Platelet-derived growth factor promotes skin wound healing by regulating the migration of bone marrow mesenchymal stem cells to wounds

doi:10.3969/j.issn.2095-4344.2015.01.007

Abstract

Abstract:

BACKGROUND: Platelet-derived growth factor has the ability of wound repair, and relevant studies mainly focus on bone tissue repair. However, there are less studies about the effect of platelet-derived growth factors in skin wound healing.
OBJECTIVE: To investigate the role of platelet-derived growth factor to promote wound healing by the regulation of bone marrow mesenchymal stem cells to the wound.
METHODS: Bone marrow mesenchymal stem cells from rats were cultured. Immunofluorescence method was conducted to detect cell surface markers of CD34 and CD44 in bone marrow mesenchymal stem cells. Thirty healthy male SD rats were divided into five groups at random. Bone marrow mesenchymal stem cells labeled with PKH-26 were injected into the rat caudal vein in each group. The rats were anesthetized 1 week after injection. On the center of rat back, a 3-cm incision was made to establish a wound healing model. Different concentrations of platelet-derived growth factor were injected via multi-points on the skin wound after modeling, and the control group was treated with the same volume of normal saline. Skin wound tissues were taken for relevant parameter measurement at 14 days after injection.
RESULTS AND CONCLUSION: Under the fluorescence microscope, platelet-derived growth factor could induce the migration and accumulation of bone marrow mesenchymal stem cells to the trauma in a dose-dependent manner and promote the wound healing. Masson staining showed that, with the concentration increase, platelet-derived growth factors could reduce inflammatory cell infiltration and increase the number of collagen fibers. Results from western blot assay showed that platelet-derived growth factor could inhibit the expression of matrix metalloproteinase-1, promote the expression of tissue inhibitor of matrix metalloproteinase 1 in the wound, and inhibit the collagen degradation, thereby promoting skin wound healing indirectly.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

全文链接：

Key words: Bone Marrow, Mesenchymal Stem Cell Transplantation, Skin, Wounds and Injuries, Platelet-Derived Growth Factor

CLC Number:

R394.2

Ding Yue, Xu Hai-long, Xie Hong. Platelet-derived growth factor promotes skin wound healing by regulating the migration of bone marrow mesenchymal stem cells to wounds[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(1): 37-43.

Figures/Tables 5

References

[1] Eming SA, Martin P, Tomic-Canic M.Wound repair and regeneration: mechanisms, signaling, and translation.Sci Transl Med. 2014;6(265):265-266.
[2] Dabiri G, Heiner D, Falanga V.The emerging use of bone marrow-derived mesenchymal stem cells in the treatment of human chronic wounds.Expert Opin Emerg Drugs. 2013; 18(4): 405-419.
[3] Kim YJ, Jeong JH.Clinical application of adipose stem cells in plastic surgery.J Korean Med Sci. 2014;29(4):462-467.
[4] Dreifke MB, Jayasuriya AA, Jayasuriya AC.Current wound healing procedures and potential care.Mater Sci Eng C Mater Biol Appl. 2015;48C:651-662.
[5] You HJ, Han SK.Cell therapy for wound healing.J Korean Med Sci. 2014;29(3):311-319.
[6] Peng LH, Mao ZY, Qi XT,et al.Transplantation of bone-marrow-derived mesenchymal and epidermal stem cells contribute to wound healing with different regenerative features. Cell Tissue Res. 2013;352(3):573-583.
[7] Kaltalioglu K, Coskun-Cevher S.A bioactive molecule in a complex wound healing process: platelet-derived growth factor.Int J Dermatol. 2014. doi: 10.1111/ijd.12731. [Epub ahead of print]
[8] Travis TE, Mauskar NA, Mino MJ,et al.Commercially available topical platelet-derived growth factor as a novel agent to accelerate burn-related wound healing.J Burn Care Res. 2014; 35(5):e321-329.
[9] Sotoca AM, Roelofs-Hendriks J, Boeren S,et al.Comparative proteome approach demonstrates that platelet-derived growth factor C and D efficiently induce proliferation while maintaining multipotency of hMSCs.Exp Cell Res. 2013; 319(17):2649-2662.
[10] Cheng P, Gao ZQ, Liu YH,et al.Platelet-derived growth factor BB promotes the migration of bone marrow-derived mesenchymal stem cells towards C6 glioma and up-regulates the expression of intracellular adhesion molecule-1.Neurosci Lett. 2009;451(1):52-56.
[11] Abramov Y, Hirsch E, Ilievski V,et al.Expression of platelet-derived growth factor-B mRNA during vaginal vs. dermal incisional wound healing in the rabbit.Eur J Obstet Gynecol Reprod Biol. 2012;162(2):216-220.
[12] Bae IH, Park JW, Kim DY.Enhanced regenerative healing efficacy of a highly skin-permeable growth factor nanocomplex in a full-thickness excisional mouse wound model.Int J Nanomedicine. 2014;9:4551-4567.
[13] Kao HK, Chen B, Murphy GF, et al.Peripheral blood fibrocytes: enhancement of wound healing by cell proliferation, re-epithelialization, contraction, and angiogenesis.Ann Surg. 2011;254(6):1066-1074.
[14] Mishima Y, Lotz M.Chemotaxis of human articular chondrocytes and mesenchymal stem cells.J Orthop Res. 2008;26(10):1407-1412.
[15] Cheng J, Ye H, Liu Z,et al.Platelet-derived growth factor-BB accelerates prostate cancer growth by promoting the proliferation of mesenchymal stem cells.J Cell Biochem. 2013; 114(7):1510-1518.
[16] Ranera B, Lyahyai J, Romero A,et al.Immunophenotype and gene expression profiles of cell surface markers of mesenchymal stem cells derived from equine bone marrow and adipose tissue.Vet Immunol Immunopathol. 2011;144(1-2):147-154.
[17] Lienemann PS, Devaud YR, Reuten R,et al.Locally controlling mesenchymal stem cell morphogenesis by 3D PDGF-BB gradients towards the establishment of an in vitro perivascular niche.Integr Biol (Camb). 2014;7(1):101-111.
[18] Fiedler J, Röderer G, Günther KP,et al.BMP-2, BMP-4, and PDGF-bb stimulate chemotactic migration of primary human mesenchymal progenitor cells.J Cell Biochem. 2002;87(3): 305-312.
[19] Pountos I, Georgouli T, Henshaw K,et al.The effect of bone morphogenetic protein-2, bone morphogenetic protein-7, parathyroid hormone, and platelet-derived growth factor on the proliferation and osteogenic differentiation of mesenchymal stem cells derived from osteoporotic bone.J Orthop Trauma. 2010;24(9):552-556.
[20] Kinzebach S, Dietz L, Klüter H,et al. Functional and differential proteomic analyses to identify platelet derived factors affecting ex vivo expansion of mesenchymal stromal cells.BMC Cell Biol. 2013;14:48.
[21] McFarlin K, Gao X, Liu YB, et al. Bone marrow-derived mesenchymal stromal cells accelerate wound healing in the rat.Wound Repair Regen. 2006;14(4):471-478.
[22] Hu Y, Cheng P, Ma JC,et al.Platelet-derived growth factor BB mediates the glioma-induced migration of bone marrow-derived mesenchymal stem cells by promoting the expression of vascular cell adhesion molecule-1 through the PI3K, P38 MAPK and NF-κB pathways.Oncol Rep. 2013; 30(6): 2755-2764.
[23] Wagner B, Gorin Y.Src tyrosine kinase mediates platelet-derived growth factor BB-induced and redox-dependent migration in metanephric mesenchymal cells.Am J Physiol Renal Physiol. 2014;306(1):F85-97.
[24] Yokota J, Chosa N, Sawada S,et al.PDGF-induced PI3K-mediated signaling enhances the TGF-β-induced osteogenic differentiation of human mesenchymal stem cells in a TGF-β-activated MEK-dependent manner.Int J Mol Med. 2014;33(3):534-542.
[25] Shin SH, Song HY, Kim MY,et al.Platelet-activating factor receptor mediates oxidized low density lipoprotein-induced migration of bone marrow-derived mesenchymal stem cells.Cell Physiol Biochem. 2010;26(4-5):689-698.
[26] Henle P, Zimmermann G, Weiss S.Matrix metalloproteinases and failed fracture healing.Bone. 2005;37(6):791-798.
[27] Gómez-Florit M, Monjo M, Ramis JM.Identification of quercitrin as a potential therapeutic agent for periodontal applications.J Periodontol. 2014;85(7):966-974.
[28] Reed MJ, Ferara NS, Vernon RB.Impaired migration, integrin function, and actin cytoskeletal organization in dermal fibroblasts from a subset of aged human donors.Mech Ageing Dev. 2001;122(11):1203-1220.
[29] Shi JH, Guan H, Shi S,et al.Protection against TGF-β1-induced fibrosis effects of IL-10 on dermal fibroblasts and its potential therapeutics for the reduction of skin scarring. Arch Dermatol Res. 2013;305(4):341-352.
[30] Chen CC, Mo FE, Lau LF.The angiogenic factor Cyr61 activates a genetic program for wound healing in human skin fibroblasts.J Biol Chem. 2001;276(50):47329-47337.
[31] Muller M, Trocme C, Lardy B,et al.Matrix metalloproteinases and diabetic foot ulcers: the ratio of MMP-1 to TIMP-1 is a predictor of wound healing.Diabet Med. 2008;25(4):419-426.
[32] He LP, Wang C, Chen DW,et al.Dynamic changes of MMP-1, MMP-9 and TIMP-1 in the refractory diabetic dermal ulcers treated by autologous Platelet-rich gel.Sichuan Da Xue Xue Bao Yi Xue Ban. 2012;43(5):757-761.