Newt cells secrete extracellular vesicles with therapeutic bioactivity in mammalian cardiomyocytes

References

• Brockes JP, Kumar A. Appendage regeneration in adult vertebrates and implications for regenerative medicine. Science. 2005;310(5756):1–15.
   Web of Science ®Google Scholar
• Zgheib C, Allukian MW, Xu J, et al. Mammalian fetal cardiac regeneration following myocardial infarction is associated with differential gene expression compared to the adult. Ann Thorac Surg. 2014;97(5):1643–1650.
   Web of Science ®Google Scholar
• van Weerd JH, Christoffels VM. The formation and function of the cardiac conduction system. Development. 2016;143(2):197–210.
   Web of Science ®Google Scholar
• Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Nat Rev Cardiol. 2012;9(11):620–633.
   PubMed Web of Science ®Google Scholar
• Oberpriller JO, Oberpriller JC. Response of the adult newt ventricle to injury. J Exp Zool. 1974;187(2):249–253.
   Google Scholar
• Oberpriller JO, Oberpriller JC, Matz DG, et al. Stimulation of proliferative events in the adult amphibian cardiac myocyte. Ann N Y Acad Sci. 1995;752:30–46.
   Web of Science ®Google Scholar
• Grassme KS, Garza-Garcia A, Delgado JP, et al. Mechanism of action of secreted newt anterior gradient protein. PLoS One. 2016;11(4):e0154176.
   Web of Science ®Google Scholar
• McGann CJ, Odelberg SJ, Keating MT. Mammalian myotube dedifferentiation induced by newt regeneration extract. Proc Natl Acad Sci U S A. 2001;98(24):13699–13704.
   Web of Science ®Google Scholar
• Kawesa S, Vanstone J, Tsilfidis C. A differential response to newt regeneration extract by C2C12 and primary mammalian muscle cells. Skelet Muscle. 2015;5:19.
   Web of Science ®Google Scholar
• Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373–383.
   PubMed Web of Science ®Google Scholar
• Tseliou E, Weixin L, Valle J, et al. Newt exosomes are bioactive on mammalian heart, enhancing proliferation of rat cardiomyocytes and improving recovery after myocardial infarction. Circulation. 2015;132:A15925.
   Web of Science ®Google Scholar
• Middleton RC, Tseliou E, Antes TJ, et al. Newt exosomes are shuttles of bioactive RNAs and proteins that have signaling capabilities in mammalian systems of cardiac repair. Circulation. 2016;134:A19422.
   Web of Science ®Google Scholar
• Griffin KJ, Fekete DM, Carlson BM. A monoclonal antibody stains myogenic cells in regenerating newt muscle. Development. 1987;101(2):267–277.
   Web of Science ®Google Scholar
• Ferretti P, Ghosh S. Expression of regeneration-associated cytoskeletal proteins reveals differences and similarities between regenerating organs. Dev Dyn. 1997;210(3):288–304.
   Web of Science ®Google Scholar
• Ibrahim AG-E, Cheng K, Marbán E. Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Rep. 2014;2:606–619.
   PubMed Web of Science ®Google Scholar
• Golden HB, Gollapudi D, Gerilechaogetu F, et al. Isolation of cardiac myocytes and fibroblasts from neonatal rat pups. Methods Mol Biol. 2012;843:205–214.
   Google Scholar
• Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–408.
   PubMed Web of Science ®Google Scholar
• Eng JK, Jahan TA, Hoopmann MR. Comet: an open-source MS/MS sequence database search tool. Proteomics. 2013;13(1):22–24.
   PubMed Web of Science ®Google Scholar
• Craig R, Beavis RC. TANDEM: matching proteins with tandem mass spectra. Bioinformatics. 2004;20(9):1466–1467.
   PubMed Web of Science ®Google Scholar
• Keller A, Nesvizhskii AI, Kolker E, et al. Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal Chem. 2002;74(20):5383–5392.
   PubMed Web of Science ®Google Scholar
• MacLean B, Tomazela DM, Shulman N, et al. Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics. 2010;26(7):966–968.
   PubMed Web of Science ®Google Scholar
• Pathan M, Keerthikumar S, Ang CS, et al. FunRich: an open access standalone functional enrichment and interaction network analysis tool. Proteomics. 2015;15(15):2597–2601.
   PubMed Web of Science ®Google Scholar
• Khan SY, Hackett SF, Riazuddin SA. Non-coding RNA profiling of the developing murine lens. Exp Eye Res. 2016;145:347–351.
   Web of Science ®Google Scholar
• Ferretti P, Brockes JP. Culture of newt cells from different tissues and their expression of a regeneration-associated antigen. J Exp Zool. 1988;247(1):77–91.
   PubMedGoogle Scholar
• Xie Y, Ibrahim A, Cheng K, et al. Importance of cell-cell contact in the therapeutic benefits of cardiosphere-derived cells. Stem Cells. 2014;32(9):2397–2406.
   PubMed Web of Science ®Google Scholar
• Janero DR, Hreniuk D, Sharif HM. Hydrogen peroxide-induced oxidative stress to the mammalian heart-muscle cell (cardiomyocyte): nonperoxidative purine and pyrimidine nucleotide depletion. J Cell Physiol. 1993;155(3):494–504.
   Web of Science ®Google Scholar
• Barile L, Lionetti V, Cervio E, et al. Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. Cardiovasc Res. 2014;103(4):530–541.
   PubMed Web of Science ®Google Scholar
• Wang YZL, Li Y, Chen L, et al. Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium. Int J Cardiol. 2015;192:61–69.
   PubMed Web of Science ®Google Scholar
• Mead B, Tomarev S. Bone marrow-derived mesenchymal stem cells-derived exosomes promote survival of retinal ganglion cells through miRNA-dependent mechanisms. Stem Cells Transl Med. 2017;6(4):1273–1285.
   PubMed Web of Science ®Google Scholar
• Toh WS, Lai RC, Hui JHP, et al. MSC exosome as a cell-free MSC therapy for cartilage regeneration: implications for osteoarthritis treatment. Semin Cell Dev Biol. 2017;67:56–64.
   PubMed Web of Science ®Google Scholar
• Yan Y, Jiang W, Tan Y, et al. hucMSC exosome-derived GPX1 is required for the recovery of hepatic oxidant injury. Mol Ther. 2017;25(2):465–479.
   PubMed Web of Science ®Google Scholar
• Essandoh K, Yang L, Wang X, et al. Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction. Biochim Biophys Acta. 2015;1852(11):2362–2371.
   PubMed Web of Science ®Google Scholar
• Trajkovic K, Hsu C, Chiantia S, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319(5867):1244–1247.
   PubMed Web of Science ®Google Scholar
• Kim DS, Kim SY, Moon SJ, et al. Ceramide inhibits cell proliferation through Akt/PKB inactivation and decreases melanin synthesis in Mel-Ab cells. Pigment Cell Res. 2001;14(2):110–115.
   Google Scholar
• Gills JJ, Zhang C, Abu-Asab MS, et al. Ceramide mediates nanovesicle shedding and cell death in response to phosphatidylinositol ether lipid analogs and perifosine. Cell Death Dis. 2012;3:e340.
   Web of Science ®Google Scholar
• Uchida Y. Ceramide signaling in mammalian epidermis. Biochim Biophys Acta. 2014;1841(3):453–462.
   Web of Science ®Google Scholar
• van Heerde WL, Robert-Offerman S, Dumont E, et al. Markers of apoptosis in cardiovascular tissues: focus on Annexin V. Cardiovasc Res. 2000;45(3):549–559.
   PubMed Web of Science ®Google Scholar
• Lin Z, Zhou P, Von Gise A, et al. Pi3kcb links Hippo-YAP and PI3K-AKT signaling pathways to promote cardiomyocyte proliferation and survival. Circ Res. 2015;116(1):35–45.
   PubMed Web of Science ®Google Scholar
• Goumans MJ, De Boer TP, Smits AM, et al. TGF-beta1 induces efficient differentiation of human cardiomyocyte progenitor cells into functional cardiomyocytes in vitro. Stem Cell Res. 2007;1(2):138–149.
   PubMed Web of Science ®Google Scholar
• Aikawa R, Nawano M, Gu Y, et al. Insulin prevents cardiomyocytes from oxidative stress-induced apoptosis through activation of PI3 kinase/Akt. Circulation. 2000;102(23):2873–2879.
   PubMed Web of Science ®Google Scholar
• Savina A, Vidal M, Colombo MI. The exosome pathway in K562 cells is regulated by Rab11. J Cell Sci. 2002;115(Pt 12):2505–2515.
   PubMed Web of Science ®Google Scholar
• Gupta S, Knowlton AA. HSP60 trafficking in adult cardiac myocytes: role of the exosomal pathway. Am J Physiol Heart Circ Physiol. 2007;292(6):H3052–H3056.
   PubMed Web of Science ®Google Scholar
• Kuhn B, del Monte F, Hajjar RJ, et al. Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nat Med. 2007;13(8):962–969.
   PubMed Web of Science ®Google Scholar
• Taniyama Y, Katsuragi N, Sanada F, et al. Selective blockade of periostin exon 17 preserves cardiac performance in acute myocardial infarction. Hypertension. 2016;67(2):356–361.
   Web of Science ®Google Scholar
• Brenmoehl J, Falk W, Goke M, et al. Inflammation modulates fibronectin isoform expression in colonic lamina propria fibroblasts (CLPF). Int J Colorectal Dis. 2008;23(10):947–955.
   Web of Science ®Google Scholar
• Nakai W, Yoshida T, Diez D, et al. A novel affinity-based method for the isolation of highly purified extracellular vesicles. Sci Rep. 2016;6:33935.
   PubMed Web of Science ®Google Scholar
• Treps L, Edmond S, Harford-Wright E, et al. Extracellular vesicle-transported Semaphorin3A promotes vascular permeability in glioblastoma. Oncogene. 2016;35(20):2615–2623.
   PubMed Web of Science ®Google Scholar
• Lu P, Takai K, Weaver VM, et al. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol. 2011;3(12).
   PubMed Web of Science ®Google Scholar
• Villarroya-Beltri C, Gutierrez-Vazquez C, Sanchez-Cabo F, et al. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun. 2013;4:2980.
   PubMed Web of Science ®Google Scholar
• Jean-Philippe J, Paz S, Caputi M. hnRNP A1: the Swiss army knife of gene expression. Int J Mol Sci. 2013;14(9):18999–19024.
   Web of Science ®Google Scholar
• Burge SW, Daub J, Eberhardt R, et al. Rfam 11.0: 10 years of RNA families. Nucleic Acids Res. 2013;41(Database issue):D226D232.
   Google Scholar
• Chen M, Xu R, Ji H, et al. Transcriptome and long noncoding RNA sequencing of three extracellular vesicle subtypes released from the human colon cancer LIM1863 cell line. Sci Rep. 2016;6:38397.
   PubMed Web of Science ®Google Scholar
• Christensen J, Bentz S, Sengstag T, et al. FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors. PLoS One. 2013;8(3):e60051.
   Web of Science ®Google Scholar
• Gasperowicz M, Surmann-Schmitt C, Hamada Y, et al. The transcriptional co-repressor TLE3 regulates development of trophoblast giant cells lining maternal blood spaces in the mouse placenta. Dev Biol. 2013;382(1):1–14.
   PubMed Web of Science ®Google Scholar
• Torres-Vazquez J, Gitler AD, Fraser SD, et al. Semaphorin-plexin signaling guides patterning of the developing vasculature. Dev Cell. 2004;7(1):117–123.
   PubMed Web of Science ®Google Scholar
• Mascrez B, Ghyselinck NB, Chambon P, et al. A transcriptionally silent RXRalpha supports early embryonic morphogenesis and heart development. Proc Natl Acad Sci U S A. 2009;106(11):4272–4277.
   PubMed Web of Science ®Google Scholar
• McGough IJ, Vincent JP. Exosomes in developmental signalling. Development. 2016;143(14):2482–2493.
   PubMed Web of Science ®Google Scholar
• Huang Q, Cai B. Exosomes as new intercellular mediators in development and therapeutics of cardiomyocyte hypertrophy. Adv Exp Med Biol. 2017;998:91–100.
   Web of Science ®Google Scholar
• Tanaka HV, Ng NC, Yang YZ, et al. A developmentally regulated switch from stem cells to dedifferentiation for limb muscle regeneration in newts. Nat Commun. 2016;7:11069.
   Web of Science ®Google Scholar
• Balbi C, Piccoli M, Barile L, et al. First characterization of human amniotic fluid stem cell extracellular vesicles as a powerful paracrine tool endowed with regenerative potential. Stem Cells Transl Med. 2017;6(5):1340–1355.
   PubMed Web of Science ®Google Scholar
• De Couto G, Liu W, Tseliou E, et al. Macrophages mediate cardioprotective cellular postconditioning in acute myocardial infarction. J Clin Invest. 2015;125(8):3147–3162.
   PubMed Web of Science ®Google Scholar
• Takahashi K, Murakami M, Yamanaka S. Role of the phosphoinositide 3-kinase pathway in mouse embryonic stem (ES) cells. Biochem Soc Trans. 2005;33(Pt 6):1522–1525.
   PubMedGoogle Scholar
• Chen J, Crawford R, Chen C, et al. The key regulatory roles of the PI3K/Akt signaling pathway in the functionalities of mesenchymal stem cells and applications in tissue regeneration. Tissue Eng Part B Rev. 2013;19(6):516–528.
   PubMed Web of Science ®Google Scholar
• Yao H, Han X, Han X. The cardioprotection of the insulin-mediated PI3K/Akt/mTOR signaling pathway. Am J Cardiovasc Drugs. 2014;14(6):433–442.
   PubMed Web of Science ®Google Scholar
• Gross SM, Rotwein P. Mapping growth-factor-modulated Akt signaling dynamics. J Cell Sci. 2016;129(10):2052–2063.
   Web of Science ®Google Scholar
• Ferreira ADF, Cunha PDS, Carregal VM, et al. Extracellular vesicles from adipose-derived mesenchymal stem/stromal cells accelerate migration and activate AKT pathway in human keratinocytes and fibroblasts independently of miR-205 activity. Stem Cells Int. 2017;2017:9841035.
   PubMed Web of Science ®Google Scholar
• Qu Z, Guo S, Fang G, et al. AKT pathway affects bone regeneration in nonunion treated with umbilical cord-derived mesenchymal stem cells. Cell Biochem Biophys. 2015;71(3):1543–1551.
   Web of Science ®Google Scholar
• Philippidou P, Dasen JS. Hox genes: choreographers in neural development, architects of circuit organization. Neuron. 2013;80(1):12–34.
   Web of Science ®Google Scholar
• Kim H, Kim S, Song Y, et al. Dual function of Wnt signaling during neuronal differentiation of mouse embryonic stem cells. Stem Cells Int. 2015;2015:459301.
   Google Scholar
• Hannenhalli S, Kaestner KH. The evolution of Fox genes and their role in development and disease. Nat Rev Genet. 2009;10(4):233–240.
   Web of Science ®Google Scholar
• Archer TC, Jin J, Casey ES. Interaction of Sox1, Sox2, Sox3 and Oct4 during primary neurogenesis. Dev Biol. 2011;350(2):429–440.
   Web of Science ®Google Scholar
• Qiao Y, Jiang X, Lee ST, et al. FOXQ1 regulates epithelial-mesenchymal transition in human cancers. Cancer Res. 2011;71(8):3076–3086.
   Web of Science ®Google Scholar
• Epstein JA, Aghajanian H, Singh MK. Semaphorin signaling in cardiovascular development. Cell Metab. 2015;21(2):163–173.
   Web of Science ®Google Scholar
• Johnson JE, Birren SJ, Anderson DJ. Two rat homologues of Drosophila achaete-scute specifically expressed in neuronal precursors. Nature. 1990;346(6287):858–861.
   Web of Science ®Google Scholar
• Hendricks T, Francis N, Fyodorov D, et al. The ETS domain factor Pet-1 is an early and precise marker of central serotonin neurons and interacts with a conserved element in serotonergic genes. J Neurosci. 1999;19(23):10348–10356.
   Web of Science ®Google Scholar
• Hinks GL, Shah B, French SJ, et al. Expression of LIM protein genes Lmo1, Lmo2, and Lmo3 in adult mouse hippocampus and other forebrain regions: differential regulation by seizure activity. J Neurosci. 1997;17(14):5549–5559.
   Web of Science ®Google Scholar
• Kumar A, Godwin JW, Gates PB, et al. Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate. Science. 2007;318(5851):772–777.
   PubMed Web of Science ®Google Scholar