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Stem Cells: Principles and Applications

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Working with Stem Cells

Abstract

Stem cell research is a promising and markedly emerging area of investigation concerning basic and clinical research. Since the 50s, the understanding that undifferentiated cells are able to originate different cell types held great promise for regenerative medicine, making until today this field to one of intense and growing research. The possibility to artificially replace damaged tissue unlocked new possibilities for clinical treatment of so far incurable diseases. This chapter highlights basic concepts about stem cells, as well as their current and potential future applications. Moreover, it brings an overview of important historical facts of the path taken by science to get to the current status of this research field.

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References

  • Alpers A, Lo B (1995) Commodification and commercialization in human embryo research. Stanf Law Policy Rev 6:39–46

    CAS  Google Scholar 

  • Amit M, Carpenter MK, Inokuma MS, Chiu CP, Harris CP, Waknitz MA, Itskovitz-Eldor J, Thomson JA (2000) Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture. Dev Biol 227:271–278

    Article  CAS  PubMed  Google Scholar 

  • Ashton BA, Allen TD, Howlett CR, Eaglesom CC, Hattori A, Owen M (1980) Formation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo. Clin Orthop Relat Res 151:294–307

    PubMed  Google Scholar 

  • Atkin NB, Baker MC, Robinson R, Gaze SE (1974) Chomosome studies on 14 near-diploid carcinomas of the ovary. Eur J Cancer 10:144–146

    CAS  PubMed  Google Scholar 

  • Bab I, Ashton BA, Gazit D, Marx G, Williamson MC, Owen ME (1986) Kinetics and differentiation of marrow stromal cells in diffusion chambers in vivo. J Cell Sci 84:139–151

    CAS  PubMed  Google Scholar 

  • Badger JL, Cordero-Llana O, Hartfield EM, Wade-Martins R (2014) Parkinson’s disease in a dish—using stem cells as a molecular tool. Neuropharmacology 76A:88–96

    Article  Google Scholar 

  • Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Dunn SJ, Martello G, Yordanov B, Emmott S, Smith AG (2014) Defining an essential transcription factor program for naive pluripotency. Science 344:1156–1160

    Article  Google Scholar 

  • Brook FA, Gardner RL (1997) The origin and efficient derivation of embryonic stem cells in the mouse. Proc Natl Acad Sci U S A 94:5709–5712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carvalho AS, Ramalho-Santos J (2013) How can ethics relate to science? The case of stem cell research. Eur J Hum Genet 21(6):591–595

    Article  PubMed  Google Scholar 

  • Castro-Malaspina H, Gay RE, Resnick G, Kapoor N, Meyers P, Chiarieri D, McKenzie S, Broxmeyer HE, Moore MA (1980) Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny. Blood 56:289–301

    CAS  PubMed  Google Scholar 

  • Chamberlain G, Fox J, Ashton B, Middleton J (2007) Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 25:2739–2749

    Article  CAS  PubMed  Google Scholar 

  • Dahéron L, Opitz SL, Zaehes H, Lensch MW, Andrews PW, Itskovitz-Eldor J, Daley GQ (2004) LIF/STAT3 signaling fails to maintain self-renewal of human embryonic stem cells. Stem Cells 22:770–778

    Article  PubMed  Google Scholar 

  • de Miguel-Beriain I (2015) The ethics of stem cells revisited. Adv Drug Deliv Rev 82–83:176–180

    Article  PubMed  Google Scholar 

  • Devolder K, Savulescu J (2006) The moral imperative to conduct embryonic stem cell and cloning research. Ethics 15:7–21

    Google Scholar 

  • Dhar D, Ho JH (2009) Stem cell research policies around the world. Yale J Biol Med 82(3):113–115

    PubMed  PubMed Central  Google Scholar 

  • Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A (1997) Cellular composition and thee-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 17:5046–5061

    CAS  PubMed  Google Scholar 

  • Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:703–716

    Article  CAS  PubMed  Google Scholar 

  • Dunn SJ, Martello G, Yordanov B, Emmott S, Smith AG (2014) Defining an essential transcription factor program for naïve pluripotency. Science 344:1156–1160

    Google Scholar 

  • Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    Article  CAS  PubMed  Google Scholar 

  • Feraud O, Vittet D (2003) Murine embryonic stem cell in vitro differentiation: applications to the study of vascular development. Histol Histopathol 18:191–199

    CAS  PubMed  Google Scholar 

  • Friedenstein AJ, Gorskaja JF, Kulagina NN (1976) Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 4:267–274

    CAS  PubMed  Google Scholar 

  • Gage FH, Kempermann G, Palmer TD, Peterson DA, Ray J (1998) Multipotent progenitor cells in the adult dentate gyrus. J Neurobiol 36:249–266

    Article  CAS  PubMed  Google Scholar 

  • Gaj T, Barbas CF 3rd (2014) Genome engineering with custom recombinases. Methods Enzymol 546:79–91

    Article  PubMed  Google Scholar 

  • Götz M, Sirko S, Beckers J, Irmler M (2015) Reactive astrocytes as neural stem or progenitor cells: in vivo lineage, In vitro potential, and Genome-wide expression analysis. Glia 63:1452–1468

    Article  PubMed  Google Scholar 

  • Green R (2002) Benefiting from “evil”: an incipient moral problem in human stem cell research. Bioethics 16:544–556

    Article  PubMed  Google Scholar 

  • Humphey RK, Beattie GM, Lopez AD, Bucay N, King CC, Firpo MT, Rose-John S, Hayek A (2004) Maintenance of pluripotency in human embryonic stem cells is STAT3 independent. Stem Cells 22:522–530

    Article  Google Scholar 

  • Kahan BW, Ephussi B (1970) Developmental potentialities of clonal in vitro cultures of mouse testicular teratoma. J Natl Cancer Inst 44:1015–1036

    CAS  PubMed  Google Scholar 

  • Kilby NJ, Snaith MR, Murray JA (1993) Site-specific recombinases: tools for genome engineering. Trends Genet 9:413–421

    Article  CAS  PubMed  Google Scholar 

  • Kleinsmith LJ, Pierce GB Jr (1964) Multipotentiality of single embryonal carcinoma cells. Cancer Res 24:1544–1551

    CAS  PubMed  Google Scholar 

  • Kucia M, Reca R, Campbell FR, Zuba-Surma E, Majka M, Ratajczak J, Ratajczak MZ (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

    Article  CAS  PubMed  Google Scholar 

  • Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringdén O (2003) HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 31:890–896

    Article  PubMed  Google Scholar 

  • Lerou PH, Daley GQ (2005) Therapeutic potential of embryonic stem cells. Blood Rev 19:321–331

    Article  PubMed  Google Scholar 

  • Liao J, Wu Z, Wang Y, Cheng L, Cui C, Gao Y, Chen T, Rao L, Chen S, Jia N, Dai H, Xin S, Kang J, Pei G, Xiao L (2008) Enhanced efficiency of generating induced pluripotent stem (iPS) cells from human somatic cells by a combination of six transcription factors. Cell Res 18:600–603

    Article  CAS  PubMed  Google Scholar 

  • Ling V, Neben S (1997) In vitro differentiation of embryonic stem cells: immunophenotypic analysis of cultured embryoid bodies. J Cell Physiol 171:104–115

    Article  CAS  PubMed  Google Scholar 

  • Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong KY, Sung KW, Lee CW, Zhao XD, Chiu KP, Lipovich L, Kuznetsov VA, Robson P, Stanton LW, Wei CL, Ruan Y, Lim B, Ng HH (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38:431–440

    Article  CAS  PubMed  Google Scholar 

  • Lowry WE, Richter L, Yachechko R, Pyle AD, Tchieu J, Sridharan R, Clark AT, Plath K (2008) Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci U S A 105:2883–2888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lupo G, Bertacchi M, Carucci N, Augusti-Tocco G, Biagioni S, Cremisi F (2014) From pluripotency to forebrain patterning: an in vitro journey astride embryonic stem cells. Cell Mol Life Sci 71:2917–2930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma S, Xie N, Li W, Yuan B, Shi Y, Wang Y (2014) Immunobiology of mesenchymal stem cells. Cell Death Differ 21:216–225

    Article  CAS  PubMed  Google Scholar 

  • Malik N, Rao MS (2013) A review of the methods for human iPSC derivation. Methods Mol Biol 997:23–33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marks H, Stunnenberg HG (2014) Transcription regulation and chomatin structure in the pluripotent ground state. Biochim Biophys Acta 1839:129–137

    Article  CAS  PubMed  Google Scholar 

  • Martin GR (1980) Teratocarcinomas and mammalian embryogenesis. Science 209:768–776

    Article  CAS  PubMed  Google Scholar 

  • Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78:7634–7638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin SE, Caplen NJ (2007) Applications of RNA interference in mammalian systems. Annu Rev Genomics Hum Genet 8:81–108

    Article  CAS  PubMed  Google Scholar 

  • Merkle FT, Alvarez-Buylla A (2006) Neural stem cells in mammalian development. Curr Opin Cell Biol 18:704–709

    Article  CAS  PubMed  Google Scholar 

  • Merkle FT, Tramontin AD, Garcia-Verdugo JM, Alvarez-Buylla A (2004) Radial glia give rise to adult neural stem cells in the subventricular zone. Proc Natl Acad Sci U S A 101:17528–17532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Musina RA, Belyavski AV, Tarusova OV, Solovyova EV, Sukhikh GT (2008) Endometrial mesenchymal stem cells isolated from the menstrual blood. Bull Exp Biol Med 145:539–543

    Article  CAS  PubMed  Google Scholar 

  • O'Malley J, Woltjen K, Kaji K (2009) New strategies to generate induced pluripotent stem cells. Curr Opin Biotechnol 20:516–521

    Article  PubMed  Google Scholar 

  • Parras CM, Galli R, Britz O, Soares S, Galichet C, Battiste J, Johnson SE, Nakafuku M, Vescovi A, Guillemot F (2004) Mash1 specifies neurons and oligodendrocytes in the postnatal brain. EMBO J 23:4495–4505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Portmann-Lanz CB, Schoeberlein A, Huber A, Sager R, Malek A, Holzgreve W, Surbek DV (2006) Placental mesenchymal stem cells as potential autologous graft for pre- and perinatal neuroregeneration. Am J Obstet Gynecol 194:664–673

    Article  CAS  PubMed  Google Scholar 

  • Potten CS, Loeffler M (1990) Stem cells: attributes, cycles, spirals, pitfalls and uncertainties: Lessons for and from the crypt. Development 110:1001–1020

    CAS  PubMed  Google Scholar 

  • Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74

    Article  CAS  PubMed  Google Scholar 

  • Ratajczak MZ, Shin DM, Liu R, Mierzejewska K, Ratajczak J, Kucia M, Zuba-Surma EK (2012) Very small embryonic/epiblast-like stem cells (VSELs) and their potential role in aging and organ rejuvenation—an update and comparison to other primitive small stem cells isolated from adult tissues. Aging (Albany NY) 4:235–246

    Article  CAS  Google Scholar 

  • Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A (2000) Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol 18:399–404

    Article  CAS  PubMed  Google Scholar 

  • Slack JM (2000) Stem cells in epithelial tissues. Science 287:1431–1433

    Article  CAS  PubMed  Google Scholar 

  • Smith AG (2012) Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol 17:435–462

    Article  Google Scholar 

  • Smith AG, Heath JK, Donaldson DD, Wong GG, Moreau J, Stahl M, Rogers D (1988) Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336:688–690

    Article  CAS  PubMed  Google Scholar 

  • Sordi V, Malosio ML, Marchesi F, Mercalli A, Melzi R, Giordano T, Belmonte N, Ferrari G, Leone BE, Bertuzzi F, Zerbini G, Allavena P, Bonifacio E, Piemonti L (2005) Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. Blood 106:419–427

    Article  CAS  PubMed  Google Scholar 

  • Spangrude GJ, Heimfeld S, Weissman IL (1988) Purification and characterization of mouse hematopoietic stem cells. Science 241:58–62

    Article  CAS  PubMed  Google Scholar 

  • Stevens LC, Little CC (1954) Spontaneous testicular teratomas in an inbred strain of mice. Proc Natl Acad Sci U S A 40:1080–1087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  CAS  PubMed  Google Scholar 

  • Takashima Y, Guo G, Loos R, Nichols J, Ficz G, Krueger F, Oxley D, Santos F, Clarke J, Mansfield W, Reik W, Bertone P, Smith A (2014) Resetting transcription factor control circuitry toward ground-state pluripotency in human. Cell 158:1254–1269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  CAS  PubMed  Google Scholar 

  • Tirino V, Paino F, d'Aquino R, Desiderio V, De Rosa A, Papaccio G (2011) Methods for the identification, characterization and banking of human DPSCs: current strategies and perspectives. Stem Cell Rev 7:608–615

    Article  PubMed  Google Scholar 

  • Van Duyne GD (2015) Cre recombinase. Microbiol Spectr 3(1):119–138

    Google Scholar 

  • Wakayama T, Perry AC, Zuccotti M, Johnson KR, Yanagimachi R (1998) Full-term development of mice from enucleated oocytes injected with cumulus. Nature 394:369–374

    Article  CAS  PubMed  Google Scholar 

  • Welling M, Geijsen N (2013) Uncovering the true identity of naive pluripotent stemcells. Trends Cell Biol 23:442–448

    Article  CAS  PubMed  Google Scholar 

  • Wernig M, Meissner A, Cassady JP, Jaenisch R (2008) c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell 2:10–12

    Article  CAS  PubMed  Google Scholar 

  • Williams RL, Hilton DJ, Pease S, Willson TA, Stewart CL, Gearing DP, Wagner EF, Metcalf D, Nicola NA, Gough NM (1988) Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 336:684–687

    Article  CAS  PubMed  Google Scholar 

  • Winkler J, Hescheler J, Sachinidis A (2004) Embryonic stem cells for basic research and potential clinical applications in cardiology. Biochim Biophys Acta 1740:240–248

    Article  PubMed  Google Scholar 

  • Xie C, Ritchie RP, Huang H, Zhang J, Chen YE (2011) Smooth muscle cell differentiation in vitro: models and underlying molecular mechanisms. Arterioscler Thomb Vasc Biol 31:1485–1494

    Article  CAS  Google Scholar 

  • Yu J, Thomson JA (2008) Pluripotent stem cell lines. Genes Dev 22:1987–1997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    Article  CAS  PubMed  Google Scholar 

  • Zaret KS, Grompe M (2008) Generation and regeneration of cells of the liver and pancreas. Science 322:1490–1494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by research grants from Brazilian funding agencies Sao Paulo Research Foundation (FAPESP; Proc. No. 2012/50880-4, 2015/13345-1), National Council for Scientific and Technological Development (CNPq; Proc. No. 467465/2014-2, 141979/2014-3, 403745/2014-4), and Provost’s Office for Research of the University of Sao Paulo, Grant number: 2011.1.9333.1.3 (NAPNA-USP), Brazil.

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  1. Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, SP, 05508-000, Brazil

    Ágatha Oliveira, Juliana da Cruz Corrêa-Velloso, Talita Glaser & Henning Ulrich

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  1. Ágatha Oliveira
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  2. Juliana da Cruz Corrêa-Velloso
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  3. Talita Glaser
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  4. Henning Ulrich
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Correspondence to Henning Ulrich .

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Oliveira, Á., Corrêa-Velloso, J.d.C., Glaser, T., Ulrich, H. (2016). Stem Cells: Principles and Applications. In: Working with Stem Cells. Springer, Cham. https://doi.org/10.1007/978-3-319-30582-0_1

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