Objective To explore the effect of exosomes derived from platelet-rich plasma (PRP-Exo) on wound healing rate and vascularization in the early stage of wound repair in rats. Methods PRP-Exo was extracted from the whole blood of 6 healthy volunteers. 40 rats were randomly divided into model group and PRP-Exo group, with 20 rats in each group. A full-thickness skin defect model was established. PRP-Exo group was injected with 200 μg of PRP-Exo, once per day. On the day of modeling (0 d) and on 3, 7, 11, 14, 17, and 20 days after modeling, photos of the wounds in each group were taken to analyze the wound contraction rate. HE and Masson staining were used to observe histopathological changes. Immunohistochemistry was used to detect the expression of CD31, α-smooth muscle actin (α-SMA), and Janus kinase 2 (JAK2). HUVEC was divided into the control group (normal culture), the PRP-Exo group (50 μg/mL PRP-Exo), and the PRP-Exo+AG490 group (50 μg/mL PRP-Exo+20 μmol/L AG490). CCK-8, scratch and angiogenesis were used to detect cell proliferation, migration and angiogenesis ability. While WB was used to detect molecules related to the JAK2/ signal transducer and activator of transcription 3 (STAT3) signaling pathway and the expression of vascular endothelial growth factor (VEGF). Results Compared with the model group, the wound contraction rate on 7, 11, and 14 days, epidermal thickness and length of new epithelial tissue on 7 day, number of microvessels, and expression levels of α-SMA and JAK2 were increased in the PRP-Exo group (P<0.05). Compared with the control group, the ability of cell proliferation, migration, angiogenesis and the expression of p-JAK2, p-STAT3 and VEGF were increased in PRP-Exo group (P<0.05). Compared with the PRP-Exo group, the ability of proliferation, migration, angiogenesis and the expression of p-JAK2, p-STAT3 and VEGF were decreased in PRP-Exo+AG490 group (P<0.05). Conclusions PRP-Exo enhances wound vascularization and promotes wound healing in rats through the JAK2/STAT3 signaling pathway.
[1] Oliveira A, Simões S, Ascenso A, et al. Therapeutic advances in wound healing[J]. J Dermatolog Treat, 2022, 33(1): 2-22. DOI: 10.1080/09546634.2020.1730296.
[2] Scopelliti F, Cattani C, Dimartino V, et al. Platelet derivatives and the immunomodulation of wound healing[J]. Int J Mol Sci, 2022, 23(15): 8370-8384. DOI: 10.3390/ijms23158370.
[3] Erratico S, Belicchi M, Meregalli M, et al. Effective high-throughput isolation of enriched platelets and circulating pro-angiogenic cells to accelerate skin-wound healing[J]. Cell Mol Life Sci, 2022, 79(5): 259-277. DOI: 10.1007/s00018-022-04284-4.
[4] Hwang J, Kiick KL, Sullivan MO. VEGF-encoding, gene-activated collagen-based matrices promote blood vessel formation and improved wound repair[J]. ACS Appl Mater Interfaces, 2023, 15(13): 16434-16447. DOI: 10.1021/acsami.2c23022.
[5] Akbarian M, Bertassoni LE, Tayebi L. Biological aspects in controlling angiogenesis: Current progress[J]. Cell Mol Life Sci, 2022, 79(7): 349-383. DOI: 10.1007/s00018-022-04348-5.
[6] Verma R, Kumar S, Garg P, et al. Platelet-rich plasma: A comparative and economical therapy for wound healing and tissue regeneration[J]. Cell Tissue Bank, 2023, 24(2): 285-306. DOI: 10.1007/s10561-022-10039-z.
[7] Meng Y, Li C, Liang Y, et al. Umbilical cord mesenchymal-stem-cell-derived exosomes exhibit anti-oxidant and antiviral effects as cell-free therapies[J]. Viruses, 2023, 15(10): 2094-2109. DOI: 10.3390/v15102094.
[8] Adelipour M, Lubman DM, Kim J. Potential applications of mesenchymal stem cells and their derived exosomes in regenerative medicine[J]. Expert Opin Biol Ther, 2023, 23(6): 491-507. DOI: 10.1080/14712598.2023.2211203.
[9] Saumell-Esnaola M, Delgado D, García Del Caño G, et al. Isolation of platelet-derived exosomes from human platelet-rich plasma: Biochemical and morphological characterization[J]. Int J Mol Sci, 2022, 23(5): 2861-2879. DOI: 10.3390/ijms23052861.
[10]Li M, Shi L, Chen X, et al. In-situ gelation of fibrin gel encapsulating platelet-rich plasma-derived exosomes promotes rotator cuff healing[J]. Commun Biol, 2024, 7(1): 205-219. DOI: 10.1038/s42003-024-05882-7.
[11]Zhou C, Zhang B, Yang Y, et al. Stem cell-derived exosomes: Emerging therapeutic opportunities for wound healing[J]. Stem Cell Res Ther, 2023, 14(1): 107-124. DOI: 10.1186/s13287-023-03345-0.
[12]Hu JC, Zheng CX, Sui BD, et al. Mesenchymal stem cell-derived exosomes: A novel and potential remedy for cutaneous wound healing and regeneration[J]. World J Stem Cells, 2022, 14(5): 318-329. DOI: 10.4252/wjsc.v14.i5.318.
[13]Bian D, Wu Y, Song G, et al. The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: A comprehensive review[J]. Stem Cell Res Ther, 2022, 13(1): 24-40. DOI: 10.1186/s13287-021-02697-9.
[14]Anitua E, Troya M, Falcon-Pérez JM, et al. Advances in platelet rich plasma-derived extracellular vesicles for regenerative medicine: A systematic-narrative review[J]. Int J Mol Sci, 2023, 24(17): 13043-13069. DOI: 10.3390/ijms241713043.
[15]Smith OJ, Talaat S, Tomouk T, et al. An evaluation of the effect of activation methods on the release of growth factors from platelet-rich plasma[J]. Plast Reconstr Surg, 2022, 149(2): 404-411. DOI: 10.1097/PRS.0000000000008772.
[16]张珑, 赵方, 景方坤, 等. 富血小板血浆治疗老年膝关节骨关节炎临床研究[J]. 辽宁中医药大学学报, 2023, 25(4): 172-176. DOI: 10.13194/j.issn.1673-842x.2023.04.037.
Zhang L, Zhao F, Jing FK, et al. Clinical Study of Platelet-rich Plasma in the Treatment of Senile Knee Osteoarthritis[J]. Journal of Liaoning University of TCM, 2023, 25(4): 172-176. DOI: 10.13194/j.issn.1673-842x.2023.04.037.
[17]郭孝菊, 戴莹, 林文华, 等. 富血小板血浆治疗慢性难愈性创面的临床疗效[J]. 生物骨科材料与临床研究, 2022, 19(4): 50-54. DOI: 10.3969/j.issn.1672-5972.2022.04.010.
Guo XJ, Dai Y, Lin WH, et al. Clinical efficacy of platelet rich plasma in the treatment of chronic refractory wounds[J]. Orthopaedic Biomechanics Materials and Clinical Study, 2022, 19(4): 50-54. DOI: 10.3969/j.issn.1672-5972.2022.04.010.
[18]Vladulescu D, Scurtu LG, Simionescu AA, et al. Platelet-rich plasma (PRP) in dermatology: Cellular and molecular mechanisms of action[J]. Biomedicines, 2023, 12(1): 7-23. DOI: 10.3390/biomedicines12010007.
[19]Yi D, Zhang Y, Li M, et al. Ultrasound-targeted microbubble destruction assisted delivery of platelet-rich plasma-derived exosomes promoting peripheral nerve regeneration[J]. Tissue Eng Part A, 2023, 29(23-24): 645-662. DOI: 10.1089/ten.TEA.2023.0133.
[20]Zhang Y, Wang X, Chen J, et al. Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis[J]. J Nanobiotechnology, 2022, 20(1): 56-77. DOI: 10.1186/s12951-022-01245-8.
[21]Dudley AC, Griffioen AW. Pathological angiogenesis: Mechanisms and therapeutic strategies[J]. Angiogenesis, 2023, 26(3): 313-347. DOI: 10.1007/s10456-023-09876-7.
[22]Filippini A, Tamagnone L, D'Alessio A. Endothelial cell metabolism in vascular functions[J]. Cancers (Basel), 2022, 14(8): 1929-1946. DOI: 10.3390/cancers14081929.
[23]Jiang Y, Xu CH, Zhao Y, et al. LINC00926 is involved in hypoxia-induced vascular endothelial cell dysfunction via miR-3194-5p regulating JAK1/STAT3 signaling pathway[J]. Eur J Histochem, 2023, 67(1): 3526-3534. DOI: 10.4081/ejh.2023.3526.
[24]Wu Y, Sun J, Lin Q, et al. Sustained release of vascular endothelial growth factor A and basic fibroblast growth factor from nanofiber membranes reduces oxygen/glucose deprivation-induced injury to neurovascular units[J]. Neural Regen Res, 2024, 19(4): 887-894. DOI: 10.4103/1673-5374.382252.
[25]Gong R, Han R, Zhuang X, et al. MiR-375 mitigates retinal angiogenesis by depressing the JAK2/STAT3 pathway[J]. Aging (Albany NY), 2022, 14(16): 6594-6604. DOI: 10.18632/aging.204232.
[26]Ha GH, Kim EJ, Park JS, et al. JAK2/STAT3 pathway mediates neuroprotective and pro-angiogenic treatment effects of adult human neural stem cells in middle cerebral artery occlusion stroke animal models[J]. Aging (Albany NY), 2022, 14(22): 8944-8969. DOI: 10.18632/aging.204410.
京ICP备08002354号-3
