Abstract
Microvesicles (MVs) are small, spherical membrane fragments shed from the cell surface or secreted from the endosomal compartment. MVs released from cells employed in regenerative medicine to rescue damaged tissues seem to play an important and underappreciated role in improving the function of damaged organs. A growing body of evidence suggests that MVs secreted from hematopoietic stem progenitor cells (HSPCs), multipotent stroma cells (MSCs), or cardiac stem cells (CSCs) employed in various treatment strategies in regenerative medicine may: (1) inhibit apoptosis of cells residing in the damaged tissues, (2) stimulate proliferation of cells that survive organ injury, and (3) stimulate vascularization of affected tissues. These proregenerative effects mediated by MVs are explained by the fact that these small, spherical membrane fragments: (1) are enriched in bioactive lipids (e.g., sphingosine-1-phosphate [S1P]), (2) may express antiapoptoic and prostimulatory growth factors or cytokines (e.g., vascular endothelial growth factor [VEGF], stem cell factor [SCF], or stromal derived factor-1 [SDF-1]) on their surface, and (3) may deliver mRNA, regulatory miRNA, and proteins to the damaged tissues that improve overall cell function. Based on these observations, the potential use of MVs, instead of whole cells, has become an exciting new concept in regenerative medicine.
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References
Majka M, Janowska-Wieczorek A, Ratajczak J, Ehrenman K, Pietrzkowski Z, Kowalska MA et al (2001) Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood 97:3075–3085
Janowska-Wieczorek A, Majka M, Ratajczak J et al (2001) Autocrine/paracrine mechanisms in human hematopoiesis. Stem Cells 19:99–107
Rustom A, Saffrich R, Markovic I, Walther P, Gerdes HH (2004) Nanotubular highways for intercellular organelle transport. Science 303:1007–1010
Vidulescu C, Clejan S, O’Connor K C (2004) Vesicle traffic through intercellular bridges in DU 145 human prostate cancer cells. J Cell Mol Med 8:388–396
George JN, Thoi LL, McManus LM et al (1982) Isolation of human platelet membrane microparticles from plasma and serum. Blood 60:834–839
Ratajczak J, Wysoczynski M, Hayek F et al (2006) Membrane-derived microvesicles (MV): important and underappreciated mediators of cell to cell communication. Leukemia 20:1487–1495
Quesenberry PJ, Dooner MS, Aliotta JM (2010) Stem cell plasticity revisited: the continuum marrow model and phenotypic changes mediated by microvesicles. Exp Hematol 38:581–592
Camussi G, Deregibus MC, Tetta C (2010) Paracrine/endocrine mechanism of stem cells on kidney repair: role of microvesicle-mediated transfer of genetic information. Curr Opin Nephrol Hypertens 19:7–12
Beaudoin AR, Grondin G (1991) Shedding of vesicular material from the cell surface of eukaryotic cells: different cellular phenomena. Biochim Biophys Acta 1071:203
Fevrier B, Raposo G (2004) Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr Opin Cell Biol Aug 16(4):415–421
Greenwalt TJ (2006) The how and why of exocytic vesicles. Transfusion 46(1):143–152
Hugel B, Martinez MC, Kunzelmann C, Freyssinet JM (2005) Membrane microparticles: two sides of the coin. Physiology (Bethesda) 20:22–27
Barry OP, FitzGerald GA (1999) Mechanisms of cellular activation by platelet microparticles. Thromb Haemost 82:794–800
Barry OP, Pratico D, Savani RC, FitzGerald GA (1998) Modulation of monocyte-endothelial cell interaction by platelet microparticles. J Clin Invest 102:136–144
VanWijk MJ, VanBavel E, Sturk A, Nieuwland R (2003) Microparticles in cardiovascular diseases. Cardiovasc Res 59(2):277–287
Horstman LL, Jy W, Jimenez JJ, Bidot C, Ahn YS (2004) New horizons in the analysis of circulating cell-derived microparticles. Keio J Med 53(4):210–230
Greco V, Hannus M, Eaton S (2001) Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell 106:633–645
Ratajczak J, Miekus K, Kucia M et al (2006) Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20:847–856
Gatti S, Bruno S, Deregibus MC et al (2011) Microvesicles derived from human adult mesenchymal stem cells protect against ischemia-reperfusion-induced acute and chronic kidney injury. Nephrol Dialysis Transplant 26:1474–1483
Spees JL, Olson SD, Whitney MJ et al (2006) Mitochondrial transfer between cells can rescue aerobic respiration. Proc Natl Acad Sci U S A 103:1283–1288
Friedman RS, Krause DS (2009) Regeneration and repair: new findings in stem cell research and aging. Ann N Y Acad Sci 1172:88–94
Joyce N, Annett G, Wirthlin L et al (2010) Mesenchymal stem cells for the treatment of neurodegenerative disease. Regen Med 5:933–946
Ratajczak MZ, Zuba-Surma EK, Wysoczynski M et al (2008) Hunt for pluripotent stem cell—regenerative medicine search for almighty cell. J Autoimmun 30:151–162
O’Malley K, Scott EW (2004) Stem cell fusion confusion. Exp Hematol 32:131–134
Ratajczak MZ, Zuba-Surma E, Ratajczak J et al (2008) Very small embryonic like (VSEL) stem cells—characterization, developmental origin and biological significance. Exp Hematol 36:742–751
Tang XL, Rokosh DG, Guo Y et al (2010) Cardiac progenitor cells and bone marrow-derived very small embryonic-like stem cells for cardiac repair after myocardial infarction. Circ J 74:390–404
Tendera M, Wojakowski W, Ruzyłło W et al (2009) Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+  cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre myocardial regeneration by intracoronary infusion of selected population of stem cells in acute myocardial infarction (REGENT) trial. Eur Heart J 30:1313–1321
Kucia M, Reca R, Campbell FR et al (2006) A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4+ stem cells identified in adult bone marrow. Leukemia 20:857–869
Collino F, Deregibus MC, Bruno S et al (2010) Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS ONE 5:e11803
Ratajczak MZ, Lee H, Wysoczynski M et al (2010) Novel insight into stem cell mobilization-plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex. Leukemia 24:976–985
Aliotta JM, Sanchez-Guijo FM, Dooner GJ et al (2007) Alteration of marrow cell gene expression, protein production, and engraftment into lung by lung-derived microvesicles: a novel mechanism for phenotype modulation. Stem Cells 25:2245–2256
Del Tatto M, Ng T, Aliotta JM et al (2011) Marrow cell genetic phenotype change induced by human lung cancer cells. Exp Hematol 39:1072–1080
Herrera MB, Fonsato V, Gatti S et al (2010) Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats. J Cell Mol Med 14(6B):1605–1618
Paczkowska E, Kucia M, Koziarska D et al (2009) Clinical evidence that very small embryonic-like stem cells are mobilized into peripheral blood in patients after stroke. Stroke 40:1237–1244
Ratajczak MZ, Kim CH, Abdel-Latif A et al (2012) A novel perspective on stem cell homing and mobilization—review on bioactive lipids as potent chemoattractants and cationic peptides as underappreciated modulators of responsiveness to SDF-1 gradients. Leukemia 26:63–72
Ratajczak J, Kijowski J, Majka M et al (2003) Biological significance of the different erythropoietic factors secreted by normal human early erythroid cells. Leuk Lymphoma 44:767–774
Acknowledgments
This work was supported by NIH grant R01 DK074720, the Stella and Henry Endowment, and the European Union structural funds (Innovative Economy Operational Program POIG.01.01.02-00-109/09-00) to MZR.
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Ratajczak, M., Mierzejewska, K., Kucia, M., Greco, N., Ratajczak, J. (2013). Microvesicles and Their Emerging Role in Cellular Therapies for Organ and Tissue Regeneration. In: Zhang, HG. (eds) Emerging Concepts of Tumor Exosome–Mediated Cell-Cell Communication. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3697-3_10
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