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Comparison of wound healing effects between Oncorhynchus keta-derived polydeoxyribonucleotide (PDRN) and Oncorhynchus mykiss-derived PDRN

  • Lee, Jong Hun (Department of Plastic and Reconstructive Surgery, Eulji General Hospital, Eulji University School of Medicine) ;
  • Han, Jin Woo (Department of Plastic and Reconstructive Surgery, Eulji General Hospital, Eulji University School of Medicine) ;
  • Byun, Jin Hwan (Department of Plastic and Reconstructive Surgery, Eulji General Hospital, Eulji University School of Medicine) ;
  • Lee, Won Mi (Department of Pathology, Eulji General Hospital, Eulji University School of Medicine) ;
  • Kim, Min Ho (Eulji Medi-Bio Research Institute, Eulji University) ;
  • Wu, Wen Hao (Eulji Medi-Bio Research Institute, Eulji University)
  • Received : 2018.01.30
  • Accepted : 2018.03.15
  • Published : 2018.03.31

Abstract

Background: Polydeoxyribonucleotide (PDRN) influencing cellular growth and differentiation is recognized to promote wound healing by stimulating tissue repair. Although PDRN can be extracted from human placentas, PDRN medications have recently been extracted from the semen of trout (Oncorhynchus mykiss) and salmon (Oncorhynchus keta). The present study was designed to evaluate the wound healing effects of O. keta-derived PDRN for injection (Rejuvenex) and PDRN cream (Rejuvenex Cream) in comparison with those of O. mykiss-derived PDRN injection (Placentex). Methods: Full-thickness skin defects were made on the back of mice (n=60). The mice were divided into the following four groups according to the dressing used for the wounds: O. mykiss-derived PDRN injection group, O. keta-derived PDRN injection group, O. ketaderived PDRN cream group, and normal saline soaked dressing group (control group). We analyzed the gross findings, wound sizes, histological findings, immunohistochemistry and enzyme-linked immunosorbent assays for the groups immediately after the treatment, and again after 4, 7, and 10 days of treatment. Results: The wound healing effects were the greatest in the O. keta-derived PDRN injection and O. mykiss-derived PDRN injection groups, which showed similar scores, followed by the O. keta-derived cream and normal saline soaked dressing groups. Conclusion: The injection of PDRN extracted from O. keta was found to be as effective at healing full-thickness skin defects as the O. mykiss-derived PDRN injection, which is currently used in the clinic. Moreover, the O. keta-derived PDRN injection was also found to reduce the time required for wound healing.

Keywords

References

  1. Hunt TK, Hopf H, Hussain Z. Physiology of wound healing. Adv Skin Wound Care 2000;13(2 Suppl):6-11.
  2. Cha J, Falanga V. Stem cells in cutaneous wound healing. Clin Dermatol 2007;25:73-8. https://doi.org/10.1016/j.clindermatol.2006.10.002
  3. Valls MD, Cronstein BN, Montesinos MC. Adenosine receptor agonists for promotion of dermal wound healing. Biochem Pharmacol 2009;77:1117-24. https://doi.org/10.1016/j.bcp.2008.11.002
  4. Montesinos MC, Gadangi P, Longaker M, Sung J, Levine J, Nilsen D, et al. Wound healing is accelerated by agonists of adenosine A2 (G alpha s-linked) receptors. J Exp Med 1997;186:1615-20. https://doi.org/10.1084/jem.186.9.1615
  5. Tonello G, Daglio M, Zaccarelli N, Sottofattori E, Mazzei M, Balbi A. Characterization and quantitation of the active polynucleotide fraction (PDRN) from human placenta, a tissue repair stimulating agent. J Pharm Biomed Anal 1996;14:1555-60. https://doi.org/10.1016/0731-7085(96)01788-8
  6. Bitto A, Polito F, Altavilla D, Minutoli L, Migliorato A, Squadrito F. Polydeoxyribonucleotide (PDRN) restores blood flow in an experimental model of peripheral artery occlusive disease. J Vasc Surg 2008;48:1292-300. https://doi.org/10.1016/j.jvs.2008.06.041
  7. Bianchini P, Tellini N, Morani AM, Folloni MG. Pharmacological data on polydeoxyribonucleotide of human placenta. Int J Tissue React 1981;3:151-4.
  8. Guizzardi S, Galli C, Govoni P, Boratto R, Cattarini G, Martini D, et al. Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: a new proposal for bone tissue repair. Life Sci 2003;73:1973-83. https://doi.org/10.1016/S0024-3205(03)00547-2
  9. Sini P, Denti A, Cattarini G, Daglio M, Tira ME, Balduini C. Effect of polydeoxyribonucleotides on human fibroblasts in primary culture. Cell Biochem Funct 1999;17:107-14. https://doi.org/10.1002/(SICI)1099-0844(199906)17:2<107::AID-CBF815>3.0.CO;2-#
  10. Galeano M, Bitto A, Altavilla D, Minutoli L, Polito F, Calo M, et al. Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse. Wound Repair Regen 2008;16:208-17. https://doi.org/10.1111/j.1524-475X.2008.00361.x
  11. Bitto A, Galeano M, Squadrito F, Minutoli L, Polito F, Dye JF, et al. Polydeoxyribonucleotide improves angiogenesis and wound healing in experimental thermal injury. Crit Care Med 2008;36:1594-602. https://doi.org/10.1097/CCM.0b013e318170ab5c
  12. Thellung S, Florio T, Maragliano A, Cattarini G, Schettini G. Polydeoxyribonucleotides enhance the proliferation of human skin fibroblasts: involvement of A2 purinergic receptor subtypes. Life Sci 1999;64:1661-74. https://doi.org/10.1016/S0024-3205(99)00104-6
  13. Belletti S, Uggeri J, Gatti R, Govoni P, Guizzardi S. Polydeoxyribonucleotide promotes cyclobutane pyrimidine dimer repair in UVB-exposed dermal fibroblasts. Photodermatol Photoimmunol Photomed 2007;23:242-9. https://doi.org/10.1111/j.1600-0781.2007.00320.x
  14. Khoa ND, Montesinos MC, Reiss AB, Delano D, Awadallah N, Cronstein BN. Inflammatory cytokines regulate function and expression of adenosine A(2A) receptors in human monocytic THP-1 cells. J Immunol 2001;167:4026-32. https://doi.org/10.4049/jimmunol.167.7.4026
  15. Chan ES, Fernandez P, Merchant AA, Montesinos MC, Trzaska S, Desai A, et al. Adenosine A2A receptors in diffuse dermal fibrosis: pathogenic role in human dermal fibroblasts and in a murine model of scleroderma. Arthritis Rheum 2006;54:2632-42. https://doi.org/10.1002/art.21974
  16. Nguyen DK, Montesinos MC, Williams AJ, Kelly M, Cronstein BN. Th1 cytokines regulate adenosine receptors and their downstream signaling elements in human microvascular endothelial cells. J Immunol 2003;171:3991-8. https://doi.org/10.4049/jimmunol.171.8.3991
  17. Yegutkin GG. Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta 2008;1783:673-94. https://doi.org/10.1016/j.bbamcr.2008.01.024
  18. Montesinos MC, Desai A, Chen JF, Yee H, Schwarzschild MA, Fink JS, et al. Adenosine promotes wound healing and mediates angiogenesis in response to tissue injury via occupancy of A(2A) receptors. Am J Pathol 2002;160:2009-18. https://doi.org/10.1016/S0002-9440(10)61151-0
  19. Victor-Vega C, Desai A, Montesinos MC, Cronstein BN. Adenosine A2A receptor agonists promote more rapid wound healing than recombinant human platelet-derived growth factor (Becaplermin gel). Inflammation 2002;26:19-24. https://doi.org/10.1023/A:1014417728325
  20. Kim JY, Pak CS, Park JH, Jeong JH, Heo CY. Effects of polydeoxyribonucleotide in the treatment of pressure ulcers. J Korean Med Sci 2014;29 Suppl 3:S222-7. https://doi.org/10.3346/jkms.2014.29.S3.S222
  21. Polito F, Bitto A, Galeano M, Irrera N, Marini H, Calo M, et al. Polydeoxyribonucleotide restores blood flow in an experimental model of ischemic skin flaps. J Vasc Surg 2012;55:479-88. https://doi.org/10.1016/j.jvs.2011.07.083
  22. De Aloe G, Rubegni P, Biagioli M, Taddeucci P, Fimiani M. Skin graft donor site and use of polydeoxyribonucleotide as a treatment for skin regeneration: a randomized, controlled, double-blind, clinical trial. Wounds 2004;16:258-63.
  23. Gallant-Behm CL, Mustoe TA. Occlusion regulates epidermal cytokine production and inhibits scar formation. Wound Repair Regen 2010;18:235-44. https://doi.org/10.1111/j.1524-475X.2010.00575.x
  24. Ravenscroft MJ, Harker J, Buch KA. A prospective, randomised, controlled trial comparing wound dressings used in hip and knee surgery: Aquacel and Tegaderm versus Cutiplast. Ann R Coll Surg Engl 2006;88:18-22.

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