Polydeoxyribonucleotides Improve Diabetic Wound Healing in Mouse Animal Model for Experimental Validation
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Background: Wound healing mechanisms is believed to have effects similar to wound healing disorders in diabetic patients, including abnormal inflammatory cells, angiogenesis disorders, and reduced collagen synthesis. Therefore, reestablishment of structural and promoted angiogenesis could be beneficial to promote wound healing process. Objective: Therefore, we investigated whether the polydeoxyribonucleotide (PDRN) that was self-production in Korea, could be useful as an intradermal injection for promoting wound healing. Also, we validate for wound healing effect of PDRN using healing-impaired (db/db) mice. Methods: In this study, we confirmed the effects of PDRN by creating wound models in in vitro and in vivo model. Using an in vitro wound healing assay, we observed that PDRN stimulated closure of wounded monolayers of human fibroblast cells. PDRN (8.25 mg/ml) or phosphate-buffered saline (0.9% NaCl) was injected once daily into the dermis adjacent to the wound for 12 days after skin injury. Results: Time course observations revealed that mice treated with PDRN showed accelerated wound closure and epidermal and dermal regeneration, enhanced angiogenesis. The wound area and depth decreased at 3, 6, 9, and 12 days after skin injury. Histological evaluation showed an increase of vascular endothelial growth factor, CD31, and collagen fibers in the PDRN group compared with the control group, indicating that PDRN was effective in the treatment of delayed wound healing caused by diabetes. Conclusion: This study suggests that our PDRN has a wound healing effect in transgenic animal models with cells and diabetes through angiogenesis.
Abstract
Background: Wound healing mechanisms is believed to have effects similar to wound healing disorders in diabetic patients, including abnormal inflammatory cells, angiogenesis disorders, and reduced collagen synthesis. Therefore, reestablishment of structural and promoted angiogenesis could be beneficial to promote wound healing process. Objective: Therefore, we investigated whether the polydeoxyribonucleotide (PDRN) that was self-production in Korea, could be useful as an intradermal injection for promoting wound healing. Also, we validate for wound healing effect of PDRN using healing-impaired (db/db) mice. Methods: In this study, we confirmed the effects of PDRN by creating wound models in in vitro and in vivo model. Using an in vitro wound healing assay, we observed that PDRN stimulated closure of wounded monolayers of human fibroblast cells. PDRN (8.25 mg/ml) or phosphate-buffered saline (0.9% NaCl) was injected once daily into the dermis adjacent to the wound for 12 days after skin injury. Results: Time course observations revealed that mice treated with PDRN showed accelerated wound closure and epidermal and dermal regeneration, enhanced angiogenesis. The wound area and depth decreased at 3, 6, 9, and 12 days after skin injury. Histological evaluation showed an increase of vascular endothelial growth factor, CD31, and collagen fibers in the PDRN group compared with the control group, indicating that PDRN was effective in the treatment of delayed wound healing caused by diabetes. Conclusion: This study suggests that our PDRN has a wound healing effect in transgenic animal models with cells and diabetes through angiogenesis.
참고문헌 (26)
- Oryan A, "Effects of insulin on wound healing : a review of animal and human evidences", Life Sci, 174, pp.59~67 (2017)
- Galeano M, "Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse", Wound Repair Regen, 16, pp.208~217 (2008)
- Jeong W, "Scar prevention and enhanced wound healing induced by polydeoxyribonucleotide in a rat incisional wound-healing model", Int J Mol Sci, 18, pp.E1698~ (2017)
- Barrientos S, "Growth factors and cytokines in wound healing", Wound Repair Regen, 16, pp.585~601 (2008)
- Ebrahimian TG, "Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing", Arterioscler Thromb Vasc Biol, 29, pp.503~510 (2009)
- Smiell JM, "Efficacy and safety of becaplermin(recombinant human platelet-derived growth factor-BB)in patients with nonhealing, lower extremity diabetic ulcers : a combined analysis of four randomized studies", Wound Repair Regen, 7, pp.335~346 (1999)
- Han G, "Chronic wound healing : a review of current management and treatments", Adv Ther, 34, pp.599~610 (2017)
- Cianfarani F, "Placenta growth factor in diabetic wound healing : altered expression and therapeutic potential", Am J Pathol, 169, pp.1167~1182 (2006)
- Powell RJ, "Safety and efficacy of patient specific intramuscular injection of HGF plasmid gene therapy on limb perfusion and wound healing in patients with ischemic lower extremity ulceration : results of the HGF-0205 trial", J Vasc Surg, 52, pp.1525~1530 (2010)
- Altavilla D, "Polydeoxyribonucleotide(PDRN) : a safe approach to induce therapeutic angiogenesis in peripheral artery occlusive disease and in diabetic foot ulcers", Cardiovasc Hematol Agents Med Chem, 7, pp.313~321 (2009)
- 김석곤, "Histologic study of bone-forming capacity on polydeoxyribonucleotide combined with demineralized dentin matrix", Maxillofacial Plastic Reconstructive Surgery, 38(2), pp.1~5 (2016), 대한악안면성형재건외과학회[DOI]
- Veronesi F, "Polydeoxyribonucleotides(PDRNs)from skin to musculoskeletal tissue regeneration via adenosine A2A receptor involvement", J Cell Physiol, 232, pp.2299~2307 (2017)
- Bitto A, "Polydeoxyribonucleotide improves angiogenesis and wound healing in experimental thermal injury", Crit Care Med, 36, pp.1594~1602 (2008)
- Squadrito F, "Pharmacological activity and clinical use of PDRN", Front Pharmacol, 8, pp.224~ (2017)
- Wu CH, "Wound healing effects of porcine placental extracts on rats with thermal injury", Br J Dermatol, 148, pp.236~245 (2003)
- Altavilla D, "Activation of adenosine A2A receptors restores the altered cell-cycle machinery during impaired wound healing in genetically diabetic mice", Surgery, 149, pp.253~261 (2011)
- Lee SJ, "1, 2, 3, 4, 6-Penta-O-galloyl-beta-D-glucose blocks endothelial cell growth and tube formation through inhibition of VEGF binding to VEGF receptor", Cancer Lett, 208, pp.89~94 (2004)
- Montesinos MC, "Adenosine promotes wound healing and mediates angiogenesis in response to tissue injury via occupancy of A(2A)receptors", Am J Pathol, 160, pp.2009~2018 (2002)
- Brem H, "Molecular markers in patients with chronic wounds to guide surgical debridement", Mol Med, 13, pp.30~39 (2007)
- Brem H, "Cellular and molecular basis of wound healing in diabetes", J Clin Invest, 117, pp.1219~1222 (2007)
- Reiber GE, "Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings", Diabetes Care, 22, pp.157~162 (1999)
- Christman AL, "Hemoglobin A1c predicts healing rate in diabetic wounds", J Invest Dermatol, 131, pp.2121~2127 (2011)
- Emmerson E, "Insulin-like growth factor-1 promotes wound healing in estrogen-deprived mice : new insights into cutaneous IGF-1R", ERα cross talk, 2012, pp.132, 2838~2848
- Lima MH, "Topical insulin accelerates wound healing in diabetes by enhancing the AKT and ERK pathways : a double-blind placebo-controlled clinical trial", PLoS One, 7, pp.e36974~ (2012)
- Polito F, "Polydeoxyribonucleotide restores blood flow in an experimental model of ischemic skin flaps", J Vasc Surg, 55, pp.479~488 (2012)
- Yan Y, "The impact of ranibizumab on the level of intercellular adhesion molecule type 1 in the vitreous of eyes with proliferative diabetic retinopathy", Acta Ophthalmol, 94, pp.358~364 (2016)