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Current Stem Cell Research & Therapy

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ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

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Mini-Review Article

Role of Extracellular Vesicles in Stem Cell Therapy

Author(s): Michael Kaiser*, Luis Rodriguez-Menocal and Evangelos V. Badiavas

Volume 19, Issue 5, 2024

Published on: 18 April, 2023

Page: [629 - 635] Pages: 7

DOI: 10.2174/1574888X17666220630162836

Price: $65

Abstract

Burn wounds are a major source of morbidity and mortality in both the military and civilian settings. Research about the pathophysiology of thermal injury has revealed possible interventions that can aid this process to reduce scarring and wound contracture. Bone Marrow derived Mesenchymal Stem Cells (BM-MSCs) have been an exciting topic in research for many years. They have been shown to facilitate wound healing and tissue regeneration, two areas that are vital in the healing process, especially in burn wounds. More recently the discovery of Extracellular Vesicles (EVs) has allowed us to further characterize the immunomodulatory roles and understand the cellular pathways implicated in wound healing. The purpose of this review is to discuss the role of EVs in wound healing, and to propose that EVs are the main mechanism that deliver cellular materials to target cells to coordinate wound healing following tissue injury.

Keywords: Extracellular vesicles, Burn wound, Mesenchymal Stem Cells

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Graphical Abstract

[1]
Champion HR, Bellamy RF, Roberts CP, Leppaniemi A. A profile of combat injury. J Trauma 2003; 54(5) (Suppl.): S13-9.
[PMID: 12768096]
[2]
Burn incidence fact sheet. American Burn Association 2016. https://ameriburn.org/who-we-are/
[3]
Hudson DA, Renshaw A. An algorithm for the release of burn contractures of the extremities. Burns 2006; 32(6): 663-8.
[http://dx.doi.org/10.1016/j.burns.2006.02.009] [PMID: 16905261]
[4]
Richard R, Baryza MJ, Carr JA, et al. Burn rehabilitation and research: Proceedings of a consensus summit. J Burn Care Res 2009; 30(4): 543-73.
[http://dx.doi.org/10.1097/BCR.0b013e3181adcd93] [PMID: 19506486]
[5]
Broughton G II, Janis JE, Attinger CE. A brief history of wound care. Plast Reconstr Surg 2006; 117(7) (Suppl.): 6S-11S.
[http://dx.doi.org/10.1097/01.prs.0000225429.76355.dd] [PMID: 16799371]
[6]
Schmauss D, Rezaeian F, Finck T, Machens HG, Wettstein R, Harder Y. Treatment of secondary burn wound progression in contact burns-a systematic review of experimental approaches. J Burn Care Res 2015; 36(3): e176-89.
[http://dx.doi.org/10.1097/BCR.0000000000000131] [PMID: 25094011]
[7]
Jackson DM. The diagnosis of the depth of burning. Br J Surg 1953; 40(164): 588-96.
[http://dx.doi.org/10.1002/bjs.18004016413] [PMID: 13059343]
[8]
Regas FC, Ehrlich HP. Elucidating the vascular response to burns with a new rat model. J Trauma 1992; 32(5): 557-63.
[http://dx.doi.org/10.1097/00005373-199205000-00004] [PMID: 1588642]
[9]
Işik S, Şahin U, Ilgan S, Güler M, Günalp B, Selmanpakoğlu N. Saving the zone of stasis in burns with recombinant tissue-type plasminogen activator (r-tPA): An experimental study in rats. Burns 1998; 24(3): 217-23.
[http://dx.doi.org/10.1016/S0305-4179(97)00116-2] [PMID: 9677024]
[10]
Shupp JW, Nasabzadeh TJ, Rosenthal DS, Jordan MH, Fidler P, Jeng JC. A review of the local pathophysiologic bases of burn wound progression. J Burn Care Res 2010; 31(6): 849-73.
[http://dx.doi.org/10.1097/BCR.0b013e3181f93571] [PMID: 21105319]
[11]
Aarabi S, Longaker MT, Gurtner GC. Hypertrophic scar formation following burns and trauma: New approaches to treatment. PLoS Med 2007; 4(9): e234.
[http://dx.doi.org/10.1371/journal.pmed.0040234] [PMID: 17803351]
[12]
Harrison CA, MacNeil S. The mechanism of skin graft contraction: An update on current research and potential future therapies. Burns 2008; 34(2): 153-63.
[http://dx.doi.org/10.1016/j.burns.2007.08.011] [PMID: 18226455]
[13]
Mendez-Eastman S. Guidelines for using negative pressure wound therapy. Adv Skin Wound Care 2001; 14(6): 314-22.
[http://dx.doi.org/10.1097/00129334-200111000-00015] [PMID: 11794443]
[14]
Kantak NA, Mistry R, Halvorson EG. A review of negative-pressure wound therapy in the management of burn wounds. Burns 2016; 42(8): 1623-33.
[http://dx.doi.org/10.1016/j.burns.2016.06.011] [PMID: 27378361]
[15]
Anzarut A, Olson J, Singh P, Rowe BH, Tredget EE. The effectiveness of pressure garment therapy for the prevention of abnormal scarring after burn injury: A meta-analysis. J Plast Reconstr Aesthet Surg 2009; 62(1): 77-84.
[http://dx.doi.org/10.1016/j.bjps.2007.10.052] [PMID: 18249046]
[16]
Friedstat JS, Hultman CS. Hypertrophic burn scar management: What does the evidence show? A systematic review of randomized controlled trials. Ann Plast Surg 2014; 72(6): S198-201.
[http://dx.doi.org/10.1097/SAP.0000000000000103] [PMID: 24835874]
[17]
Bloemen MC, van der Veer WM, Ulrich MM, van Zuijlen PP, Niessen FB, Middelkoop E. Prevention and curative management of hypertrophic scar formation. Burns 2009; 35(4): 463-75.
[http://dx.doi.org/10.1016/j.burns.2008.07.016] [PMID: 18951704]
[18]
Atiyeh BS, Hayek SN, Gunn SW. New technologies for burn wound closure and healing--review of the literature. Burns 2005; 31(8): 944-56.
[http://dx.doi.org/10.1016/j.burns.2005.08.023] [PMID: 16274932]
[19]
Sheridan RL, Tompkins RG. What’s new in burns and metabolism. J Am Coll Surg 2004; 198(2): 243-63.
[http://dx.doi.org/10.1016/j.jamcollsurg.2003.11.007] [PMID: 14759783]
[20]
Mansilla E. Marın G, Drago H, et al. Bloodstream cells phenotypically identical to human mesenchymal bone marrow stem cells circulate in large amounts under the influence of acute large skin damage: New evidence for their use in regenerative medicine. Transplantation proceedings: 2006. Elsevier 2006; pp. 967-9.
[http://dx.doi.org/10.1016/j.transproceed.2006.02.053]
[21]
Jung KJ, Lee GW, Park CH, et al. Mesenchymal stem cells decrease oxidative stress in the bowels of Interleukin-10 knockout mice. Gut Liver 2020; 14(1): 100-7.
[http://dx.doi.org/10.5009/gnl18438] [PMID: 31158947]
[22]
Jiang D, Muschhammer J, Qi Y, et al. Suppression of neutrophil‐mediated tissue damage-a novel skill of mesenchymal stem cells. Stem Cells 2016; 34(9): 2393-406.
[http://dx.doi.org/10.1002/stem.2417] [PMID: 27299700]
[23]
Ceccariglia S, Cargnoni A, Silini AR, Parolini O. Autophagy: A potential key contributor to the therapeutic action of mesenchymal stem cells. Autophagy 2020; 16(1): 28-37.
[http://dx.doi.org/10.1080/15548627.2019.1630223] [PMID: 31185790]
[24]
Rasulov MF, Vasilchenkov AV, Onishchenko NA, et al. First experience of the use bone marrow mesenchymal stem cells for the treatment of a patient with deep skin burns. Bull Exp Biol Med 2005; 139(1): 141-4.
[http://dx.doi.org/10.1007/s10517-005-0232-3] [PMID: 16142297]
[25]
Clover AJ, Kumar AH, Isakson M, et al. Allogeneic mesenchymal stem cells, but not culture modified monocytes, improve burn wound healing. Burns 2015; 41(3): 548-57.
[http://dx.doi.org/10.1016/j.burns.2014.08.009] [PMID: 25234958]
[26]
Wang M, Xu X, Lei X, Tan J, Xie H. Mesenchymal stem cell-based therapy for burn wound healing. Burns Trauma 2021; 9: b002.
[http://dx.doi.org/10.1093/burnst/tkab002] [PMID: 34212055]
[27]
Hassan WU, Greiser U, Wang W. Role of adipose-derived stem cells in wound healing. Wound Repair Regen 2014; 22(3): 313-25.
[http://dx.doi.org/10.1111/wrr.12173] [PMID: 24844331]
[28]
Yoshikawa T, Mitsuno H, Nonaka I, et al. Wound therapy by marrow mesenchymal cell transplantation. Plast Reconstr Surg 2008; 121(3): 860-77.
[http://dx.doi.org/10.1097/01.prs.0000299922.96006.24] [PMID: 18317135]
[29]
van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 2018; 19(4): 213-28.
[http://dx.doi.org/10.1038/nrm.2017.125] [PMID: 29339798]
[30]
Bray ER, Oropallo AR, Grande DA, Kirsner RS, Badiavas EV. Extracellular vesicles as therapeutic tools for the treatment of chronic wounds. Pharmaceutics 2021; 13(10): 1543.
[http://dx.doi.org/10.3390/pharmaceutics13101543] [PMID: 34683836]
[31]
Chaput N, Théry C. Exosomes: Immune properties and potential clinical implementations. Seminars in immunopathology: 2011. Springer 2011; p. 419-40.
[http://dx.doi.org/10.1007/s00281-010-0233-9]
[32]
Yáñez-Mó M, Siljander PR-M, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles 2015; 4(1): 27066.
[http://dx.doi.org/10.3402/jev.v4.27066] [PMID: 25979354]
[33]
Abels ER, Breakefield XO. Introduction to extracellular vesicles: Biogenesis, RNA cargo selection, content, release, and uptake. Cell Mol Neurobiol 2016; 36(3): 301-12.
[http://dx.doi.org/10.1007/s10571-016-0366-z] [PMID: 27053351]
[34]
Zhu J, Lu K, Zhang N, et al. Myocardial reparative functions of exosomes from mesenchymal stem cells are enhanced by hypoxia treatment of the cells via transferring microRNA-210 in an nSMase2-dependent way. Artif Cells Nanomed Biotechnol 2018; 46(8): 1659-70.
[PMID: 29141446]
[35]
Ban J-J, Lee M, Im W, Kim M. Low pH increases the yield of exosome isolation. Biochem Biophys Res Commun 2015; 461(1): 76-9.
[http://dx.doi.org/10.1016/j.bbrc.2015.03.172] [PMID: 25849885]
[36]
Guo S, Debbi L, Zohar B, et al. Stimulating extracellular vesicles production from engineered tissues by mechanical forces. Nano Lett 2021; 21(6): 2497-504.
[http://dx.doi.org/10.1021/acs.nanolett.0c04834] [PMID: 33709717]
[37]
Bai Y, Han YD, Yan XL, et al. Adipose mesenchymal stem cell-derived exosomes stimulated by hydrogen peroxide enhanced skin flap recovery in ischemia-reperfusion injury. Biochem Biophys Res Commun 2018; 500(2): 310-7.
[http://dx.doi.org/10.1016/j.bbrc.2018.04.065] [PMID: 29654765]
[38]
Hoang DH, Nguyen TD, Nguyen H-P, et al. Differential wound healing capacity of mesenchymal stem cell-derived exosomes originated from bone marrow, adipose tissue and umbilical cord under serum-and xeno-free condition. Front Mol Biosci 2020; 7: 119.
[http://dx.doi.org/10.3389/fmolb.2020.00119] [PMID: 32671095]
[39]
Xu R, Greening DW, Zhu H-J, Takahashi N, Simpson RJ. Extracellular vesicle isolation and characterization: Toward clinical application. J Clin Invest 2016; 126(4): 1152-62.
[http://dx.doi.org/10.1172/JCI81129] [PMID: 27035807]
[40]
Casado-Díaz A, Quesada-Gómez JM, Dorado G. Extracellular vesicles derived from mesenchymal stem cells (MSC) in regenerative medicine: Applications in skin wound healing. Front Bioeng Biotechnol 2020; 8: 146.
[http://dx.doi.org/10.3389/fbioe.2020.00146] [PMID: 32195233]
[41]
Théry C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol 2006; 30(1)
[http://dx.doi.org/10.1002/0471143030.cb0322s30]
[42]
Shabbir A, Cox A, Rodriguez-Menocal L, Salgado M, Van Badiavas E. Mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro. Stem Cells Dev 2015; 24(14): 1635-47.
[http://dx.doi.org/10.1089/scd.2014.0316] [PMID: 25867197]
[43]
McBride JD, Rodriguez-Menocal L, Guzman W, Candanedo A, Garcia-Contreras M, Badiavas EV. Bone marrow mesenchymal stem cell-derived CD63+ exosomes transport wnt3a exteriorly and enhance dermal fibroblast proliferation, migration, and angiogenesis in vitro. Stem Cells Dev 2017; 26(19): 1384-98.
[http://dx.doi.org/10.1089/scd.2017.0087] [PMID: 28679315]
[44]
McBride JD, Rodriguez-Menocal L, Candanedo A, Guzman W, Garcia-Contreras M, Badiavas EV. Dual mechanism of type VII collagen transfer by bone marrow mesenchymal stem cell extracellular vesicles to recessive dystrophic epidermolysis bullosa fibroblasts. Biochimie 2018; 155: 50-8.
[http://dx.doi.org/10.1016/j.biochi.2018.04.007] [PMID: 29653141]
[45]
Brown C, McKee C, Bakshi S, et al. Mesenchymal stem cells: Cell therapy and regeneration potential. J Tissue Eng Regen Med 2019; 13(9): 1738-55.
[http://dx.doi.org/10.1002/term.2914] [PMID: 31216380]
[46]
Rani S, Ryan AE, Griffin MD, Ritter T. Mesenchymal stem cell-derived extracellular vesicles: Toward cell-free therapeutic applications. Mol Ther 2015; 23(5): 812-23.
[http://dx.doi.org/10.1038/mt.2015.44] [PMID: 25868399]
[47]
Gangadaran P, Rajendran RL, Lee HW, et al. Extracellular vesicles from mesenchymal stem cells activates VEGF receptors and accelerates recovery of hindlimb ischemia. J Control Release 2017; 264: 112-26.
[http://dx.doi.org/10.1016/j.jconrel.2017.08.022] [PMID: 28837823]
[48]
Zhu YZ, Hu X, Zhang J, Wang ZH, Wu S, Yi YY. Extracellular vesicles derived from human adipose-derived stem cell prevent the formation of hypertrophic scar in a rabbit model. Ann Plast Surg 2020; 84(5): 602-7.
[http://dx.doi.org/10.1097/SAP.0000000000002357] [PMID: 32282497]
[49]
McBride JD, Rodriguez-Menocal L, Guzman W, et al. Proteomic analysis of bone marrow-derived mesenchymal stem cell extracellular vesicles from healthy donors: Implications for proliferation, angiogenesis, Wnt signaling, and the basement membrane. Stem Cell Res Ther 2021; 12(1): 328.
[http://dx.doi.org/10.1186/s13287-021-02405-7] [PMID: 34090527]
[50]
Chen M, Marinkovich MP, Veis A, et al. Interactions of the amino-terminal noncollagenous (NC1) domain of type VII collagen with extracellular matrix components. A potential role in epidermal-dermal adherence in human skin. J Biol Chem 1997; 272(23): 14516-22.
[http://dx.doi.org/10.1074/jbc.272.23.14516] [PMID: 9169408]
[51]
Guerra L, Odorisio T, Zambruno G, Castiglia D. Stromal microenvironment in type VII collagen-deficient skin: The ground for squamous cell carcinoma development. Matrix Biol 2017; 63: 1-10.
[http://dx.doi.org/10.1016/j.matbio.2017.01.002] [PMID: 28126522]
[52]
Abreu-Velez AM, Howard MS. Collagen IV in normal skin and in pathological processes. N Am J Med Sci 2012; 4(1): 1-8.
[http://dx.doi.org/10.4103/1947-2714.92892] [PMID: 22393540]
[53]
Desai RA, Gao L, Raghavan S, Liu WF, Chen CS. Cell polarity triggered by cell-cell adhesion via E-cadherin. J Cell Sci 2009; 122(Pt 7): 905-11.
[http://dx.doi.org/10.1242/jcs.028183] [PMID: 19258396]
[54]
Cabral J, Ryan AE, Griffin MD, Ritter T. Extracellular vesicles as modulators of wound healing. Adv Drug Deliv Rev 2018; 129: 394-406.
[http://dx.doi.org/10.1016/j.addr.2018.01.018] [PMID: 29408181]
[55]
Dauer DJ, Ferraro B, Song L, et al. Stat3 regulates genes common to both wound healing and cancer. Oncogene 2005; 24(21): 3397-408.
[http://dx.doi.org/10.1038/sj.onc.1208469] [PMID: 15735721]
[56]
Kano A, Wolfgang MJ, Gao Q, et al. Endothelial cells require STAT3 for protection against endotoxin-induced inflammation. J Exp Med 2003; 198(10): 1517-25.
[http://dx.doi.org/10.1084/jem.20030077] [PMID: 14623907]
[57]
Li X, Liu L, Yang J, et al. Exosome derived from human umbilical cord mesenchymal stem cell mediates MiR-181c attenuating burn-induced excessive inflammation. EBioMedicine 2016; 8: 72-82.
[http://dx.doi.org/10.1016/j.ebiom.2016.04.030] [PMID: 27428420]
[58]
Than UTT, Guanzon D, Leavesley D, Parker T. Association of extracellular membrane vesicles with cutaneous wound healing. Int J Mol Sci 2017; 18(5): 956.
[http://dx.doi.org/10.3390/ijms18050956] [PMID: 28468315]
[59]
Batsali AK, Georgopoulou A, Mavroudi I, Matheakakis A, Pontikoglou CG, Papadaki HA. The role of bone marrow mesenchymal stem cell derived extracellular vesicles (MSC-EVs) in normal and abnormal hematopoiesis and their therapeutic potential. J Clin Med 2020; 9(3): 856.
[http://dx.doi.org/10.3390/jcm9030856] [PMID: 32245055]
[60]
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): 2648-57.
[http://dx.doi.org/10.1038/jid.2014.169] [PMID: 24714203]
[61]
Gomzikova MO, James V, Rizvanov AA. Mitochondria donation by mesenchymal stem cells: Current understanding and mitochondria transplantation strategies. Front Cell Dev Biol 2021; 9: 653322.
[http://dx.doi.org/10.3389/fcell.2021.653322] [PMID: 33898449]
[62]
Ratajczak J, Miekus K, Kucia M, et al. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: Evidence for horizontal transfer of mRNA and protein delivery. Leukemia 2006; 20(5): 847-56.
[http://dx.doi.org/10.1038/sj.leu.2404132] [PMID: 16453000]
[63]
Klyachko NL, Arzt CJ, Li SM, Gololobova OA, Batrakova EV. Extracellular vesicle-based therapeutics: Preclinical and clinical investigations. Pharmaceutics 2020; 12(12): 1171.
[http://dx.doi.org/10.3390/pharmaceutics12121171] [PMID: 33271883]

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