Paracrine Effects of Fetal Stem Cells
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.
KeywordsEmbryonic stem cells Paracrine effects Extracellular microvesicles Regenerative medicine Embryogenesis Argosomes
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.
- 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.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
- 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
- 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
- 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