Skip to main content
SpringerLink
Log in
Book cover

Perinatal Stem Cells pp 3–15Cite as

Amniotic Fluid Stem Cells for Cardiac Regeneration

  • Chapter
  • First Online:

  • 944 Accesses

Abstract

In recent years cardiac regenerative medicine has emerged as a fast-developing exploratory field with tremendous potential to treat end-stage heart disease. Different approaches have been investigated for the repair of cardiovascular ischemic injuries such as myocardial infarction, in order to improve heart performance in the long term. In this scenario, stem cell-based medicine has received a lot of attention, and several stem sources have been evaluated to identify the most suitable therapeutic approach. Cardiac regeneration has become a multidisciplinary research area based primarily on different stem cell- and tissue engineering-based strategies, with the ultimate goal of preventing or reversing heart failure.

Amniotic fluid stem (AFS) cells are broadly multipotent and clonogenic cells which have emerged as a potent therapeutic agent in regenerative medicine and which can be easily obtained throughout pregnancy from surplus samples taken for prenatal diagnostic procedures. In this chapter we will discuss the most significant findings in the field of stem cell therapy for cardiac regeneration, focusing on the recent results using AFS cells.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

3D:

Three dimensional

AF-MSC:

Amniotic fluid-derived mesenchymal stem cells

AFS:

Amniotic fluid stem

bFGF:

Basic fibroblast growth factor

BM-MSC:

Bone marrow-derived mesenchymal stem cells

CMTMR:

(5-(and-6)-(((4-Chloromethyl)benzoyl)amino)tetramethylrhodamine)

CPC:

Cardiac progenitor cells

cTnT:

Cardiac troponin T

EC:

Endothelial cell

EGM-2:

Endothelial growth medium 2

ES:

Embryonic stem

GFP:

Green fluorescent protein

hAFS:

Human amniotic fluid stem cells

hFGF:

Human fibroblast growth factor

HGF:

Hepatocyte growth factor

HIF-1α:

Hypoxia-inducible factor 1-alpha

HLA-DR:

Human leucocyte antigen-DR

hptMyosin:

Human-specific anti-platelet nonmuscle myosin

IGF-1:

Insulin growth factor-1

IL-8:

Interleukin 8

iPS:

Induced pluripotent stem cells

MCP-1:

Monocyte chemoattractant protein-1

MI:

Myocardial infarction

MMP9:

Matrix metallopeptidase 9

MRI:

Magnetic resonance imaging

MSC:

Mesenchymal stem cells

NOD-SCID:

Non-obese diabetic-severe combined immunodeficiency

PCR:

Polymerase chain reaction

PDGF-AA/BB:

Platelet-derived growth factor-AA/BB

PLGA:

[Poly(d,l-lactic-co-glycolic acid)]

rAFS:

Rat amniotic fluid stem cells

SDF-1:

Stromal growth factor-1

SM:

Smooth muscle

SMA:

Alpha smooth muscle actin

SSEA4:

Stage-specific embryonic antigen 4

TGFβ:

Transforming growth factor beta

Tβ4:

Thymosin beta 4

VEGF:

Vascular endothelial growth factor

vWf:

von Willebrand factor

References

  1. Gnecchi M, He H, Noiseux N, Liang OD, Zhang L, Morello F, et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 2006;20(6):661–9.

    Article  CAS  PubMed  Google Scholar 

  2. 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(6983):664–8.

    Article  CAS  PubMed  Google Scholar 

  3. Tomita S, Li RK, Weisel RD, Mickle DA, Kim EJ, Sakai T, et al. Autologous transplantation of bone marrow cells improves damaged heart function. Circulation. 1999;100(19 Suppl):II247–56.

    CAS  PubMed  Google Scholar 

  4. Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, et al. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007;167(10):989–97.

    Article  PubMed  Google Scholar 

  5. Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res. 2008;103(11): 1204–19.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Martin-Rendon E, Brunskill S, Doree C, Hyde C, Watt S, Mathur A, et al. Stem cell treatment for acute myocardial infarction. Cochrane Database Syst Rev. 2008;4, CD006536.

    PubMed  Google Scholar 

  7. Yan B, Abdelli LS, Singla DK. Transplanted induced pluripotent stem cells improve cardiac function and induce neovascularization in the infarcted hearts of db/db mice. Mol Pharm. 2011;8(5):1602–10.

    Article  CAS  PubMed  Google Scholar 

  8. Davis DR, Stewart DJ. Autologous cell therapy for cardiac repair. Expert Opin Biol Ther. 2011;11(4):489–508.

    Article  PubMed  Google Scholar 

  9. Suuronen EJ, Sheardown H, Newman KD, McLaughlin CR, Griffith M. Building in vitro models of organs. Int Rev Cytol. 2005;244:137–73.

    Article  CAS  PubMed  Google Scholar 

  10. Suuronen EJ, Veinot JP, Wong S, Kapila V, Price J, Griffith M, et al. Tissue-engineered injectable collagen-based matrices for improved cell delivery and vascularization of ischemic tissue using CD133+ progenitors expanded from the peripheral blood. Circulation. 2006;114(1 Suppl):I138–44.

    PubMed  Google Scholar 

  11. Zimmermann WH, Melnychenko I, Wasmeier G, Didie M, Naito H, Nixdorff U, et al. Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat Med. 2006;12(4):452–8.

    Article  CAS  PubMed  Google Scholar 

  12. In ‘t Anker PS, Scherjon SA, der Kleijburg-van KC, Noort WA, Claas FH, Willemze R, et al. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood. 2003;102(4):1548–9.

    Article  PubMed  Google Scholar 

  13. Tsai MS, Lee JL, Chang YJ, Hwang SM. Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum Reprod. 2004;19(6):1450–6.

    Article  PubMed  Google Scholar 

  14. De Coppi P, Bartsch Jr G, Siddiqui MM, Xu T, Santos CC, Perin L, et al. Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol. 2007;25(1):100–6.

    Article  PubMed  Google Scholar 

  15. Sessarego N, Parodi A, Podesta M, Benvenuto F, Mogni M, Raviolo V, et al. Multipotent mesenchymal stromal cells from amniotic fluid: solid perspectives for clinical application. Haematologica. 2008;93(3):339–46.

    Article  PubMed  Google Scholar 

  16. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145–7.

    Article  CAS  PubMed  Google Scholar 

  17. Verfaillie CM. Adult stem cells: assessing the case for pluripotency. Trends Cell Biol. 2002;12(11):502–8.

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    Article  CAS  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Qian L, Huang Y, Spencer CI, Foley A, Vedantham V, Liu L, et al. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature. 2012;485(7400):593–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Wang M, Yang Y, Yang D, Luo F, Liang W, Guo S, et al. The immunomodulatory activity of human umbilical cord blood-derived mesenchymal stem cells in vitro. Immunology. 2009;126(2):220–32.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Yen BL, Huang HI, Chien CC, Jui HY, Ko BS, Yao M, et al. Isolation of multipotent cells from human term placenta. Stem Cells. 2005;23(1):3–9.

    Article  CAS  PubMed  Google Scholar 

  24. Resca E, Zavatti M, Bertoni L, Maraldi T, De Biasi S, Pisciotta A, et al. Enrichment in c-Kit enhances mesodermal and neural differentiation of human chorionic placental cells. Placenta. 2013;34(7):526–35.

    Article  CAS  PubMed  Google Scholar 

  25. Kadner A, Hoerstrup SP, Tracy J, Breymann C, Maurus CF, Melnitchouk S, et al. Human umbilical cord cells: a new cell source for cardiovascular tissue engineering. Ann Thorac Surg. 2002; 74(4):S1422–8.

    Article  PubMed  Google Scholar 

  26. Ventura C, Cantoni S, Bianchi F, Lionetti V, Cavallini C, Scarlata I, et al. Hyaluronan mixed esters of butyric and retinoic Acid drive cardiac and endothelial fate in term placenta human mesenchymal stem cells and enhance cardiac repair in infarcted rat hearts. J Biol Chem. 2007;282(19):14243–52.

    Article  CAS  PubMed  Google Scholar 

  27. Schmidt D, Mol A, Neuenschwander S, Breymann C, Gossi M, Zund G, et al. Living patches engineered from human umbilical cord derived fibroblasts and endothelial progenitor cells. Eur J Cardiothorac Surg. 2005;27(5):795–800.

    Article  PubMed  Google Scholar 

  28. Leor J, Guetta E, Feinberg MS, Galski H, Bar I, Holbova R, et al. Human umbilical cord blood-derived CD133+ cells enhance function and repair of the infarcted myocardium. Stem Cells. 2006; 24(3):772–80.

    Article  PubMed  Google Scholar 

  29. Zhao P, Ise H, Hongo M, Ota M, Konishi I, Nikaido T. Human amniotic mesenchymal cells have some characteristics of cardiomyocytes. Transplantation. 2005;79(5):528–35.

    Article  PubMed  Google Scholar 

  30. Fujimoto KL, Miki T, Liu LJ, Hashizume R, Strom SC, Wagner WR, et al. Naive rat amnion-derived cell transplantation improved left ventricular function and reduced myocardial scar of postinfarcted heart. Cell Transplant. 2009;18(4):477–86.

    Article  PubMed  Google Scholar 

  31. Kara RJ, Bolli P, Karakikes I, Matsunaga I, Tripodi J, Tanweer O, et al. Fetal cells traffic to injured maternal myocardium and undergo cardiac differentiation. Circ Res. 2012;110(1):82–93.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Martin-Rendon E, Sweeney D, Lu F, Girdlestone J, Navarrete C, Watt SM. 5-Azacytidine-treated human mesenchymal stem/progenitor cells derived from umbilical cord, cord blood and bone marrow do not generate cardiomyocytes in vitro at high frequencies. Vox Sang. 2008;95(2):137–48.

    Article  CAS  PubMed  Google Scholar 

  33. Roura S, Farre J, Hove-Madsen L, Prat-Vidal C, Soler-Botija C, Galvez-Monton C, et al. Exposure to cardiomyogenic stimuli fails to transdifferentiate human umbilical cord blood-derived mesenchymal stem cells. Basic Res Cardiol. 2010;105(3):419–30.

    Article  PubMed  Google Scholar 

  34. Zhang P, Baxter J, Vinod K, Tulenko TN, Di Muzio PJ. Endothelial differentiation of amniotic fluid-derived stem cells: synergism of biochemical and shear force stimuli. Stem Cells Dev. 2009;18(9): 1299–308.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. De Coppi P, Callegari A, Chiavegato A, Gasparotto L, Piccoli M, Taiani J, et al. Amniotic fluid and bone marrow derived mesenchymal stem cells can be converted to smooth muscle cells in the cryo-injured rat bladder and prevent compensatory hypertrophy of surviving smooth muscle cells. J Urol. 2007;177(1):369–76.

    Article  PubMed  Google Scholar 

  36. Iop L, Chiavegato A, Callegari A, Bollini S, Piccoli M, Pozzobon M, et al. Different cardiovascular potential of adult- and fetal-type mesenchymal stem cells in a rat model of heart cryoinjury. Cell Transplant. 2008;17(6):679–94.

    Article  PubMed  Google Scholar 

  37. Chiavegato A, Bollini S, Pozzobon M, Callegari A, Gasparotto L, Taiani J, et al. Human amniotic fluid-derived stem cells are rejected after transplantation in the myocardium of normal, ischemic, immuno-suppressed or immuno-deficient rat. J Mol Cell Cardiol. 2007;42(4):746–59.

    Article  CAS  PubMed  Google Scholar 

  38. Bollini S, Pozzobon M, Nobles M, Riegler J, Dong X, Piccoli M, et al. In vitro and in vivo cardiomyogenic differentiation of amniotic fluid stem cells. Stem Cell Rev. 2011;7(2):364–80.

    Article  PubMed  Google Scholar 

  39. Guan X, Delo DM, Atala A, Soker S. In vitro cardiomyogenic potential of human amniotic fluid stem cells. J Tissue Eng Regen Med. 2011;5(3):220–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Yeh YC, Wei HJ, Lee WY, Yu CL, Chang Y, Hsu LW, et al. Cellular cardiomyoplasty with human amniotic fluid stem cells: in vitro and in vivo studies. Tissue Eng Part A. 2010;16(6):1925–36.

    Article  CAS  PubMed  Google Scholar 

  41. Bai J, Wang Y, Liu L, Chen J, Yang W, Gao L, et al. Human amniotic fluid-derived c-kit(+) and c-kit (−) stem cells: growth characteristics and some differentiation potential capacities comparison. Cytotechnology. 2012;64(5):577–89.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Moschidou D, Mukherjee S, Blundell MP, Drews K, Jones GN, Abdulrazzak H, et al. Valproic acid confers functional pluripotency to human amniotic fluid stem cells in a transgene-free approach. Mol Ther. 2012;20(10):1953–67.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Lee WY, Wei HJ, Lin WW, Yeh YC, Hwang SM, Wang JJ, et al. Enhancement of cell retention and functional benefits in myocardial infarction using human amniotic-fluid stem-cell bodies enriched with endogenous ECM. Biomaterials. 2011;32(24):5558–67.

    Article  CAS  PubMed  Google Scholar 

  44. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med. 2005;11(4): 367–8.

    Article  CAS  PubMed  Google Scholar 

  45. Cerrada I, Ruiz-Sauri A, Carrero R, Trigueros C, Dorronsoro A, Sanchez-Puelles JM, et al. Hypoxia-inducible factor 1 alpha contributes to cardiac healing in mesenchymal stem cells-mediated cardiac repair. Stem Cells Dev. 2013;22(3):501–11.

    Article  CAS  PubMed  Google Scholar 

  46. Nakanishi C, Yamagishi M, Yamahara K, Hagino I, Mori H, Sawa Y, et al. Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells. Biochem Biophys Res Commun. 2008;374(1):11–6.

    Article  CAS  PubMed  Google Scholar 

  47. Amado LC, Saliaris AP, Schuleri KH, St JM, Xie JS, Cattaneo S, et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A. 2005;102(32):11474–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Urbich C, Aicher A, Heeschen C, Dernbach E, Hofmann WK, Zeiher AM, et al. Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J Mol Cell Cardiol. 2005;39(5):733–42.

    Article  CAS  PubMed  Google Scholar 

  49. Loffredo FS, Steinhauser ML, Gannon J, Lee RT. Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell. 2011;8(4): 389–98.

    Article  CAS  PubMed  Google Scholar 

  50. Mirabella T, Cilli M, Carlone S, Cancedda R, Gentili C. Amniotic liquid derived stem cells as reservoir of secreted angiogenic factors capable of stimulating neo-arteriogenesis in an ischemic model. Biomaterials. 2011;32(15):3689–99.

    Article  CAS  PubMed  Google Scholar 

  51. Mirabella T, Hartinger J, Lorandi C, Gentili C, van GM, Cancedda R. Proangiogenic soluble factors from amniotic fluid stem cells mediate the recruitment of endothelial progenitors in a model of ischemic fasciocutaneous flap. Stem Cells Dev. 2012;21(12): 2179–88.

    Article  CAS  PubMed  Google Scholar 

  52. Roubelakis MG, Tsaknakis G, Pappa KI, Anagnou NP, Watt SM. Spindle shaped human mesenchymal stem/stromal cells from amniotic fluid promote neovascularization. PLoS One. 2013;8(1): e54747.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Bollini S, Cheung KK, Riegler J, Dong X, Smart N, Ghionzoli M, et al. Amniotic fluid stem cells are cardioprotective following acute myocardial infarction. Stem Cells Dev. 2011;20(11):1985–94.

    Article  CAS  PubMed  Google Scholar 

  54. Hinkel R, El-Aouni C, Olson T, Horstkotte J, Mayer S, Muller S, et al. Thymosin beta4 is an essential paracrine factor of embryonic endothelial progenitor cell-mediated cardioprotection. Circulation. 2008;117(17):2232–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Bock-Marquette I, Shrivastava S, Pipes GC, Thatcher JE, Blystone A, Shelton JM, et al. Thymosin beta4 mediated PKC activation is essential to initiate the embryonic coronary developmental program and epicardial progenitor cell activation in adult mice in vivo. J Mol Cell Cardiol. 2009;46(5):728–38.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Bock-Marquette I, Saxena A, White MD, DiMaio JM, Srivastava D. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432(7016):466–72.

    Article  CAS  PubMed  Google Scholar 

  57. Smart N, Risebro CA, Melville AA, Moses K, Schwartz RJ, Chien KR, et al. Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature. 2007;445(7124): 177–82.

    Article  CAS  PubMed  Google Scholar 

  58. Smart N, Bollini S, Dube KN, Vieira JM, Zhou B, Davidson S, et al. De novo cardiomyocytes from within the activated adult heart after injury. Nature. 2011;474(7353):640–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Kaihara S, Vacanti JP. Tissue engineering: toward new solutions for transplantation and reconstructive surgery. Arch Surg. 1999;134(11):1184–8.

    Article  CAS  PubMed  Google Scholar 

  60. Zimmermann WH, Eschenhagen T. Cardiac tissue engineering for replacement therapy. Heart Fail Rev. 2003;8(3):259–69.

    Article  CAS  PubMed  Google Scholar 

  61. Zimmermann WH, Eschenhagen T. Embryonic stem cells for cardiac muscle engineering. Trends Cardiovasc Med. 2007;17(4): 134–40.

    Article  CAS  PubMed  Google Scholar 

  62. Giraud MN, Armbruster C, Carrel T, Tevaearai HT. Current state of the art in myocardial tissue engineering. Tissue Eng. 2007;13(8): 1825–36.

    Article  PubMed  Google Scholar 

  63. Atala A. Engineering tissues, organs and cells. J Tissue Eng Regen Med. 2007;1(2):83–96.

    Article  CAS  PubMed  Google Scholar 

  64. Stevens KR, Pabon L, Muskheli V, Murry CE. Scaffold-free human cardiac tissue patch created from embryonic stem cells. Tissue Eng Part A. 2009;15(6):1211–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14(2):213–21.

    Article  CAS  PubMed  Google Scholar 

  66. Singelyn JM, DeQuach JA, Seif-Naraghi SB, Littlefield RB, Schup-Magoffin PJ, Christman KL. Naturally derived myocardial matrix as an injectable scaffold for cardiac tissue engineering. Biomaterials. 2009;30(29):5409–16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Tsur-Gang O, Ruvinov E, Landa N, Holbova R, Feinberg MS, Leor J, et al. The effects of peptide-based modification of alginate on left ventricular remodeling and function after myocardial infarction. Biomaterials. 2009;30(2):189–95.

    Article  CAS  PubMed  Google Scholar 

  68. Guo HD, Wang HJ, Tan YZ, Wu JH. Transplantation of marrow-derived cardiac stem cells carried in fibrin improves cardiac function after myocardial infarction. Tissue Eng Part A. 2011;17(1–2): 45–58.

    Article  CAS  PubMed  Google Scholar 

  69. Godier-Furnemont AF, Martens TP, Koeckert MS, Wan L, Parks J, Arai K, et al. Composite scaffold provides a cell delivery platform for cardiovascular repair. Proc Natl Acad Sci U S A. 2011;108(19):7974–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Yeh YC, Lee WY, Yu CL, Hwang SM, Chung MF, Hsu LW, et al. Cardiac repair with injectable cell sheet fragments of human amniotic fluid stem cells in an immune-suppressed rat model. Biomaterials. 2010;31(25):6444–53.

    Article  CAS  PubMed  Google Scholar 

  71. Huang CC, Wei HJ, Yeh YC, Wang JJ, Lin WW, Lee TY, et al. Injectable PLGA porous beads cellularized by hAFSCs for cellular cardiomyoplasty. Biomaterials. 2012;33(16):4069–77.

    Article  CAS  PubMed  Google Scholar 

  72. Gardiner HM. The case for fetal cardiac intervention. Heart. 2009;95(20):1648–52.

    Article  CAS  PubMed  Google Scholar 

  73. Lanfranchi A, Porta F, Chirico G. Stem cells and the frontiers of neonatology. Early Hum Dev. 2009;85(10 Suppl):S15–8.

    Article  CAS  PubMed  Google Scholar 

  74. Billingham RE, Brent L, Medawar PB. ‘Actively acquired tolerance’ of foreign cells. 1953. Transplantation. 2003;76(10):1409–12.

    Article  CAS  PubMed  Google Scholar 

  75. Roybal JL, Santore MT, Flake AW. Stem cell and genetic therapies for the fetus. Semin Fetal Neonatal Med. 2010;15(1):46–51.

    Article  PubMed  Google Scholar 

  76. Shaw SW, Bollini S, Nader KA, Gastadello A, Mehta V, Filppi E, et al. Autologous transplantation of amniotic fluid-derived mesenchymal stem cells into sheep fetuses. Cell Transplant. 2011;20(7): 1015–31.

    Article  PubMed  Google Scholar 

  77. Menasche P. Cell-based therapy for heart disease: a clinically oriented perspective. Mol Ther. 2009;17(5):758–66.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Polak DJ. Regenerative medicine: a primer for paediatricians. Early Hum Dev. 2009;85(11):685–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

S.B. was partially supported by PO CRO Fondo Sociale Europeo Regione Liguria 2007–2013 Asse IV “Capitale Umano” Ob. Specifico, Genoa, Italy; M.P. is supported by Fondazione Istituto Ricerca Pediatrica Città Della Speranza, Padua, Italy; N.S. is supported by the British Heart Foundation, UK; P.D.C. is supported by Great Ormond Street Hospital and Institute of Child Health Charity, London, UK.

Conflicts of Interest Statement 

The authors confirm that there are no conflicts of interest and have no disclosure to declare.

Author information

Authors and Affiliations

  1. Regenerative Medicine Laboratory, Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy

    Sveva Bollini Ph.D.

  2. IRCCS Azienda Ospedaliera Universitaria San Martino – IST, National Institute for Cancer Research, Genoa, Italy

    Sveva Bollini Ph.D.

  3. Foundation Pediatric Research Institute Città della Speranza, Padua, Italy

    Michela Pozzobon Ph.D.

  4. Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3PT, UK

    Nicola Smart Ph.D.

  5. Surgery Unit, University College London Institute of Child Health and Great Ormond Street Hospital, London, UK

    Paolo De Coppi M.D., Ph.D.

Authors
  1. Sveva Bollini Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michela Pozzobon Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicola Smart Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paolo De Coppi M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sveva Bollini Ph.D. .

Editor information

Editors and Affiliations

  1. Wake Forest Baptist Medical Center, Institute for Regenerative Medicine, Winston-Salem, North Carolina, USA

    Anthony Atala

  2. Wake Forest Baptist Medical Center, Institute for Regenerative Medicine, Winston-Salem, North Carolina, USA

    Sean V. Murphy

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Bollini, S., Pozzobon, M., Smart, N., De Coppi, P. (2014). Amniotic Fluid Stem Cells for Cardiac Regeneration. In: Atala, A., Murphy, S. (eds) Perinatal Stem Cells. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1118-9_1

Download citation

Publish with us

Policies and ethics

Search

Navigation