PRP – PLATELET RICH PLASMA (PRP) IN SPORTS MEDICINE AND OSTEOARTHRITIS

PRP which consists of various medical uses is widely known for its restorative properties, as platelets release growth factors or “healing factors”, that promote the regeneration of bone, skin, muscle tendons and tissues has applications in many degenerative disorders and sports injuries. This innovative treatment has piqued clinicians’ interest, particularly specialists in physical medicine and sports traumatology, more so because the production of PRP is relatively easy, making it one of the best natural therapy to be trusted by many sports personalities.

Injuries including rotator cuff tears, shoulder impingement syndrome, tennis elbow, golfers elbow (elbow epicondylitis), anterior cruciate ligament (ACL) injuries, patellar tendinopathy, and Achilles tendinopathy are some that PRP is known to heal due to its regenerative properties. Platelet-rich therapy injections have been used as a source of the main treatment, and surgical augmentation procedures in which platelet-rich therapy was applied during surgery; following ACL reconstruction and surgical repair or reconstructions of tendons and ligaments. PRP in regenerative medicine plays an important role when conservative treatment has failed and the next treatment option is an invasive surgical procedure.

Benefits of choosing PRP are that it provides enhanced healing, improved pain relief and improved function and recovery. It Gets you back to sports and routine activities sooner.

PRP Treatment Efficacy for Tendinopathy: A Review of Basic Science Studies,

Yiqin Zhou  and  James H-C. Wang ( 2016)

PRP is a popular cell-free therapy that is used worldwide to treat tendinopathy. Recent studies have consistently shown the beneficial effects of PRP on tendons including increased tendon cell growth, increased expression of anabolic genes and proteins, and reduced tendon inflammation. Platelets have long been recognized to maintain tissue hemostasis. But accumulating evidence indicates that platelets may have a much wider role in tissue healing because they store and release a wide range of bioactive factors including growth factors (e.g., TGF-β and HGF). These factors are secreted by the dense granules, α-granules, and lysosomes in platelets. Apart from platelets, PRP also has other components such as plasma, leukocytes, neutrophils, and monocytes with some leukocyte-containing PRP (L-PRP) containing residual erythrocytes, which also contain and/or release some bioactive factors. Plasma contains proteins such as albumin, globulins, fibrinogen, complement, and clotting factors and electrolytes, hormones, and biomarkers. The key components of leukocytes are neutrophils and monocytes, which may also release many bioactive factors and proteins. Neutrophils mainly release myeloperoxidase, bactericidal phagocytins, collagenase, gelatinase, and proteases. Monocytes secrete platelet-activating factor, TGF-β, VEGF, FGF, and EGF. Many of these factors have been shown to influence tendon healing.

To read more bout this research kindly visit:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004020/

Clinical Applications of Platelet-Rich Plasma in Patellar Tendinopathy

D. U. Jeong, C.-R. LeeJ. H. LeeJ. PakL.-W. KangB. C. JeongS. H. Lee-  (2014)

Platelet-rich plasma (PRP), a blood derived substance with high concentrations of platelets, has been found to have high levels of autologous growth factors (GFs), “healing factors” such as transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), fibroblastic growth factor (FGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) that all support the healing potential in an injury. These GFs and other biological active proteins of PRP can promote tissue healing through the regulation of fibrosis and angiogenesis. PRP has the potential to recruit numerous GFs necessary for wound healing. Due to its ability to regulate fibrosis and angiogenesis, it can be applied on tendon injury. PRP has an autologous nature and no critical complications or side effects have been reported, suggesting that this treatment could be considered safe. PRP treatment  promotes the formation of tendon stem cell (TSC) into active tenocytes exhibiting high proliferation rates and collagen production capability. PRP has also been successfully used as a cell culture additive to facilitate growth and differentiation of autologous mesenchymal stem cells (MSCs). So, PRP in combination with cell therapy could be promising in the patellar tendinopathy. To determine the real effectiveness of this combination therapy in the management of chronic patellar tendinopathy, intensive research needs to be performed using different groups of study. This review concludes the injection therapy of PRP is effective for the treatment of patellar tendinopathy and has the promising potential to restore patients to their activities of daily living, work, and sports.

To read more about this research kindly visit:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127290/

Infiltration of Autologous Growth Factors in Chronic Tendinopathies

Crescibene A, Napolitano M, Sbano R, Costabile E  (2015)

Achilles tendinopathy and patellar tendinopathy are among the most frequent diagnoses in sports medicine. Therapeutic treatment of the disease is difficult, particularly in chronic cases. In literature, several studies suggest the employment of Platelet-Rich Plasma as a therapeutic alternative in tendinopathies. The choice of employing this method is based on the activity of growth factors contained in platelets which activate, amplify, and optimize the healing process. 14 patients were selected for this studythat were affected by Achilles tendinopathy and 7 patients affected by patellar tendinopathy, with a two-year final follow-up. These patients underwent a cycle of three tendinous infiltrations, after clinical and instrumental evaluation carried out by means of specific questionnaires and repeated ultrasound scans. Ultrasound scans of 18 patients showed signs of reduction in insertional irregularities. The result is confirmed by complete functional recovery of the patients, with painful symptomatology disappearing. The patients showed a clear pain reduction, along with an enhanced VISA score after the 24-month follow-up, equal to 84.2 points on a scale of 0 to 100. In conclusion, the present study provides evidence to suggest that PRP infiltration is a valid option to patients with chronic tendinopathy who did not benefit from other treatments.

To read more about this research kindly visit:

https://www.hindawi.com/journals/jbt/2015/924380/

APS – AUTOLOGOUS PROTEIN SOLUTION FOR OSTEOARTHRITIS

The benefit of choosing APS is known to improve pain and function in your joints caused by osteoarthritis for up to 3 years following a single injection therapy. It also has a potential effect protecting cartilage and hence delaying wear and tear of arthritis affecting your joints.

Autologous Protein Solution prepared from blood of Osteoarthritic Patients, contain enhanced profile of anti-inflammatory cytokines and anabolic growth factors. – Journal of Orthopaedic Research. (2014)

 Woodell-May J, Matuska A, Oyster M, Welch Z, O’Shaughnessey K, Hoeppner J.

This trial performed a study on 105 patients exhibiting radiographic evidence of knee Osteoarthritis. Blood samples were extracted from the same patients and were processed in a device to form autologous protein solution (APS), with preferentially increased concentration of anti-inflammatory cytokines or “good” proteins (IL-1ra, sIL-1R, sTNF-RI and sTNF-RII ) were seen after obtaining the APS. These proteins were found to block the inflammatory cytokines or “bad” proteins ( IL-1 and TNFa) that initiate pain and cartilage degeneration. 98% of the patients in this study showed an increased number of anti inflammatory proteins obtained in the APS, then the inflammatory proteins. The results were as follows 39,000 ± 20,000 pg/ml IL-1ra, 21,000 ± 5,000 pg/ml sIL-1RII, 2,100 ± 570 pg/ml sTNF-RI, and 4,200 ± 1,500 pg/ml sTNF-RII.

This study significantly shows that if the APS solution contained from the blood of osteoarthritic patients contains healing factors in order to outnumber the inflammatory proteins that causes knee pain, stiffness and degeneration.

To read more about the trial and findings of this research kindly visit:

https://www.ncbi.nlm.nih.gov/pubmed/24981198

Innovative regenerative medicine in the management of knee OA: The role of Autologous Protein Solution.- Journal of Clinical Orthopaedic Trauma (2018)

N. Vitale, L. Laura et. al

The primary aim of this paper is to report the current concepts on regenerative medicine for knee OA with a particular focus on Autologous Protein solution (APS). APS is a blood derived product obtained by using a proprietary device, made of APS Separator, which isolates WBCs and platelets in a small volume of plasma, and APS Concentrator, which further concentrates platelets, WBCs and plasma proteins. The result is a peculiar formulation differing from other biologic products as it contains high levels of growth factors (EGF, IGF-1, PDGF-AB, PDGF-BB, VEGF, TGF-β1) along with high concentrations of anti-inflammatory mediators “ good” proteins (IL-1ra, sIL-1RII, sTNF-RI, sTNF-RII) and low levels of pro-inflammatory cytokines or ‘bad’ proteins(Il-1β and TNF-α).

To read more about the trial and findings of this research kindly visit:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349612/

Safety and Treatment Effectiveness of a Single Autologous Protein Solution Injection in Patients with Knee Osteoarthritis – (2016)

 Rogier A.M. van Drumpt, Walter van der Weegen, William King, Krista Toler, and Mitchell M. Macenski

The therapy used here is Autologous Protein Solution (APS), formed from a patient’s blood and contains high concentrations of anti-inflammatory and anabolic proteins. This study assessed the safety and treatment effects of APS. Eleven subjects participated in this recent study that involved the participants to have been suffering from OA knee conditions and have failed at least one conservative therapy. The participants were treated with the APS Knee injections. Subjects were closely monitored for adverse events (AE) following the injection. AE and clinical outcomes were assessed at 1 and 2 weeks postinjection and 1, 3, and 6 months post injection. There were no serious AE or AE that were reported by the investigator as greater than mild in severity. Mean Western Ontario and McMaster Universities Arthritis Index (WOMAC)(WOMAC Score is used to score a patient’s  pain score, stiffness score, walking score)  composite scores and pain, stiffness, and function subscale scores all showed significant improvement compared to baseline by 2 weeks post injection.

The data presented here suggest that the treatment is safe and show a complication profile that is mild and consistent with similar treatments. A single injection of APS for treatment of early to moderate knee OA led to symptom improvement over the study course.

To read more about the trial and findings of this research kindly visit:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031090/

STEM CELL THERAPY IN SPORTS INJURIES AND OSTEOARTHRITIS

Mesenchymal stem cell therapy has been used in treating osteoarthritis, sports injuries and tendinopathy conditions.

Stem cells can divide and duplicate themselves, both in the body and in a lab. A small amount of stem cells can be harvested from human tissue and processed and prepared and injected into the affected area. These cells differentiate and can develop into different types of cells. For example, it is possible for a stem cell to develop into a blood cell, bone, cartilage etc.

This gives us the ability to repair and regenerate tissues such as cartilage and bone more effectively.

Through many trials and research around the world clinicians and scientists have injected OA patients with Bone marrow derived cells. Their results have been thoroughly compared by peers and patients, evaluating pain scores and walking ability post treatments. Some of the trials showed that in patients with knee OA treated with intra-articular injection of autologous bone marrow-derived stem cells (BM-SCs) observed that the patients demonstrated rapid and progressive improvement of functional indices by 1 year and also showed a highly significant decrease of poor cartilage areas with improvement of cartilage quality.

Another study carried out in injections of BM-SCs in knee OA was shown to improve pain, functional status of the knee, and walking distance without any adverse events. An increase in cartilage thickness and a considerable decrease in the size of oedematous subchondral bone were noticed. A trial in Germany showed a good defect filling and repair of tissue with BM-SCs in patients with knee OA and a significant clinical improvement. Another study reported that BMSCs in patients with medial femoral condyle lesions, could result into normal arthroscopic appearance.

Long-Term Follow-up of Intra-Articular Injection of Autologous Mesenchymal Stem Cells in Patients with Knee, Ankle or Hip Osteoarthritis- (Department of Regenerative Biomedicine at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran)- 2015

Mohsen Emadedin , Maede Ghorbani Liastani , Roghayeh Fazeli MD, Fatemeh Mohseni MD, Reza Moghadasali PhD, Soura Mardpour MSc1, Seyyedeh Esmat Hosseini BS, Maryam Niknejadi MD, Fatemeh Moeininia MD, Aslan Aghahossein Fanni MSc, Reza Baghban Eslaminejhad PhD, Ahmad Vosough Dizaji MD, Narges Labibzadeh MD, Ali Mirazimi Bafghi MD, Hossein Baharvand PhD, Nasser Aghdami MD PhD

This study aims to investigate the safety of treatment with autologous bone marrow (BM)-derived mesenchymal stem cells. They enrolled 18 patients with different joint involvements (knee, ankle, or hip OA) .BM samples were taken from the patients, after which BM-derived MSCs were isolated and cultured. The trial conducted three separate studies according to the principles of the Declaration of Helsinki which were approved by the Ethics Committee of Royan Institute . Each patient received one MSC injection. Patients were followed with no severe adverse events such as pulmonary embolism, death, or systemic complications. A limited number of patients had very minor localized adverse effects such as rash and erythema. There were no changes in liver function, hematology, or bio- chemistry analyses before and after cell therapy. There was no evidence of tumor or neoplastic changes in the patients during the 30-month.

The clinical and imaging outcomes of all patients: All groups of OA patients during the 30 months of follow-up. All OA groups showed improvements in the total WOMAC score and sub-scores that included stiffness as well as pain and physical functions

Knee OA group : The mean walking distance in the knee OA group was 88.3 ± 93.2 m at 427.2 m and at 30 months (1222.0 ± 1032.9 m) after MSC treatment. The total WOMAC score reduced in these patients at months 6 (45.5 vs. 72.7; P < 0.008), 12 (47.2 vs. 72.7, P < 0.002), and 30 (43.4 vs. 72.7; P < 0.05) after treatment compared with baseline

Hip OA Group: The mean walking distances in hip OA patients were 1170 m at 6 and 1000 m at 30 months after MSC treatment compared with 370 m at baseline. The mean total WOMAC scores were 27.9 ± 20.8 at 6 months, 26.3 ± 11.6 at 12 months and 29.1 ± 18.9 at 30 months after treatment compared to the baseline score of 45.2 ± 10.0 .

Ankle OA group: The mean walking distance in ankle OA patients was 1625 m at 6 months and 2333 m at 30 months after MSC treatment compared to 1010 m at baseline. Reductions were observed in mean total WOMAC scores at 12 months (P < 0.05) and 30 months (P < 0.05) after treatment.

Imaging outcomes: There was reduced subchondral edema in three of the six patients with knee OA who were treated with MSCs. Articular cartilage re- with hip OA. Decreased signal intensity related to subchondral edema was seen in four of the six patients with ankle OA at six months after the injections. Radiological analysis, as improvements in all patients were mainly observed during the first six months after transplantation.

To read more about this article kindly follow the link:

https://www.ncbi.nlm.nih.gov/pubmed/26058927

Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II)- Journal of Translational Medicine- 2016.

Lamo-Espinosa JM,  Mora G,  Blanco JF,  Granero-Moltó F,  Nuñez-Córdoba JM,  Sánchez-Echenique C, Bondía JM, Aquerreta JD, Andreu EJ,  Ornilla E , Villarón EM,  Valentí-Azcárate A,  Sánchez-Guijo F, Valentí-Nin JR, Prósper F

This research paper focuses on developing a phase I/II randomized clinical trial with active controls. Thirty patients diagnosed with knee OA were randomly assigned to intra articularly administered hyaluronic acid alone (control), or together with autologous BM-MSCsor Bone Marrow derived stem cells called as mesenchymal cell, and followed up for 12 months. Pain and function were assessed using VAS and WOMAC and by measuring the knee motion range. X-ray and magnetic resonance imaging analyses were performed to analyse joint damage.

RESULTS: 

No adverse effects were reported after BM-MSC administration or during follow-up. BM-MSC-administered patients improved according to VAS during all follow-up evaluations and median value (IQR) for control, low-dose and high-dose groups change from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 4 (3, 5), 2 (1, 3) and 2 (0,4) respectively at 12 months (low-dose vs control group p = 0.005 and high-dose vs control group p < 0.009). BM-MSC-administered patients were also superior according to WOMAC, although improvement in control and low-dose patients could not be significantly sustained beyond 6 months. On the other hand, the BM-MSC high-dose group exhibited an improvement of 16.5 (12, 19) points at 12 months (p < 0.01). Consistent with WOMAC and VAS values, motion ranges remained unaltered in the control group but improved at 12 months with BM-MSCs. X-ray revealed a reduction of the knee joint space width in the control group that was not seen in BM-MSCs high-dose group. MRI (WORMS protocol) showed that joint damage decreased only in the BM-MSC high-dose group, albeit slightly.

CONCLUSIONS: 

The single intra articular injection of in vitro expanded autologous BM-MSCs together with HA is a safe and feasible procedure that results in a clinical and functional improvement of knee OA, especially when cells are administered. These results pave the way for a clinical application of Bone marrow derived stem cells.

To read more about this article visit

https://www.ncbi.nlm.nih.gov/pubmed/27565858