Advertisement

Paracrine Effects of Fetal Stem Cells

  • Mariusz Z. Ratajczak
  • Gabriela Schneider
  • Janina Ratajczak
Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

Embryonic stem cells (ESCs) are pluripotent stem cells able to differentiate into cells belonging to all three germ layers. Unfortunately, the major problem with their application in the clinic is that they grow teratomas in the host tissues. Nevertheless, ESCs secrete also several soluble factors (peptides, bioactive lipids, extracellular nucleotides) as well small, spherical membrane fragments that are shed from the cell surface or secreted from the endosomal compartment; called extracellular microvesicles (ExMVs). These paracrine mediators play an important role in cell–cell communication and tissue/organ development and could be employed in regenerative medicine. Thus, until appropriate strategies that will harness in vivo application of ESCs in the clinic will be developed, conditioned media harvested from cultured in vitro ESCs, enriched in soluble factors and ExMVs, could be employed in regenerative medicine as therapeutics to treat damaged organs. ExMVs known as argosomes are also secreted during embryogenesis by some fetal cells and are involved in tissue patterning and organ development. In this chapter we will discuss potential applications of in vitro generated ESCs-derived paracrine factors as an option to harness therapeutic potential of these cells in regenerative medicine.

Keywords

Embryonic stem cells Paracrine effects Extracellular microvesicles Regenerative medicine Embryogenesis Argosomes 

Notes

Acknowledgments

This work was supported by NIH grants 2R01 DK074720 and R01HL112788, the Stella and Henry Endowment, and Maestro grant 2011/02/A/NZ4/00035 to MZR.

References

  1. 1.
    Ratajczak MZ, Kucia M, Jadczyk T, Greco NJ, Wojakowski W, Tendera M, et al. Pivotal role of paracrine effects in stem cell therapies in regenerative medicine: can we translate stem cell-secreted paracrine factors and microvesicles into better therapeutic strategies? Leukemia. 2012;6:1166–73.CrossRefGoogle Scholar
  2. 2.
    Majka M, Janowska-Wieczorek A, Ratajczak J, Ehrenman K, Pietrzkowski Z, Kowalska MA, et al. 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. 2001;97:3075–85.CrossRefPubMedGoogle Scholar
  3. 3.
    Janowska-Wieczorek A, Majka M, Ratajczak J, Ratajczak MZ. Autocrine/paracrine mechanisms in human hematopoiesis. Stem Cells. 2001;19:99–107.CrossRefPubMedGoogle Scholar
  4. 4.
    Sahoo S, Klychko E, Thorne T, Misener S, Schults KM, Millay M, et al. Exosomesfrom human CD34+ stem cells mediate their proangiopoietic paracrine activity. Circ Res. 2011;109:724–8.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Lataillade JJ, Clay D, Bourin P, Hérodin F, Dupuy C, Jasmin C, et al. Stromal cell-derived factor 1 regulates primitive hematopoiesis by suppressing apoptosis and by promoting G(0)/G(1) transition in CD34(+) cells: evidence for an autocrine/paracrine mechanism. Blood. 2002;99:1117–29.CrossRefPubMedGoogle Scholar
  6. 6.
    Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ. Membrane-derived microvesicles (MV): important and underappreciated mediators of cell to cell communication. Leukemia. 2006;20:1487–95.CrossRefPubMedGoogle Scholar
  7. 7.
    George JN, Thoi LL, McManus L, Reimann TA. Isolation of human platelet membrane microparticles from plasma and serum. Blood. 1982;60:834–9.PubMedGoogle Scholar
  8. 8.
    Yuan A, Faber EL, Rapoport AL, Tejada D, Deniskin R, Akhmedov NB, et al. Transfer of miRNA by embryonic stem cell microvesicles. PLoS One. 2009;4:e4722.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Quesenberry PJ, Dooner MS, Aliotta JM. Stem cell plasticity revisited: the continuum marrow model and phenotypic changes mediated by microvesicles. Exp Hematol. 2010;38:581–92.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Camussi G, Deregibus MC, Tetta C. Paracrine/endocrine mechanism of stem cells on kidney repair: role of microvesicle-mediated transfer of genetic information. Curr Opin Nephrol Hypertens. 2010;19:7–12.CrossRefPubMedGoogle Scholar
  11. 11.
    Beaudoin AR, Grondin G. Shedding of vesicular material from the cell surface of eukaryotic cells: different cellular phenomena. Biochim Biophys Acta. 1991;1071:203–19.CrossRefPubMedGoogle Scholar
  12. 12.
    Fevrier B, Raposo G. Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr Opin Cell Biol. 2004;16:415–21.CrossRefPubMedGoogle Scholar
  13. 13.
    Gatti S, Bruno S, Deregibus MC, Sordi A, Cantaluppi V, Tetta C, et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischemia-reperfusion-induced acute and chronic kidney injury. Nephrol Dialysis Transplant. 2011;26:1474–83.CrossRefGoogle Scholar
  14. 14.
    Friedman RS, Krause DS. Regeneration and repair: new findings in stem cell research and aging. Ann N Y Acad Sci. 2009;1172:88–94.CrossRefPubMedGoogle Scholar
  15. 15.
    Joyce N, Annett G, Wirthlin L, Olson S, Bauer G, Nolta JA. Mesenchymal stem cells for the treatment of neurodegenerative disease. Regen Med. 2010;5:933–46.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ratajczak MZ, Zuba-Surma EK, Wysoczynski M, Wan W, Ratajczak J, Wojakowski W, et al. Hunt for pluripotent stem cell – regenerative medicine search for almighty cell. J Autoimmun. 2008;30:151–62.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Tang XL, Rokosh DG, Guo Y, Bolli R. Cardiac progenitor cells and bone marrow-derived very small embryonic-like stem cells for cardiac repair after myocardial infarction. Circ J. 2010;74:390–404.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tendera M, Wojakowski W, Ruzyłło W, Chojnowska L, Kepka C, Tracz W, et al. 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. 2009;30:1313–21.CrossRefPubMedGoogle Scholar
  19. 19.
    Corti S, Locatelli F, Donadoni C, Strazzer S, Salani S, Del Bo R, et al. Neuroectodermal and microglial differentiation of bone marrow cells in the mouse spinal cord and sensory ganglia. J Neurosci Res. 2002;70:721–33.CrossRefPubMedGoogle Scholar
  20. 20.
    Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, et al. Bone marrow as a potential source of hepatic oval cells. Science. 1999;284:1168–70.CrossRefPubMedGoogle Scholar
  21. 21.
    Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science. 2002;297:2256–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature. 2004;428:664–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Castro RF, Jackson KA, Goodell MA, Robertson CS, Liu H, Shine HD. Failure of bone marrow cells to transdifferentiate into neural cells in vivo. Science. 2002;297:1299.CrossRefPubMedGoogle Scholar
  24. 24.
    Kucia M, Ratajczak J, Ratajczak MZ. Are bone marrow stem cells plastic or heterogenous – that is the question. Exp Hematol. 2005;33:613–23.CrossRefPubMedGoogle Scholar
  25. 25.
    O'Malley K, Scott EW. Stem cell fusion confusion. Exp Hematol. 2004;32:131–4.CrossRefPubMedGoogle Scholar
  26. 26.
    Kucia M, Reca R, Campbell FR, Zuba-Surma E, Majka M, Ratajczak J, et al. A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4+ stem cells identified in adult bone marrow. Leukemia. 2006;20:857–69.CrossRefPubMedGoogle Scholar
  27. 27.
    Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P, et al. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia. 2006;20:847–56.CrossRefPubMedGoogle Scholar
  28. 28.
    Ratajczak J, Kucia M, Mierzejewska K, Marlicz W, Pietrzkowski Z, Wojakowski W, et al. Paracrine proangiopoietic effects of human umbilical cord blood-derived purified CD133+ cells-implications for stem cell therapies in regenerative medicine. Stem Cells Dev. 2013;22:422–30.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Myers TJ, Granero-Molto F, Longobardi L, Li T, Yan Y, Spagnoli A. Mesenchymal stem cells at the intersection of cell and gene therapy. Expert Opin Biol Ther. 2010;10:1663–79.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Greenwalt TJ. The how and why of exocytic vesicles. Transfusion. 2006;46:143–52.CrossRefPubMedGoogle Scholar
  31. 31.
    Greco V, Hannus M, Eaton S. Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell. 2001;106:633–45.CrossRefPubMedGoogle Scholar
  32. 32.
    Del Tatto M, Ng T, Aliotta JM, et al. Marrow cell genetic phenotype change induced by human lung cancer cells. Exp Hematol. 2011;39:1072–80.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Herrera MB, Fonsato V, Gatti S, et al. Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats. J Cell Mol Med. 2010;14(6B):1605–18.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Mariusz Z. Ratajczak
    • 1
  • Gabriela Schneider
    • 1
  • Janina Ratajczak
    • 1
  1. 1.Department of Medicine, James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleUSA

Personalised recommendations