Regenexx Blog
Dr. Chris Centeno
Considering a PRP Injection? Please Read This…
September 17, 2019
PRP treatment has become a big deal this past decade. It’s being used by professional athletes and weekend warriors alike. So what is a PRP injection and does it work? Let’s dig in.
What is PRP
PRP stands for platelet-rich plasma, which is created by taking blood and concentrating the platelets in plasma (1). Why do this? The platelets in your blood are responsible for clotting. They also have growth factors in them which help stimulate repair of the damaged tissue.
PRP can be made in a lab or at the bedside by an automated centrifuge. The vast majority of PRP made in the US is through a bedside machine while in Europe and elsewhere there is more lab involvement. The patient’s blood sample is commonly spun in a centrifuge which creates layers in the sample. How hard the sample is centrifuged determines where the platelets end up. Hence removing certain fractions of the blood at that point will create different types of PRP.
What are growth factors? Think of growth factors like espresso shots for local repair cells. They stimulate other cells to do more work and can even call the needed repair cells to the area. In the platelet, they live in packets called alpha granules (left).
Is PRP a Stem Cell Therapy?
No, PRP is not really a stem cell therapy. In fact, the blood contains few circulating stem cells, so using a blood product will always be stem cell poor. For example, some mesenchymal stem cells (MSCs) may be present, however, for comparison, this would be a very small fraction of the number of MSCs seen in your bone marrow (2). Most of the few stem cells in the blood are released from the bone marrow. This means that patients can be given drugs which will kick stem cells out of the bone marrow where they can be concentrated through a process called apheresis.
Are There Different Types of PRP?
There are two main types of PRP that are commonly used for injection (3):
-Red in color which is rich in white and red blood cells (leukocyte rich or LR-PRP)
-Amber in color which is white and red blood cell poor (leukocyte poor or LP-PRP)
On the left is red LR-PRP versus on the right is amber LP-PRP. Both have highly concentrated platelets, but the LR has red and white blood cells (hence it’s color) and the LP does not. https://regenexx.com/blog/prp-injection/
Are there clinical differences between these two preparations? There seems to be based on the research. However, all of this is still an open debate at physician conferences.
For example, red LR-PRP seems to cause more injury to synovial cells in the knee than amber LP-PRP (17). Of the two, amber PRP stimulated cartilage cells better than red (18). Amber also beat out red for the positive effects produced in knee arthritis patients (16). In addition, taking the white blood cells out of the PRP doesn’t impact its ability to heal tissue (22).
On the other hand, in one study of cartilage repair in the lab red PRP beat amber PRP (23). In another study, both red and amber helped ligament cells from the ACL in the knee grow (24). In addition, in our as of yet unpublished data, we observed that highly concentrated red PRP was better at killing a common bacteria that can be found in low back discs (p. acnes) than amber PRP.
Are There Platelet Concentration Differences in PRP?
The concentration of the platelets in PRP is also a critical factor (4). There is low concentration, usually 1-3 times the natural concentration of platelets in your blood. Medium concentration is 3-7 times concentrated and high concentration is 7-20X. Our lab has noted dramatic differences in how well PRP can stimulate cell growth based on this concentration (19). For example, when it came to younger tendon cells, the concentration mattered less, but in older cells, the concentration was a key factor in getting the cells to grow and heal a defect. Hence, we often go to higher PRP concentration in middle-aged and older patients.
How Long Does It Take for a PRP Injection to Work? How Long Does it Take to Recover from Platelet Rich Plasma?
Much of this depends on what’s being treated. For example, if it’s knee arthritis, a PRP injection procedure can be an excellent choice to treat mild arthritis. Patients often have an initial inflammatory flare-up from a few days to a week and then often feel better in a few weeks. This flare-up doesn’t seem to be different between red and amber types of PRP (16).
While the effects on joints can be quick, tendon or ligament treatment often takes longer to show results. In these types of treatments, most patients take 2-4 months to improve. For example, in one study on tennis elbow, significantly more patients were reporting results at 6 months compared to 3 months (20). See my video below for more details on what’s behind that delayed response:
How Much does Platelet Rich Plasma Therapy Cost? Is PRP Covered by Insurance?
PRP is not covered by most health insurance plans, other than the Regenexx PRP procedures that are covered by some employer-sponsored health plans. Some worker’s comp or auto accident insurance will cover these procedures. The costs for patients paying out of pocket are generally in the $1-2,000 range for a single joint. If you have more sites injected, this tends to push the cost higher.
Is PRP Really Effective?
The outcomes research on PRP is getting more and more clear by the day. Here are the areas where we have very good research:
Knee Arthritis – In a recent larger review of many different high-level studies, PRP was shown to be effective in treating knee arthritis (7). Some research shows that PRP tends to work better in patients with less severe arthritis (8), while another shows that the severity of arthritis makes no difference (15).
Tennis Elbow – PRP injection has also been shown to be more effective than steroid shots in the treatment of tennis elbow (lateral epicondylitis) (9).
Spine – PRP works better than steroid shots for the treatment of sacroiliac (SI) pain (10). PRP also helps patients with low back pain caused by bad and painful discs (11). PRP has also been shown to be more effective than steroid injections for facet joint pain (12).
Achilles Tendinopathy – This one is a bit murkier, but the most recent research shows that PRP likely works for treating Achilles tendon pain (13). In addition, one study went so far as to take a small piece of the Achilles after injection treatment which showed better collagen structure in the PRP injected tendon than the one injected with placebo (25).
Other things PRP may be able to help include partial rotator cuff tears – (a small study has shown that PRP injection can help, but no high-level research has been done) (14). Having said that, we routinely use high-dose LP-PRP to help these patients.
Is PRP Treatment Permanent?
If the treatment is focused on arthritis, which is a degenerative disease, it’s unlikely that PRP will have permanent effects. In my clinical experience, for mild arthritis, it may provide 1-2 years of relief and in more severe arthritis only a few to 6 months of relief. In contrast, for partial tendon or ligament injuries, there may be permanent relief as the prevailing thought is that PRP may heal the tear.
Is PRP Better than Stem Cell?
PRP is different from a stem cell injection. Think of PRP as a stimulus for repair, sort of like an espresso shot for all of the local repair cells. Stem cells are like a general contractor for the repair job that can also turn into the brick and mortar needed. In general, for example, my observation is that PRP tends to work better for mild arthritis and partial ligament and tendon tears. However, bone marrow stem cells tend to be better at treating more severe arthritis and bigger tendon tears (5,6).
The upshot? PRP injection can help many different types of pain problems. However, doing some homework on what can be helped and which type of PRP is best for your condition is a good idea!
____________________________________
References:
(1) Alsousou J, Thompson M, Hulley P, Noble A, Willett K.. The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery. J Bone Joint Surg Br. 2009 Aug;91(8):987-96. doi: 10.1302/0301-620X.91B8.22546.
(2) Liangliang X, Gang L. Circulating mesenchymal stem cells and their clinical implications. Journal of Orthopaedic Translation,
Volume 2, Issue 1, 2014, Pages 1-7. https://www.sciencedirect.com/science/article/pii/S2214031X1300048X
(3) Mautner K, Malanga GA, Smith J, Shiple B, Ibrahim V, Sampson S, Bowen JE. A call for a standard classification system for future biologic research: the rationale for new PRP nomenclature. PM R. 2015 Apr;7(4 Suppl):S53-S59. doi: 10.1016/j.pmrj.2015.02.005.
(4) Dhurat R, Sukesh M. Principles and Methods of Preparation of Platelet-Rich Plasma: A Review and Author’s Perspective. J Cutan Aesthet Surg. 2014;7(4):189–197. doi:10.4103/0974-2077.150734
(5) Centeno C, Sheinkop M, Dodson E, et al. A specific protocol of autologous bone marrow concentrate and platelet products versus exercise therapy for symptomatic knee osteoarthritis: a randomized controlled trial with 2 year follow-up. J Transl Med. 2018;16(1):355. Published 2018 Dec 13. doi:10.1186/s12967-018-1736-8
(6) Centeno CJ, Al-Sayegh H, Bashir J, Goodyear S, Freeman MD. A prospective multi-site registry study of a specific protocol of autologous bone marrow concentrate for the treatment of shoulder rotator cuff tears and osteoarthritis. J Pain Res. 2015;8:269–276. Published 2015 Jun 5. doi:10.2147/JPR.S80872
(7) Xing D, Wang B, Zhang W, Yang Z, Hou Y1,2, Chen Y, Lin J. Intra-articular platelet-rich plasma injections for knee osteoarthritis: An overview of systematic reviews and risk of bias considerations. Int J Rheum Dis. 2017 Nov;20(11):1612-1630. doi: 10.1111/1756-185X.13233.
(8) Filardo G, Kon E, Buda R, Timoncini A, Di Martino A, Cenacchi A, Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2011 Apr;19(4):528-35. doi: 10.1007/s00167-010-1238-6.
(9) Xu Q, Chen J, Cheng L. Comparison of platelet rich plasma and corticosteroids in the management of lateral epicondylitis: A meta-analysis of randomized controlled trials. Int J Surg. 2019 Jul;67:37-46. doi: 10.1016/j.ijsu.2019.05.003.
(10) Singla V, Batra YK, Bharti N, Goni VG, Marwaha N. Steroid vs. Platelet-Rich Plasma in Ultrasound-Guided Sacroiliac Joint Injection for Chronic Low Back Pain. Pain Pract. 2017 Jul;17(6):782-791. doi: 10.1111/papr.12526.
(11) Monfett M, Harrison J, Boachie-Adjei K, Lutz G. Intradiscal platelet-rich plasma (PRP) injections for discogenic low back pain: an update. Int Orthop. 2016 Jun;40(6):1321-8. doi: 10.1007/s00264-016-3178-3.
(12) Wu J, Zhou J, Liu C1, Zhang J, Xiong W, Lv Y, Liu R, Wang R, Du Z, Zhang G, Liu Q. A Prospective Study Comparing Platelet-Rich Plasma and Local Anesthetic (LA)/Corticosteroid in Intra-Articular Injection for the Treatment of Lumbar Facet Joint Syndrome. Pain Pract. 2017 Sep;17(7):914-924. doi: 10.1111/papr.12544.
(13) Wang Y, Han C, Hao J, Ren Y, Wang J. Efficacy of platelet-rich plasma injections for treating Achilles tendonitis : Systematic review of high-quality randomized controlled trials. Orthopade. 2019 Sep;48(9):784-791. doi: 10.1007/s00132-019-03711-y.
(14) Sengodan VC, Kurian S, Ramasamy R. Treatment of Partial Rotator Cuff Tear with Ultrasound-guided Platelet-rich Plasma. J Clin Imaging Sci. 2017;7:32. Published 2017 Aug 14. doi:10.4103/jcis.JCIS_26_17
(15) Burchard R, Huflage H, Soost C, Richter O, Bouillon B, Graw JA. Efficiency of platelet-rich plasma therapy in knee osteoarthritis does not depend on level of cartilage damage. J Orthop Surg Res. 2019;14(1):153. Published 2019 May 24. doi:10.1186/s13018-019-1203-0
(16) Riboh JC, Saltzman BM, Yanke AB, Fortier L, Cole BJ. Effect of Leukocyte Concentration on the Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis. Am J Sports Med. 2016 Mar;44(3):792-800. doi: 10.1177/0363546515580787.
(17) Braun HJ, Kim HJ, Chu CR, Dragoo JL. The effect of platelet-rich plasma formulations and blood products on human synoviocytes: implications for intra-articular injury and therapy. Am J Sports Med. 2014;42(5):1204–1210. doi:10.1177/0363546514525593
(18) Cavallo C, Filardo G, Mariani E, Kon E1 Marcacci M, Pereira Ruiz MT, Facchini A, Grigolo B. Comparison of platelet-rich plasma formulations for cartilage healing: an in vitro study. J Bone Joint Surg Am. 2014 Mar 5;96(5):423-9. doi: 10.2106/JBJS.M.00726.
(19) Berger DR, Centeno CJ, Steinmetz NJ. Platelet lysates from aged donors promote human tenocyte proliferation and migration in a concentration-dependent manner. Bone Joint Res. 2019;8(1):32–40. Published 2019 Feb 2. doi:10.1302/2046-3758.81.BJR-2018-0164.R1
(20) Mishra AK, Skrepnik NV, Edwards SG, Jones GL, Sampson S, Vermillion DA, Ramsey ML, Karli DC, Rettig AC. Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients. Am J Sports Med. 2014 Feb;42(2):463-71. doi: 10.1177/0363546513494359.
(21) Melve GK, Ersvaer E, Eide GE, Kristoffersen EK, Bruserud Ø. Peripheral Blood Stem Cell Mobilization in Healthy Donors by Granulocyte Colony-Stimulating Factor Causes Preferential Mobilization of Lymphocyte Subsets. Front Immunol. 2018;9:845. Published 2018 May 2. doi:10.3389/fimmu.2018.00845
(22) Giusti I, Di Francesco M, D’Ascenzo S, et al. Leukocyte depletion does not affect the in vitro healing ability of platelet rich plasma. Exp Ther Med. 2018;15(4):4029–4038. doi: 10.3892/etm.2018.5887
(23) Yaşar Şirin D1, Yılmaz İ, İsyar M, Öznam K, Mahiroğulları M. Does leukocyte-poor or leukocyte-rich platelet-rich plasma applied with biopolymers have superiority to conventional platelet-rich plasma applications on chondrocyte proliferation? Eklem Hastalik Cerrahisi. 2017 Dec;28(3):142-51. doi: 10.5606/ehc.2017.55186.
(24) Krismer AM, Cabra RS, May RD, Frauchiger DA, Kohl S, Ahmad SS, Gantenbein B. Biologic response of human anterior cruciate ligamentocytes on collagen-patches to platelet-rich plasma formulations with and without leucocytes. J Orthop Res. 2017 Dec;35(12):2733-2739. doi: 10.1002/jor.23599.
(25) Alsousou J, Thompson M, Harrison P, Willett K, Franklin S. Effect of platelet-rich plasma on healing tissues in acute ruptured Achilles tendon: a human immunohistochemistry study. Lancet. 2015 Feb 26;385 Suppl 1:S19. doi: 10.1016/S0140-6736(15)60334-8.
Dr. Chris Centeno
Considering a PRP Injection? Please Read This…
September 17, 2019
PRP treatment has become a big deal this past decade. It’s being used by professional athletes and weekend warriors alike. So what is a PRP injection and does it work? Let’s dig in.
What is PRP
PRP stands for platelet-rich plasma, which is created by taking blood and concentrating the platelets in plasma (1). Why do this? The platelets in your blood are responsible for clotting. They also have growth factors in them which help stimulate repair of the damaged tissue.
PRP can be made in a lab or at the bedside by an automated centrifuge. The vast majority of PRP made in the US is through a bedside machine while in Europe and elsewhere there is more lab involvement. The patient’s blood sample is commonly spun in a centrifuge which creates layers in the sample. How hard the sample is centrifuged determines where the platelets end up. Hence removing certain fractions of the blood at that point will create different types of PRP.
What are growth factors? Think of growth factors like espresso shots for local repair cells. They stimulate other cells to do more work and can even call the needed repair cells to the area. In the platelet, they live in packets called alpha granules (left).
Is PRP a Stem Cell Therapy?
No, PRP is not really a stem cell therapy. In fact, the blood contains few circulating stem cells, so using a blood product will always be stem cell poor. For example, some mesenchymal stem cells (MSCs) may be present, however, for comparison, this would be a very small fraction of the number of MSCs seen in your bone marrow (2). Most of the few stem cells in the blood are released from the bone marrow. This means that patients can be given drugs which will kick stem cells out of the bone marrow where they can be concentrated through a process called apheresis.
Are There Different Types of PRP?
There are two main types of PRP that are commonly used for injection (3):
-Red in color which is rich in white and red blood cells (leukocyte rich or LR-PRP)
-Amber in color which is white and red blood cell poor (leukocyte poor or LP-PRP)
On the left is red LR-PRP versus on the right is amber LP-PRP. Both have highly concentrated platelets, but the LR has red and white blood cells (hence it’s color) and the LP does not. https://regenexx.com/blog/prp-injection/
Are there clinical differences between these two preparations? There seems to be based on the research. However, all of this is still an open debate at physician conferences.
For example, red LR-PRP seems to cause more injury to synovial cells in the knee than amber LP-PRP (17). Of the two, amber PRP stimulated cartilage cells better than red (18). Amber also beat out red for the positive effects produced in knee arthritis patients (16). In addition, taking the white blood cells out of the PRP doesn’t impact its ability to heal tissue (22).
On the other hand, in one study of cartilage repair in the lab red PRP beat amber PRP (23). In another study, both red and amber helped ligament cells from the ACL in the knee grow (24). In addition, in our as of yet unpublished data, we observed that highly concentrated red PRP was better at killing a common bacteria that can be found in low back discs (p. acnes) than amber PRP.
Are There Platelet Concentration Differences in PRP?
The concentration of the platelets in PRP is also a critical factor (4). There is low concentration, usually 1-3 times the natural concentration of platelets in your blood. Medium concentration is 3-7 times concentrated and high concentration is 7-20X. Our lab has noted dramatic differences in how well PRP can stimulate cell growth based on this concentration (19). For example, when it came to younger tendon cells, the concentration mattered less, but in older cells, the concentration was a key factor in getting the cells to grow and heal a defect. Hence, we often go to higher PRP concentration in middle-aged and older patients.
How Long Does It Take for a PRP Injection to Work? How Long Does it Take to Recover from Platelet Rich Plasma?
Much of this depends on what’s being treated. For example, if it’s knee arthritis, a PRP injection procedure can be an excellent choice to treat mild arthritis. Patients often have an initial inflammatory flare-up from a few days to a week and then often feel better in a few weeks. This flare-up doesn’t seem to be different between red and amber types of PRP (16).
While the effects on joints can be quick, tendon or ligament treatment often takes longer to show results. In these types of treatments, most patients take 2-4 months to improve. For example, in one study on tennis elbow, significantly more patients were reporting results at 6 months compared to 3 months (20). See my video below for more details on what’s behind that delayed response:
How Much does Platelet Rich Plasma Therapy Cost? Is PRP Covered by Insurance?
PRP is not covered by most health insurance plans, other than the Regenexx PRP procedures that are covered by some employer-sponsored health plans. Some worker’s comp or auto accident insurance will cover these procedures. The costs for patients paying out of pocket are generally in the $1-2,000 range for a single joint. If you have more sites injected, this tends to push the cost higher.
Is PRP Really Effective?
The outcomes research on PRP is getting more and more clear by the day. Here are the areas where we have very good research:
Knee Arthritis – In a recent larger review of many different high-level studies, PRP was shown to be effective in treating knee arthritis (7). Some research shows that PRP tends to work better in patients with less severe arthritis (8), while another shows that the severity of arthritis makes no difference (15).
Tennis Elbow – PRP injection has also been shown to be more effective than steroid shots in the treatment of tennis elbow (lateral epicondylitis) (9).
Spine – PRP works better than steroid shots for the treatment of sacroiliac (SI) pain (10). PRP also helps patients with low back pain caused by bad and painful discs (11). PRP has also been shown to be more effective than steroid injections for facet joint pain (12).
Achilles Tendinopathy – This one is a bit murkier, but the most recent research shows that PRP likely works for treating Achilles tendon pain (13). In addition, one study went so far as to take a small piece of the Achilles after injection treatment which showed better collagen structure in the PRP injected tendon than the one injected with placebo (25).
Other things PRP may be able to help include partial rotator cuff tears – (a small study has shown that PRP injection can help, but no high-level research has been done) (14). Having said that, we routinely use high-dose LP-PRP to help these patients.
Is PRP Treatment Permanent?
If the treatment is focused on arthritis, which is a degenerative disease, it’s unlikely that PRP will have permanent effects. In my clinical experience, for mild arthritis, it may provide 1-2 years of relief and in more severe arthritis only a few to 6 months of relief. In contrast, for partial tendon or ligament injuries, there may be permanent relief as the prevailing thought is that PRP may heal the tear.
Is PRP Better than Stem Cell?
PRP is different from a stem cell injection. Think of PRP as a stimulus for repair, sort of like an espresso shot for all of the local repair cells. Stem cells are like a general contractor for the repair job that can also turn into the brick and mortar needed. In general, for example, my observation is that PRP tends to work better for mild arthritis and partial ligament and tendon tears. However, bone marrow stem cells tend to be better at treating more severe arthritis and bigger tendon tears (5,6).
The upshot? PRP injection can help many different types of pain problems. However, doing some homework on what can be helped and which type of PRP is best for your condition is a good idea!
____________________________________
References:
(1) Alsousou J, Thompson M, Hulley P, Noble A, Willett K.. The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery. J Bone Joint Surg Br. 2009 Aug;91(8):987-96. doi: 10.1302/0301-620X.91B8.22546.
(2) Liangliang X, Gang L. Circulating mesenchymal stem cells and their clinical implications. Journal of Orthopaedic Translation,
Volume 2, Issue 1, 2014, Pages 1-7. https://www.sciencedirect.com/science/article/pii/S2214031X1300048X
(3) Mautner K, Malanga GA, Smith J, Shiple B, Ibrahim V, Sampson S, Bowen JE. A call for a standard classification system for future biologic research: the rationale for new PRP nomenclature. PM R. 2015 Apr;7(4 Suppl):S53-S59. doi: 10.1016/j.pmrj.2015.02.005.
(4) Dhurat R, Sukesh M. Principles and Methods of Preparation of Platelet-Rich Plasma: A Review and Author’s Perspective. J Cutan Aesthet Surg. 2014;7(4):189–197. doi:10.4103/0974-2077.150734
(5) Centeno C, Sheinkop M, Dodson E, et al. A specific protocol of autologous bone marrow concentrate and platelet products versus exercise therapy for symptomatic knee osteoarthritis: a randomized controlled trial with 2 year follow-up. J Transl Med. 2018;16(1):355. Published 2018 Dec 13. doi:10.1186/s12967-018-1736-8
(6) Centeno CJ, Al-Sayegh H, Bashir J, Goodyear S, Freeman MD. A prospective multi-site registry study of a specific protocol of autologous bone marrow concentrate for the treatment of shoulder rotator cuff tears and osteoarthritis. J Pain Res. 2015;8:269–276. Published 2015 Jun 5. doi:10.2147/JPR.S80872
(7) Xing D, Wang B, Zhang W, Yang Z, Hou Y1,2, Chen Y, Lin J. Intra-articular platelet-rich plasma injections for knee osteoarthritis: An overview of systematic reviews and risk of bias considerations. Int J Rheum Dis. 2017 Nov;20(11):1612-1630. doi: 10.1111/1756-185X.13233.
(8) Filardo G, Kon E, Buda R, Timoncini A, Di Martino A, Cenacchi A, Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2011 Apr;19(4):528-35. doi: 10.1007/s00167-010-1238-6.
(9) Xu Q, Chen J, Cheng L. Comparison of platelet rich plasma and corticosteroids in the management of lateral epicondylitis: A meta-analysis of randomized controlled trials. Int J Surg. 2019 Jul;67:37-46. doi: 10.1016/j.ijsu.2019.05.003.
(10) Singla V, Batra YK, Bharti N, Goni VG, Marwaha N. Steroid vs. Platelet-Rich Plasma in Ultrasound-Guided Sacroiliac Joint Injection for Chronic Low Back Pain. Pain Pract. 2017 Jul;17(6):782-791. doi: 10.1111/papr.12526.
(11) Monfett M, Harrison J, Boachie-Adjei K, Lutz G. Intradiscal platelet-rich plasma (PRP) injections for discogenic low back pain: an update. Int Orthop. 2016 Jun;40(6):1321-8. doi: 10.1007/s00264-016-3178-3.
(12) Wu J, Zhou J, Liu C1, Zhang J, Xiong W, Lv Y, Liu R, Wang R, Du Z, Zhang G, Liu Q. A Prospective Study Comparing Platelet-Rich Plasma and Local Anesthetic (LA)/Corticosteroid in Intra-Articular Injection for the Treatment of Lumbar Facet Joint Syndrome. Pain Pract. 2017 Sep;17(7):914-924. doi: 10.1111/papr.12544.
(13) Wang Y, Han C, Hao J, Ren Y, Wang J. Efficacy of platelet-rich plasma injections for treating Achilles tendonitis : Systematic review of high-quality randomized controlled trials. Orthopade. 2019 Sep;48(9):784-791. doi: 10.1007/s00132-019-03711-y.
(14) Sengodan VC, Kurian S, Ramasamy R. Treatment of Partial Rotator Cuff Tear with Ultrasound-guided Platelet-rich Plasma. J Clin Imaging Sci. 2017;7:32. Published 2017 Aug 14. doi:10.4103/jcis.JCIS_26_17
(15) Burchard R, Huflage H, Soost C, Richter O, Bouillon B, Graw JA. Efficiency of platelet-rich plasma therapy in knee osteoarthritis does not depend on level of cartilage damage. J Orthop Surg Res. 2019;14(1):153. Published 2019 May 24. doi:10.1186/s13018-019-1203-0
(16) Riboh JC, Saltzman BM, Yanke AB, Fortier L, Cole BJ. Effect of Leukocyte Concentration on the Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis. Am J Sports Med. 2016 Mar;44(3):792-800. doi: 10.1177/0363546515580787.
(17) Braun HJ, Kim HJ, Chu CR, Dragoo JL. The effect of platelet-rich plasma formulations and blood products on human synoviocytes: implications for intra-articular injury and therapy. Am J Sports Med. 2014;42(5):1204–1210. doi:10.1177/0363546514525593
(18) Cavallo C, Filardo G, Mariani E, Kon E1 Marcacci M, Pereira Ruiz MT, Facchini A, Grigolo B. Comparison of platelet-rich plasma formulations for cartilage healing: an in vitro study. J Bone Joint Surg Am. 2014 Mar 5;96(5):423-9. doi: 10.2106/JBJS.M.00726.
(19) Berger DR, Centeno CJ, Steinmetz NJ. Platelet lysates from aged donors promote human tenocyte proliferation and migration in a concentration-dependent manner. Bone Joint Res. 2019;8(1):32–40. Published 2019 Feb 2. doi:10.1302/2046-3758.81.BJR-2018-0164.R1
(20) Mishra AK, Skrepnik NV, Edwards SG, Jones GL, Sampson S, Vermillion DA, Ramsey ML, Karli DC, Rettig AC. Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients. Am J Sports Med. 2014 Feb;42(2):463-71. doi: 10.1177/0363546513494359.
(21) Melve GK, Ersvaer E, Eide GE, Kristoffersen EK, Bruserud Ø. Peripheral Blood Stem Cell Mobilization in Healthy Donors by Granulocyte Colony-Stimulating Factor Causes Preferential Mobilization of Lymphocyte Subsets. Front Immunol. 2018;9:845. Published 2018 May 2. doi:10.3389/fimmu.2018.00845
(22) Giusti I, Di Francesco M, D’Ascenzo S, et al. Leukocyte depletion does not affect the in vitro healing ability of platelet rich plasma. Exp Ther Med. 2018;15(4):4029–4038. doi: 10.3892/etm.2018.5887
(23) Yaşar Şirin D1, Yılmaz İ, İsyar M, Öznam K, Mahiroğulları M. Does leukocyte-poor or leukocyte-rich platelet-rich plasma applied with biopolymers have superiority to conventional platelet-rich plasma applications on chondrocyte proliferation? Eklem Hastalik Cerrahisi. 2017 Dec;28(3):142-51. doi: 10.5606/ehc.2017.55186.
(24) Krismer AM, Cabra RS, May RD, Frauchiger DA, Kohl S, Ahmad SS, Gantenbein B. Biologic response of human anterior cruciate ligamentocytes on collagen-patches to platelet-rich plasma formulations with and without leucocytes. J Orthop Res. 2017 Dec;35(12):2733-2739. doi: 10.1002/jor.23599.
(25) Alsousou J, Thompson M, Harrison P, Willett K, Franklin S. Effect of platelet-rich plasma on healing tissues in acute ruptured Achilles tendon: a human immunohistochemistry study. Lancet. 2015 Feb 26;385 Suppl 1:S19. doi: 10.1016/S0140-6736(15)60334-8.