Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review
TL;DR: It is unlikely that a mix of GFs some of which have negative effects in the OA joint, as present in PRP, will be of benefit in OA, so future directions of PRP application may concentrate on seeking an appropriate and innocuous agent like anti-VEGF antibody that can modulate and control the effect ofPRP.
About: This article is published in Osteoarthritis and Cartilage.The article was published on 2013-11-01 and is currently open access. It has received 309 citations till now. The article focuses on the topics: Hyaline cartilage & Osteoarthritis.
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TL;DR: An exploration of the structural, mechanical, biochemical and biological information present in native human tissue for bioengineering applications is focused on to provide inspiration for the design of future biomaterials.
754 citations
TL;DR: LP-PRP results in improved functional outcome scores compared with hyaluronic acid and placebo when used for treatment of knee osteoarthritis and was the highest ranked treatment for both measures of clinical efficacy.
Abstract: Background:Leukocyte-poor platelet-rich plasma (LP-PRP) is hypothesized to be more suitable for intra-articular injection than leukocyte-rich PRP (LR-PRP) in the treatment of knee osteoarthritis.Purpose:To compare clinical outcomes and rates of adverse reactions between LP-PRP and LR-PRP for this application.Study Design:Meta-analysis.Methods:The MEDLINE, EMBASE, and Cochrane databases were reviewed. The primary outcome was the incidence of local adverse reactions. Secondary outcomes were the changes in International Knee Documentation Committee (IKDC) subjective score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score between baseline and final follow-up measurements. A Bayesian network meta-analysis was performed, with a post hoc meta-regression to correct for baseline differences in WOMAC scores. Treatment rankings were based on surface under the cumulative ranking (SUCRA) probabilities.Results:Included in the analysis were 6 randomized controlled trials (evidence level 1)...
301 citations
TL;DR: There is no data that any of the IA injections will cause osteophytes to regress or cartilage and meniscus to regenerate in patients with substantial and irreversible bone and cartilage damage, so IA corticosteroid injections are safe and have positive effects for patient satisfaction.
Abstract: Osteoarthritis (OA) is a complex “whole joint” disease pursued by inflammatory mediators, rather than purely a process of “wear and tear”. Besides cartilage degradation, synovitis, subchondral bone remodeling, degeneration of ligaments and menisci, and hypertrophy of the joint capsule take parts in the pathogenesis. Pain is the hallmark symptom of OA, but the extent to which structural pathology in OA contributes to the pain experience is still not well known. For the knee OA, intraarticular (IA) injection (corticosteroids, viscosupplements, blood-derived products) is preferred as the last nonoperative modality, if the other conservative treatment modalities are ineffective. IA corticosteroid injections provide short term reduction in OA pain and can be considered as an adjunct to core treatment for the relief of moderate to severe pain in people with OA. IA hyaluronic acid (HA) injections might have efficacy and might provide pain reduction in mild OA of knee up to 24 wk. But for HA injections, the cost-effectiveness is an important concern that patients must be informed about the efficacy of these preparations. Although more high-quality evidence is needed, recent studies indicate that IA platelet rich plasma injections are promising for relieving pain, improving knee function and quality of life, especially in younger patients, and in mild OA cases. The current literature and our experience indicate that IA injections are safe and have positive effects for patient satisfaction. But, there is no data that any of the IA injections will cause osteophytes to regress or cartilage and meniscus to regenerate in patients with substantial and irreversible bone and cartilage damage.
292 citations
TL;DR: PRP does not provide a superior clinical improvement with respect to HA, and therefore it should not be preferred to viscosupplementation as injective treatment of patients affected by knee cartilage degeneration and OA.
Abstract: Background:Osteoarthritis (OA) is a common disease that will affect almost half the population at some point in their lives through pain and decreased functional capacity. New nonoperative options are being proposed to treat earlier stages of joint degeneration to provide symptomatic relief and delay surgical intervention.Purpose:To evaluate the benefit provided by platelet-rich plasma (PRP) injections to treat knee joint degeneration in comparison with hyaluronic acid (HA), the most common injective treatment currently adopted for this condition.Study Design:Randomized controlled trial; Level of evidence, 1.Methods:A total of 443 patients were screened, and 192 of them were enrolled in the study according to the following inclusion criteria: (1) unilateral symptomatic knee with history of chronic pain (at least 4 months) or swelling and (2) imaging findings of degenerative changes (Kellgren-Lawrence score of 0-3 at radiographs or MRI evidence of degenerative chondropathy). Patients underwent 3 weekly int...
265 citations
Cites background from "Basic science and clinical applicat..."
...4 (4-300) ns Previous treatment, n ns None 12 7 Nonoperative 29 34 Surgical 53 48 Kellgren-Lawrence score, mean 6 SD 2....
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TL;DR: The pathogenesis of osteoarthritis and how mesenchymal stem cells may play a role in future management strategies of this disabling condition are explored.
Abstract: Osteoarthritis is a leading cause of pain and disability across the world. With an aging population its prevalence is likely to further increase. Current accepted medical treatment strategies are aimed at symptom control rather than disease modification. Surgical options including joint replacement are not without possible significant complications. A growing interest in the area of regenerative medicine, led by an improved understanding of the role of mesenchymal stem cells in tissue homeostasis and repair, has seen recent focused efforts to explore the potential of stem cell therapies in the active management of symptomatic osteoarthritis. Encouragingly, results of pre-clinical and clinical trials have provided initial evidence of efficacy and indicated safety in the therapeutic use of mesenchymal stem cell therapies for the treatment of knee osteoarthritis. This paper explores the pathogenesis of osteoarthritis and how mesenchymal stem cells may play a role in future management strategies of this disabling condition.
212 citations
Cites background from "Basic science and clinical applicat..."
...TGFβ1 is seen to reduce collagen type I gene expression and up regulate expression of collage type II and aggrecan genes [131]....
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References
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01 Jan 2006
TL;DR: Animal Models and Therapy, Directed Differentiation and Characterization of Genetically Modified Embryonic Stem Cells for Therapy, and Use of Differentiating Embryonics Stem cells in the Parkinsonian Mouse Model are reviewed.
Abstract: Isolation and Maintenance.- Isolation and Differentiation of Medaka Embryonic Stem Cells.- Maintenance of Chicken Embryonic Stem Cells In Vitro.- Derivation and Culture of Mouse Trophoblast Stem Cells In Vitro.- Derivation, Maintenance, and Characterization of Rat Embryonic Stem Cells In Vitro.- Derivation, Maintenance, and Induction of the Differentiation In Vitro of Equine Embryonic Stem Cells.- Generation and Characterization of Monkey Embryonic Stem Cells.- Derivation and Propagation of Embryonic Stem Cells in Serum- and Feeder-Free Culture.- Signaling in Embryonic Stem Cell Differentiation.- Internal Standards in Differentiating Embryonic Stem Cells In Vitro.- Matrix Assembly, Cell Polarization, and Cell Survival.- Phosphoinositides, Inositol Phosphates, and Phospholipase C in Embryonic Stem Cells.- Cripto Signaling in Differentiating Embryonic Stem Cells.- The Use of Embryonic Stem Cells to Study Hedgehog Signaling.- Transfection and Promoter Analysis in Embryonic Stem Cells.- SAGE Analysis to Identify Embryonic Stem Cell-Predominant Transcripts.- Utilization of Digital Differential Display to Identify Novel Targets of Oct3/4.- Gene Silencing Using RNA Interference in Embryonic Stem Cells.- Genetic Manipulation of Embryonic Stem Cells.- Efficient Transfer of HSV-1 Amplicon Vectors Into Embryonic Stem Cells and Their Derivatives.- Lentiviral Vector-Mediated Gene Transfer in Embryonic Stem Cells.- Use of the Cytomegalovirus Promoter for Transient and Stable Transgene Expression in Mouse Embryonic Stem Cells.- Use of Simian Immunodeficiency Virus Vectors for Simian Embryonic Stem Cells.- Generation of Green Fluorescent Protein-Expressing Monkey Embryonic Stem Cells.- DNA Damage Response and Mutagenesis in Mouse Embryonic Stem Cells.- Ultraviolet-Induced Apoptosis in Embryonic Stem Cells In Vitro.- Use of Embryonic Stem Cells in Pharmacological and Toxicological Screens.- Use of Differentiating Embryonic Stem Cells in Pharmacological Studies.- Embryonic Stem Cells as a Source of Differentiated Neural Cells for Pharmacological Screens.- Use of Murine Embryonic Stem Cells in Embryotoxicity Assays.- Use of Chemical Mutagenesis in Mouse Embryonic Stem Cells.- Epigenetic Analysis of Embryonic Stem Cells.- Nuclear Reprogramming of Somatic Nucleus Hybridized With Embryonic Stem Cells by Electrofusion.- Methylation in Embryonic Stem Cells In Vitro.- Tumor-Like Properties.- Identification of Genes Involved in Tumor-Like Properties of Embryonic Stem Cells.- In Vivo Tumor Formation From Primate Embryonic Stem Cells.- Animal Models and Therapy.- Directed Differentiation and Characterization of Genetically Modified Embryonic Stem Cells for Therapy.- Use of Differentiating Embryonic Stem Cells in the Parkinsonian Mouse Model.
3,665 citations
TL;DR: This classification of the different platelet concentrates into four categories, depending on their leucocyte and fibrin content, should help to elucidate successes and failures that have occurred so far, as well as providing an objective approach for the further development of these techniques.
1,454 citations
"Basic science and clinical applicat..." refers methods in this paper
...To more precisely 74 delineate these products based on their leukocyte and fibrin content, they have been called 75 pure PRP, leukocyte-rich PRP, pure platelet-rich fibrin, and leukocyte- and platelet-rich fibrin 76 [4]....
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TL;DR: This study shows the distinct phenotype, morphology, and method of isolation of BM MPCs, which may have implications for defining the physiologic roles of MPCs in arthritis, bone diseases, and joint regeneration.
Abstract: Objective
There is an increased interest in rheumatology in mesenchymal progenitor/stem cells (MPCs) and their roles in rheumatic diseases, but little is known about the phenotype of these cells in vivo. The aim of this study was to isolate and characterize human bone marrow (BM) MPCs.
Methods
Fluorescence microscopy was used to identify putative MPCs among adherent BM cells. To purify them, a positive selection with antifibroblast microbeads was used, combined with fluorescence-activated cell sorting (FACS) for microbead+,CD45low cells. A more detailed phenotype of these cells was determined using 4-color flow cytometry, and standard chondrogenic, osteogenic, and adipogenic assays were used to investigate their differentiation potentials.
Results
Putative MPCs microscopically identified as large, fibroblast-like, D7-FIB+ cells were purified using positive selection with D7-FIB–conjugated (antifibroblast) microbeads followed by FACS for specifically bound microbead+,CD45low cells. These cells represented 0.01% of mononuclear cells in the BM. They were uniformly positive for CD105, LNGFR, HLA–DR, CD10, CD13, CD90, STRO-1, and bone morphogenetic protein receptor type IA (BMPRIA) and were negative for CD14, CD34, CD117, and CD133. Only cells with this phenotype could proliferate and produce adherent cell monolayers capable of chondrogenic, osteogenic, and adipogenic differentiation. D7-FIB− cells in the BM lacked any MPC activity. Uncultured skin fibroblasts had a phenotype similar to that of BM MPCs, but were negative for LNGFR, STRO-1, HLA–DR, and BMPRIA.
Conclusion
This study shows the distinct phenotype, morphology, and method of isolation of BM MPCs. The findings may have implications for defining the physiologic roles of MPCs in arthritis, bone diseases, and joint regeneration.
664 citations
TL;DR: A single dose of WBC-filtered PRP in concentrations of 10 times the normal amount is as effective as 2 injections to alleviate symptoms in early knee OA, but the results, however, deteriorate after 6 months.
Abstract: Background:Specific growth factors have been proposed as therapeutic proteins for cartilage repair.Hypothesis:Platelet-rich plasma (PRP) provides symptomatic relief in early osteoarthritis (OA) of the knee.Study Design:Randomized controlled trial; Level of evidence, 1.Methods:A total of 78 patients (156 knees) with bilateral OA were divided randomly into 3 groups. Group A (52 knees) received a single injection of PRP, group B (50 knees) received 2 injections of PRP 3 weeks apart, and group C (46 knees) received a single injection of normal saline. White blood cell (WBC)–filtered PRP with a platelet count 3 times that of baseline (PRP type 4B) was administered in all. All the groups were homogeneous and comparable in baseline characteristics. Clinical outcome was evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire before treatment and at 6 weeks, 3 months, and 6 months after treatment. They were also evaluated for pain by a visual analog scale, and overall sa...
655 citations
TL;DR: The preliminary results indicate that the treatment with PRP injections is safe and has the potential to reduce pain and improve knee function and quality of live in younger patients with low degree of articular degeneration.
Abstract: Platelet-rich plasma (PRP) is a natural concentrate of autologous blood growth factors experi- mented in different fields of medicine in order to test its potential to enhance tissue regeneration. The aim of our study is to explore this novel approach to treat degenerative lesions of articular cartilage of the knee. One hundred con- secutive patients, affected by chronic degenerative condi- tion of the knee, were treated with PRP intra-articular injections (115 knees treated). The procedure consisted of 150-ml of venous blood collected and twice centrifugated: 3 PRP units of 5 ml each were used for the injections. Patients were clinically prospectively evaluated before and at the end of the treatment, and at 6 and 12 months follow-up. IKDC, objective and subjective, and EQ VAS were used for clinical evaluation. Statistical analysis was performed to evaluate the significance of sex, age, grade of OA and BMI. A sta- tistically significant improvement of all clinical scores was obtained from the basal evaluation to the end of the therapy and at 6-12 months follow-up (P \ 0.0005). The results remained stable from the end of the therapy to 6 months follow up, whereas they became significantly worse at 12 months follow up (P = 0.02), even if still significantly higher respect to the basal level (P \ 0.0005). The pre- liminary results indicate that the treatment with PRP injec- tions is safe and has the potential to reduce pain and improve knee function and quality of live in younger patients with low degree of articular degeneration.
530 citations