Abstract
The rapidly evolving collective fields of tissue engineering and regenerative medicine (TERM) have high potential for development of new clinical therapies for treatment of peripheral nerve injuries. The positive results of experimental nerve repair strategies incorporating transplanted cells are now largely attributed to the secretion of paracrine factors, rather than cell engraftment. Extracellular vesicles (EVs), which make up part of the cell secretome, have emerged as important intercellular communicators in various biological processes. The bioactivity of EVs is mediated by their cargoes of various types of nucleic acids and proteins. In this chapter we present an overview of the biogenesis, isolation, and characterization of EVs, and describe how EVs might be useful adjuncts in TERM for peripheral nerve repair. In summary, EVs enhance axonal growth in vitro and in vivo, modulate Schwann cell function, and are highly likely to influence the neuroimmune and vascular cell reactions activated by peripheral nerve injury. Thus EVs have high potential for use as a new cell-free therapeutic approach for nerve repair.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akers JC, Gonda D, Kim R, Carter BS, Chen CC (2013) Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neuro-Oncol 113:1–11. https://doi.org/10.1007/s11060-013-1084-8
Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29:341–345. https://doi.org/10.1038/nbt.1807
Amorim MG et al (2017) A total transcriptome profiling method for plasma-derived extracellular vesicles: applications for liquid biopsies. Sci Rep 7:14395. https://doi.org/10.1038/s41598-017-14264-5
Antes TJ et al (2018) Targeting extracellular vesicles to injured tissue using membrane cloaking and surface display. J Nanobiotechnology 16:61. https://doi.org/10.1186/s12951-018-0388-4
Ashraf R, Sofi HS, Beigh MA, Sheikh FA (2019) Recent trends in peripheral nervous regeneration using 3D biomaterials. Tissue Cell 59:70–81. https://doi.org/10.1016/j.tice.2019.06.003
Bjorge IM, Kim SY, Mano JF, Kalionis B, Chrzanowski W (2017) Extracellular vesicles, exosomes and shedding vesicles in regenerative medicine – a new paradigm for tissue repair. Biomater Sci 6:60–78. https://doi.org/10.1039/c7bm00479f
Brini AT et al (2017) Therapeutic effect of human adipose-derived stem cells and their secretome in experimental diabetic pain. Sci Rep 7:9904. https://doi.org/10.1038/s41598-017-09487-5
Bucan V, Vaslaitis D, Peck CT, Strauss S, Vogt PM, Radtke C (2019) Effect of exosomes from rat adipose-derived mesenchymal stem cells on neurite outgrowth and sciatic nerve regeneration after crush injury. Mol Neurobiol 56:1812–1824. https://doi.org/10.1007/s12035-018-1172-z
Buschmann D et al (2018) Evaluation of serum extracellular vesicle isolation methods for profiling miRNAs by next-generation sequencing. J Extracell Vesicles 7:1481321. https://doi.org/10.1080/20013078.2018.1481321
Carvalho CR, Oliveira JM, Reis RL (2019) Modern trends for peripheral nerve repair and regeneration: beyond the hollow nerve guidance conduit. Front Bioeng Biotechnol 7:337. https://doi.org/10.3389/fbioe.2019.00337
Cattin AL et al (2015) Macrophage-induced blood vessels guide Schwann cell-mediated regeneration of peripheral nerves. Cell 162:1127–1139. https://doi.org/10.1016/j.cell.2015.07.021
Chen J et al (2019) Exosomes from human adipose-derived stem cells promote sciatic nerve regeneration via optimizing Schwann cell function. J Cell Physiol 234:23097–23110. https://doi.org/10.1002/jcp.28873
Ching RC, Wiberg M, Kingham PJ (2018) Schwann cell-like differentiated adipose stem cells promote neurite outgrowth via secreted exosomes and RNA transfer. Stem Cell Res Ther 9:266. https://doi.org/10.1186/s13287-018-1017-8
Chuo ST, Chien JC, Lai CP (2018) Imaging extracellular vesicles: current and emerging methods. J Biomed Sci 25:91. https://doi.org/10.1186/s12929-018-0494-5
Crescitelli R et al (2013) Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes. J Extracell Vesicles 2. https://doi.org/10.3402/jev.v2i0.20677
de Rivero Vaccari JP et al (2016) Exosome-mediated inflammasome signaling after central nervous system injury. J Neurochem 136(Suppl 1):39–48. https://doi.org/10.1111/jnc.13036
Di Rocco G, Baldari S, Toietta G (2016) Towards therapeutic delivery of extracellular vesicles: strategies for in vivo tracking and biodistribution analysis. Stem Cells Int 2016:5029619. https://doi.org/10.1155/2016/5029619
Dong R, Liu Y, Yang Y, Wang H, Xu Y, Zhang Z (2019) MSC-Derived exosomes-based therapy for peripheral nerve injury: a novel therapeutic strategy. Biomed Res Int 2019:6458237. https://doi.org/10.1155/2019/6458237
Dragovic RA et al (2011) Sizing and phenotyping of cellular vesicles using nanoparticle tracking analysis. Nanomedicine 7:780–788. https://doi.org/10.1016/j.nano.2011.04.003
Eldh M, Ekstrom K, Valadi H, Sjostrand M, Olsson B, Jernas M, Lotvall J (2010) Exosomes communicate protective messages during oxidative stress; possible role of exosomal shuttle RNA. PLoS One 5:e15353. https://doi.org/10.1371/journal.pone.0015353
Ezquer FE, Ezquer ME, Vicencio JM, Calligaris SD (2017) Two complementary strategies to improve cell engraftment in mesenchymal stem cell-based therapy: increasing transplanted cell resistance and increasing tissue receptivity. Cell Adhes Migr 11:110–119. https://doi.org/10.1080/19336918.2016.1197480
Feng D et al (2010) Cellular internalization of exosomes occurs through phagocytosis. Traffic 11:675–687. https://doi.org/10.1111/j.1600-0854.2010.01041.x
Gama KB et al (2018) Conditioned medium of bone marrow-derived mesenchymal stromal cells as a therapeutic approach to neuropathic pain: a preclinical evaluation. Stem Cells Int 2018:8179013. https://doi.org/10.1155/2018/8179013
Gandham S et al (2020) Technologies and standardization in research on extracellular vesicles. Trends Biotechnol. https://doi.org/10.1016/j.tibtech.2020.05.012
Gibbings DJ, Ciaudo C, Erhardt M, Voinnet O (2009) Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol 11:1143–1149. https://doi.org/10.1038/ncb1929
Grinblat GA, Khan RS, Dine K, Wessel H, Brown L, Shindler KS (2018) RGC Neuroprotection Following Optic Nerve Trauma Mediated By Intranasal Delivery of Amnion Cell Secretome. Invest Ophthalmol Vis Sci 59:2470–2477. https://doi.org/10.1167/iovs.18-24096
Guo SC, Tao SC, Dawn H (2018) Microfluidics-based on-a-chip systems for isolating and analysing extracellular vesicles. J Extracell Vesicles 7:1508271. https://doi.org/10.1080/20013078.2018.1508271
Gutmann E (1962) Denervation and disuse atrophy in crosstriated muscle. Rev Can Biol 21:353–365
Haertinger M, Weiss T, Mann A, Tabi A, Brandel V, Radtke C (2020) Adipose stem cell-derived extracellular vesicles induce proliferation of schwann cells via internalization. Cell 9:163. https://doi.org/10.3390/cells9010163
Han C et al (2019) Delivery of miR-675 by stem cell-derived exosomes encapsulated in silk fibroin hydrogel prevents aging-induced vascular dysfunction in mouse hindlimb. Mater Sci Eng C Mater Biol Appl 99:322–332. https://doi.org/10.1016/j.msec.2019.01.122
Haney MJ et al (2015) Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release 207:18–30. https://doi.org/10.1016/j.jconrel.2015.03.033
Hart AM, Terenghi G, Wiberg M (2008) Neuronal death after peripheral nerve injury and experimental strategies for neuroprotection. Neurol Res 30:999–1011. https://doi.org/10.1179/174313208X362479
Hartjes TA, Mytnyk S, Jenster GW, van Steijn V, van Royen ME (2019) Extracellular vesicle quantification and characterization: common methods and emerging approaches. Bioengineering (Basel):6. https://doi.org/10.3390/bioengineering6010007
Helwa I et al (2017) A comparative study of serum exosome isolation using differential ultracentrifugation and three commercial reagents. PLoS One 12:e0170628. https://doi.org/10.1371/journal.pone.0170628
Hobson MI, Brown R, Green CJ, Terenghi G (1997) Inter-relationships between angiogenesis and nerve regeneration: a histochemical study. Br J Plast Surg 50:125–131. https://doi.org/10.1016/s0007-1226(97)91325-4
Jangamreddy JR et al (2018) Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants. Acta Biomater 69:120–130. https://doi.org/10.1016/j.actbio.2018.01.011
Jean-Toussaint R, Tian Y, Chaudhuri AD, Haughey NJ, Sacan A, Ajit SK (2020) Proteome characterization of small extracellular vesicles from spared nerve injury model of neuropathic pain. J Proteome 211:103540. https://doi.org/10.1016/j.jprot.2019.103540
Kang T et al (2016) Adipose-derived stem cells induce angiogenesis via microvesicle transport of miRNA-31. Stem CellsTransl Med 5:440–450. https://doi.org/10.5966/sctm.2015-0177
Kehoe S, Zhang XF, Boyd D (2012) FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy. Injury 43:553–572. https://doi.org/10.1016/j.injury.2010.12.030
Kolar MK, Kingham PJ (2014) Regenerative effects of adipose-tissue-derived stem cells for treatment of peripheral nerve injuries. Biochem Soc Trans 42:697–701. https://doi.org/10.1042/BST20140004
Krawczenko A, Bielawska-Pohl A, Paprocka M, Kraskiewicz H, Szyposzynska A, Wojdat E, Klimczak A (2020) Microvesicles from human immortalized cell lines of endothelial progenitor cells and mesenchymal stem/stromal cells of adipose tissue origin as carriers of bioactive factors facilitating angiogenesis. Stem Cells Int 2020:1289380. https://doi.org/10.1155/2020/1289380
Kusuma GD, Barabadi M, Tan JL, Morton DAV, Frith JE, Lim R (2018) To protect and to preserve: novel preservation strategies for extracellular vesicles. Front Pharmacol 9:1199. https://doi.org/10.3389/fphar.2018.01199
Lai RC et al (2012) Proteolytic potential of the msc exosome proteome: implications for an exosome-mediated delivery of therapeutic proteasome. Int J Proteomics 2012:971907. https://doi.org/10.1155/2012/971907
Li W et al (2018) Tissue-engineered bone immobilized with human adipose stem cells-derived exosomes promotes bone regeneration. ACS Appl Mater Interfaces 10:5240–5254. https://doi.org/10.1021/acsami.7b17620
Liu CY et al (2020) Effect of exosomes from adipose-derived stem cells on the apoptosis of Schwann cells in peripheral nerve injury. CNS Neurosci Ther 26:189–196. https://doi.org/10.1111/cns.13187
Lopatina T, Bruno S, Tetta C, Kalinina N, Porta M, Camussi G (2014) Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential. Cell Commun Signal 12:26. https://doi.org/10.1186/1478-811X-12-26
Lopez-Verrilli MA, Picou F, Court FA (2013) Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. Glia 61:1795–1806. https://doi.org/10.1002/glia.22558
Lotvall J et al (2014) Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles 3:26913. https://doi.org/10.3402/jev.v3.26913
Ma Y, Ge S, Zhang J, Zhou D, Li L, Wang X, Su J (2017) Mesenchymal stem cell-derived extracellular vesicles promote nerve regeneration after sciatic nerve crush injury in rats. Int J Clin Exp Pathol 10:10032–10039
Ma Y et al (2019) Extracellular vesicles from human umbilical cord mesenchymal stem cells improve nerve regeneration after sciatic nerve transection in rats. J Cell Mol Med 23:2822–2835. https://doi.org/10.1111/jcmm.14190
Madison RD, Robinson GA (2019) Muscle-derived extracellular vesicles influence motor neuron regeneration accuracy. Neuroscience 419:46–59. https://doi.org/10.1016/j.neuroscience.2019.08.028
Madison RD, McGee C, Rawson R, Robinson GA (2014) Extracellular vesicles from a muscle cell line (C2C12) enhance cell survival and neurite outgrowth of a motor neuron cell line (NSC-34). J Extracell Vesicles 3. https://doi.org/10.3402/jev.v3.22865
Mao Q, Nguyen PD, Shanti RM, Shi S, Shakoori P, Zhang Q, Le AD (2019) Gingiva-derived mesenchymal stem cell-extracellular vesicles activate schwann cell repair phenotype and promote nerve regeneration tissue. Eng Part A 25:887–900. https://doi.org/10.1089/ten.TEA.2018.0176
Mead B, Tomarev S (2017) Bone marrow-derived mesenchymal stem cells-derived exosomes promote survival of retinal ganglion cells through mirna-dependent mechanisms. Stem Cells Transl Med 6:1273–1285. https://doi.org/10.1002/sctm.16-0428
Mead B, Chamling X, Zack DJ, Ahmed Z, Tomarev S (2020a) TNFα-mediated priming of mesenchymal stem cells enhances their neuroprotective effect on retinal ganglion cells. Invest Ophthalmol Vis Sci 61:6. https://doi.org/10.1167/iovs.61.2.6
Mead B, Cullather E, Nakaya N, Niu Y, Kole C, Ahmed Z, Tomarev S (2020b) Viral delivery of multiple miRNAs promotes retinal ganglion cell survival and functional preservation after optic nerve crush injury. Exp Eye Res 197:108071. https://doi.org/10.1016/j.exer.2020.108071
Moon GJ et al (2019) Application of mesenchymal stem cell-derived extracellular vesicles for stroke: biodistribution and microrna study. Transl Stroke Res 10:509–521. https://doi.org/10.1007/s12975-018-0668-1
Morelli AE et al (2004) Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 104:3257–3266. https://doi.org/10.1182/blood-2004-03-0824
Muangsanit P, Shipley RJ, Phillips JB (2018) Vascularization strategies for peripheral nerve tissue engineering. Anat Rec (Hoboken) 301:1657–1667. https://doi.org/10.1002/ar.23919
Mueller M, Leonhard C, Wacker K, Ringelstein EB, Okabe M, Hickey WF, Kiefer R (2003) Macrophage response to peripheral nerve injury: the quantitative contribution of resident and hematogenous macrophages. Lab Investig 83:175–185. https://doi.org/10.1097/01.lab.0000056993.28149.bf
Mulcahy LA, Pink RC, Carter DR (2014) Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles 3. https://doi.org/10.3402/jev.v3.24641
Nanbo A, Kawanishi E, Yoshida R, Yoshiyama H (2013) Exosomes derived from Epstein-Barr virus-infected cells are internalized via caveola-dependent endocytosis and promote phenotypic modulation in target cells. J Virol 87:10334–10347. https://doi.org/10.1128/JVI.01310-13
Pascucci L et al (2014) Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery. J Control Release 192:262–270. https://doi.org/10.1016/j.jconrel.2014.07.042
Patel DB, Gray KM, Santharam Y, Lamichhane TN, Stroka KM, Jay SM (2017) Impact of cell culture parameters on production and vascularization bioactivity of mesenchymal stem cell-derived extracellular vesicles. Bioeng Transl Med 2:170–179. https://doi.org/10.1002/btm2.10065
Patel DB, Santoro M, Born LJ, Fisher JP, Jay SM (2018) Towards rationally designed biomanufacturing of therapeutic extracellular vesicles: impact of the bioproduction microenvironment. Biotechnol Adv 36:2051–2059. https://doi.org/10.1016/j.biotechadv.2018.09.001
Ramasubramanian L, Kumar P, Wang A (2019) Engineering extracellular vesicles as nanotherapeutics for regenerative medicine. Biomolecules:10. https://doi.org/10.3390/biom10010048
Rao F et al (2019) Exosomes from human gingiva-derived mesenchymal stem cells combined with biodegradable chitin conduits promote rat sciatic nerve regeneration. Stem Cells Int 2019:2546367. https://doi.org/10.1155/2019/2546367
Ren R et al (2019) Bone marrow mesenchymal stem cell-derived exosome uptake and retrograde transport can occur at peripheral nerve endings. Artif Cells Nanomed Biotechnol 47:2918–2929. https://doi.org/10.1080/21691401.2019.1640713
Riau AK, Ong HS, Yam GHF, Mehta JS (2019) Sustained delivery system for stem cell-derived exosomes. Front Pharmacol 10:1368. https://doi.org/10.3389/fphar.2019.01368
Rotshenker S (2011) Wallerian degeneration: the innate-immune response to traumatic nerve injury. J Neuroinflammation 8:109. https://doi.org/10.1186/1742-2094-8-109
Saito H, Kanje M, Dahlin LB (2009) Delayed nerve repair increases number of caspase 3 stained Schwann cells. Neurosci Lett 456:30–33. https://doi.org/10.1016/j.neulet.2009.03.075
Shi Q et al (2017) GMSC-derived exosomes combined with a chitosan/silk hydrogel sponge accelerates wound healing in a diabetic rat skin defect model. Front Physiol 8:904. https://doi.org/10.3389/fphys.2017.00904
Shiue SJ, Rau RH, Shiue HS, Hung YW, Li ZX, Yang KD, Cheng JK (2019) Mesenchymal stem cell exosomes as a cell-free therapy for nerve injury-induced pain in rats. Pain 160:210–223. https://doi.org/10.1097/j.pain.0000000000001395
Siemionow M, Brzezicki G (2009) Chapter 8: Current techniques and concepts in peripheral nerve repair. Int Rev Neurobiol 87:141–172. https://doi.org/10.1016/S0074-7742(09)87008-6
Simeoli R et al (2017) Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma. Nat Commun 8:1778. https://doi.org/10.1038/s41467-017-01841-5
Smyth T et al (2014) Surface functionalization of exosomes using click chemistry. Bioconjug Chem 25:1777–1784. https://doi.org/10.1021/bc500291r
Sohn EJ, Park HT, Shin YK (2020) Exosomes derived from differentiated Schwann cells inhibit Schwann cell migration via microRNAs. Neuroreport 31:515–522. https://doi.org/10.1097/WNR.0000000000001435
Stephens L, Ellson C, Hawkins P (2002) Roles of PI3Ks in leukocyte chemotaxis and phagocytosis. Curr Opin Cell Biol 14:203–213. https://doi.org/10.1016/s0955-0674(02)00311-3
Subang MC, Richardson PM (2001) Influence of injury and cytokines on synthesis of monocyte chemoattractant protein-1 mRNA in peripheral nervous tissue. Eur J Neurosci 13:521–528. https://doi.org/10.1046/j.1460-9568.2001.01425.x
Sugimura-Wakayama Y, Katagiri W, Osugi M, Kawai T, Ogata K, Sakaguchi K, Hibi H (2015) Peripheral nerve regeneration by secretomes of stem cells from human exfoliated deciduous teeth. Stem Cells Dev 24:2687–2699. https://doi.org/10.1089/scd.2015.0104
Tang X, Sun C (2020) The roles of MicroRNAs in neural regenerative medicine. Exp Neurol 332:113394. https://doi.org/10.1016/j.expneurol.2020.113394
Tapp M, Wenzinger E, Tarabishy S, Ricci J, Herrera FA (2019) The epidemiology of upper extremity nerve injuries and associated cost in the US emergency departments. Ann Plast Surg 83:676–680. https://doi.org/10.1097/SAP.0000000000002083
Taraboletti G, D’Ascenzo S, Borsotti P, Giavazzi R, Pavan A, Dolo V (2002) Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. Am J Pathol 160:673–680. https://doi.org/10.1016/S0002-9440(10)64887-0
Taskinen HS, Roytta M (1997) The dynamics of macrophage recruitment after nerve transection. Acta Neuropathol 93:252–259. https://doi.org/10.1007/s004010050611
Thery C (2011) Exosomes: secreted vesicles and intercellular communications F1000. Biol Reprod 3:15. https://doi.org/10.3410/B3-15
Thery C et al (2018) Minimal information for studies of extracellular vesicles 2018 (MISEV 2018): a position statement of the international society for extracellular vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 7:1535750. https://doi.org/10.1080/20013078.2018.1535750
Ti D et al (2015) LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b. J Transl Med 13:308. https://doi.org/10.1186/s12967-015-0642-6
Todorova D, Simoncini S, Lacroix R, Sabatier F, Dignat-George F (2017) Extracellular vesicles in angiogenesis. Circ Res 120:1658–1673. https://doi.org/10.1161/CIRCRESAHA.117.309681
Tofaris GK, Patterson PH, Jessen KR, Mirsky R (2002) Denervated Schwann cells attract macrophages by secretion of leukemia inhibitory factor (LIF) and monocyte chemoattractant protein-1 in a process regulated by interleukin-6 and LIF. J Neurosci 22:6696–6703. https://doi.org/10.1523/JNEUROSCI.22-15-06696.2002
Tohill M, Mantovani C, Wiberg M, Terenghi G (2004) Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration. Neurosci Lett 362:200–203. https://doi.org/10.1016/j.neulet.2004.03.077
Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659. https://doi.org/10.1038/ncb1596
Wakao S, Matsuse D, Dezawa M (2014) Mesenchymal stem cells as a source of Schwann cells: their anticipated use in peripheral nerve regeneration. Cells Tissues Organs 200:31–41. https://doi.org/10.1159/000368188
Wang LH, Rothberg KG, Anderson RG (1993) Mis-assembly of clathrin lattices on endosomes reveals a regulatory switch for coated pit formation. J Cell Biol 123:1107–1117. https://doi.org/10.1083/jcb.123.5.1107
Wang L et al (2020) Exosomes derived from Schwann cells ameliorate peripheral neuropathy in type 2 diabetic mice. Diabetes 69:749–759. https://doi.org/10.2337/db19-0432
Watson DC et al (2016) Efficient production and enhanced tumor delivery of engineered extracellular vesicles. Biomaterials 105:195–205. https://doi.org/10.1016/j.biomaterials.2016.07.003
Watson DC et al (2018) Scalable, cGMP-compatible purification of extracellular vesicles carrying bioactive human heterodimeric IL-15/lactadherin complexes. J Extracell vesicles 7:1442088. https://doi.org/10.1080/20013078.2018.1442088
West CA, Hart AM, Terenghi G, Wiberg M (2007) Analysis of the dose-response of N-acetylcysteine in the prevention of sensory neuronal loss after peripheral nerve injury. Acta Neurochir Suppl 100:29–31. https://doi.org/10.1007/978-3-211-72958-8_6
Xia B et al (2019) Extracellular vesicles derived from olfactory ensheathing cells promote peripheral nerve regeneration in rats. Front Cell Neurosci 13:548. https://doi.org/10.3389/fncel.2019.00548
Zhan C, Ma CB, Yuan HM, Cao BY, Zhu JJ (2015) Macrophage-derived microvesicles promote proliferation and migration of Schwann cell on peripheral nerve repair. Biochem Biophys Res Commun 468:343–348. https://doi.org/10.1016/j.bbrc.2015.10.097
Zhang B, Yin Y, Lai RC, Tan SS, Choo AB, Lim SK (2014) Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev 23:1233–1244. https://doi.org/10.1089/scd.2013.0479
Zhang H et al (2018) Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat Cell Biol 20:332–343. https://doi.org/10.1038/s41556-018-0040-4
Zhang Y, Wang WT, Gong CR, Li C, Shi M (2020) Combination of olfactory ensheathing cells and human umbilical cord mesenchymal stem cell-derived exosomes promotes sciatic nerve regeneration. Neural Regen Res 15:1903–1911. https://doi.org/10.4103/1673-5374.280330
Zhou D, Zhai W, Zhang M (2018) Mesenchymal stem cell-derived extracellular vesicles promote apoptosis in RSC96 Schwann cells through the activation of the ERK pathway. Int J Clin Exp Pathol 11:5157–5170
Zigmond RE, Echevarria FD (2019) Macrophage biology in the peripheral nervous system after injury. Prog Neurobiol 173:102–121. https://doi.org/10.1016/j.pneurobio.2018.12.001
Acknowledgments
The Laboratory of Neural Repair and Cellular Therapy is funded in part by a grant from Vinnova – Sweden’s Innovation Agency (Project CAMP, contract number 2017-02130). Dr. Gustav Andersson is an associated researcher at the Wallenberg Centre for Molecular Medicine (Umeå University).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Switzerland AG
About this entry
Cite this entry
Andersson, G., Kingham, P.J. (2021). Extracellular Vesicles for Nerve Regeneration. In: Phillips, J., Hercher, D., Hausner, T. (eds) Peripheral Nerve Tissue Engineering and Regeneration. Reference Series in Biomedical Engineering(). Springer, Cham. https://doi.org/10.1007/978-3-030-06217-0_8-1
Download citation
DOI: https://doi.org/10.1007/978-3-030-06217-0_8-1
Received:
Accepted:
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-06217-0
Online ISBN: 978-3-030-06217-0
eBook Packages: Springer Reference EngineeringReference Module Computer Science and Engineering