Advertisement

Heart Failure pp 711-725 | Cite as

Physiology of Stem Cells

  • Jos Domen
  • Kimberly Gandy
Chapter
First Online:

Abstract

Stem cells are rare cells that have the ability to choose between self-renewal and differentiation. They can be found in an organism during development, starting with the pluripotent zygote, and continue to be present in organisms throughout their lifespans. In tissues with high turnover like blood, stem cells are continuously needed to produce new cells. In view of their proliferative potential stem cell regulation has to be extensive and complex. Much of it occurs in specialized sites known as stem cell niches. In addition to the stem cells that are present in the body, it is now possible to transform cells without stem cell potential into pluripotent stem cells using gene transfer. Stem cells have enormous clinical potential due to their diverse functional capabilities. Currently, the field of hematopoiesis has been the most successful in harnessing stem cell potential, and hematopoietic stem cells have become part of routine clinical care. Applications to other organ systems, including heart, are under active investigation and are the subjects of ongoing clinical trials.

Keywords

Stem Cell Progenitor Cell Niche Homeostasis Embryonic Stem Cell Induced Pluripotent Stem Cell Adult Stem Cell 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Jacobsen LO, Marks EK, Robson MJ, Gaston EO, Zirkle RE. Effect of spleen protection on mortality following x-irradiation. J Lab Clin Med. 1949;34:1538.Google Scholar
  2. 2.
    Lorenz E, Uphoff D, Reid TR, Shelton E. Modification of irradiation injury in mice and guinea pigs by bone marrow injections. J Natl Cancer Inst. 1951;12:197–201.PubMedGoogle Scholar
  3. 3.
    Becker AJ, Mc CE, Till JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature. 1963;197:452–4.PubMedCrossRefGoogle Scholar
  4. 4.
    Siminovitch L, McCulloch EA, Till JE. The distribution of colony-forming cells among spleen colonies. J Cell Physiol. 1963;62:327–36.CrossRefGoogle Scholar
  5. 5.
    Wu AM, Till JE, Siminovitch L, McCulloch EA. Cytological evidence for a relationship between normal hemotopoietic colony-forming cells and cells of the lymphoid system. J Exp Med. 1968;127(3):455–64.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Spooncer E, Lord BI, Dexter TM. Defective ability to self-renew in vitro of highly purified primitive haematopoietic cells. Nature. 1985;316(6023):62–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Spangrude GJ, Heimfeld S, Weissman IL. Purification and characterization of mouse hematopoietic stem cells. Science. 1988;241(4861):58–62.PubMedCrossRefGoogle Scholar
  8. 8.
    Gratwohl A, Baldomero H, Aljurf M, Pasquini MC, Bouzas LF, Yoshimi A, et al. Hematopoietic stem cell transplantation: a global perspective. JAMA. 2010;303(16):1617–24.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Harrison DE, Astle CM. Loss of stem cell repopulating ability upon transplantation. Effects of donor age, cell number, and transplantation procedure. J Exp Med. 1982;156(6):1767–79.PubMedCrossRefGoogle Scholar
  10. 10.
    Pawliuk R, Eaves C, Humphries RK. Evidence of both ontogeny and transplant dose-regulated expansion of hematopoietic stem cells in vivo. Blood. 1996;88(8):2852–8.PubMedGoogle Scholar
  11. 11.
    Iscove NN, Nawa K. Hematopoietic stem cells expand during serial transplantation in vivo without apparent exhaustion. Curr Biol. 1997;7(10):805–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med. 2000;6(11):1229–34.PubMedCrossRefGoogle Scholar
  13. 13.
    Mezey. E, Chandross KJ, Harta G, Maki RA, McKercher SR. Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science. 2000;290(5497):1779–82.PubMedCrossRefGoogle Scholar
  14. 14.
    Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell. 2004;116(5):639–48.PubMedCrossRefGoogle Scholar
  15. 15.
    Camargo FD, Chambers SM, Goodell MA. Stem cell plasticity: from transdifferentiation to macrophage fusion. Cell Prolif. 2004;37(1):55–65.PubMedCrossRefGoogle Scholar
  16. 16.
    Raff M. Adult stem cell plasticity: fact or artifact? Annu Rev Cell Dev Biol. 2003;19:1–22.PubMedCrossRefGoogle Scholar
  17. 17.
    Ho PJ, Yen ML, Yet SF, Yen BL. Current applications of human pluripotent stem cells: possibilities and challenges. Cell Transplant. 2012;21(5):801–14.PubMedCrossRefGoogle Scholar
  18. 18.
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72.PubMedCrossRefGoogle Scholar
  19. 19.
    Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.PubMedCrossRefGoogle Scholar
  20. 20.
    Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–20.PubMedCrossRefGoogle Scholar
  21. 21.
    Zwi-Dantsis L, Gepstein L. Induced pluripotent stem cells for cardiac repair. Cell Mol Life Sci. 2012;69(19):3285–99.PubMedCrossRefGoogle Scholar
  22. 22.
    Benitah SA, Frye M. Stem cells in ectodermal development. J Mol Med (Berl). 2012;90(7):783–90.CrossRefGoogle Scholar
  23. 23.
    Domen J, Wagers AJ, Weissman IL. Bone marrow (hematopoietic stem cells). Regen Med. 2006;2006:13–34. Available from: http://stemcells.nih.gov/info/scireport/2006report.htm.
  24. 24.
    Lensch MW. An evolving model of hematopoietic stem cell functional identity. Stem Cell Rev. 2012;8(2):551–60.PubMedCrossRefGoogle Scholar
  25. 25.
    Takizawa H, Manz MG. In vivo divisional tracking of hematopoietic stem cells. Ann N Y Acad Sci. 2012;1266:40–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Hombria JC, Brown S. The fertile field of Drosophila Jak/STAT signalling. Curr Biol. 2002;12(16):R569–75.PubMedCrossRefGoogle Scholar
  27. 27.
    Resende LP, Jones DL. Local signaling within stem cell niches: insights from Drosophila. Curr Opin Cell Biol. 2012;24(2):225–31.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Christensen JL, Wright DE, Wagers AJ, Weissman IL. Circulation and chemotaxis of fetal hematopoietic stem cells. PLoS Biol. 2004;2(3):E75.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Hoggatt J, Pelus LM. Mobilization of hematopoietic stem cells from the bone marrow niche to the blood compartment. Stem Cell Res Ther. 2011;2(2):13.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Greenbaum AM, Link DC. Mechanisms of G-CSF-mediated hematopoietic stem and progenitor mobilization. Leukemia. 2011;25(2):211–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Shiozawa Y, Havens AM, Pienta KJ, Taichman RS. The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites. Leukemia. 2008;22(5):941–50.PubMedCrossRefGoogle Scholar
  32. 32.
    Garrett RW, Emerson SG. Bone and blood vessels: the hard and the soft of hematopoietic stem cell niches. Cell Stem Cell. 2009;4(6):503–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Lilly AJ, Johnson WE, Bunce CM. The haematopoietic stem cell niche: new insights into the mechanisms regulating haematopoietic stem cell behaviour. Stem Cells Int. 2011;2011:274564.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Mercier FE, Ragu C, Scadden DT. The bone marrow at the crossroads of blood and immunity. Nat Rev Immunol. 2012;12(1):49–60.CrossRefGoogle Scholar
  35. 35.
    Tieu KS, Tieu RS, Martinez-Agosto JA, Sehl ME. Stem cell niche dynamics: from homeostasis to carcinogenesis. Stem Cells Int. 2012;2012:367567.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Shiozawa Y, Taichman RS. Getting blood from bone: an emerging understanding of the role that osteoblasts play in regulating hematopoietic stem cells within their niche. Exp Hematol. 2012;40(9):685–94.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. 2004;118(2):149–61.PubMedCrossRefGoogle Scholar
  38. 38.
    Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425(6960):841–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425(6960):836–41.PubMedCrossRefGoogle Scholar
  40. 40.
    Ding L, Saunders TL, Enikolopov G, Morrison SJ. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 2012;481(7382):457–62.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Sugiyama T, Kohara H, Noda M, Nagasawa T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity. 2006;25(6):977–88.PubMedCrossRefGoogle Scholar
  42. 42.
    Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature. 2009;460(7252):259–63.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010;466(7308):829–34.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003;423(6938):409–14.PubMedCrossRefGoogle Scholar
  45. 45.
    Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 2003;423(6938):448–52.PubMedCrossRefGoogle Scholar
  46. 46.
    Murdoch B, Chadwick K, Martin M, Shojaei F, Shah KV, Gallacher L, et al. Wnt-5 A augments repopulating capacity and primitive hematopoietic development of human blood stem cells in vivo. Proc Natl Acad Sci U S A. 2003;100(6):3422–7.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Luis TC, Naber BA, Roozen PP, Brugman MH, de Haas EF, Ghazvini M, et al. Canonical wnt signaling regulates hematopoiesis in a dosage-dependent fashion. Cell Stem Cell. 2011;9(4):345–56.PubMedCrossRefGoogle Scholar
  48. 48.
    Varnum-Finney B, Xu L, Brashem-Stein C, Nourigat C, Flowers D, Bakkour S, et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med. 2000;6(11):1278–81.PubMedCrossRefGoogle Scholar
  49. 49.
    Varnum-Finney B, Brashem-Stein C, Bernstein ID. Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability. Blood. 2003;101(5):1784–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger RL, Bernstein ID. Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med. 2010;16(2):232–6.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Zhang CC, Lodish HF. Insulin-like growth factor 2 expressed in a novel fetal liver cell population is a growth factor for hematopoietic stem cells. Blood. 2004;103(7):2513–21.PubMedCrossRefGoogle Scholar
  52. 52.
    Huynh H, Iizuka S, Kaba M, Kirak O, Zheng J, Lodish HF, et al. Insulin-like growth factor-binding protein 2 secreted by a tumorigenic cell line supports ex vivo expansion of mouse hematopoietic stem cells. Stem Cells. 2008;26(6):1628–35.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Zhang CC, Kaba M, Iizuka S, Huynh H, Lodish HF. Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells as assayed by NOD/SCID transplantation. Blood. 2008;111(7):3415–23.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Sherr CJ. Principles of tumor suppression. Cell. 2004;116(2):235–46.PubMedCrossRefGoogle Scholar
  55. 55.
    He S, Nakada D, Morrison SJ. Mechanisms of stem cell self-renewal. Annu Rev Cell Dev Biol. 2009;25:377–406.PubMedCrossRefGoogle Scholar
  56. 56.
    Allsopp RC, Morin GB, DePinho R, Harley CB, Weissman IL. Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation. Blood. 2003;102(2):517–20.PubMedCrossRefGoogle Scholar
  57. 57.
    Rossi DJ, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman IL. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature. 2007;447(7145):725–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Hoffmeyer K, Raggioli A, Rudloff S, Anton R, Hierholzer A, Del Valle I, et al. Wnt/beta-catenin signaling regulates telomerase in stem cells and cancer cells. Science. 2012;336(6088):1549–54.PubMedCrossRefGoogle Scholar
  59. 59.
    Walasek MA, van Os R, de Haan G. Hematopoietic stem cell expansion: challenges and opportunities. Ann N Y Acad Sci. 2012;1266:138–50.PubMedCrossRefGoogle Scholar
  60. 60.
    Jaenisch R, Young R. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell. 2008;132(4):567–82.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    De Los Angeles A, Loh YH, Tesar PJ, Daley GQ. Accessing naive human pluripotency. Curr Opin Genet Dev. 2012;22(3):272–82.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Li M, Liu GH, Izpisua Belmonte JC. Navigating the epigenetic landscape of pluripotent stem cells. Nat Rev Mol Cell Biol. 2012;13(8):524–35.PubMedCrossRefGoogle Scholar
  63. 63.
    Dejosez M, Krumenacker JS, Zitur LJ, Passeri M, Chu LF, Songyang Z, et al. Ronin is essential for embryogenesis and the pluripotency of mouse embryonic stem cells. Cell. 2008;133(7):1162–74.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Negrin RS, Atkinson K, Leemhuis T, Hanania E, Juttner C, Tierney K, et al. Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with metastatic breast cancer. Biol Blood Marrow Transplant. 2000;6(3):262–71.PubMedCrossRefGoogle Scholar
  65. 65.
    Muller AM, Kohrt HE, Cha S, Laport G, Klein J, Guardino AE, et al. Long-term outcome of patients with metastatic breast cancer treated with high-dose chemotherapy and transplantation of purified autologous hematopoietic stem cells. Biol Blood Marrow Transplant. 2012;18(1):125–33.PubMedCrossRefGoogle Scholar
  66. 66.
    Harris AC, Ferrara JL, Levine JE. Advances in predicting acute GVHD. Br J Haematol. 2013;160(3):288–302 . Published online 2012 Dec 4. doi: 10.1111/bjh.12142.PubMedCrossRefGoogle Scholar
  67. 67.
    Harris AC, Levine JE, Ferrara JL. Have we made progress in the treatment of GVHD? Best Pract Res Clin Haematol. 2012;25(4):473–8.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Petersdorf EW. Genetics of graft-versus-host disease: The major histocompatibility complex. Blood Rev. 2013;27(1):1–12. doi: 10.1016/j.blre.2012.10.001 . Epub 2012 Nov 20.PubMedCrossRefGoogle Scholar
  69. 69.
    Domen J, Gandy K, Dalal J. Emerging uses for pediatric hematopoietic stem cells. Pediatr Res. 2012;71(4–2):411–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Sullivan KM, Muraro P, Tyndall A. Hematopoietic cell transplantation for autoimmune disease: updates from Europe and the United States. Biol Blood Marrow Transplant. 2010;16(1 Suppl):S48–56.PubMedCrossRefGoogle Scholar
  71. 71.
    Prasad VK, Kurtzberg J. Cord blood and bone marrow transplantation in inherited metabolic diseases: scientific basis, current status and future directions. Br J Haematol. 2010;148(3):356–72.PubMedCrossRefGoogle Scholar
  72. 72.
    Strober S. Protective conditioning against GVHD and graft rejection after combined organ and hematopoietic cell transplantation. Blood Cells Mol Dis. 2008;40(1):48–54.PubMedCrossRefGoogle Scholar
  73. 73.
    Strober S, Spitzer TR, Lowsky R, Sykes M. Translational studies in hematopoietic cell transplantation: Treatment of hematologic malignancies as a stepping stone to tolerance induction. Semin Immunol. 2011;23(4):273–81.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Sachs DH, Sykes M, Kawai T, Cosimi AB. Immuno-intervention for the induction of transplantation tolerance through mixed chimerism. Semin Immunol. 2011;23(3):165–73.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Ghadially R. 25 years of epidermal stem cell research. J Invest Dermatol. 2012;132(3 Pt 2):797–810.PubMedCrossRefGoogle Scholar
  76. 76.
    Goldstein J, Horsley V. Home sweet home: skin stem cell niches. Cell Mol Life Sci. 2012;69(15):2573–82.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Yan X, Owens DM. The skin: a home to multiple classes of epithelial progenitor cells. Stem Cell Rev. 2008;4(2):113–8.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Dalal J, Gandy K, Domen J. Role of mesenchymal stem cell therapy in Crohn’s disease. Pediatr Res. 2012;71(4–2):445–51.PubMedCrossRefGoogle Scholar
  79. 79.
    Harrop JS, Hashimoto R, Norvell D, Raich A, Aarabi B, Grossman RG, et al. Evaluation of clinical experience using cell-based therapies in patients with spinal cord injury: a systematic review. J Neurosurg Spine. 2012;17(1 Suppl):230–46.PubMedCrossRefGoogle Scholar
  80. 80.
    Keating A. Mesenchymal stromal cells: new directions. Cell Stem Cell. 2012;10(6):709–16.PubMedCrossRefGoogle Scholar
  81. 81.
    Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, et al. Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA. 2012;308(22):2369–79.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Miettinen JA, Salonen RJ, Ylitalo K, Niemela M, Kervinen K, Saily M, et al. The effect of bone marrow microenvironment on the functional properties of the therapeutic bone marrow-derived cells in patients with acute myocardial infarction. J Transl Med. 2012;10:66.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Mathiasen AB, Jorgensen E, Qayyum AA, Haack-Sorensen M, Ekblond A, Kastrup J. Rationale and design of the first randomized, double-blind, placebo-controlled trial of intramyocardial injection of autologous bone-marrow derived Mesenchymal Stromal Cells in chronic ischemic Heart Failure (MSC-HF Trial). Am Heart J. 2012;164(3):285–91.PubMedCrossRefGoogle Scholar
  84. 84.
    Ishikawa T, Banas A, Teratani T, Iwaguro H, Ochiya T. Regenerative cells for transplantation in hepatic failure. Cell Transplant. 2012;21(2–3):387–99.PubMedCrossRefGoogle Scholar
  85. 85.
    Kondziolka D, Wechsler L, Goldstein S, Meltzer C, Thulborn KR, Gebel J, et al. Transplantation of cultured human neuronal cells for patients with stroke. Neurology. 2000;55(4):565–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Luan Z, Liu W, Qu S, Du K, He S, Wang Z, et al. Effects of neural progenitor cell transplantation in children with severe cerebral palsy. Cell Transplant. 2012;21(Suppl 1):S91–8.PubMedCrossRefGoogle Scholar
  87. 87.
    Riley J, Federici T, Polak M, Kelly C, Glass J, Raore B, et al. Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: a phase I safety trial, technical note, and lumbar safety outcomes. Neurosurgery. 2012;71(2):405–16 ; discussion 416.PubMedCrossRefGoogle Scholar
  88. 88.
    Ben-David U, Kopper O, Benvenisty N. Expanding the boundaries of embryonic stem cells. Cell Stem Cell. 2012;10(6):666–77.PubMedCrossRefGoogle Scholar
  89. 89.
    Serra M, Brito C, Correia C, Alves PM. Process engineering of human pluripotent stem cells for clinical application. Trends Biotechnol. 2012;30(6):350–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Zhu Y, Wan S, Zhan RY. Inducible pluripotent stem cells for the treatment of ischemic stroke: current status and problems. Rev Neurosci. 2012;23(4):393–402.PubMedCrossRefGoogle Scholar
  91. 91.
    Wang H, Doering LC. Induced pluripotent stem cells to model and treat neurogenetic disorders. Neural Plast. 2012;2012:346053.PubMedPubMedCentralGoogle Scholar
  92. 92.
    van Bekkum DW, Mikkers HM. Prospects and challenges of induced pluripotent stem cells as a source of hematopoietic stem cells. Ann N Y Acad Sci. 2012;1266:179–88.PubMedCrossRefGoogle Scholar
  93. 93.
    Kao DI, Chen S. Pluripotent stem cell-derived pancreatic beta-cells: potential for regenerative medicine in diabetes. Regen Med. 2012;7(4):583–93.PubMedCrossRefGoogle Scholar
  94. 94.
    Boral D, Nie D. Cancer stem cells and niche mircoenvironments. Front Biosci (Elite Ed). 2012;4:2502–14.Google Scholar
  95. 95.
    Verga Falzacappa MV, Ronchini C, Reavie LB, Pelicci PG. Regulation of self-renewal in normal and cancer stem cells. FEBS J. 2012;279(19):3559–72.PubMedCrossRefGoogle Scholar
  96. 96.
    Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11.PubMedCrossRefGoogle Scholar
  97. 97.
    Al-Hajj M, Becker MW, Wicha M, Weissman I, Clarke MF. Therapeutic implications of cancer stem cells. Curr Opin Genet Dev. 2004;14(1):43–7.PubMedCrossRefGoogle Scholar
  98. 98.
    Dick JE. Acute myeloid leukemia stem cells. Ann N Y Acad Sci. 2005;1044:1–5.PubMedCrossRefGoogle Scholar
  99. 99.
    Alison MR, Lin WR, Lim SM, Nicholson LJ. Cancer stem cells: in the line of fire. Cancer Treat Rev. 2012;38(6):589–98.PubMedCrossRefGoogle Scholar
  100. 100.
    Magee JA, Piskounova E, Morrison SJ. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell. 2012;21(3):83–96.CrossRefGoogle Scholar
  101. 101.
    Vermeulen L. de Sousa e Melo F, Richel DJ, Medema JP. The developing cancer stem-cell model: clinical challenges and opportunities. Lancet Oncol. 2012;13(2):e83–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F, et al. Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol. 2008;26(11):1276–84.PubMedCrossRefGoogle Scholar
  103. 103.
    Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K, et al. Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science. 2008;321(5889):699–702.PubMedCrossRefGoogle Scholar
  104. 104.
    Hanna J, Markoulaki S, Schorderet P, Carey BW, Beard C, Wernig M, et al. Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell. 2008;133(2):250–64.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Chambers SM, Studer L. Cell fate plug and play: direct reprogramming and induced pluripotency. Cell. 2011;145(6):827–30.PubMedCrossRefGoogle Scholar
  106. 106.
    Stadtfeld M, Hochedlinger K. Induced pluripotency: history, mechanisms, and applications. Genes Dev. 2010;24(20):2239–63.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M. Direct conversion of fibroblasts to functional neurons by defined factors. Nature. 2010;463(7284):1035–41.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, et al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell. 2010;142(3):375–86.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Riley PR. An epicardial floor plan for building and rebuilding the mammalian heart. Curr Top Dev Biol. 2012;100:233–51.PubMedCrossRefGoogle Scholar
  110. 110.
    Lui KO, Bu L, Li RA, Chan CW. Pluripotent stem cell-based heart regeneration: from the developmental and immunological perspectives. Birth Defects Res C Embryo Today. 2012;96(1):98–108.PubMedCrossRefGoogle Scholar
  111. 111.
    Buckingham M, Meilhac S, Zaffran S. Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet. 2005;6(11):826–35.PubMedCrossRefGoogle Scholar
  112. 112.
    Bernstein HS, Srivastava D. Stem cell therapy for cardiac disease. Pediatr Res. 2012;71(4 Pt 2):491–9.PubMedCrossRefGoogle Scholar
  113. 113.
    Ptaszek LM, Mansour M, Ruskin JN, Chien KR. Towards regenerative therapy for cardiac disease. Lancet. 2012;379(9819):933–42.PubMedCrossRefGoogle Scholar
  114. 114.
    Hotkar AJ, Balinsky W. Stem cells in the treatment of cardiovascular disease--an overview. Stem Cell Rev. 2012;8(2):494–502.PubMedCrossRefGoogle Scholar
  115. 115.
    Dimarakis I, Menasche P, Habib NA, Gordon MY, editors. Handbook of cardiac stem cell therapy. London: Imperial College Press; 2009. p. 1–285.Google Scholar
  116. 116.
    Mullenix PS, Huddleston SJ, Stojadinovic A, Trachiotis GD, Alexander EP. A new heart: somatic stem cells and myocardial regeneration. J Surg Oncol. 2012;105(5):475–80.PubMedCrossRefGoogle Scholar
  117. 117.
    Takamiya M, Haider KH, Ashraf M. Identification and characterization of a novel multipotent sub-population of Sca-1(+) cardiac progenitor cells for myocardial regeneration. PLoS One. 2011;6(9):e25265.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Ye J, Boyle A, Shih H, Sievers RE, Zhang Y, Prasad M, et al. Sca-1+ cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury. PLoS One. 2012;7(1):e30329.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    van Wijk B, Gunst QD, Moorman AF, van den Hoff MJ. Cardiac regeneration from activated epicardium. PLoS One. 2012;7(9):e44692.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, et al. Mammalian heart renewal by pre-existing cardiomyocytes. Nature. 2013;493(7432):433–6. doi: 10.1038/nature11682 . Epub 2012 Dec 5.PubMedCrossRefGoogle Scholar
  121. 121.
    Eulalio A, Mano M, Ferro MD, Zentilin L, Sinagra G, Zacchigna S, et al. Functional screening identifies miRNAs inducing cardiac regeneration. Nature. 2012;492(7429):376–81. doi: 10.1038/nature11739 . Epub 2012 Dec 5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2017

Authors and Affiliations

  1. 1.Section of Cardiac SurgeryChildren’s Mercy Hospital and Clinics and University of MissouriKansas CityUSA
  2. 2.Department of Biomedical and Health InformaticsUniversity of MissouriKansas CityUSA

Personalised recommendations

Cite chapter

Buy options