The Platelet Cargo: A Regenerative Cellution
Main Article Content
Abstract
Background: PRP has gained significant traction in clinical settings in recent decades and is now considered a standard procedure in fields like dermatology, cosmetology, wound healing, and orthopedics. The growth factors and other constituents present in platelets play a crucial role in using PRP.
Review results: The therapeutic value of PRP is attributed to the “soup” of factors present in granules of the platelets, namely alpha and dense granules. There is an orchestrated release of over 800 proteins that get involved in tissue regeneration. It is critical to have a harmonized approach for preparing PRP and its derivatives. More important is the development of an acellular approach as opposed to the conventional application of PRP. Platelet activation leads to degranulation which in turn releases these growth factors responsible for regeneration. The presence of RBCs in PRP preparations could be detrimental in certain therapeutic applications, therefore the use of them in an acellular form would be desirable.
Discussion: Since the activation of platelets releases several factors and is an orchestrated play of factors from the various granules present in the platelets, it makes it evident that the removal of cellular debris from the degranulated platelets and having an RBC-free environment would increase the efficacy of this regenerative therapy. An acellular approach to the preparation is rapidly gaining popularity with its ease of use and superior yields of growth factors.
Clinical Significance: PRP has been in clinical practice for the past 7 decades, and the field is rapidly evolving offering newer insights and offering newer therapeutic applications.
Article Details

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The Journals licensing terms of CC-BY-NC-SA 4.0 speaks that you are free to Share (copy and redistribute the material in any medium or format), Adapt (remix, transform, and build upon the material) under proper terms of Attribution (You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.), NonCommercial (You may not use the material for commercial purposes.), ShareAlike (If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original.) and No additional restrictions (You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.)
References
Squires JE. Indications for platelet transfusion in patients with thrombocytopenia. Blood Transfus [Internet]. 2015;13(2):221–6. Available from: http://dx.doi.org/10.2450/2014.0105-14
Andia I. Platelet-rich plasma biology. In: Alves R, Grimalt R, editors. Clinical Indications and Treatment Protocols with Platelet-Rich Plasma in Dermatology. Barcelona, Ediciones Mayo; 2016. p. 3–15.
Montero C, Santos F, Fernández S. Platelet-rich plasma: applications in dermatology. Actas Dermosifiliogr. 2015;106:104–11.
Lynch MD, Bashir S. Applications of platelet-rich plasma in dermatology: A critical appraisal of the literature. J Dermatolog Treat [Internet]. 2016;27(3):285–9. Available from: http://dx.doi.org/10.3109/09546634.2015.1094178
Andia I, Rubio-Azpeitia E, Martin JI, Abate M. Current concepts and translational uses of platelet rich plasma biotechnology. In: Biotechnology. InTech; 2015.
Li ZJ, Choi H-I, Choi D-K, Sohn K-C, Im M, Seo Y-J, et al. Autologous platelet-rich plasma: a potential therapeutic tool for promoting hair growth. Dermatol Surg [Internet]. 2012;38(7 Pt 1):1040–6. Available from: http://dx.doi.org/10.1111/j.1524-4725.2012.02394.x
Sommeling CE, Heyneman A, Hoeksema H, Verbelen J, Stillaert FB, Monstrey S. The use of platelet-rich plasma in plastic surgery: a systematic review. J Plast Reconstr Aesthet Surg [Internet]. 2013;66(3):301–11. Available from: http://dx.doi.org/10.1016/j.bjps.2012.11.009
Salazar-Álvarez AE, Riera-Del-Moral LF, García-Arranz M, Alvarez-García J, Concepción-Rodriguez NA. Riera-de-Cubas L: Use of platelet-rich plasma in the healing of chronic ulcers of the lower extremity. Actas Dermosifiliogr. 2014;105:597–604.
Picard F, Hersant B, Bosc R, Meningaud JP. Should we use platelet-rich plasma as an adjunct therapy to treat “acute wounds”, “burns”, and “laser therapies”: a review and a proposal of a quality criteria checklist for further studies. Wound Repair Regen. 2015;23:163–70.
Cobos R, Aizpuru F, Parraza N, Anitua E, Orive G. Effectiveness and efficiency of platelet rich plasma in the treatment of diabetic ulcers. Curr Pharm Biotechnol [Internet]. 2015;16(7):630–4. Available from: http://dx.doi.org/10.2174/138920101607150427111926
Sclafani AP, Azzi J. Platelet preparations for use in facial rejuvenation and wound healing: A critical review of current literature. Aesthetic Plast Surg [Internet]. 2015;39(4):495–505. Available from: http://dx.doi.org/10.1007/s00266-015-0504-x
Montero C. Clinical Indications and Treatment Protocols with Platelet-Rich Plasma in Dermatology. Alves R, Grimalt R, editors. Barcelona, Ediciones Mayo; 2016.
Kim DH, Je YJ, Kim CD, Lee YH, Seo YJ, Lee JH, et al. Can platelet-rich plasma be used for skin rejuvenation? Evaluation of effects of platelet-rich plasma on human dermal fibroblast. Ann Dermatol [Internet]. 2011;23(4):424–31. Available from: http://dx.doi.org/10.5021/ad.2011.23.4.424
Sclafani AP, McCormick SA. Induction of dermal collagenesis, angiogenesis, and adipogenesis in human skin by injection of platelet-rich fibrin matrix. Arch Facial Plast Surg [Internet]. 2012;14(2):132–6. Available from: http://dx.doi.org/10.1001/archfaci.2011.784
Alves R, Grimalt R, editors. Lola Bou Camps: PRP in cosmetic dermatology. In: Clinical Indications and Treatment Protocols with Platelet-Rich Plasma in Dermatology. Barcelona, Ediciones Mayo; 2016. p. 45–57.
Girão L. PRP and other applications in dermatology. In: Alves R, Grimalt R, editors. Clinical Indications and Treatment Protocols with Platelet-Rich Plasma in Dermatology. Barcelona, Ediciones Mayo; 2016. p. 73–8.
Giordano S, Romeo M, Lankinen P. Platelet-rich plasma for androgenetic alopecia: Does it work? Evidence from meta analysis. J Cosmet Dermatol [Internet]. 2017;16(3):374–81. Available from: http://dx.doi.org/10.1111/jocd.12331
Harvey JW. The feline blood film: 2. Leukocyte and platelet morphology. J Feline Med Surg [Internet]. 2017;19(7):747–57. Available from: http://dx.doi.org/10.1177/1098612x17706471
Becker RC, Sexton T, Smyth SS. Translational implications of platelets as vascular first responders. Circ Res [Internet]. 2018;122(3):506–22. Available from: http://dx.doi.org/10.1161/CIRCRESAHA.117.310939
Uchimido R, Schmidt EP, Shapiro NI. The glycocalyx: a novel diagnostic and therapeutic target in sepsis. Crit Care [Internet]. 2019;23(1):16. Available from: http://dx.doi.org/10.1186/s13054-018-2292-6
Koseoglu S, Flaumenhaft R. Advances in platelet granule biology. Curr Opin Hematol [Internet]. 2013;20(5):464–71. Available from: http://dx.doi.org/10.1097/moh.0b013e3283632e6b
Thon JN, Peters CG, Machlus KR, Aslam R, Rowley J, Macleod H, et al. T granules in human platelets function in TLR9 organization and signaling. J Cell Biol [Internet]. 2012;198(4):561–74. Available from: http://dx.doi.org/10.1083/jcb.201111136
Thon JN, Italiano JE. Platelets: production, morphology and ultrastructure. Handb Exp Pharmacol [Internet]. 2012;(210):3–22. Available from: http://dx.doi.org/10.1007/978-3-642-29423-5_1
Chen CH, Lo RW, Urban D, Pluthero FG, Kahr WHA. Α-granule biogenesis: From disease to discovery. Platelets [Internet]. 2017;28(2):147–54. Available from: http://dx.doi.org/10.1080/09537104.2017.1280599
Ambrosio AL, Di Pietro SM. Storage pool diseases illuminate platelet dense granule biogenesis. Platelets [Internet]. 2017;28(2):138–46. Available from: http://dx.doi.org/10.1080/09537104.2016.1243789
Farndale RW, Hargreaves PG, Dietrich JL, Keogh RJ. Measurement of platelet arachidonic acid metabolism. Methods Mol Biol [Internet]. 2004;272:121–33. Available from: http://dx.doi.org/10.1385/1-59259-782-3:121
King SM, Reed GL. Development of platelet secretory granules. Semin Cell Dev Biol [Internet]. 2002;13(4):293–302. Available from: http://dx.doi.org/10.1016/s1084952102000599
Blair P, Flaumenhaft R. Platelet alpha-granules: basic biology and clinical correlates. Blood Rev [Internet]. 2009;23(4):177–89. Available from: http://dx.doi.org/10.1016/j.blre.2009.04.001
McNicol A, Israels SJ. Platelet dense granules: structure, function and implications for haemostasis. Thromb Res [Internet]. 1999;95(1):1–18. Available from: http://dx.doi.org/10.1016/s0049-3848(99)00015-8
Ghoshal K, Bhattacharyya M. Overview of platelet physiology: its hemostatic and nonhemostatic role in disease pathogenesis. ScientificWorldJournal [Internet]. 2014;2014:781857. Available from: http://dx.doi.org/10.1155/2014/781857
Ozaki Y, Suzuki-Inoue K, Inoue O. Platelet receptors activated via mulitmerization: glycoprotein VI, GPIb-IX-V, and CLEC-2. J Thromb Haemost [Internet]. 2013;11 Suppl 1:330–9. Available from: http://dx.doi.org/10.1111/jth.12235
Thomas MR, Storey RF. The role of platelets in inflammation. Thromb Haemost [Internet]. 2015;114(3):449–58. Available from: http://dx.doi.org/10.1160/TH14-12-1067
Yadav S, Storrie B. The cellular basis of platelet secretion: Emerging structure/function relationships. Platelets [Internet]. 2017;28(2):108–18. Available from: http://dx.doi.org/10.1080/09537104.2016.1257786
Jobling L, Eyre L. Haemostasis, blood platelets and coagulation. Anaesth Intensive Care Med [Internet]. 2013;14(2):51–3. Available from: http://dx.doi.org/10.1016/j.mpaic.2012.12.001
Fortier LA, Barker JU, Strauss EJ, McCarrel TM, Cole BJ. The role of growth factors in cartilage repair. Clin Orthop Relat Res [Internet]. 2011;469(10):2706–15. Available from: http://dx.doi.org/10.1007/s11999-011-1857-3
Wu MY, Hill CS. Tgf-beta superfamily signaling in embryonic development and homeostasis. Dev Cell [Internet]. 2009;16(3):329–43. Available from: http://dx.doi.org/10.1016/j.devcel.2009.02.012
Ellman MB, An HS, Muddasani P, Im H-J. Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis. Gene [Internet]. 2008;420(1):82–9. Available from: http://dx.doi.org/10.1016/j.gene.2008.04.019
Kurth T, Hedbom E, Shintani N, Sugimoto M, Chen FH, Haspl M, et al. Chondrogenic potential of human synovial mesenchymal stem cells in alginate. Osteoarthritis Cartilage [Internet]. 2007;15(10):1178–89. Available from: http://dx.doi.org/10.1016/j.joca.2007.03.015
Lee CH, Cook JL, Mendelson A, Moioli EK, Yao H, Mao JJ. Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet [Internet]. 2010;376(9739):440–8. Available from: http://dx.doi.org/10.1016/S0140-6736(10)60668-X
Lotz M, Rosen F, McCabe G, Quach J, Blanco F, Dudler J, et al. Interleukin 1 beta suppresses transforming growth factor-induced inorganic pyrophosphate (PPi) production and expression of the PPi-generating enzyme PC-1 in human chondrocytes. Proc Natl Acad Sci U S A [Internet]. 1995;92(22):10364–8. Available from: http://dx.doi.org/10.1073/pnas.92.22.10364
Fan J, Gong Y, Ren L, Varshney RR, Cai D, Wang D-A. In vitro engineered cartilage using synovium-derived mesenchymal stem cells with injectable gellan hydrogels. Acta Biomater [Internet]. 2010;6(3):1178–85. Available from: http://dx.doi.org/10.1016/j.actbio.2009.08.042
Cheng M-T, Liu C-L, Chen T-H, Lee OK. Optimization of culture conditions for stem cells derived from human anterior cruciate ligament and bone marrow. Cell Transplant [Internet]. 2014;23(7):791–803. Available from: http://dx.doi.org/10.3727/096368912X666430
Kang and others, Five-year results of intracoronary infusion of the mobilized peripheral blood stem cells by granulocyte colony-stimulating factor in patients with myocardial infarction. European Heart Journal. 2012;33(24):3062–9.
Popescu MN, Iliescu MG, Beiu C. “Autologous Platelet-Rich Plasma Efficacy in the Field of Regenerative Medicine: Product and Quality Control. Hindawi BioMed Research International. 2021;2021.
Ojea-Perez AM, Acebes-Huerta A. Implementation of a closed platelet-rich-plasma preparation method using the local blood bank infrastructure at the Principality of Asturias (Spain): back to basic methodology and a demographics perspective after 1 year. Transfusion and Apheresis Science. 2019;58(5):701–4.
Božič D, Vozel D, Hočevar M, Jeran M, Jan Z, Pajnič M, et al. Enrichment of plasma in platelets and extracellular vesicles by the counterflow to erythrocyte settling. Platelets [Internet]. 2022;33(4):592–602. Available from: http://dx.doi.org/10.1080/09537104.2021.1961716
Pulcini S, Merolle L, Marraccini C. Apheresis platelet rich-plasma for regenerative medicine: an in vitro study on osteogenic potential. International Journal of Molecular Sciences. 22(16).
Shimojo AA, Perez AG, Galdames SE, Brissac IC, Santana MH. Stabilization of porous chitosan improves the performance of its association with platelet-rich plasma as a composite scaffold. Materials Science and Engineering; C. 2016;60:538–46.
Nandanwar M, Sharma V, Karade A, Sharma A, Kansagara A, Sakhalkar U, et al. Assessment of wound healing efficacy of Growth Factor Concentrate (GFC) in non-diabetic and diabetic Sprague Dawley rats. J Diabetes Metab Disord [Internet]. 2021;20(2):1583–95. Available from: http://dx.doi.org/10.1007/s40200-021-00906-z
Patil C, Sthalekar B, Agarwal M, Sharma V, Desai M. Prospective study of growth factor concentrate therapy for treatment of melasma. Indian Dermatol Online J [Internet]. 2021;12(4):549. Available from: http://dx.doi.org/10.4103/idoj.idoj_750_20
Mastim MA, Borana C, Shah V, Dhadiwal R, Malhotra R, Kidiyoor B, et al. An open-labeled randomized prospective multi-center study to evaluate the efficacy and safety of intra-articular injection of OSSINEXTTM, an autologous growth factor concentrate (AGFC) compared to hyaluronic acid (HA) in knee osteoarthritis. Cureus [Internet]. 2022;14(11):e31058. Available from: http://dx.doi.org/10.7759/cureus.31058
Anuka S, Vijay S, Parag RG, Arefa P, Ulka S, Mudit K. Prospective Trial of Osteoarthritis Knee Treatment with Growth Factor Concentrate Therapy for its Efficacy and Safety: ‘Progress. Trial. :2022–4.
Repsold L, Joubert AM. Eryptosis: An erythrocyte’s suicidal type of cell death. Biomed Res Int [Internet]. 2018;2018:1–10. Available from: http://dx.doi.org/10.1155/2018/9405617