Revista de Medicina Desportiva (English) May 2018 - Page 18

The growth factors usually present in a PRP solution include IGD-1 , PDGF and TGF-B , among other molecules of anabolic interest and anti-inflammatory . 23 These factors act on the chondrocytes , promoting the synthesis of the extracellular matrix of the cartilage , increasing the growth and cellular migration in the areas of injury and facilitating the transcription of proteins . In addition to this effect , at the level of the joint metabolism , the PRP has also demonstrated efficacy in the control of inflammatory cytokines , notably NFK-B and IL-6 . 20
In this sense , the rational purpose for its use in the knee with OA is justified by the supraphysiologic release of these platelet growth factors in articular cartilage with lesion , stimulating and accelerating in this way the natural inflammatory cascade and the processes of proliferation and regeneration tissue , mediating at the same time the inflammatory response . 21
The literature published to date with regard to the efficacy of the PRP in the treatment of the knee OA presents a great variability of results . Some recent studies , well conducted and with good statistical power , compared two types of intervention in the mild to moderate OA of the knee , notably articular injection of HA vs articular injection of PRP , with better clinical outcomes with the biological therapy . 22 , 23 Several meta-analyses compared the efficacy of intraarticular injections of PRP vs placebo or other type of treatments for the knee OA demonstrated superior benefit in terms of decreased pain and optimization of the function with the PRP . 24 26 Of these , the systematic revision of 2014 , of Chang et al ., analyzed 16 studies involving 1.543 patients , concluding that the PRP was better than HA with regard to the decrease of the pain . The positive effects of the PRP lasted up to one year and were more pronounced in patients with moderate OA .
In 2014 , Braun et al . conducted a meta-analysis in which they concluded that 71 % of the studies involving PRP demonstrated some degree of anabolic effect on the chondrocytes , notably in the deposition of type II collagen . 27
The adverse effects of this intervention are the same as other joint injection .
4 . Mesenchymal stem cells A newer biological therapy is the articular injection of bone marrow mesenchymal stem cells ( Bone marrow mesenchymal stem cells – BM- MSC ). 28 The BM-MSC are considered pluripotent cells , with the potential to differentiate in any type of cellular lineage , including those of interest for the joint microenvironment , namely chondrocytes , adipocytes and osteoblasts / osteocytes . 29 These conclusions are based on various studies in animal models and on a small number of clinical trials in humans .
The BM-MSC are autologous and they are obtained notably at the level of the iliac crest . However , some studies have also demonstrated that this type of pluripotent cells can be obtained from differentiated tissue , specifically of skeletal muscle cells , synovial tissue and adipose tissue , as well from embryonic tissue , notably umbilical cord . 30 Like other products of a biological and regenerative nature , BM-MSC have also strong anti-inflammatory properties , with antagonists action over the receptor of IL-1 ( IL-1Ra ), with direct action on the inhibition of inflammatory
31 , 32
cytokines secretion . From an experimental standpoint , recent animal models have demonstrated that BM-MSC crops in enriched media with TGF-B and IGF-1 ( anabolic and anti-inflammatory molecules for the joint regeneration process ) have developed a rich microenvironment rich on type II collagen components , aggrecans and other proteoglycans , which are fundamental and physiological constituents of a healthy joint . 33 In this sense , it is evident that , as demonstrated by Faqeh et al . in 2012 , the BM-MSC association to growth factors has a greater regenerative and growth potential of cartilage , in animal tissues with induced OA , in relation to control groups with BM-MSC only 32 . This indicates of the ability of this treatment to optimize a potential response for reversal of the lesion and inflammation , with consequent regeneration of the damaged tissue .
As far as therapeutic results are concerned in human , Ahmad et al . carried out in 2014 one prospective study with 10 patients with OA of the knee , subjected to a joint injection of BM-MSC . They found a 29 % statistically significant decrease on the pain on the WOMAC ( Western Ontario and McMaster Universities Osteoarthritis Index ) subscale for pain since the beginning of the treatment up to one year . At the same time , in evaluation by MRI , the authors were able to demonstrate an increase in the thickness of the cartilage in 41 % of the joint compartments evaluated , which proves the potential of reversal of the disease and the joint regeneration that this therapy presents . 33
The side adverse effects are related to joint injection . However , despite these promising results , it is important to reinforce the notion that human clinical trials are limited , and that further research should naturally be conducted to gauge the real value of this therapeutic in the treatment of OA Knee . Conclusion Options such as HA , PRP , and MSC have been presented as alternatives with the potential to change the panorama of knee OA treatment to a minimally invasive perspective with regenerative potential . More research with free scientific evidence will be needed so that these options are universally accepted as reliable and safe alternatives in the approach of the knee OA .
The authors declare no conflict of interests
Correspondence to José Luís Carvalho Hospital da Prelada – Porto jo . luis . carvalho @ gmail . com
Bibliography
1 . Lawrence R , Felson D , Helmick C et al . Estimates of the prevalence of arthritis and other rheumatic conditions in the United States part II . Arthritis Rheum 2008 ; 58:23-26 .
2 . Pintan G , Oliveira A , Lenza M et al . Update on biological therapies for knee injuries : osteoarthritis . Curr Rev Musculoskeletal Med 2014 ; 263-269 .
3 . Pearle D , Warren R , Rodeo S . Basic science of articular cartilage and osteoarthritis , Clinics in Sports Medicine 2005 ; 24:1-12 .
16 may 2018 www . revdesportiva . pt
The growth factors usually present in a PRP solution include IGD-1, PDGF and TGF-B, among other molecules of anabolic interest and anti-inflammatory. 23 These factors act on the chondrocytes, promoting the synthesis of the extracellular matrix of the cartilage, increasing the growth and cellular migration in the areas of injury and facilitating the transcription of proteins. In addi- tion to this effect, at the level of the joint metabolism, the PRP has also demonstrated efficacy in the control of inflammatory cytokines, notably NFK-B and IL-6. 20 In this sense, the rational purpose for its use in the knee with OA is justified by the supraphysiologic release of these platelet growth factors in articular cartilage with lesion, stimulating and accelerating in this way the natural inflamma- tory cascade and the processes of proliferation and regeneration tis- sue, mediating at the same time the inflammatory response. 21 The literature published to date with regard to the efficacy of the PRP in the treatment of the knee OA presents a great variability of results. Some recent studies, well conducted and with good statisti- cal power, compared two types of intervention in the mild to moder- ate OA of the knee, notably articular injection of HA vs articular injection of PRP, with better clinical outcomes with the biological therapy. 22,23 Sev- eral meta-analyses compared the efficacy of intraarticular injections of PRP vs placebo or other type of treatments for the knee OA dem- onstrated superior benefit in terms of decreased pain and optimization of the function with the PRP. 24–26 Of these, the systematic revision of 2014, of Chang et al., analyzed 16 studies involving 1.543 patients, con- cluding that the PRP was better than HA with regard to the decrease of the pain. The positive effects of the PRP lasted up to one year and were more pronounced in patients with moderate OA. In 2014, Braun et al. conducted a meta-analysis in which they concluded that 71% of the studies involving PRP demonstrated some degree of anabolic effect on the chondrocytes, notably in the deposi- tion of type II collagen. 27 16 may 2018 www.revdesportiva.pt The adverse effects of this inter- vention are the same as other joint injection. 4. Mesenchymal stem cells A newer biological therapy is the articular injection of bone marrow mesenchymal stem cells (Bone mar- row mesenchymal stem cells – BM- MSC). 28 The BM-MSC are considered pluripotent cells, with the potential to differentiate in any type of cellu- lar lineage, including those of inter- est for the joint microenvironment, namely chondrocytes, adipocytes and osteoblasts/osteocytes. 29 These conclusions are based on various studies in animal models and on a small number of clinical trials in humans. The BM-MSC are autologous and they are obtained notably at the level of the iliac crest. However, some studies have also demonstrated that this type of pluripotent cells can be obtained from differentiated tissue, specifically of skeletal muscle cells, synovial tissue and adipose tissue, as well from embryonic tissue, notably umbilical cord. 30 Like other prod- ucts of a biological and regenerative nature, BM-MSC have also strong anti-inflammatory properties, with antagonists action over the receptor of IL-1 (IL-1Ra), with direct action on the inhibition of inflammatory cytokines secretion. 31,32 From an experimental stand- point, recent animal models have demonstrated that BM-MSC crops in enriched media with TGF-B and IGF-1 (anabolic and anti-inflamma- tory molecules for the joint regen- eration process) have developed a rich microenvironment rich on type II collagen components, aggrecans and other proteoglycans, which are fundamental and physiological constituents of a healthy joint. 33 In this sense, it is evident that, as dem- onstrated by Faqeh et al. in 2012, the BM-MSC association to growth factors has a greater regenerative and growth potential of cartilage, in animal tissues with induced OA, in relation to control groups with BM-MSC only 32 . This indicates of the ability of this treatment to optimize a potential response for reversal of the lesion and inflammation, with consequent regeneration of the damaged tissue. As far as therapeutic results are concerned in human, Ahmad et al. carried out in 2014 one prospective study with 10 patients with OA of the knee, subjected to a joint injection of BM-MSC. They found a 29% statisti- cally significant decrease on the pain on the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) subscale for pain since the beginning of the treatment up to one year. At the same time, in evalua- tion by MRI, the authors were able to demonstrate an increase in the thick- ness of the cartilage in 41% of the joint compartments evaluated, which proves the potential of reversal of the disease and the joint regeneration that this therapy presents. 33 The side adverse effects are related to joint injection. However, despite these promising results, it is important to reinforce the notion that human clinical trials are limited, and that further research should naturally be conducted to gauge the real value of this thera- peutic in the treatment of OA Knee. Conclusion O ѥ́Ս́!AI@5M )ٔɕ͕ѕ́ѕɹѥٕ)ݥѠѡѕѥѼѡ)Ʌ=ɕѵЁѼ)䁥مͥٔѥٔ)ݥѠɕɅѥٔѕѥ5ɔ)ɕ͕ɍݥѠɕ͍ѥ٤)ݥͼѡЁѡ͔)ѥ́ɔչٕͅ䁅ѕ)ɕͅѕɹѥٕ́ѡ)ɽѡ= )Qѡ́ɔЁ)ѕɕ) ɕѼ))1́ م)!хAɕLAѼ)ե̹م) Ʌ(ĸ$1ɕHͽ! ЁѤ)ѕ́ѡɕمѡɥѥ́ѡ)ɡյѥѥ́ѡUѕMхѕ́)%$ѡɥѥ́Iմ̴ظ(ȸ$Aх=ٕɄ1鄁4ЁUє)ѡɅ́ȁɥ)ѕѡɥѥ̸ ȁI؁5͍ձͭх5(̴(̸$Aɱ]ɕHIL ͍ͥ)ѥձȁѥѕѡɥѥ̰ ́)Ḿ5Ĵȸ