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Therapeutic Potential of Hematopoietic Stem Cell-Derived Exosomes in Cardiovascular Disease

  • Jana RadosinskaEmail author
  • Monika Bartekova
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 998)

Abstract

As other stem cells, hematopoietic stem cells (HSCs) are able to produce extracellular vesicles (EVs) including exosomes and microvesicles. This chapter summarizes the knowledge about the production of EVs by the HSCs, their role in the intercellular communication, and will discuss the cargo of these EVs as well as protective effects of HSCs-derived exosomes and microvesicles in cardiovascular diseases (CVD). Available data showed that cardioprotective action of injected HSCs could not be explained by direct transdifferentiationof injected cells into the cardiomyocytes, this effect is suggested to be mediated via paracrine communication (by EVs) between donor and recipient cells. Among the cargo molecules of HSCs-derived vesicles several miRNAs, and pro-angiogenic and anti-apoptotic proteins are proposed to be the mediators of heart regeneration, mostly via neovascularization. However, the direct evidence of cardioprotective effects of HSCs-derived exosomes and microvesicles is still lacking in the literature. On the other hand, EVs produced in HSCs-derived cells, specifically dendritic cells and endothelial progenitor cells, have been shown to provide direct cardioprotective effects in CVD. Anyway, further studies are needed to be performed to assess the therapeutic potential of HSCs-derived EVs-based cardiac regenerative therapies.

Keywords

Hematopoietic stem cells Exosomes Microvesicles Cardioprotection 

References

  1. 1.
    Verfaillie CM (2002) Hematopoietic stem cells for transplantation. Nat Immunol 3(4):314–317PubMedCrossRefGoogle Scholar
  2. 2.
    Aoki J, Ohashi K, Mitsuhashi M, Murakami T, Oakes M, Kobayashi T, Doki N, Kakihana K, Sakamaki H (2014) Posttransplantation bone marrow assessment by quantifying hematopoietic cell-derived mRNAs in plasma exosomes/microvesicles. Clin Chem 60(4):675–682PubMedCrossRefGoogle Scholar
  3. 3.
    Fais S, Logozzi M, Lugini L, Federici C, Azzarito T, Zarovni N, Chiesi A (2013) Exosomes: the ideal nanovectors for biodelivery. Biol Chem 394(1):1–15PubMedCrossRefGoogle Scholar
  4. 4.
    Katakowski M, Buller B, Zheng X, Lu Y, Rogers T, Osobamiro O, Shu W, Jiang F, Chopp M (2013) Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett 335(1):201–204PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    He J, Wang Y, Sun S, Yu M, Wang C, Pei X, Zhu B, Wu J, Zhao W (2012) Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model. Nephrology (Carlton) 17(5):493–500CrossRefGoogle Scholar
  6. 6.
    Yang X, Meng S, Jiang H, Zhu C, Wu W (2011) Exosomes derived from immature bone marrow dendritic cells induce tolerogenicity of intestinal transplantation in rats. J Surg Res 171(2):826–832PubMedCrossRefGoogle Scholar
  7. 7.
    Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, Viltono L, Tetta C, Camussi G (2010) Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One 5(7):e11803PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C (2005) Exosomal-like vesicles are present in human blood plasma. Int Immunol 17(7):879–887PubMedCrossRefGoogle Scholar
  9. 9.
    Pan BT, Johnstone RM (1983) Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 33(3):967–978PubMedCrossRefGoogle Scholar
  10. 10.
    Harding C, Heuser J, Stahl P (1984) Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: demonstration of a pathway for receptor shedding. Eur J Cell Biol 35(2):256–263PubMedGoogle Scholar
  11. 11.
    Rieu S, Geminard C, Rabesandratana H, Sainte-Marie J, Vidal M (2000) Exosomes released during reticulocyte maturation bind to fibronectin via integrin alpha4beta1. Eur J Biochem 267(2):583–590PubMedCrossRefGoogle Scholar
  12. 12.
    Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183(3):1161–1172PubMedCrossRefGoogle Scholar
  13. 13.
    Théry C, Amigorena S (1999) Molecular characterization of dendritic cell-derived exosomes: selective accumulation of the heat shock protein hsc73. J Cell Biol 147(3):599–610PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Thery C, Boussac M, Veron P, Ricciardi-Castagnoli P, Raposo G, Garin J, Amigorena S (2001) Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol (Baltimore, Md: 1950) 166(12):7309–7318CrossRefGoogle Scholar
  15. 15.
    Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 4(5):594–600PubMedCrossRefGoogle Scholar
  16. 16.
    Peters PJ, Geuze HJ, van der Donk HA, Borst J (1990) A new model for lethal hit delivery by cytotoxic T lymphocytes. Immunol Today 11(1):28–32PubMedCrossRefGoogle Scholar
  17. 17.
    Peters PJ, Borst J, Oorschot V, Fukuda M, Krahenbuhl O, Tschopp J, Slot JW, Geuze HJ (1991) Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes. J Exp Med 173(5):1099–1109PubMedCrossRefGoogle Scholar
  18. 18.
    Blanchard N, Lankar D, Faure F, Regnault A, Dumont C, Raposo G, Hivroz C (2002) TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. J Immunol (Baltimore, Md: 1950) 168(7):3235–3241CrossRefGoogle Scholar
  19. 19.
    Raposo G, Tenza D, Mecheri S, Peronet R, Bonnerot C, Desaymard C (1997) Accumulation of major histocompatibility complex class II molecules in mast cell secretory granules and their release upon degranulation. Mol Biol Cell 8(12):2631–2645PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Skokos D, Le Panse S, Villa I, Rousselle JC, Peronet R, David B, Namane A, Mecheri S (2001) Mast cell-dependent B and T lymphocyte activation is mediated by the secretion of immunologically active exosomes. J Immunol 166(2):868–876PubMedCrossRefGoogle Scholar
  21. 21.
    Bauer N, Wilsch-Brauninger M, Karbanova J, Fonseca AV, Strauss D, Freund D, Thiele C, Huttner WB, Bornhauser M, Corbeil D (2011) Haematopoietic stem cell differentiation promotes the release of prominin-1/CD133-containing membrane vesicles—a role of the endocytic-exocytic pathway. EMBO Mol Med 3(7):398–409PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Bakhti M, Winter C, Simons M (2011) Inhibition of myelin membrane sheath formation by oligodendrocyte-derived exosome-like vesicles. J Biol Chem 286(1):787–796PubMedCrossRefGoogle Scholar
  23. 23.
    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(12):e15353PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Janowska-Wieczorek A, Majka M, Kijowski J, Baj-Krzyworzeka M, Reca R, Turner AR, Ratajczak J, Emerson SG, Kowalska MA, Ratajczak MZ (2001) Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment. Blood 98(10):3143–3149PubMedCrossRefGoogle Scholar
  25. 25.
    Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ (2006) Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia 20(9):1487–1495PubMedCrossRefGoogle Scholar
  26. 26.
    Simons M, Raposo G (2009) Exosomes—vesicular carriers for intercellular communication. Curr Opin Cell Biol 21(4):575–581PubMedCrossRefGoogle Scholar
  27. 27.
    Thery C, Ostrowski M, Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9(8):581–593PubMedCrossRefGoogle Scholar
  28. 28.
    Freund D, Fonseca AV, Janich P, Bornhauser M, Corbeil D (2010) Differential expression of biofunctional GM1 and GM3 gangliosides within the plastic-adherent multipotent mesenchymal stromal cell population. Cytotherapy 12(2):131–142PubMedCrossRefGoogle Scholar
  29. 29.
    Gillette JM, Larochelle A, Dunbar CE, Lippincott-Schwartz J (2009) Intercellular transfer to signalling endosomes regulates an ex vivo bone marrow niche. Nat Cell Biol 11(3):303–311PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, Scadden DT, Ma’ayan A, Enikolopov GN, Frenette PS (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466(7308):829–834PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Han C, Sun X, Liu L, Jiang H, Shen Y, Xu X, Li J, Zhang G, Huang J, Lin Z, Xiong N, Wang T (2016) Exosomes and their therapeutic potentials of stem cells. Stem Cells Int 2016:7653489PubMedGoogle Scholar
  32. 32.
    Riazifar M, Pone EJ, Lotvall J, Zhao W (2017) Stem cell extracellular vesicles: extended messages of regeneration. Annu Rev Pharmacol Toxicol 57:125–154PubMedCrossRefGoogle Scholar
  33. 33.
    Chou J, Mackman N, Merrill-Skoloff G, Pedersen B, Furie BC, Furie B (2004) Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood 104(10):3190–3197PubMedCrossRefGoogle Scholar
  34. 34.
    Ratajczak J, Kucia M, Mierzejewska K, Marlicz W, Pietrzkowski Z, Wojakowski W, Greco NJ, Tendera M, Ratajczak MZ (2013) Paracrine proangiopoietic effects of human umbilical cord blood-derived purified CD133+ cells—implications for stem cell therapies in regenerative medicine. Stem Cells Dev 22(3):422–430PubMedCrossRefGoogle Scholar
  35. 35.
    Salvucci O, Jiang K, Gasperini P, Maric D, Zhu J, Sakakibara S, Espigol-Frigole G, Wang S, Tosato G (2012) MicroRNA126 contributes to granulocyte colony-stimulating factor-induced hematopoietic progenitor cell mobilization by reducing the expression of vascular cell adhesion molecule 1. Haematologica 97(6):818–826PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Yao Y, Wang C, Wei W, Shen C, Deng X, Chen L, Ma L, Hao S (2014) Dendritic cells pulsed with leukemia cell-derived exosomes more efficiently induce antileukemic immunities. PLoS One 9(3):e91463PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Raimondo S, Saieva L, Corrado C, Fontana S, Flugy A, Rizzo A, De Leo G, Alessandro R (2015) Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism. Cell Commun Signal 13:8PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Garbern JC, Lee RT (2013) Cardiac stem cell therapy and the promise of heart regeneration. Cell Stem Cell 12(6):689–698PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Govaert JA, Swijnenburg RJ, Schrepfer S, Xie X, van der Bogt KE, Hoyt G, Stein W, Ransohoff KJ, Robbins RC, Wu JC (2009) Poor functional recovery after transplantation of diabetic bone marrow stem cells in ischemic myocardium. J Heart Lung Transplant 28(11):1158–1165. e1151PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Loffredo FS, Steinhauser ML, Gannon J, Lee RT (2011) Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell 8(4):389–398PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Yellon DM, Davidson SM (2014) Exosomes: nanoparticles involved in cardioprotection? Circ Res 114(2):325–332PubMedCrossRefGoogle Scholar
  42. 42.
    Baffour R, Pakala R, Hellinga D, Joner M, Okubagzi P, Epstein SE, Waksman R (2006) Bone marrow-derived stem cell interactions with adult cardiomyocytes and skeletal myoblasts in vitro. Cardiovasc Revasc Med 7(4):222–230PubMedCrossRefGoogle Scholar
  43. 43.
    Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Noiseux N, Zhang L, Pratt RE, Ingwall JS, Dzau VJ (2005) Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 11(4):367–368PubMedCrossRefGoogle Scholar
  44. 44.
    Iso Y, Spees JL, Serrano C, Bakondi B, Pochampally R, Song YH, Sobel BE, Delafontaine P, Prockop DJ (2007) Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment. Biochem Biophys Res Commun 354(3):700–706PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Williams AR, Hare JM (2011) Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res 109(8):923–940PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    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(6):654–659PubMedCrossRefGoogle Scholar
  47. 47.
    Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, Braun T, Urbich C, Boon RA, Dimmeler S (2012) Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 14(3):249–256PubMedCrossRefGoogle Scholar
  48. 48.
    Montecalvo A, Larregina AT, Shufesky WJ, Stolz DB, Sullivan ML, Karlsson JM, Baty CJ, Gibson GA, Erdos G, Wang Z, Milosevic J, Tkacheva OA, Divito SJ, Jordan R, Lyons-Weiler J, Watkins SC, Morelli AE (2012) Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 119(3):756–766PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Mackie AR, Klyachko E, Thorne T, Schultz KM, Millay M, Ito A, Kamide CE, Liu T, Gupta R, Sahoo S, Misener S, Kishore R, Losordo DW (2012) Sonic hedgehog-modified human CD34+ cells preserve cardiac function after acute myocardial infarction. Circ Res 111(3):312–321PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Seeger FH, Zeiher AM, Dimmeler S (2013) MicroRNAs in stem cell function and regenerative therapy of the heart. Arterioscler Thromb Vasc Biol 33(8):1739–1746PubMedCrossRefGoogle Scholar
  51. 51.
    Ranghino A, Cantaluppi V, Grange C, Vitillo L, Fop F, Biancone L, Deregibus MC, Tetta C, Segoloni GP, Camussi G (2012) Endothelial progenitor cell-derived microvesicles improve neovascularization in a murine model of hindlimb ischemia. Int J Immunopathol Pharmacol 25(1):75–85PubMedCrossRefGoogle Scholar
  52. 52.
    Camussi G, Deregibus MC, Bruno S, Grange C, Fonsato V, Tetta C (2011) Exosome/microvesicle-mediated epigenetic reprogramming of cells. Am J Cancer Res 1(1):98–110PubMedGoogle Scholar
  53. 53.
    Macri S, Pavesi E, Crescitelli R, Aspesi A, Vizziello C, Botto C, Corti P, Quarello P, Notari P, Ramenghi U, Ellis SR, Dianzani I (2015) Immunophenotypic profiling of erythroid progenitor-derived extracellular vesicles in diamond-blackfan anaemia: a new diagnostic strategy. PLoS One 10(9):e0138200PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Sahoo S, Klychko E, Thorne T, Misener S, Schultz KM, Millay M, Ito A, Liu T, Kamide C, Agrawal H, Perlman H, Qin G, Kishore R, Losordo DW (2011) Exosomes from human CD34(+) stem cells mediate their proangiogenic paracrine activity. Circ Res 109(7):724–728PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Mocharla P, Briand S, Giannotti G, Dorries C, Jakob P, Paneni F, Luscher T, Landmesser U (2013) AngiomiR-126 expression and secretion from circulating CD34(+) and CD14(+) PBMCs: role for proangiogenic effects and alterations in type 2 diabetics. Blood 121(1):226–236PubMedCrossRefGoogle Scholar
  56. 56.
    Cantaluppi V, Biancone L, Figliolini F, Beltramo S, Medica D, Deregibus MC, Galimi F, Romagnoli R, Salizzoni M, Tetta C, Segoloni GP, Camussi G (2012) Microvesicles derived from endothelial progenitor cells enhance neoangiogenesis of human pancreatic islets. Cell Transplant 21(6):1305–1320PubMedCrossRefGoogle Scholar
  57. 57.
    Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY, Srivastava D (2008) miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 15(2):272–284PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M (2010) Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res 107(6):810–817PubMedCrossRefGoogle Scholar
  59. 59.
    Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, Weber M, Hamm CW, Roxe T, Muller-Ardogan M, Bonauer A, Zeiher AM, Dimmeler S (2010) Circulating microRNAs in patients with coronary artery disease. Circ Res 107(5):677–684PubMedCrossRefGoogle Scholar
  60. 60.
    Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, Fichtner S, Korte T, Hornig B, Messinger D, Arseniev L, Hertenstein B, Ganser A, Drexler H (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364(9429):141–148PubMedCrossRefGoogle Scholar
  61. 61.
    Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Pasumarthi KB, Virag JI, Bartelmez SH, Poppa V, Bradford G, Dowell JD, Williams DA, Field LJ (2004) Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428(6983):664–668PubMedCrossRefGoogle Scholar
  62. 62.
    Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428(6983):668–673PubMedCrossRefGoogle Scholar
  63. 63.
    Kamihata H, Matsubara H, Nishiue T, Fujiyama S, Tsutsumi Y, Ozono R, Masaki H, Mori Y, Iba O, Tateishi E, Kosaki A, Shintani S, Murohara T, Imaizumi T, Iwasaka T (2001) Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines. Circulation 104(9):1046–1052PubMedCrossRefGoogle Scholar
  64. 64.
    Ziegelhoeffer T, Fernandez B, Kostin S, Heil M, Voswinckel R, Helisch A, Schaper W (2004) Bone marrow-derived cells do not incorporate into the adult growing vasculature. Circ Res 94(2):230–238PubMedCrossRefGoogle Scholar
  65. 65.
    Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, Epstein SE (2004) Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res 94(5):678–685PubMedCrossRefGoogle Scholar
  66. 66.
    Heil M, Ziegelhoeffer T, Mees B, Schaper W (2004) A different outlook on the role of bone marrow stem cells in vascular growth: bone marrow delivers software not hardware. Circ Res 94(5):573–574PubMedCrossRefGoogle Scholar
  67. 67.
    Massa M, Rosti V, Ferrario M, Campanelli R, Ramajoli I, Rosso R, De Ferrari GM, Ferlini M, Goffredo L, Bertoletti A, Klersy C, Pecci A, Moratti R, Tavazzi L (2005) Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction. Blood 105(1):199–206PubMedCrossRefGoogle Scholar
  68. 68.
    Wojakowski W, Tendera M, Michalowska A, Majka M, Kucia M, Maslankiewicz K, Wyderka R, Ochala A, Ratajczak MZ (2004) Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation 110(20):3213–3220PubMedCrossRefGoogle Scholar
  69. 69.
    Leone AM, Rutella S, Bonanno G, Abbate A, Rebuzzi AG, Giovannini S, Lombardi M, Galiuto L, Liuzzo G, Andreotti F, Lanza GA, Contemi AM, Leone G, Crea F (2005) Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function. Eur Heart J 26(12):1196–1204PubMedCrossRefGoogle Scholar
  70. 70.
    Aicher A, Zeiher AM, Dimmeler S (2005) Mobilizing endothelial progenitor cells. Hypertension 45(3):321–325PubMedCrossRefGoogle Scholar
  71. 71.
    Gyongyosi M, Posa A, Pavo N, Hemetsberger R, Kvakan H, Steiner-Boker S, Petrasi Z, Manczur F, Pavo IJ, Edes IF, Wojta J, Glogar D, Huber K (2010) Differential effect of ischaemic preconditioning on mobilisation and recruitment of haematopoietic and mesenchymal stem cells in porcine myocardial ischaemia-reperfusion. Thromb Haemost 104(2):376–384PubMedCrossRefGoogle Scholar
  72. 72.
    Wang Y, Johnsen HE, Mortensen S, Bindslev L, Ripa RS, Haack-Sorensen M, Jorgensen E, Fang W, Kastrup J (2006) Changes in circulating mesenchymal stem cells, stem cell homing factor, and vascular growth factors in patients with acute ST elevation myocardial infarction treated with primary percutaneous coronary intervention. Heart 92(6):768–774PubMedCrossRefGoogle Scholar
  73. 73.
    Losordo DW, Schatz RA, White CJ, Udelson JE, Veereshwarayya V, Durgin M, Poh KK, Weinstein R, Kearney M, Chaudhry M, Burg A, Eaton L, Heyd L, Thorne T, Shturman L, Hoffmeister P, Story K, Zak V, Dowling D, Traverse JH, Olson RE, Flanagan J, Sodano D, Murayama T, Kawamoto A, Kusano KF, Wollins J, Welt F, Shah P, Soukas P, Asahara T, Henry TD (2007) Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation 115(25):3165–3172PubMedCrossRefGoogle Scholar
  74. 74.
    Losordo DW, Henry TD, Davidson C, Sup Lee J, Costa MA, Bass T, Mendelsohn F, Fortuin FD, Pepine CJ, Traverse JH, Amrani D, Ewenstein BM, Riedel N, Story K, Barker K, Povsic TJ, Harrington RA, Schatz RA, Investigators AC (2011) Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res 109(4):428–436PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Quyyumi AA, Waller EK, Murrow J, Esteves F, Galt J, Oshinski J, Lerakis S, Sher S, Vaughan D, Perin E, Willerson J, Kereiakes D, Gersh BJ, Gregory D, Werner A, Moss T, Chan WS, Preti R, Pecora AL (2011) CD34(+) cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent. Am Heart J 161(1):98–105PubMedCrossRefGoogle Scholar
  76. 76.
    Chaput N, Thery C (2011) Exosomes: immune properties and potential clinical implementations. Semin Immunopathol 33(5):419–440PubMedCrossRefGoogle Scholar
  77. 77.
    Kawamoto A, Tkebuchava T, Yamaguchi J, Nishimura H, Yoon YS, Milliken C, Uchida S, Masuo O, Iwaguro H, Ma H, Hanley A, Silver M, Kearney M, Losordo DW, Isner JM, Asahara T (2003) Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation 107(3):461–468PubMedCrossRefGoogle Scholar
  78. 78.
    Kawamoto A, Iwasaki H, Kusano K, Murayama T, Oyamada A, Silver M, Hulbert C, Gavin M, Hanley A, Ma H, Kearney M, Zak V, Asahara T, Losordo DW (2006) CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells. Circulation 114(20):2163–2169PubMedCrossRefGoogle Scholar
  79. 79.
    Shintani S, Kusano K, Ii M, Iwakura A, Heyd L, Curry C, Wecker A, Gavin M, Ma H, Kearney M, Silver M, Thorne T, Murohara T, Losordo DW (2006) Synergistic effect of combined intramyocardial CD34+ cells and VEGF2 gene therapy after MI. Nat Clin Pract Cardiovasc Med 3(Suppl 1):S123–S128PubMedCrossRefGoogle Scholar
  80. 80.
    Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S (2001) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89(1):E1–E7PubMedCrossRefGoogle Scholar
  81. 81.
    Vasa M, Fichtlscherer S, Adler K, Aicher A, Martin H, Zeiher AM, Dimmeler S (2001) Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 103(24):2885–2890PubMedCrossRefGoogle Scholar
  82. 82.
    Valgimigli M, Rigolin GM, Fucili A, Porta MD, Soukhomovskaia O, Malagutti P, Bugli AM, Bragotti LZ, Francolini G, Mauro E, Castoldi G, Ferrari R (2004) CD34+ and endothelial progenitor cells in patients with various degrees of congestive heart failure. Circulation 110(10):1209–1212PubMedCrossRefGoogle Scholar
  83. 83.
    Agouni A, Mostefai HA, Porro C, Carusio N, Favre J, Richard V, Henrion D, Martinez MC, Andriantsitohaina R (2007) Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release. FASEB J 21(11):2735–2741PubMedCrossRefGoogle Scholar
  84. 84.
    Benameur T, Soleti R, Porro C, Andriantsitohaina R, Martinez MC (2010) Microparticles carrying Sonic hedgehog favor neovascularization through the activation of nitric oxide pathway in mice. PLoS One 5(9):e12688PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Liehn EA, Bucur O, Weber C (2012) Role of microparticles as messengers enhancing stem cell activity after genetic engineering. Circ Res 111(3):265–267PubMedCrossRefGoogle Scholar
  86. 86.
    Liu K, Nussenzweig MC (2010) Origin and development of dendritic cells. Immunol Rev 234(1):45–54PubMedCrossRefGoogle Scholar
  87. 87.
    Gutierrez-Vazquez C, Villarroya-Beltri C, Mittelbrunn M, Sanchez-Madrid F (2013) Transfer of extracellular vesicles during immune cell-cell interactions. Immunol Rev 251(1):125–142PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Pitt JM, Charrier M, Viaud S, Andre F, Besse B, Chaput N, Zitvogel L (2014) Dendritic cell-derived exosomes as immunotherapies in the fight against cancer. J Immunol 193(3):1006–1011PubMedCrossRefGoogle Scholar
  89. 89.
    Naslund TI, Gehrmann U, Qazi KR, Karlsson MC, Gabrielsson S (2013) Dendritic cell-derived exosomes need to activate both T and B cells to induce antitumor immunity. J Immunol 190(6):2712–2719PubMedCrossRefGoogle Scholar
  90. 90.
    Peche H, Heslan M, Usal C, Amigorena S, Cuturi MC (2003) Presentation of donor major histocompatibility complex antigens by bone marrow dendritic cell-derived exosomes modulates allograft rejection. Transplantation 76(10):1503–1510PubMedCrossRefGoogle Scholar
  91. 91.
    Liu H, Gao W, Yuan J, Wu C, Yao K, Zhang L, Ma L, Zhu J, Zou Y, Ge J (2016) Exosomes derived from dendritic cells improve cardiac function via activation of CD4(+) T lymphocytes after myocardial infarction. J Mol Cell Cardiol 91:123–133PubMedCrossRefGoogle Scholar
  92. 92.
    Hofmann U, Beyersdorf N, Weirather J, Podolskaya A, Bauersachs J, Ertl G, Kerkau T, Frantz S (2012) Activation of CD4+ T lymphocytes improves wound healing and survival after experimental myocardial infarction in mice. Circulation 125(13):1652–1663PubMedCrossRefGoogle Scholar
  93. 93.
    Goldie LC, Nix MK, Hirschi KK (2008) Embryonic vasculogenesis and hematopoietic specification. Organogenesis 4(4):257–263PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Zovein AC, Hofmann JJ, Lynch M, French WJ, Turlo KA, Yang Y, Becker MS, Zanetta L, Dejana E, Gasson JC, Tallquist MD, Iruela-Arispe ML (2008) Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell Stem Cell 3(6):625–636PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Morrison SJ, Spradling AC (2008) Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 132(4):598–611PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK, Goodell MA (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107(11):1395–1402PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Chao H, Hirschi KK (2010) Hemato-vascular origins of endothelial progenitor cells? Microvasc Res 79(3):169–173PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Khakoo AY, Finkel T (2005) Endothelial progenitor cells. Annu Rev Med 56:79–101PubMedCrossRefGoogle Scholar
  99. 99.
    Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C, Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler S (2003) Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 102(4):1340–1346PubMedCrossRefGoogle Scholar
  100. 100.
    Mobius-Winkler S, Hollriegel R, Schuler G, Adams V (2009) Endothelial progenitor cells: implications for cardiovascular disease. Cytometry A 75(1):25–37PubMedCrossRefGoogle Scholar
  101. 101.
    Deregibus MC, Cantaluppi V, Calogero R, Lo Iacono M, Tetta C, Biancone L, Bruno S, Bussolati B, Camussi G (2007) Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 110(7):2440–2448PubMedCrossRefGoogle Scholar
  102. 102.
    Li X, Chen C, Wei L, Li Q, Niu X, Xu Y, Wang Y, Zhao J (2016) Exosomes derived from endothelial progenitor cells attenuate vascular repair and accelerate reendothelialization by enhancing endothelial function. Cytotherapy 18(2):253–262PubMedCrossRefGoogle Scholar
  103. 103.
    Chen CW, Venkataraman CM, Wang LL, Hung G, Gaffey AC, Chung JJ, Liccardi A, Trubelja A, Seeholzer SH, Burdick JA (2016) Sustained release of endothelial progenitor cell derived exosomes from shear-thinning hydrogel improves angiogenesis and promotes function after myocardial infarction. American Heart Association A19338Google Scholar
  104. 104.
    Krenning G, van Luyn MJ, Harmsen MC (2009) Endothelial progenitor cell-based neovascularization: implications for therapy. Trends Mol Med 15(4):180–189PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Faculty of MedicineInstitute of Physiology, Comenius University in BratislavaBratislavaSlovak Republic
  2. 2.Institute for Heart Research, Slovak Academy of SciencesBratislavaSlovak Republic

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