It is apparent that whilst many reports are available regarding platelet-rich-plasma (PRP), the larger majority of these have been mainly focussed on autologous sources, and for good reason. Issues relating to allogenic source have been consciously avoided owing to concerns of cross infectivity and immune rejection. However, this topic today is now revisited and is of interest since progress over the year has demonstrated its safety, efficacy, and its abundance of supply. The present systematic review was thus conducted to elucidate advances made in this area, with the aim to provide a wider and deeper understanding of studies relevant to the application of allogenic PRP in cartilage repair. Literature search was conducted systematically using Medline, ProQuest, Web of Science, Cochrane Central Register of Controlled Trials, and snowballing searching strategy to identify relevant studies using topic-specific keywords in various combinations including “allogenic, platelet, rich, plasma” OR “allogeneic, platelet, rich, plasma” OR “allogenic platelet-rich plasma” OR “allogeneic platelet-rich plasma” OR “allogenic platelet rich plasma” OR “allogeneic platelet rich plasma” AND cartilage OR chondrocytes OR synoviocytes OR stem cells. Studies that used allogenic PRP in an attempt to facilitate cartilage repair were included. The risk of bias was assessed by the SYRCLE’s checklist. Of 206 studies identified, 12 were found eligible. Only those studies that are clearly related and specific to allogenic PRP were included. Of these, nine investigated the efficacy of allogenic PRP in animal models, while three articles employed an in vitro model. Allogenic PRP promotes cell proliferation, cartilage matrix production, and anti-inflammatory effects in vitro. The in vivo studies reported histological evidence of significant acceleration of cartilage repair in treated animals. Despite several conflicting findings, all studies agreed that allogenic PRP is safe and potentially efficacious for cartilage repair, with the advantages of allogenic sources apparent.

1.
Andonegui G, Kerfoot SM, McNagny K, Ebbert KVJ, Patel KD, Kubes P. Platelets express functional Toll-like receptor-4. Blood. 2005;106(7):2417–23.
2.
Araya N, Miyatake K, Tsuji K, Katagiri H, Nakagawa Y, Hoshino T, et al. Intra-articular injection of pure platelet-rich plasma is the most effective treatment for joint pain by modulating synovial inflammation and calcitonin gene-related peptide expression in a rat arthritis model. Am J Sports Med. 2020;48(8):2004–12.
3.
Arnoczky SP, Sheibani-Rad S. The basic science of platelet-rich plasma (PRP): what clinicians need to know. Sports Med Arthrosc. 2013;21(4):180–5.
4.
Bartolotti I, Roseti L, Petretta M, Grigolo B, Desando G. A roadmap of in vitro models in osteoarthritis: a focus on their biological relevance in regenerative medicine. J Clin Med. 2021;10(9):1920.
5.
Becchi C, Al Malyan M, Fabbri LP, Marsili M, Boddi V, Boncinelli S. Mean platelet volume trend in sepsis: is it a useful parameter?Minerva Anestesiol. 2006;72(9):749–56.
6.
Belmont PJ, Goodman GP, Kusnezov NA, Magee C, Bader JO, Waterman BR, et al. Postoperative myocardial infarction and cardiac arrest following primary total knee and hip arthroplasty: rates, risk factors, and time of occurrence. J Bone Joint Surg Am. 2014;96(24):2025–31.
7.
Bennell KL, Paterson KL, Metcalf BR, Duong V, Eyles J, Kasza J, et al. Effect of intra-articular platelet-rich plasma verus placebo injection on pain and medial tibial cartilage volume in patients with knee osteoarthritis: the RESTORE randomized clinical trial. JAMA. 2021;326(20):2021–30.
8.
Bottegoni C, Dei Giudici L, Salvemini S, Chiurazzi E, Bencivenga R, Gigante A. Homologous platelet-rich plasma for the treatment of knee osteoarthritis in selected elderly patients: an open-label, uncontrolled, pilot study. Ther Adv Musculoskelet Dis. 2016;8(2):35–41.
9.
Carmona JU, Ríos DL, López C, Álvarez ME, Pérez JE, Bohórquez ME. In vitro effects of platelet-rich gel supernatants on histology and chondrocyte apoptosis scores, hyaluronan release and gene expression of equine cartilage explants challenged with lipopolysaccharide. BMC Vet Res. 2016;12(1):135–13.
10.
Carneiro Md O, Barbieri CH, Barbieri Neto J. Platelet-rich plasma gel promotes regeneration of articular cartilage in knees of sheeps. Acta Ortop Bras. 2013;21(2):80–6.
11.
Cavallo C, Roffi A, Grigolo B, Mariani E, Pratelli L, Merli G, et al. Platelet-rich plasma: the choice of activation method affects the release of bioactive molecules. Biomed Res Int. 2016;2016:6591717.
12.
Chahla J, Cinque ME, Piuzzi NS, Mannava S, Geeslin AG, Murray IR, et al. A call for standardization in platelet-rich plasma preparation protocols and composition reporting: a systematic review of the clinical orthopaedic literature. J Bone Joint Surg Am. 2017;99(20):1769–79.
13.
Chapman LM, Aggrey AA, Field DJ, Srivastava K, Ture S, Yui K, et al. Platelets present antigen in the context of MHC class I. J Immunol. 2012;189(2):916–23.
14.
Chouhan DK, Dhillon MS, Patel S, Bansal T, Bhatia A, Kanwat H. Multiple platelet-rich plasma injections versus single platelet-rich plasma injection in early osteoarthritis of the knee: an experimental study in a Guinea pig model of early knee osteoarthritis. Am J Sports Med. 2019;47(10):2300–7.
15.
Cole BJ, Karas V, Hussey K, Pilz K, Fortier LA, Fortier LA. Hyaluronic acid versus platelet-rich plasma: a prospective, double-blind randomized controlled trial comparing clinical outcomes and effects on intra-articular biology for the treatment of knee osteoarthritis. Am J Sports Med. 2017;45(2):339–46.
16.
Di Martino A, Di Matteo B, Papio T, Tentoni F, Selleri F, Cenacchi A, et al. Platelet-rich plasma versus hyaluronic acid injections for the treatment of knee osteoarthritis: results at 5 years of a double-blind, randomized controlled trial. Am J Sports Med. 2019;47(2):347–54.
17.
Di Martino A, Boffa A, Andriolo L, Romandini I, Altamura SA, Cenacchi A, et al. Leukocyte-rich versus leukocyte-poor platelet-rich plasma for the treatment of knee osteoarthritis: a double-blind randomized trial. Am J Sports Med. 2022;50(3):609–17.
18.
El-Gohary R, Diab A, El-Gendy H, Fahmy H, Gado KH. Using intra-articular allogenic lyophilized growth factors in primary knee osteoarthritis: a randomized pilot study. Regen Med. 2021;16(2):113–5.
19.
Elder S, Thomason J. Effect of platelet-rich plasma on chondrogenic differentiation in three-dimensional culture. Open Orthop J. 2014;8(1):78–84.
20.
Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med. 2009;37(11):2259–72.
21.
Freitas NPP, Maior MMMS, Silva BAP, Bezerra MRL, Nunes JF, Neto GS, et al. In-vitro production and pre-validation of lyophilized canine platelet-rich plasma for therapeutic use. Pesq Vet Bras. 2021;41.
22.
Garbin LC, McIlwraith CW, Frisbie DD. Evaluation of allogeneic freeze-dried platelet lysate in cartilage exposed to interleukin 1-β in vitro. BMC Vet Res. 2019;15(1):1–10.
23.
Garbin LC, Contino EK, Olver CS, Frisbie DD. A safety evaluation of allogeneic freeze-dried platelet-rich plasma or conditioned serum compared to autologous frozen products equivalents in equine healthy joints. BMC Vet Res. 2022;18(1):141.
24.
Gato-Calvo L, Magalhaes J, Ruiz-Romero C, Blanco FJ, Burguera EF. Platelet-rich plasma in OA treatment: review of current evidence. Ther Adv Vaccin. 2019;10:1–18.
25.
GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204–22.
26.
Glynn LG, Mustafa A, Casey M, Krawczyk J, Blom J, Galvin R, et al. Platelet-rich plasma (PRP) therapy for knee arthritis: a feasibility study in primary care. Pilot Feasibility Stud. 2018;4(1):93.
27.
Gordon JL. Platelet in biology and pathology. North Holl Publ; 1976. Vol. 1.
28.
Guclu E, Durmaz Y, Karabay O. Effect of severe sepsis on platelet count and their indices. Afr Health Sci. 2013;13(2):333–8.
29.
Guo L, Shen S, Rowley JW, Tolley ND, Jia W, Manne BK, et al. Platelet MHC class I mediates CD8+ T-cell suppression during sepsis. Blood. 2021;138(5):401–16.
30.
Han SS, Baker BL. The ultrastructural of megakaryocytes and blood platelets in the rat spleen. Anat Rec. 1964;149:251–67.
31.
He Y, Li Z, Alexander PG, Ocasio-Nieves BD, Yocum L, Lin H, et al. Pathogenesis of osteoarthritis: risk factors, regulatory pathways in chondrocytes, and experimental models. Biology. 2020;9(8):194.
32.
Hooijmans CR, Rovers MM, De Vries RBM, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol. 2014;14(1):43–9.
33.
Hsu H, Siwiec RM. Knee osteoarthritis. Treasure Island (FL): StatPearls Publishing; 2022.
34.
Huang J, Li X, Shi X, Zhu M, Wang J, Huang S, et al. Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting. J Hematol Oncol. 2019;12(1):1–22.
35.
Huang GS, Peng YJ, Hwang DW, Lee HS, Chang YC, Chiang SW, et al. Assessment of the efficacy of intra-articular platelet rich plasma treatment in an ACLT experimental model by dynamic contrast enhancement MRI of knee subchondral bone marrow and MRI T2* measurement of articular cartilage. Osteoarthr Cartil. 2021;29(5):718–27.
36.
Jalali Jivan S, Monzavi SM, Zargaran B, Hamidi Alamdari D, Tavakol Afshari J, Etemad-Rezaie A, et al. Comparative analysis of the effectiveness of intra-articular injection of platelet-rich plasma versus hyaluronic acid for knee osteoarthritis: results of an open-label trial. Arch Bone Jt Surg. 2021;9(5):487–95.
37.
Jubert NJ, Rodríguez L, Reverté-Vinaixa MM, Navarro A. Platelet-rich plasma injections for advanced knee osteoarthritis: a prospective, randomized, double-blinded clinical trial. Orthop J Sport Med. 2017;5(2):1–11.
38.
Kanwat H, Singh DM, Kumar CD, Alka B, Biman S, Aman H. The effect of intra-articular allogenic platelet rich plasma in Dunkin-Hartley Guinea pig model of knee osteoarthritis. Muscle Ligaments Tendons J. 2017;7(3):426–34.
39.
Kaufman RM, Djulbegovic B, Gernsheimer T, Kleinman S, Tinmouth AT, Capocelli KE, et al. Platelet transfusion: a clinical practice guideline from the AABB. Ann Intern Med. 2015;162(3):205–13.
40.
Khan AI, Anwer F. Platelet Transfusion. StatPearls Publishing; 2022.
41.
Lacci KM, Dardik A. Platelet-rich plasma: support for its use in wound healing. Yale J Biol Med. 2010;83(1):1–9.
42.
Lalmohamed A, Vestergaard P, Klop C, Grove EL, de Boer A, Leufkens HGM, et al. Timing of acute myocardial infarction in patients undergoing total hip or knee replacement: a nationwide cohort study. Arch Intern Med. 2012;172(16):1229–35.
43.
Lee JW, Kwon OH, Kim TK, Cho YK, Choi KY, Chung HY, et al. Platelet-rich plasma: quantitative assessment of growth factor levels and comparative analysis of activated and inactivated groups. Arch Plast Surg. 2013;40(5):530–5.
44.
Lee JS, Guo P, Klett K, Hall M, Sinha K, Ravuri S, et al. VEGF-attenuated platelet-rich plasma improves therapeutic effect on cartilage repair. Biomater Sci. 2022;10(9):2172–81.
45.
Li H, Li B. PRP as a new approach to prevent infection: preparation and in vitro antimicrobial properties of PRP. J Vis Exp. 2013;74:50351–7.
46.
Lohan P, Treacy O, Lynch K, Barry F, Murphy M, Griffin MD, et al. Culture expanded primary chondrocytes have potent immunomodulatory properties and do not induce an allogeneic immune response. Osteoarthritis Cartilage. 2016;24(3):521–33.
47.
Lu N, Misra D, Neogi T, Choi HK, Zhang Y. Total joint arthroplasty and the risk of myocardial infarction: a general population, propensity score-matched cohort study. Arthritis Rheumatol. 2015;67(10):2771–9.
48.
Maouia A, Rebetz J, Kapur R, Semple JW. The immune nature of platelets revisited. Transfu Med Rev. 2020;34(4):209–20.
49.
Marlovits S, Mousavi M, Gäbler C, Erdös J, Vécsei V. A new simplified technique for producing platelet-rich plasma: a short technical note. Eur Spine J. 2004;13(Suppl 1):102–6.
50.
Marx RE. Platelet-Rich Plasma (PRP): what is PRP and what is not PRP?Implant Dent. 2001;10(4):225–8.
51.
Mezger M, Nording H, Sauter R, Graf T, Heim C, von Bubnoff N, et al. Platelets and immune responses during thromboinflammation. Front Immunol. 2019;10:1731.
52.
Middleton KK, Barro V, Muller B, Terada S, Fu FH. Evaluation of the effects of platelet-rich plasma (PRP) therapy involved in the healing of sports-related soft tissue injuries. Iowa Orthop J. 2012;32:150–63.
53.
Milano G, Sanna Passino E, Deriu L, Careddu G, Manunta L, Manunta A, et al. The effect of platelet rich plasma combined with microfractures on the treatment of chondral defects: an experimental study in a sheep model. Osteoarthritis Cartilage. 2010;18(7):971–80.
54.
Morris VK, Spraker HL, Howard SC, Ware RE, Reiss UM. Severe thrombocytopenia with iron deficiency anemia. Pediatr Hematol Oncol. 2010;27(5):413–9.
55.
National Blood Centre and Malaysian Blood Transfusion Society. Handbook on clinical use of blood. 3rd ed.; 2020.
56.
Nie L, Zhao K, Ruan J, Xue J. Effectiveness of platelet-rich plasma in the treatment of knee osteoarthritis: a meta-analysis of randomized controlled clinical trials. Orthop J Sport Med. 2021;9(3):2325967120973284.
57.
Niroomand Sadabad H, Behzadifar M, Arasteh F, Behzadifar M, Dehghan HR. Efficacy of platelet-rich plasma versus hyaluronic acid for treatment of knee osteoarthritis: a systematic review and meta-analysis. Electron Physician. 2016;8(3):2115–22.
58.
Ponomarev ED. Fresh evidence for platelets as neuronal and innate immune cells: their role in the activation, differentiation, and deactivation of Th1, Th17, and tregs during tissue inflammation. Front Immunol. 2018;9:406–7.
59.
Raeissadat SA, Rayegani SM, Ahangar AG, Abadi PH, Mojgani P, Ahangar OG. Efficacy of intra-articular injection of a newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid on pain and function of patients with knee osteoarthritis: a single-blinded randomized clinical trial. Clin Med Insights Arthritis Musculoskelet Disord. 2017;10:1179544117733452.
60.
Rayes J, Bourne JH, Brill A, Watson SP. The dual role of platelet-innate immune cell interactions in thrombo-inflammation. Res Pract Thromb Haemost. 2020;4(1):23–35.
61.
Rikkers M, Dijkstra K, Terhaard BF, Admiraal J, Levato R, Malda J, et al. Platelet-rich plasma does not inhibit inflammation or promote regeneration in human osteoarthritic chondrocytes in vitro despite increased proliferation. Cartilage. 2021;13(2 Suppl):991S–1003S.
62.
Robinson WH, Lepus CM, Wang Q, Raghu H, Mao R, Lindstrom TM, et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016;12(10):580–92.
63.
Rossaint J, Zarbock A. Platelets in leucocyte recruitment and function. Cardiovasc Res. 2015;107(3):386–95.
64.
Rossaint J, Margraf A, Zarbock A. Role of platelets in leukocyte recruitment and resolution of inflammation. Front Immunol. 2018;9:2712–3.
65.
Rowley JW, Oler AJ, Tolley ND, Hunter BN, Low EN, Nix DA, et al. Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes. Blood. 2011;118(14):101–11.
66.
Salvalaggio PR, Graff RJ, Pinsky B, Schnitzler MA, Takemoto SK, Burroughs TE, et al. Crossmatch testing in kidney transplantation: patterns of practice and associations with rejection and graft survival. Saudi J Kidney Dis Transpl. 2009;20(4):577–89.
67.
Semple JW, Freedman J. Platelets and innate immunity. Cell Mol Life Sci. 2010;67(4):499–511.
68.
Semple JW, Italiano JE, Freedman J. Platelets and the immune continuum. Nat Rev Immunol. 2011;11(4):264–74.
69.
Shen L, Yuan T, Chen S, Xie X, Zhang C. The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials. J Orthop Surg Res. 2017;12(1):16–2.
70.
Silva LQ, Huber SC, Montalvão SADL, Bassora FDS, De Paula EV, Annichino-Bizzacchi J. Platelet activation is not crucial for Platelet-Rich Plasma (PRP), when used as autologous therapeutic product, and could be lyophilized without any growth factor loss. Blood. 2016;128(22):2639.
71.
Slimi F, Zribi W, Trigui M, Amri R, Gouiaa N, Abid C, et al. The effectiveness of platelet-rich plasma gel on full-thickness cartilage defect repair in a rabbit model. Bone Joint Res. 2021;10(3):192–202.
72.
Spreafico A, Chellini F, Frediani B, Bernardini G, Niccolini S, Serchi T, et al. Biochemical investigation of the effects of human platelet releasates on human articular chondrocytes. J Cell Biochem. 2009;108(5):1153–65.
73.
Stefani RM, Halder SS, Estell EG, Lee AJ, Silverstein AM, Sobczak E, et al. A functional tissue-engineered synovium model to study osteoarthritis progression and treatment. Tissue Eng Part A. 2019;25(7–8):538–53.
74.
Steller D, Herbst N, Pries R, Juhl D, Hakim SG. Impact of incubation method on the release of growth factors in non-Ca 2+ -activated PRP, Ca 2+ -activated PRP, PRF and A-PRF. J Craniomaxillofac Surg. 2019;47(2):365–72.
75.
Stukelj R, Schara K, Bedina-Zavec A, Sustar V, Pajnic M, Paden L, et al. Effect of shear stress in the flow through the sampling needle on concentration of nanovesicles isolated from blood. Eur J Pharm Sci. 2017;98:17–29.
76.
Sumner SM, Naskou MC, Thoresen M, Copland I, Peroni JF. Platelet lysate obtained via plateletpheresis performed in standing and awake equine donors. Transfusion. 2017;57(7):1755–62.
77.
Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med. 2011;39(10):2135–40.
78.
Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, et al. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med. 2014;42(1):35–41.
79.
Taniguchi Y, Yoshioka T, Kanamori A, Aoto K, Sugaya H, Yamazaki M. Intra-articular platelet-rich plasma (PRP) injections for treating knee pain associated with osteoarthritis of the knee in the Japanese population: A phase I and IIa clinical trial. Nagoya J Med Sci. 2018;80(1):39–51.
80.
Vahabi S, Yadegari Z, Mohammad-Rahimi H. Comparison of the effect of activated or non-activated PRP in various concentrations on osteoblast and fibroblast cell line proliferation. Cell Tissue Bank. 2017;18(3):347–53.
81.
van Gils JM, Zwaginga JJ, Hordijk PL. Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases. J Leukoc Biol. 2009;85(2):195–204.
82.
Vinod E, Vinod Francis D, Manickam Amirtham S, Sathishkumar S, Boopalan PRJVC. Allogeneic platelet rich plasma serves as a scaffold for articular cartilage derived chondroprogenitors. Tissue Cell. 2019;56:107–13.
83.
Wang L, Zhao L, Shen L, Fang Q, Yang Z, Wang R, et al. Comparison of the effects of autologous and allogeneic purified platelet-rich plasma on cartilage damage in a rabbit model of knee osteoarthritis. Front Surg. 2022;9:911468.
84.
Xu Z, Luo J, Huang X, Wang B, Zhang J, Zhou A. Efficacy of platelet-rich plasma in pain and self-report function in knee osteoarthritis: a best-evidence synthesis. Am J Phys Med Rehabil. 2017;96(11):793–800.
85.
Zhou Y, Yasumoto A, Lei C, Huang CJ, Kobayashi H, Wu Y, et al. Intelligent classification of platelet aggregates by agonist type. Elife. 2020;9:e52938.
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