Increased serial levels of platelet‐derived growth factor using hypoxic mesenchymal stem cell‐conditioned medium to promote closure acceler‐ ation in a full‐thickness wound
Pangesti Drawina(1), Agung Putra(2*), Taufiqurrachman Nasihun(3), Yan Wisnu Prajoko(4), Bayu Tirta Dirja(5), Nur Dina Amalina(6)
(1) Postgraduated Student of Biomedical Sciences, Postgraduate Program, Medical Faculty, Sultan Agung Islamic University (UNISSULA), Semarang 50112, Indonesia
(2) Stem Cell and Cancer Research (SCCR) Indonesia, Kaligawe Raya Km.4 Semarang 50112, Indonesia; Department of Pathology, Medical Faculty, Sultan Agung Islamic University (UNISSULA), Kaligawe Raya Km.4 Semarang 50112, Indonesia; Department of Postgraduate Biomedical Science, Medical Faculty, Sultan Agung Islamic University (UNISSULA), Kaligawe Raya Km.4 Semarang 50112, Indonesia
(3) Department of Biochemistry, Medical Faculty, Sultan Agung Islamic University (UNISSULA), Kaligawe Raya Km.4 Semarang 50112, Indonesia
(4) Department of Surgery, Faculty of Medicine, Diponegoro University, Jl. Prof. Sudarto SH, Tembalang, Semarang 50275, Indonesia
(5) Department of Microbiology, Medical Faculty, Universitas Mataram, Jalan Majapahit No.62, Mataram 83115, Nusa Tengara Barat, Indonesia
(6) Pharmacy Study Program, Chemistry Department, Faculty of Mathematics and Natural Sciences, Universitas Negeri Semarang, Jalan Ir. Sutami 36 Kentingan, Surakarta 57126, Indonesia
(*) Corresponding Author
Abstract
The healing process of a full‐thickness wound involves a complex cascade of cellular responses to reverse skin integrity formation. These processes require growth factors, particularly platelet‐derived growth factor (PDGF). Conversely, hypoxic mesenchymal stem‐cell‐conditioned medium (HMSC‐CM)‐contained growth factors notably contribute to acceleration of wound healing. This study aims to investigate the role of HMSC‐CM in controlling the serial levels of PDGF associated with accelerated wound closure in full‐thickness wounds. Twenty male Wistar rats with full‐thickness wounds were developed as animal models. The animals were randomly assigned to four groups, comprising two treatment groups (treated using HMSC‐CM at a high dose as P1 and at a low dose as P2), a control group (administration of base gel), and sham group (healthy group). PDGF levels were examined using an enzyme‐linked immunosorbent assay. Using ImageJ software, wound closure percentages were determined photographically. The study showed that there was a significant increase in PDGF levels on days 3 and 6 after HMSC‐CM treatment, followed by a decrease in PDGF levels on day 9. In line with these findings, wound closure percentage also increased significantly on days 6 and 9. In the rat model, HMSC‐CM administration may promote acceleration of wound closure by increasing serial PDGF levels in the full‐thickness wound.
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Bartaula-Brevik S. 2017. Secretome of Mesenchymal Stem Cells Grown in Hypoxia Accelerates Wound Healing and Vessel Formation In Vitro. Int. J. Stem cell Res. Ther. 4(1). doi:10.23937/2469-570x/1410045.
Burlacu A, Grigorescu G, Rosca AM, Preda MB, Simionescu M. 2013. Factors secreted by mesenchymal stem cells and endothelial progenitor cells have complementary effects on angiogenesis in vitro. Stem Cells Dev. 22(4). doi:10.1089/scd.2012.0273.
Chen L, Tredget EE, Wu PY, Wu Y, Wu Y. 2008. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One 3(4). doi:10.1371/journal.pone.0001886.
Chen L, Xu Y, Zhao J, Zhang Z, Yang R, Xie J, Liu X, Qi S. 2014. Conditioned medium from hypoxic bone marrow-derived mesenchymal stem cells enhances wound healing in mice. PLoS One 9(4). doi:10.1371/journal.pone.0096161.
Darlan DM, Munir D, Putra A, Jusuf NK. 2021. MSCsreleased TGFβ1 generate CD4+CD25+Foxp3+ in Treg cells of human SLE PBMC. J. Formos. Med. Assoc. 120(1). doi:10.1016/j.jfma.2020.06.028. De Oliveira S, Rosowski EE, Huttenlocher A. 2016. Neutrophil migration in infection and wound repair: Going forward in reverse. doi:10.1038/nri.2016.49.
Dehkordi AN, Babaheydari FM, Chehelgerdi M, Dehkordi SR. 2019. Skin tissue engineering: Wound healing based on stem-cell-based therapeutic strategies. Stem Cell Res. Ther. 10(1). doi:10.1186/s13287-019-1212-2.
Desjardins-Park HE, Foster DS, Longaker MT. 2018. Fibroblasts and wound healing: An update. doi:10.2217/rme-2018-0073.
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini FC, Krause DS, Deans RJ, Keating A, Prockop DJ, Horwitz EM. 2006. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317. doi:10.1080/14653240600855905.
Fischer AN, Fuchs E, Mikula M, Huber H, Beug H, Mikulits W. 2007. PDGF essentially links TGF-β signaling to nuclear β-catenin accumulation in hepatocellular carcinoma progression. Oncogene 26(23). doi:10.1038/sj.onc.1210121.
Hamra NF, Putra A, Tjipta A, Amalina ND, Nasihun T. 2021. Hypoxia mesenchymal stem cells accelerate wound closure improvement by controlling α- smooth muscle actin expression in the full-thickness animal model. Open Access Maced. J. Med. Sci. 9. doi:10.3889/oamjms.2021.5537.
Herrera A, Herrera M, Guerra-Perez N, Galindo-Pumariño C, Larriba MJ, García-Barberán V, Gil B, GiménezMoyano S, Ferreiro-Monteagudo R, Veguillas P, Candia A, Peña R, Pinto J, García-Bermejo ML, Muñoz
A, García de Herreros A, Bonilla F, Carrato A, Peña C. 2018. Endothelial cell activation on 3Dmatrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1. Oncogenesis 7(9). doi:10.1038/s41389-018-0085-z.
Hu MS, Borrelli MR, Lorenz HP, Longaker MT, Wan DC. 2018. Mesenchymal stromal cells and cutaneous wound healing: A comprehensive review of the background, role, and therapeutic potential. Stem Cells Int. 2018. doi:10.1155/2018/6901983.
Hu MS, Maan ZN, Wu JC, Rennert RC, Hong WX, Lai TS, Cheung AT, Walmsley GG, Chung MT, McArdle A, Longaker MT, Lorenz HP. 2014. Tissue engineering and regenerative repair in wound healing. Ann. Biomed. Eng. 42(7):1494–1507. doi:10.1007/s10439-014-1010-z.
Kardas G, Daszyńska-Kardas A, Marynowski M, Brza-kalska O, Kuna P, Panek M. 2020. Role of Platelet-Derived Growth Factor (PDGF) in Asthma as an Immunoregulatory Factor Mediating Airway Remodeling and Possible Pharmacological Target. doi:10.3389/fphar.2020.00047.
Landén NX, Li D, Ståhle M. 2016. Transition from inflammation to proliferation: a critical step during wound healing. doi:10.1007/s00018-016-2268-0.
Li M, Luan F, Zhao Y, Hao H, Liu J, Dong L, Fu X, Han W. 2017. Mesenchymal stem cell-conditioned medium accelerates wound healing with fewer scars. Int. Wound J. 14(1). doi:10.1111/iwj.12551.
Lv FJ, Tuan RS, Cheung KM, Leung VY. 2014. Concise review: The surface markers and identity of human mesenchymal stem cells. doi:10.1002/stem.1681.
Mehanna RA, Nabil I, Attia N, Bary AA, Razek KA, Ahmed TA, Elsayed F. 2015. The Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Media Topically Delivered in Fibrin Glue on Chronic Wound Healing in Rats. Biomed Res. Int. 2015. doi:10.1155/2015/846062.
Muhar AM, Putra A, Warli SM, Munir D. 2019. Hypoxiamesenchymal stem cells inhibit intra-peritoneal adhesions formation by upregulation of the il-10 expression. Open Access Maced. J. Med. Sci. 7(23).
doi:10.3889/oamjms.2019.713.
Mulholland EJ. 2020. Electrospun Biomaterials in the Treatment and Prevention of Scars in Skin Wound Healing. doi:10.3389/fbioe.2020.00481.
Noronha NDC, Mizukami A, Caliári-Oliveira C, Cominal JG, Rocha JLM, Covas DT, Swiech K, Malmegrim KC. 2019. Correction to: Priming approaches to improve the efficacy of mesenchymal stromal cellbased therapies (Stem Cell Research and Therapy (2019) 10 (131) DOI: 10.1186/s13287-019-1224-y). doi:10.1186/s13287-019-1259-0.
Okur ME, Karantas ID, Şenyiğit Z, Üstündağ Okur N, Siafaka PI. 2020. Recent trends on wound management: New therapeutic choices based on polymeric carriers. doi:10.1016/j.ajps.2019.11.008.
Park U, Kim K. 2017. Multiple growth factor delivery for skin tissue engineering applications. doi:10.1007/s12257-017-0436-1.
Phipps MC, Xu Y, Bellis SL. 2012. Delivery of platelet-derived growth factor as a chemotactic factor for mesenchymal stem cells by bonemimetic electrospun scaffolds. PLoS One 7(7). doi:10.1371/journal.pone.0040831.
Putra A, Pertiwi D, Milla MN, Indrayani UD, Jannah D, Sahariyani M, Trisnadi S, Wibowo JW. 2019. Hypoxia-preconditioned MSCs have superior effect in ameliorating renal function on acute renal failure animal model. Open Access Maced. J. Med. Sci. 7(3). doi:10.3889/oamjms.2019.049.
Ramirez H, Patel SB, Pastar I. 2014. The Role of TGFβ Signaling in Wound Epithelialization. Adv. Wound Care 3(7). doi:10.1089/wound.2013.0466.
Ridiandries A, Tan JT, Bursill CA. 2018. The role of chemokines in wound healing. doi:10.3390/ijms19103217.
Riis S, Newman R, Ipek H, Andersen JI, Kuninger D, Boucher S, Vemuri MC, Pennisi CP, Zachar V, Fink T. 2017. Hypoxia enhances the wound-healing potential of adipose-derived stem cells in a novel human primarykeratinocyte-based scratch assay. Int. J. Mol. Med. 39(3). doi:10.3892/ijmm.2017.2886.
Saheli M, Bayat M, Ganji R, Hendudari F, Kheirjou R, Pakzad M, Najar B, Piryaei A. 2020. Human mesenchymal stem cells-conditioned medium improves diabetic wound healing mainly through modulating fibroblast behaviors. Arch. Dermatol. Res. 312(5). doi:10.1007/s00403-019-02016-6.
Wu LW, Chen WL, Huang SM, Chan JYH. 2019. Plateletderived growth factor-AA is a substantial factor in the ability of adipose-derived stem cells and endothelial progenitor cells to enhance wound healing. FASEB J. 33(2). doi:10.1096/fj.201800658R.
Xiang D, Feng Y, Wang J, Zhang X, Shen J, Zou R, Yuan Y. 2019. Plateletderived growth factorBB promotes proliferation and migration of retinal microvascular pericytes by upregulating the expression of CXC chemokine receptor types 4. Exp. Ther. Med. doi:10.3892/etm.2019.8016.
Zhang QZ, Su WR, Shi SH, Wilder-Smith P, Xiang AP, Wong A, Nguyen AL, Kwon CW, Le AD. 2010. Human gingiva-derived mesenchymal stem cells elicit polarization of M2 macrophages and enhance cutaneous wound healing. Stem Cells 28(10). doi:10.1002/stem.503.
DOI: https://doi.org/10.22146/ijbiotech.64021
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