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Paracrine Effects of Fetal Stem Cells

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Fetal Stem Cells in Regenerative Medicine

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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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.

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References

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  3. Janowska-Wieczorek A, Majka M, Ratajczak J, Ratajczak MZ. Autocrine/paracrine mechanisms in human hematopoiesis. Stem Cells. 2001;19:99–107.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  7. George JN, Thoi LL, McManus L, Reimann TA. Isolation of human platelet membrane microparticles from plasma and serum. Blood. 1982;60:834–9.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  12. Fevrier B, Raposo G. Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr Opin Cell Biol. 2004;16:415–21.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  21. Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science. 2002;297:2256–9.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  25. O'Malley K, Scott EW. Stem cell fusion confusion. Exp Hematol. 2004;32:131–4.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Greenwalt TJ. The how and why of exocytic vesicles. Transfusion. 2006;46:143–52.

    Article  PubMed  Google Scholar 

  31. Greco V, Hannus M, Eaton S. Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell. 2001;106:633–45.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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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.

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Authors and Affiliations

  1. Department of Medicine, James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Louisville, KY, 40202, USA

    Mariusz Z. Ratajczak M.D., Ph.D., D.Sci., Gabriela Schneider Ph.D. & Janina Ratajczak M.D., Ph.D., D.Sci.

Authors
  1. Mariusz Z. Ratajczak M.D., Ph.D., D.Sci.
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  2. Gabriela Schneider Ph.D.
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  3. Janina Ratajczak M.D., Ph.D., D.Sci.
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Corresponding author

Correspondence to Mariusz Z. Ratajczak M.D., Ph.D., D.Sci. .

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Editors and Affiliations

  1. Department of Surgery, Childrens Hosp Boston & Harvard Med, Boston, Massachusetts, USA

    Dario O. Fauza

  2. Department of Cellular and Molecular Med, University of Ottawa, Faculty of Medicin, OTTAWA, Ontario, Canada

    Mahmud Bani

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Ratajczak, M.Z., Schneider, G., Ratajczak, J. (2016). Paracrine Effects of Fetal Stem Cells. In: Fauza, D., Bani, M. (eds) Fetal Stem Cells in Regenerative Medicine. Stem Cell Biology and Regenerative Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3483-6_3

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