ApoSEVs-Mediated Modulation of Versatile Target Cells Promotes Diabetic Wound Healing: Unveiling a Promising Strategy

References

• Chen L, Gao Y, Li Y, et al. Severe intermittent hypoxia modulates the macrophage phenotype and impairs wound healing through downregulation of HIF-2α. Nat Sci Sleep. 2022;14:1511–1520. doi:10.2147/NSS.S382275
   PubMed Web of Science ®Google Scholar
• Patel S, Srivastava S, Singh MR, Singh D. Mechanistic insight into diabetic wounds: pathogenesis, molecular targets and treatment strategies to pace wound healing. Biomed Pharmacother. 2019;112:108615. doi:10.1016/j.biopha.2019.108615
   PubMed Web of Science ®Google Scholar
• Lim JZ, Ng NS, Thomas C. Prevention and treatment of diabetic foot ulcers. J R Soc Med. 2017;110(3):104–109. doi:10.1177/0141076816688346
   PubMed Web of Science ®Google Scholar
• Bowling FL, Rashid ST, Boulton AJ. Preventing and treating foot complications associated with diabetes mellitus. Nat Rev Endocrinol. 2015;11(10):606–616. doi:10.1038/nrendo.2015.130
   PubMed Web of Science ®Google Scholar
• Kerr M, Rayman G, Jeffcoate WJ. Cost of diabetic foot disease to the National Health Service in England. Diabet Med. 2014;31(12):1498–1504. doi:10.1111/dme.12545
   PubMed Web of Science ®Google Scholar
• Grennan D. Diabetic Foot Ulcers. JAMA. 2019;321(1):114. doi:10.1001/jama.2018.18323
   PubMedGoogle Scholar
• Chen L, Sun S, Gao Y, Ran X. Global mortality of diabetic foot ulcer: a systematic review and meta-analysis of observational studies. Diabetes Obes Metab. 2023;25(1):36–45. doi:10.1111/dom.14840
   PubMed Web of Science ®Google Scholar
• Everett E, Mathioudakis N. Update on management of diabetic foot ulcers. Ann N Y Acad Sci. 2018;1411(1):153–165. doi:10.1111/nyas.13569
   PubMed Web of Science ®Google Scholar
• Powers JG, Higham C, Broussard K, Phillips TJ. Wound healing and treating wounds: chronic wound care and management. J Am Acad Dermatol. 2016;74(4):607–625; quiz 625–606. doi:10.1016/j.jaad.2015.08.070
   Web of Science ®Google Scholar
• Broughton G, Janis JE, Attinger CE. The basic science of wound healing. Plast Reconstr Surg. 2006;117(7 Suppl):12s–34s. doi:10.1097/01.prs.0000225430.42531.c2
   PubMed Web of Science ®Google Scholar
• Li D, Wu N. Mechanism and application of exosomes in the wound healing process in diabetes mellitus. Diabetes Res Clin Pract. 2022;187:109882. doi:10.1016/j.diabres.2022.109882
   PubMed Web of Science ®Google Scholar
• Louiselle AE, Niemiec SM, Zgheib C, Liechty KW. Macrophage polarization and diabetic wound healing. Transl Res. 2021;236:109–116. doi:10.1016/j.trsl.2021.05.006
   PubMed Web of Science ®Google Scholar
• Kaur R, Kaur M, Singh J. Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies. Cardiovasc Diabetol. 2018;17(1):121. doi:10.1186/s12933-018-0763-3
   PubMed Web of Science ®Google Scholar
• Lopes L, Setia O, Aurshina A, et al. Stem cell therapy for diabetic foot ulcers: a review of preclinical and clinical research. Stem Cell Res Ther. 2018;9(1):188. doi:10.1186/s13287-018-0938-6
   PubMedGoogle Scholar
• Kanji S, Das H. Advances of stem cell therapeutics in cutaneous wound healing and regeneration. Mediators Inflamm. 2017;2017:5217967. doi:10.1155/2017/5217967
   PubMed Web of Science ®Google Scholar
• Zhu LP, Tian T, Wang JY, et al. Hypoxia-elicited mesenchymal stem cell-derived exosomes facilitates cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction. Theranostics. 2018;8(22):6163–6177. doi:10.7150/thno.28021
   PubMed Web of Science ®Google Scholar
• Eirin A, Zhu XY, Puranik AS, et al. Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation. Kidney Int. 2017;92(1):114–124. doi:10.1016/j.kint.2016.12.023
   PubMed Web of Science ®Google Scholar
• Zhu YG, Feng XM, Abbott J, et al. Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin-induced acute lung injury in mice. Stem Cells. 2014;32(1):116–125. doi:10.1002/stem.1504
   PubMed Web of Science ®Google Scholar
• Shigemoto-Kuroda T, Oh JY, Kim DK, et al. MSC-derived extracellular vesicles attenuate immune responses in two autoimmune murine models: type 1 diabetes and uveoretinitis. Stem Cell Rep. 2017;8(5):1214–1225. doi:10.1016/j.stemcr.2017.04.008
   PubMed Web of Science ®Google Scholar
• Kfoury Y, Scadden DT. Mesenchymal cell contributions to the stem cell niche. Cell Stem Cell. 2015;16(3):239–253. doi:10.1016/j.stem.2015.02.019
   PubMed Web of Science ®Google Scholar
• Liu J, Qiu X, Lv Y, et al. Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages. Stem Cell Res Ther. 2020;11(1):507. doi:10.1186/s13287-020-02014-w
   PubMed Web of Science ®Google Scholar
• Liu S, Jiang L, Li H, et al. Mesenchymal stem cells prevent hypertrophic scar formation via inflammatory regulation when undergoing apoptosis. J Invest Dermatol. 2014;134(10):2648–2657. doi:10.1038/jid.2014.169
   PubMed Web of Science ®Google Scholar
• Liu H, Liu S, Qiu X, et al. Donor MSCs release apoptotic bodies to improve myocardial infarction via autophagy regulation in recipient cells. Autophagy. 2020;16(12):2140–2155. doi:10.1080/15548627.2020.1717128
   PubMed Web of Science ®Google Scholar
• Green DR. The coming decade of cell death research: five riddles. Cell. 2019;177(5):1094–1107. doi:10.1016/j.cell.2019.04.024
   PubMed Web of Science ®Google Scholar
• Nagata S. Apoptosis and clearance of apoptotic cells. Annu Rev Immunol. 2018;36:489–517. doi:10.1146/annurev-immunol-042617-053010
   PubMed Web of Science ®Google Scholar
• Elliott MR, Ravichandran KS. The dynamics of apoptotic cell clearance. Dev Cell. 2016;38(2):147–160. doi:10.1016/j.devcel.2016.06.029
   PubMed Web of Science ®Google Scholar
• Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26(4):239–257. doi:10.1038/bjc.1972.33
   PubMed Web of Science ®Google Scholar
• Poon IKH, Parkes MAF, Jiang L, et al. Moving beyond size and phosphatidylserine exposure: evidence for a diversity of apoptotic cell-derived extracellular vesicles in vitro. J Extracell Vesicles. 2019;8(1):1608786. doi:10.1080/20013078.2019.1608786
   PubMed Web of Science ®Google Scholar
• Park SJ, Kim JM, Kim J, et al. Molecular mechanisms of biogenesis of apoptotic exosome-like vesicles and their roles as damage-associated molecular patterns. Proc Natl Acad Sci U S A. 2018;115(50):E11721–e11730. doi:10.1073/pnas.1811432115
   PubMed Web of Science ®Google Scholar
• Li M, Liao L, Tian W. Extracellular vesicles derived from apoptotic cells: an essential link between death and regeneration. Front Cell Dev Biol. 2020;8:573511. doi:10.3389/fcell.2020.573511
   PubMed Web of Science ®Google Scholar
• Ma L, Chen C, Liu D, et al. Apoptotic extracellular vesicles are metabolized regulators nurturing the skin and hair. Bioact Mater. 2023;19:626–641. doi:10.1016/j.bioactmat.2022.04.022
   PubMed Web of Science ®Google Scholar
• Zheng C, Sui B, Zhang X, et al. Apoptotic vesicles restore liver macrophage homeostasis to counteract type 2 diabetes. J Extracell Vesicles. 2021;10(7):e12109. doi:10.1002/jev2.12109
   PubMed Web of Science ®Google Scholar
• Wang R, Hao M, Kou X, et al. Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling. Bioact Mater. 2023;25:472–484. doi:10.1016/j.bioactmat.2022.07.026
   PubMed Web of Science ®Google Scholar
• Zhang X, Tang J, Kou X, et al. Proteomic analysis of MSC-derived apoptotic vesicles identifies Fas inheritance to ameliorate haemophilia a via activating platelet functions. J Extracell Vesicles. 2022;11(7):e12240. doi:10.1002/jev2.12240
   PubMed Web of Science ®Google Scholar
• Wilson A, Chee M, Butler P, Boyd AS. Isolation and characterisation of human adipose-derived stem cells. Methods Mol Biol. 2019;1899:3–13.
   PubMedGoogle Scholar
• Yang J, Gao X, Xing X, et al. An isolation system to collect high quality and purity extracellular vesicles from serum. Int J Nanomedicine. 2021;16:6681–6692. doi:10.2147/IJN.S328325
   PubMedGoogle Scholar
• Chen D, Zhao Z, Zhang K, Jin F, Zheng C, Jin Y. Protocol for differential centrifugation-based separation and characterization of apoptotic vesicles derived from human mesenchymal stem cells. STAR Protoc. 2022;3(4):101695. doi:10.1016/j.xpro.2022.101695
   PubMedGoogle Scholar
• Boniakowski AE, Kimball AS, Jacobs BN, Kunkel SL, Gallagher KA. Macrophage-mediated inflammation in normal and diabetic wound healing. J Immunol. 2017;199(1):17–24. doi:10.4049/jimmunol.1700223
   PubMed Web of Science ®Google Scholar
• Aitcheson SM, Frentiu FD, Hurn SE, Edwards K, Murray RZ. Skin wound healing: normal macrophage function and macrophage dysfunction in diabetic wounds. Molecules. 2021;26(16). doi:10.3390/molecules26164917
   PubMed Web of Science ®Google Scholar
• Bannon P, Wood S, Restivo T, Campbell L, Hardman MJ, Mace KA. Diabetes induces stable intrinsic changes to myeloid cells that contribute to chronic inflammation during wound healing in mice. Dis Model Mech. 2013;6(6):1434–1447. doi:10.1242/dmm.012237
   PubMed Web of Science ®Google Scholar
• Theocharidis G, Thomas BE, Sarkar D, et al. Single cell transcriptomic landscape of diabetic foot ulcers. Nat Commun. 2022;13(1):181. doi:10.1038/s41467-021-27801-8
   PubMed Web of Science ®Google Scholar
• Wang J, Cao Z, Wang P, et al. Apoptotic extracellular vesicles ameliorate multiple myeloma by restoring fas-mediated apoptosis. ACS Nano. 2021;15(9):14360–14372. doi:10.1021/acsnano.1c03517
   PubMed Web of Science ®Google Scholar
• Oh EJ, Gangadaran P, Rajendran RL, et al. Extracellular vesicles derived from fibroblasts promote wound healing by optimizing fibroblast and endothelial cellular functions. Stem Cells. 2021;39(3):266–279. doi:10.1002/stem.3310
   PubMed Web of Science ®Google Scholar
• Yoo SY, Kwon SM. Angiogenesis and its therapeutic opportunities. Mediators Inflamm. 2013;2013:127170. doi:10.1155/2013/127170
   PubMed Web of Science ®Google Scholar
• Suga H, Rennert RC, Rodrigues M, et al. Tracking the elusive fibrocyte: identification and characterization of collagen-producing hematopoietic lineage cells during murine wound healing. Stem Cells. 2014;32(5):1347–1360. doi:10.1002/stem.1648
   PubMed Web of Science ®Google Scholar
• Zhao D, Yu Z, Li Y, Wang Y, Li Q, Han D. GelMA combined with sustained release of HUVECs derived exosomes for promoting cutaneous wound healing and facilitating skin regeneration. J Mol Histol. 2020;51(3):251–263. doi:10.1007/s10735-020-09877-6
   PubMed Web of Science ®Google Scholar
• Wu K, He C, Wu Y, et al. Preservation of small extracellular vesicle in gelatin methacryloyl hydrogel through reduced particles aggregation for therapeutic applications. Int J Nanomedicine. 2021;16:7831–7846. doi:10.2147/IJN.S334194
   PubMed Web of Science ®Google Scholar
• Wang Y, Cao Z, Wei Q, et al. VH298-loaded extracellular vesicles released from gelatin methacryloyl hydrogel facilitate diabetic wound healing by HIF-1α-mediated enhancement of angiogenesis. Acta Biomater. 2022;147:342–355. doi:10.1016/j.actbio.2022.05.018
   PubMed Web of Science ®Google Scholar
• Yue K, Trujillo-de santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2015;73:254–271. doi:10.1016/j.biomaterials.2015.08.045
   PubMed Web of Science ®Google Scholar
• Liang C, Liang Q, Xu X, et al. Bone morphogenetic protein 7 mediates stem cells migration and angiogenesis: therapeutic potential for endogenous pulp regeneration. Int J Oral Sci. 2022;14(1):38. doi:10.1038/s41368-022-00188-y
   PubMed Web of Science ®Google Scholar
• Chen YH, Rao ZF, Liu YJ, et al. Multifunctional injectable hydrogel loaded with cerium-containing bioactive glass nanoparticles for diabetic wound healing. Biomolecules. 2021;11(5):702. doi:10.3390/biom11050702
   PubMed Web of Science ®Google Scholar
• Okonkwo UA, DiPietro LA. Diabetes and wound angiogenesis. Int J Mol Sci. 2017;18(7):1419. doi:10.3390/ijms18071419
   PubMed Web of Science ®Google Scholar
• Wilkinson HN, Hardman MJ. Wound healing: cellular mechanisms and pathological outcomes. Open Biol. 2020;10(9):200223. doi:10.1098/rsob.200223
   PubMed Web of Science ®Google Scholar
• Gibello L, D’Antico S, Salafia M, et al. First pilot case-control interventional study using autologous extracellular vesicles to treat chronic venous ulcers unresponsive to conventional treatments. Pharmacol Res. 2023;190:106718. doi:10.1016/j.phrs.2023.106718
   PubMed Web of Science ®Google Scholar
• Frese L, Dijkman PE, Hoerstrup SP. Adipose tissue-derived stem cells in regenerative medicine. Transfus Med Hemother. 2016;43(4):268–274. doi:10.1159/000448180
   PubMed Web of Science ®Google Scholar
• Domenis R, Lazzaro L, Calabrese S, et al. Adipose tissue derived stem cells: in vitro and in vivo analysis of a standard and three commercially available cell-assisted lipotransfer techniques. Stem Cell Res Ther. 2015;6(1):2. doi:10.1186/scrt536
   PubMedGoogle Scholar
• Kokai LE, Marra K, Rubin JP. Adipose stem cells: biology and clinical applications for tissue repair and regeneration. Transl Res. 2014;163(4):399–408. doi:10.1016/j.trsl.2013.11.009
   PubMed Web of Science ®Google Scholar
• Shu W, Shu YT, Dai CY, Zhen QZ. Comparing the biological characteristics of adipose tissue-derived stem cells of different persons. J Cell Biochem. 2012;113(6):2020–2026. doi:10.1002/jcb.24070
   PubMed Web of Science ®Google Scholar
• Shingyochi Y, Orbay H, Mizuno H. Adipose-derived stem cells for wound repair and regeneration. Expert Opin Biol Ther. 2015;15(9):1285–1292. doi:10.1517/14712598.2015.1053867
   PubMed Web of Science ®Google Scholar
• Sheng L, Yang M, Liang Y, Li Q. Adipose tissue-derived stem cells (ADSCs) transplantation promotes regeneration of expanded skin using a tissue expansion model. Wound Repair Regen. 2013;21(5):746–754. doi:10.1111/wrr.12080
   PubMed Web of Science ®Google Scholar
• Xu L, Liu Y, Tang L, Xiao H, Yang Z, Wang S. Preparation of recombinant human collagen III protein hydrogels with sustained release of extracellular vesicles for skin wound healing. Int J Mol Sci. 2022;23(11):6289.
   PubMed Web of Science ®Google Scholar
• Wen B, Huang Y, Qiu T, et al. Reparative dentin formation by dentin matrix proteins and small extracellular vesicles. J Endod. 2021;47(2):253–262. doi:10.1016/j.joen.2020.11.017
   PubMed Web of Science ®Google Scholar
• He X, Dong Z, Cao Y, et al. MSC-derived exosome promotes M2 polarization and enhances cutaneous wound healing. Stem Cells Int. 2019;2019:7132708. doi:10.1155/2019/7132708
   PubMed Web of Science ®Google Scholar
• Fu Y, Sui B, Xiang L, et al. Emerging understanding of apoptosis in mediating mesenchymal stem cell therapy. Cell Death Dis. 2021;12(6):596. doi:10.1038/s41419-021-03883-6
   PubMed Web of Science ®Google Scholar
• Fuchs Y, Steller H. Live to die another way: modes of programmed cell death and the signals emanating from dying cells. Nat Rev Mol Cell Biol. 2015;16(6):329–344. doi:10.1038/nrm3999
   PubMed Web of Science ®Google Scholar
• Doerflinger M, Deng Y, Whitney P, et al. Flexible usage and interconnectivity of diverse cell death pathways protect against intracellular infection. Immunity. 2020;53(3):533–547.e537. doi:10.1016/j.immuni.2020.07.004
   PubMed Web of Science ®Google Scholar
• Zhang Y, Chen X, Gueydan C, Han J. Plasma membrane changes during programmed cell deaths. Cell Res. 2018;28(1):9–21.
   PubMed Web of Science ®Google Scholar
• Fogarty CE, Bergmann A. Killers creating new life: caspases drive apoptosis-induced proliferation in tissue repair and disease. Cell Death Differ. 2017;24(8):1390–1400. doi:10.1038/cdd.2017.47
   PubMed Web of Science ®Google Scholar
• Gupta KH, Goldufsky JW, Wood SJ, et al. Apoptosis and compensatory proliferation signaling are coupled by CrkI-containing microvesicles. Dev Cell. 2017;41(6):674–684.e675. doi:10.1016/j.devcel.2017.05.014
   PubMed Web of Science ®Google Scholar
• Lee RH, Pulin AA, Seo MJ, et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 2009;5(1):54–63. doi:10.1016/j.stem.2009.05.003
   PubMed Web of Science ®Google Scholar
• Caruso S, Poon IKH. Apoptotic cell-derived extracellular vesicles: more than just debris. Front Immunol. 2018;9:1486. doi:10.3389/fimmu.2018.01486
   PubMed Web of Science ®Google Scholar
• Catalano M, O’Driscoll L. Inhibiting extracellular vesicles formation and release: a review of EV inhibitors. J Extracell Vesicles. 2020;9(1):1703244. doi:10.1080/20013078.2019.1703244
   PubMed Web of Science ®Google Scholar
• Atkin-Smith GK, Tixeira R, Paone S, et al. A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-A-string membrane structure. Nat Commun. 2015;6:7439. doi:10.1038/ncomms8439
   PubMed Web of Science ®Google Scholar
• Dieudé M, Bell C, Turgeon J, et al. The 20S proteasome core, active within apoptotic exosome-like vesicles, induces autoantibody production and accelerates rejection. Sci Transl Med. 2015;7(318):318ra200. doi:10.1126/scitranslmed.aac9816
   PubMed Web of Science ®Google Scholar
• Li M, Xing X, Huang H, et al. BMSC-derived ApoEVs promote craniofacial bone repair via ROS/JNK signaling. J Dent Res. 2022;101(6):714–723. doi:10.1177/00220345211068338
   PubMed Web of Science ®Google Scholar
• Liu D, Kou X, Chen C, et al. Circulating apoptotic bodies maintain mesenchymal stem cell homeostasis and ameliorate osteopenia via transferring multiple cellular factors. Cell Res. 2018;28(9):918–933. doi:10.1038/s41422-018-0070-2
   PubMed Web of Science ®Google Scholar
• Dou G, Tian R, Liu X, et al. Chimeric apoptotic bodies functionalized with natural membrane and modular delivery system for inflammation modulation. Sci Adv. 2020;6(30):eaba2987. doi:10.1126/sciadv.aba2987
   PubMed Web of Science ®Google Scholar
• Lleo A, Zhang W, McDonald WH, et al. Shotgun proteomics: identification of unique protein profiles of apoptotic bodies from biliary epithelial cells. Hepatology. 2014;60(4):1314–1323. doi:10.1002/hep.27230
   PubMed Web of Science ®Google Scholar
• Hu H, Dong L, Bu Z, et al. miR-23a-3p-abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration. J Extracell Vesicles. 2020;9(1):1778883. doi:10.1080/20013078.2020.1778883
   PubMed Web of Science ®Google Scholar