could be exploited for clinical dermatology and skin rejuvenation.
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Affiliation(s)
- Eun Byul Cho
- Department of Dermatology, College of Medicine, Hallym University, Anyang, Korea
| | - Gil Soon Park
- Department of Dermatology, Hallym Institute for Translational medicine, Anyang, Korea
| | - Seok Soon Park
- Asan Institute for Life Sciences, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ye Ji Jang
- Department of Dermatology, College of Medicine, Hallym University, Anyang, Korea
| | - Kwang Ho Kim
- Department of Dermatology, College of Medicine, Hallym University, Anyang, Korea
| | - Kwang Joong Kim
- Department of Dermatology, College of Medicine, Hallym University, Anyang, Korea
| | - Eun Joo Park
- Department of Dermatology, College of Medicine, Hallym University, Anyang, Korea
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da Silva LQ, Montalvão SADL, Justo-Junior ADS, Cunha Júnior JLR, Huber SC, Oliveira CC, Annichino-Bizzacchi JM. Platelet-rich plasma lyophilization enables growth factor preservation and functionality when compared with fresh platelet-rich plasma. Regen Med 2018; 13:775-784. [DOI: 10.2217/rme-2018-0035] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Aims: To compare levels and activity of the growth factors between fresh and lyophilized platelet-rich plasma (PRP). Methods: Analysis of platelet concentration using fibroblast and human umbilical vein endothelial cell cultures were compared between fresh and lyophilized PRP obtained from peripheral blood. Results: After lyophilization, 54% of platelets were intact whereas the fresh showed no aggregation with agonists (levels under 20%). The concentration of growth factors (VEGF, EGF, TGF-β and PDGF) in both products were similar. Fresh and lyophilized PRPs induced proliferation in the fibroblasts at 24 h (0.303 vs 0.300, respectively). Conclusion: Lyophilized PRP appears to be an alternative to fresh PRP and the results evidenced the role of growth factors as a key element in the activity of this product.
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Affiliation(s)
- Letícia Queiroz da Silva
- Hemocentro, Haemostasis Laboratory, State University of Campinas–UNICAMP. 13083-970, Campinas, São Paulo, Brazil
| | | | - Amauri da Silva Justo-Junior
- Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas–UNICAMP. 13083-970, Campinas, São Paulo, Brazil
| | | | - Stephany Cares Huber
- Hemocentro, Haemostasis Laboratory, State University of Campinas–UNICAMP. 13083-970, Campinas, São Paulo, Brazil
| | - Carolina Caliári Oliveira
- Faculty of Medical Sciences, State University of Campinas–UNICAMP. 13083-970, Campinas, São Paulo, Brazil
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Ali M, Oderuth E, Atchia I, Malviya A. The use of platelet-rich plasma in the treatment of greater trochanteric pain syndrome: a systematic literature review. J Hip Preserv Surg 2018; 5:209-219. [PMID: 30393547 PMCID: PMC6206702 DOI: 10.1093/jhps/hny027] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Revised: 05/01/2018] [Accepted: 07/08/2018] [Indexed: 12/12/2022] Open
Abstract
This review aims to determine whether platelet-rich plasma (PRP) has any role in improving clinical outcomes in patients with symptomatic greater trochanteric pain syndrome (GTPS). A search of NICE healthcare database advanced search (HDAS) via Athens (PubMed, MEDLINE, CINAHL, EMBASE and AMED databases) was conducted from their year of inception to April 2018 with the keywords: ‘greater trochanteric pain syndrome’ or ‘GTPS’ or ‘gluteus medius’ or ‘trochanteric bursitis’ and ‘platelet rich plasma’ (PRP). A quality assessment was performed using the JADAD score for RCTs and MINORS for non-RCT studies. Five full-text articles were included for analysis consisting of three RCTs and two case series. We also identified four additional studies from published conference abstracts (one RCT and three case series). The mean age in 209 patients was 58.4 years (range 48–76.2 years). The majority of patients were females and the minimum duration of symptoms was three months. Diagnosis was made using ultrasound or MRI. Included studies used a variety of outcome measures. Improvement was observed during the first 3 months after injection. Significant improvement was also noted when patients were followed up till 12 months post treatment. PRP seems a viable alternative injectable option for GTPS refractory to conservative measures. The current literature has revealed that PRP is relatively safe and can be effective. Considering the limitations in these studies, more large-sample and high-quality randomized clinical trials are required in the future to provide further evidence of the efficacy for PRP as a treatment in GTPS.
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Affiliation(s)
- Mohammed Ali
- Trauma and Orthopedics, Northumbria Healthcare NHS foundation Trust, North Shields, UK
| | | | - Ismael Atchia
- Consultant Rheumatologist, Northumbria Healthcare NHS foundation Trust, Northumberland, UK
| | - Ajay Malviya
- Trauma and Orthopedics, Northumbria Healthcare NHS foundation Trust, North Shields, UK
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Vácz G, Major B, Gaál D, Petrik L, Horváthy DB, Han W, Holczer T, Simon M, Muir JM, Hornyák I, Lacza Z. Hyperacute serum has markedly better regenerative efficacy than platelet-rich plasma in a human bone oxygen-glucose deprivation model. Regen Med 2018; 13:531-543. [PMID: 30132395 DOI: 10.2217/rme-2017-0141] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
AIM Platelet-rich plasma (PRP) and hyperacute serum (HAS) were compared in a novel human model of ex vivo bone damage induced by oxygen-glucose deprivation (OGD). MATERIALS & METHODS Osteoarthritic subchondral bone pieces were harvested from discarded femoral heads during hip replacement surgery and subjected to transient OGD. RESULTS Proteome profiling revealed that PRP is more angiopoietic, whereas HAS is more antiangiopoietic in composition. However, treatment of OGD-exposed bone with multiple PRP preparations had no effect on cell counts, whereas HAS restored cell proliferation capacity and rescued viable cell number following OGD. CONCLUSION A similar pro-proliferation effect was observed with recombinant growth factors, indicating that HAS may be an alternative agent for enhancing the regeneration of damaged bone cells.
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Affiliation(s)
- Gabriella Vácz
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Bálint Major
- Polyclinic of the Hospitaller Brothers of St. John of God in Budapest, Orthopaedic Department, Frankel Leo u. 54., Budapest, Hungary, 1023
| | - Dorottya Gaál
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Laura Petrik
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Dénes Balázs Horváthy
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Weiping Han
- Bioimaging Consortium, A-STAR, Singapore, Helios, Biopolis Way 11
| | - Tünde Holczer
- Department of Laboratory Medicine, Semmelweis University, Nagyvárad t. 4, Budapest, Hungary, 1089
| | - Melinda Simon
- Institute of Clinical Experimental Research, Semmelweis University, Tűzoltó u. 37-47, Budapest, Hungary, 1094
| | - Jeffrey M Muir
- Motion Research, 3-35 Stone Church Rd, Suite 215, Ancaster, Ontario, L9K 3S9 Canada
| | - István Hornyák
- OrthoSera GmbH, Dr. Karl-Dorrek-Straße 23-29, 3500 Krems an der Donau, Austria
| | - Zsombor Lacza
- OrthoSera GmbH, Dr. Karl-Dorrek-Straße 23-29, 3500 Krems an der Donau, Austria.,University of Physical Education, Alkotás u. 44, Budapest, Hungary 1123
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DURUKSU G, POLAT S, KAYİŞ L, EKİMCİ GÜRCAN N, GACAR G, YAZIR Y. Improvement of the insulin secretion from beta cells encapsulated in alginate/poly-L- histidine/alginate microbeads by platelet-rich plasma. Turk J Biol 2018; 42:297-306. [PMID: 30814893 PMCID: PMC6392160 DOI: 10.3906/biy-1802-13] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Type 1 diabetes is clinically characterized as the loss of control of glucose homeostasis due to the reduced number of insulinproducing cells. Long-term glycemic control after implantation could be maintained by preserving the cell viability and tissue-specific functions during the process of microencapsulation. In this study, alginate solution was supplemented with platelet-rich plasma (PRP) to improve the viability and preserve the cell functions during the encapsulation of a beta cell line (BRIN-BD11). Cell viability was assessed and insulin secretion and insulin stimulation index were evaluated. eTh polymerization of alginate with PRP enhanced the viability up to 61% in the alginate microbeads. PRP supplementation to the alginate composition not only increased the number of viable cells by 1.95-fold, but the insulin secretion also improved by about 66%. eTh stimulation index, however, was not affected by the PRP supplementation.
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Affiliation(s)
- Gökhan DURUKSU
- Center for Stem Cell and Gene eThrapies Research and Practice, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
- Department of Stem Cells, Institute of Health Sciences, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
| | - Selen POLAT
- Department of Stem Cells, Institute of Health Sciences, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
| | - Leyla KAYİŞ
- Department of Stem Cells, Institute of Health Sciences, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
| | - Nur EKİMCİ GÜRCAN
- Department of Stem Cells, Institute of Health Sciences, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
| | - Gülçin GACAR
- Center for Stem Cell and Gene eThrapies Research and Practice, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
- Department of Stem Cells, Institute of Health Sciences, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
| | - Yusufhan YAZIR
- Center for Stem Cell and Gene eThrapies Research and Practice, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
- Department of Histology and Embryology, School of Medicine, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
- Department of Stem Cells, Institute of Health Sciences, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
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JUN H, LEI D, QIFANG Y, YUAN X, DEQIN Y. Effects of concentrated growth factors on the angiogenic properties of dental pulp cells and endothelial cells: an in vitro study. Braz Oral Res 2018; 32:e48. [DOI: 10.1590/1807-3107bor-2018.vol32.0048] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 04/23/2018] [Indexed: 12/17/2022] Open
Affiliation(s)
- Huan JUN
- Chongqing Medical University, China
| | - Dou LEI
- Chongqing Medical University, China
| | | | - Xu YUAN
- Chongqing Medical University, China
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Huan J, Dou L, Yan QF, Yang DQ. [An in vitro study of the angiogenic effects of concentrate growth factor on human umbilical vein endothelial cells]. HUA XI KOU QIANG YI XUE ZA ZHI = HUAXI KOUQIANG YIXUE ZAZHI = WEST CHINA JOURNAL OF STOMATOLOGY 2018; 36:247-251. [PMID: 29984922 DOI: 10.7518/hxkq.2018.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
OBJECTIVE This study aimed to explore the effects of concentrate growth factor extracts (CGFe) on human umbilical vein endothelial cells (HUVECs) in vitro. METHODS Concentrate growth factor (CGF) were prepared from the peripheral blood of healthy donors, followed by CGFe. Four groups were designed based on cell culture medium, as follows: 2%CGFe, 5%CGFe, 10%CGFe, and control. The proliferation activity of HUVECs was detected by cell cycle and CCK-8 assays. The migration of HUVECs was detected by scratch assay. The mRNA expression levels of vascular endothelial growth factor (VEGF), chemokine receptor 4 (CXCR4), and platelet derived growth factor (PDGF) were examined by quantitative real time polymerase chain reaction (qRT-PCR). RESULTS Results of CCK-8 and cell cycle assays showed that CGFe promoted the proliferation capability of HUVECs in a dose-dependent manner, and the data had statistical significance among four groups (P<
0.05). The cell migration assay indicated that CGF accelerated wound closure in a dose-dependent manner after 12 h of culture (P<0.05). The results of qRT-PCR showed that CGF upregulated the expression levels of VEGF, CXCR4, and PDGF in HUVECs. CONCLUSIONS CGFe can promote the proliferation, migration, and angiogenic differentiation of HUVECs. Thus, CGF might be an appropriate cure for dental pulp revascularization.
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Affiliation(s)
- Jun Huan
- Dept. of Conservative Dentistry and Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing 401147, China;Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401147, China;Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
| | - Lei Dou
- Dept. of Conservative Dentistry and Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing 401147, China;Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401147, China;Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
| | - Qi-Fang Yan
- Dept. of Conservative Dentistry and Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing 401147, China;Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401147, China;Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
| | - De-Qin Yang
- Dept. of Conservative Dentistry and Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing 401147, China;Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401147, China;Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
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Lan Y, Li Y, Li D, Li P, Wang J, Diao Y, Ye G, Li Y. Engulfment of platelets delays endothelial cell aging via girdin and its phosphorylation. Int J Mol Med 2018; 42:988-997. [PMID: 29786109 DOI: 10.3892/ijmm.2018.3685] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 05/10/2018] [Indexed: 11/06/2022] Open
Abstract
Endothelial cells are critical in angiogenesis and maintain the homeostasis of the blood‑brain barrier (BBB). Platelets (PLTs) are essential in vascular biology, including angiogenesis. The present study aimed to investigate the effect of PLTs on the aging of endothelial cells. Human brain microvascular endothelial cells (HBMECs) and human astrocytes were co‑cultured to mimic the BBB. Transmission electron microscopy was used to observe the engulfment of PLTs. Confocal microscopy was used to observe the co‑localization of PLTs, girders of actin filament (girdin) and phosphorylated (p‑)girdin. Senescence‑associated β‑galactosidase (β‑gal) staining, 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide and flow cytometry were performed to examine the cell senescence, viability and apoptosis, respectively. Transwell assays were performed to examine cell invasion and migration. Western blot analysis was performed to detect the expression of girdin, AKT and p‑AKT. PLTs delayed senescence, and promoted the viability and resistance to apoptosis of the HBMECs. Cell invasion and migration were enhanced by PLTs. In addition, girdin and p‑girdin were essential to the engulfment of HBMECs to PLTs. Mechanically, the inhibition of AKT signals reversed the effect of PLTs on HBMECs by increasing the activity of β‑gal, decreasing the cell viability, and inhibiting the invasion and migration of the HBMECs. The engulfment of PLTs assisted in delaying the aging of endothelial cells via girdin and p‑girdin, in which the AKT signal was involved. The present study indicated a potential strategy for delaying endothelial cell aging in the treatment of central nervous system diseases.
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Affiliation(s)
- Yong Lan
- National Center of Gerontology, Department of Vascular Surgery, Beijing Hospital, Beijing 100730, P.R. China
| | - Yongjun Li
- National Center of Gerontology, Department of Vascular Surgery, Beijing Hospital, Beijing 100730, P.R. China
| | - Dajun Li
- National Center of Gerontology, Department of Vascular Surgery, Beijing Hospital, Beijing 100730, P.R. China
| | - Peng Li
- National Center of Gerontology, Department of Vascular Surgery, Beijing Hospital, Beijing 100730, P.R. China
| | - Jiyang Wang
- National Center of Gerontology, Department of Vascular Surgery, Beijing Hospital, Beijing 100730, P.R. China
| | - Yongpeng Diao
- National Center of Gerontology, Department of Vascular Surgery, Beijing Hospital, Beijing 100730, P.R. China
| | - Guodong Ye
- National Center of Gerontology, Department of Vascular Surgery, Beijing Hospital, Beijing 100730, P.R. China
| | - Yangfang Li
- Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, P.R. China
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Wang Y, Wang J, Li Y, Wang S, Zhu X. Platelet-rich Plasma Protects HUVECs against oX-LDL-induced Injury. Open Med (Wars) 2018; 13:41-52. [PMID: 29607413 PMCID: PMC5874509 DOI: 10.1515/med-2018-0007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Accepted: 12/13/2017] [Indexed: 01/26/2023] Open
Abstract
Platelet-rich plasma (PRP) contains a variety of cytokines, some of which ameliorate oX-LDL (oxidized low-density lipoprotein)-induced endothelial cell (EC) injury. Therefore, we hypothesized that PRP might alleviate oX-LDL-induced injury. METHODOLOGY Human umbilical vein endothelial cells (HUVECs) were divided into four groups: a PPP (platelet-poor plasma) group, an oX-LDL group, an oX-LDL+PRP group and a PRP group. CCK-8 (Cell Counting Kit) assay, Annexin V-FITC/7-AAD and Hochest 33342 staining were performed to assess cell proliferation and apoptosis. Tube formation and cell migration assays were performed to evaluate HUVEC-mediated vasculogenesis and migration. Expression levels of Bcl-2, Bax, caspase-3, cleaved caspase-3, PI3K, Akt, eNOS p-Akt, p-eNOS, IL-6 and IL-1 were detected by western blotting or immunofluorescence. PRINCIPAL FINDINGS PRP promoted HUVEC proliferation in a non-linear pattern, protected HUVECs against oX-LDL-induced apoptosis and attenuated oX-LDL-mediated inhibition of HUVEC migration and vasculogenesis. Additionally, compared to the PPP group, PRP downregulated pro-apoptotic proteins (ratio of Bax/Bcl-2, caspase-3 and cleaved caspase-3) as well as IL-6 and IL-1. Moreover, the PI3K/Akt/eNOS pathway was activated by PRP and inactivated by oX-LDL. CONCLUSIONS It was demonstrated that PRP protected HUVECs against oX-LDL-induced injury and that the PI3K/Akt/eNOS pathway was activated in this process.
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Affiliation(s)
- Yang Wang
- First Affiliated Hospital of Sun Yat-Sen University, GuangZhou, GuangDong, China
| | - Jinsong Wang
- First Affiliated Hospital of Sun Yat-Sen University, GuangZhou, GuangDong, China
| | - Yonghui Li
- First Affiliated Hospital of Sun Yat-Sen University, GuangZhou, GuangDong, China
| | - Shenming Wang
- First Affiliated Hospital of Sun Yat-Sen University, GuangZhou, GuangDong, China
| | - Xiaonan Zhu
- Sun Yat-sen University Zhongshan School of Medicine, GuangZhou, China
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Bayer A, Tohidnezhad M, Berndt R, Lippross S, Behrendt P, Klüter T, Pufe T, Jahr H, Cremer J, Rademacher F, Simanski M, Gläser R, Harder J. Platelet-released growth factors inhibit proliferation of primary keratinocytes in vitro. Ann Anat 2018; 215:1-7. [DOI: 10.1016/j.aanat.2017.09.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Revised: 09/02/2017] [Accepted: 09/02/2017] [Indexed: 12/22/2022]
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Bonazza V, Borsani E, Buffoli B, Parolini S, Inchingolo F, Rezzani R, Rodella LF. In vitro treatment with concentrated growth factors (CGF) and sodium orthosilicate positively affects cell renewal in three different human cell lines. Cell Biol Int 2017; 42:353-364. [DOI: 10.1002/cbin.10908] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 10/27/2017] [Indexed: 12/13/2022]
Affiliation(s)
- Veronica Bonazza
- Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences; University of Brescia; V.le Europa 11 Brescia 25123 Italy
| | - Elisa Borsani
- Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences; University of Brescia; V.le Europa 11 Brescia 25123 Italy
- Interdipartimental University Center of Research “Adaption and Regeneration of Tissues and Organs-(ARTO)”; University of Brescia; Brescia 25123 Italy
| | - Barbara Buffoli
- Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences; University of Brescia; V.le Europa 11 Brescia 25123 Italy
- Interdipartimental University Center of Research “Adaption and Regeneration of Tissues and Organs-(ARTO)”; University of Brescia; Brescia 25123 Italy
| | - Silvia Parolini
- Department of Molecular and Translational Medicine; University of Brescia; Brescia 25123 Italy
| | - Francesco Inchingolo
- Department of Interdisciplinary Medicine; University of Bari “Aldo Moro”; Bari 70121 Italy
| | - Rita Rezzani
- Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences; University of Brescia; V.le Europa 11 Brescia 25123 Italy
- Interdipartimental University Center of Research “Adaption and Regeneration of Tissues and Organs-(ARTO)”; University of Brescia; Brescia 25123 Italy
| | - Luigi Fabrizio Rodella
- Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences; University of Brescia; V.le Europa 11 Brescia 25123 Italy
- Interdipartimental University Center of Research “Adaption and Regeneration of Tissues and Organs-(ARTO)”; University of Brescia; Brescia 25123 Italy
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Platelet-rich plasma: combinational treatment modalities for musculoskeletal conditions. Front Med 2017; 12:139-152. [DOI: 10.1007/s11684-017-0551-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Accepted: 04/30/2017] [Indexed: 12/12/2022]
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Shahidi M, Vatanmakanian M, Arami MK, Sadeghi Shirazi F, Esmaeili N, Hydarporian S, Jafari S. A comparative study between platelet-rich plasma and platelet-poor plasma effects on angiogenesis. Med Mol Morphol 2017; 51:21-31. [DOI: 10.1007/s00795-017-0168-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 08/01/2017] [Indexed: 12/24/2022]
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The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes. Mediators Inflamm 2017; 2017:6157491. [PMID: 28811680 PMCID: PMC5547724 DOI: 10.1155/2017/6157491] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Accepted: 07/06/2017] [Indexed: 11/17/2022] Open
Abstract
Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF®)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR). In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds.
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Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes. Mediators Inflamm 2017; 2017:5671615. [PMID: 28808357 PMCID: PMC5541813 DOI: 10.1155/2017/5671615] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 06/07/2017] [Accepted: 06/22/2017] [Indexed: 11/17/2022] Open
Abstract
Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs) or their clinically related formulations (e.g., Vivostat PRF®) came recently into the physicians' focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo. Therefore, we investigated the expression of early (keratin 1 and keratin 10) and late (transglutaminase-1 and involucrin) differentiation markers. PRGF treatment of primary human keratinocytes decreased keratin 1 and keratin 10 gene expression but induced involucrin and transglutaminase-1 gene expression in an epidermal growth factor receptor- (EGFR-) dependent manner. In concordance with these results, microscopic analyses revealed that PRGF-treated human keratinocytes displayed morphological features typical of keratinocytes undergoing terminal differentiation. In vivo treatment of artificial human wounds with Vivostat PRF revealed a significant induction of involucrin and transglutaminase-1 gene expression. Together, our results indicate that PRGF and Vivostat PRF induce terminal differentiation of primary human keratinocytes. This potential mechanism may contribute to the observed beneficial effects in the treatment of hard-to-heal wounds with autologous thrombocyte concentrate lysates in vivo.
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Jeong D, Irfan M, Kim SD, Kim S, Oh JH, Park CK, Kim HK, Rhee MH. Ginsenoside Rg3-enriched red ginseng extract inhibits platelet activation and in vivo thrombus formation. J Ginseng Res 2017; 41:548-555. [PMID: 29021703 PMCID: PMC5628340 DOI: 10.1016/j.jgr.2016.11.003] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 11/28/2016] [Indexed: 11/27/2022] Open
Abstract
Background Korean Red Ginseng has been used for several decades to treat many diseases, enhancing both immunity and physical strength. Previous studies have documented the therapeutic effects of ginseng, including its anticancer, antiaging, and anti-inflammatory activities. These activities are mediated by ginsenosides present in the ginseng plant. Ginsenoside Rg3, an effective compound from red ginseng, has been shown to have antiplatelet activity in addition to its anticancer and anti-inflammatory activities. Platelets are important for both primary hemostasis and the repair of the vessels after injury; however, they also play a crucial role in the development of acute coronary diseases. We prepared ginsenoside Rg3-enriched red ginseng extract (Rg3-RGE) to examine its role in platelet physiology. Methods To examine the effect of Rg3-RGE on platelet activation in vitro, platelet aggregation, granule secretion, intracellular calcium ([Ca2+]i) mobilization, flow cytometry, and immunoblot analysis were carried out using rat platelets. To examine the effect of Rg3-RGE on platelet activation in vivo, a collagen plus epinephrine-induced acute pulmonary thromboembolism mouse model was used. Results We found that Rg3-RGE significantly inhibited collagen-induced platelet aggregation and [Ca2+]i mobilization in a dose-dependent manner in addition to reducing ATP release from collagen-stimulated platelets. Furthermore, using immunoblot analysis, we found that Rg3-RGE markedly suppressed mitogen-activated protein kinase phosphorylation (i.e., extracellular stimuli-responsive kinase, Jun N-terminal kinase, p38) as well as the PI3K (phosphatidylinositol 3 kinase)/Akt pathway. Moreover, Rg3-RGE effectively reduced collagen plus epinephrine-induced mortality in mice. Conclusion These data suggest that ginsenoside Rg3-RGE could be potentially be used as an antiplatelet therapeutic agent against platelet-mediated cardiovascular disorders.
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Affiliation(s)
- Dahye Jeong
- Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Muhammad Irfan
- Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Sung-Dae Kim
- Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan, Republic of Korea
| | - Suk Kim
- College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea
| | - Jun-Hwan Oh
- Research and Development Headquarters, Korean Ginseng Corporation, Daejeon, Republic of Korea
| | - Chae-Kyu Park
- Research and Development Headquarters, Korean Ginseng Corporation, Daejeon, Republic of Korea
| | - Hyun-Kyoung Kim
- Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Man Hee Rhee
- Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
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Kraeutler MJ, Garabekyan T, Mei-Dan O. The use of platelet-rich plasma to augment conservative and surgical treatment of hip and pelvic disorders. Muscles Ligaments Tendons J 2016; 6:410-419. [PMID: 28066748 DOI: 10.11138/mltj/2016.6.3.410] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND In recent years, platelet-rich plasma (PRP) has gained popularity within the orthopaedic community as a treatment modality to enhance tissue healing. PURPOSE This review aims to concisely present the current indications for PRP injections in the treatment of hip and pelvic pathologies and to describe some novel applications for PRP which have not yet been reported in the literature. METHODS We reviewed the literature on the non-operative and operative indications for PRP in the treatment of hip and pelvic pathologies. CONCLUSIONS With regard to hip and pelvic pathologies, PRP injections are used most commonly as a non-operative intervention, and have been described in the literature to treat osteoarthritis of the hip joint as well as tendinopathy of the hamstrings, adductor longus, and gluteus medius. In contrast, most of the surgical applications of PRP for the hip are novel, with few reported studies in the literature. Because of the increasing awareness of PRP's beneficial effects on musculoskeletal healing and thus the growing number of indications for its use, this review also describes some novel applications for PRP, including osteitis pubis, post-microfracture of the hip, tears of the rectus femoris, and avulsion of the sartorius muscle. LEVEL OF EVIDENCE V.
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Affiliation(s)
- Matthew J Kraeutler
- University of Colorado School of Medicine, Department of Orthopedics, Aurora, USA
| | | | - Omer Mei-Dan
- Hip Preservation/Sports Medicine/Orthopedics University of Colorado
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Yan S, Yang B, Shang C, Ma Z, Tang Z, Liu G, Shen W, Zhang Y. Platelet-rich plasma promotes the migration and invasion of synovial fibroblasts in patients with rheumatoid arthritis. Mol Med Rep 2016; 14:2269-75. [DOI: 10.3892/mmr.2016.5500] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Accepted: 07/06/2016] [Indexed: 11/06/2022] Open
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Platelet-Rich Plasma Influences Expansion and Paracrine Function of Adipose-Derived Stromal Cells in a Dose-Dependent Fashion. Plast Reconstr Surg 2016; 137:554e-565e. [PMID: 26910700 DOI: 10.1097/01.prs.0000479995.04255.bb] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND Lipofilling is a treatment modality to restore tissue volume. Both platelet-rich plasma and adipose-derived stromal cells have been reported to augment the efficacy of lipofilling, yet results are not conclusive. The authors hypothesized that the variation reported in literature is caused by a dose-dependent influence of platelet-rich plasma on adipose-derived stromal cells. METHODS Whole blood (n = 3) was used to generate platelet-rich plasma, which was diluted with Dulbecco's Modified Eagle Medium to 15%, 5%, and 1.7%, with 15% platelet-poor plasma and 10% fetal calf serum as controls. Pooled adipose-derived stromal cells (n = 3) were cultured in these media. Gene expression was assessed, along with angiogenic sprouting of endothelial cells by conditioned medium and platelet-rich plasma. RESULTS platelet-rich plasma in culture medium affected the expression of genes in a dose-dependent manner. The 15% concentration stimulated proliferation almost eightfold. Mesenchymal markers were unaffected. Interestingly, expression of collagens type 1 and 3 increased at lower concentrations, whereas transforming growth factor-β showed reduced expression in lower concentrations. Proangiogenic gene expression was unaltered or strongly reduced in a dose-dependent manner. platelet-rich plasma promoted endothelial sprouting and survival in a dose-dependent manner; however, conditioned medium from adipose-derived stromal cells exposed to platelet-rich plasma blocked endothelial sprouting capabilities. CONCLUSION The dose-dependent influence of platelet-rich plasma on the therapeutic capacity of adipose-derived stromal cells conditioned medium in vitro warrants caution in clinical trials.
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Hara T, Kakudo N, Morimoto N, Ogawa T, Lai F, Kusumoto K. Platelet-rich plasma stimulates human dermal fibroblast proliferation via a Ras-dependent extracellular signal-regulated kinase 1/2 pathway. J Artif Organs 2016; 19:372-377. [PMID: 27389012 DOI: 10.1007/s10047-016-0913-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Accepted: 06/17/2016] [Indexed: 01/12/2023]
Abstract
Platelet-rich plasma (PRP) contains a high concentration of several growth factors and contributes to soft-tissue engineering and wound healing. However, the effect of PRP on human dermal fibroblast proliferation and responses is unknown. This was investigated in the present study using PRP prepared from the whole human blood using the double-spin method. Human dermal fibroblast cultures were established from skin samples collected during plastic surgery. Platelet concentration and growth factor levels in PRP were estimated, and a cell proliferation assay was carried out after PRP treatment. The role of Ras-dependent extracellular signal-regulated kinase (ERK)1/2 in the effects of PRP was investigated in human dermal fibroblasts by suppressing ERK1/2 expression with an inhibitor or by short interfering (si)RNA-mediated knockdown, and assessing ERK1/2 phosphorylation by western blotting as well as proliferation in PRP-treated cells. We found that PRP stimulated human dermal fibroblast proliferation, which was suppressed by ERK1/2 inhibitor treatment (P < 0.01). ERK1/2 phosphorylation was increased in the presence of PRP, while siRNA-mediated knockdown of ERK1/2 blocked cell proliferation normally induced by PRP treatment (P < 0.01). These results demonstrate that PRP induces human dermal fibroblast proliferation via activation of ERK1/2 signaling. Our findings provide a basis for the development of agents that can promote wound healing and can be applied to soft-tissue engineering.
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Affiliation(s)
- Tomoya Hara
- Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan. .,Department of Oral Implantology, Osaka Dental University, 1-5-17 Otemae, Chuo-ku, Osaka, 540-0008, Japan.
| | - Natsuko Kakudo
- Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
| | - Naoki Morimoto
- Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Takeshi Ogawa
- Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Fangyuan Lai
- Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Kenji Kusumoto
- Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan
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Platelet-Rich Plasma Obtained with Different Anticoagulants and Their Effect on Platelet Numbers and Mesenchymal Stromal Cells Behavior In Vitro. Stem Cells Int 2016; 2016:7414036. [PMID: 27340410 PMCID: PMC4909912 DOI: 10.1155/2016/7414036] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 04/09/2016] [Accepted: 04/27/2016] [Indexed: 02/06/2023] Open
Abstract
There are promising results in the use of platelet-rich plasma (PRP) for musculoskeletal tissue repair. However, the variability in the methodology for its obtaining may cause different and opposing findings in the literature. Particularly, the choice of the anticoagulant is the first definition to be made. In this work, blood was collected with sodium citrate (SC), ethylenediaminetetraacetic acid (EDTA), or anticoagulant citrate dextrose (ACD) solution A, as anticoagulants, prior to PRP obtaining. Hematological analysis and growth factors release quantification were performed, and the effects on mesenchymal stromal cell (MSC) culture, such as cytotoxicity and cell proliferation (evaluated by MTT method) and gene expression, were evaluated. The use of EDTA resulted in higher platelet yield in whole blood; however, it induced an increase in the mean platelet volume (MPV) following the blood centrifugation steps for PRP obtaining. The use of SC and ACD resulted in higher induction of MSC proliferation. On the other hand, PRP obtained in SC presented the higher platelet recovery after the blood first centrifugation step and a minimal change in MSC gene expression. Therefore, we suggest the use of SC as the anticoagulant for PRP obtaining.
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