Skip to main content

Human Embryonic Stem Cells

  • Chapter
  • First Online:
Regenerative Medicine - from Protocol to Patient

Abstract

Stem cells can be isolated from a variety of sources and they are typically classified based on their tissue of origin. Embryonic stem cells are, as the name indicates, derived from the inner cell mass of pre-implantation stage blastocysts at day 5–7 post fertilisation. These cells possess qualities such as pluripotency and a seemingly limitless capacity to proliferate in vitro in their undifferentiated state. Embryonic stem cells were first derived from mouse embryos in the early 1980s but have now been derived from a number of different species including rat, rabbit, sheep, pig, horse and human. This chapter focuses on human embryonic stem cells and describes techniques used for their derivation and culture. In addition, the basic properties of these cells are illustrated, including some examples of their capacity to differentiate to various precursors and functional cell types. Finally, some areas of applications for these cells are discussed with emphasis on their possible future use in regenerative medicine including current clinical trials.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

Institutional subscriptions

References

  • 2001/20/EC, E.D (2001) EU Directive 2001/20/EC

    Google Scholar 

  • 2005/28/EC, E.D (2005) EU Directive 2005/28/EC

    Google Scholar 

  • Adewumi O, Aflatoonian B, Ahrlund-Richter L, Amit M, Andrews PW, Beighton G, Bello PA, Benvenisty N, Berry LS, Bevan S et al (2007) Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat Biotechnol 25:803–816

    Article  CAS  PubMed  Google Scholar 

  • Advanced Cell Technology clinical trials. http://www.advancedcell.com/patients/clinical-trial-information/

  • Agarwal S, Holton KL, Lanza R (2008) Efficient differentiation of functional hepatocytes from human embryonic stem cells. Stem Cells 26:1117–1127

    Article  CAS  PubMed  Google Scholar 

  • Alper J (2009) Geron gets green light for human trial of ES cell-derived product. Nat Biotechnol 27:213–214

    Article  CAS  PubMed  Google Scholar 

  • Amit M (2007) Feeder-layer free culture system for human embryonic stem cells. Methods Mol Biol 407:11–20

    Article  CAS  PubMed  Google Scholar 

  • Amit M, Itskovitz-Eldor J (2006) Feeder-free culture of human embryonic stem cells. Methods Enzymol 420:37–49

    Article  CAS  PubMed  Google Scholar 

  • Andrews PD, Becroft M, Aspegren A, Gilmour J, James MJ, McRae S, Kime R, Allcock RW, Abraham A, Jiang Z, Strehl R, Mountford JC, Milligan G, Houslay MD, Adams DR, Frearson JA (2010) High-content screening of feeder-free human embryonic stem cells to identify pro-survival small molecules. Biochem J 432(1):21–33

    Article  CAS  PubMed  Google Scholar 

  • Baharvand H, Hashemi SM, Shahsavani M (2008) Differentiation of human embryonic stem cells into functional hepatocyte-like cells in a serum-free adherent culture condition. Differentiation 76:465–477

    Article  CAS  PubMed  Google Scholar 

  • Barad L, Schick R, Zeevi-Levin N, Itskovitz-Eldor J, Binah O (2014) Human embryonic stem cells vs human induced pluripotent stem cells for cardiac repair. Can J Cardiol 30(11):1279–1287

    Article  PubMed  Google Scholar 

  • Barde Y (2009) Caution urged in trial of stem cells to treat spinal-cord injury. Nature 458:29

    Article  CAS  PubMed  Google Scholar 

  • Beqqali A, Kloots J, Ward-van Oostwaard D, Mummery C, Passier R (2006) Genome-wide transcriptional profiling of human embryonic stem cells differentiating to cardiomyocytes. Stem Cells 24:1956–1967

    Article  CAS  PubMed  Google Scholar 

  • Bongso A, Fong CY, Ng SC, Ratnam S (1994) Isolation and culture of inner cell mass cells from human blastocysts. Hum Reprod 9:2110–2117

    CAS  PubMed  Google Scholar 

  • Borowiak M, Melton DA (2009) How to make beta cells? Curr Opin Cell Biol 21(6):727–732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K et al (2004) Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nat Biotechnol 22:707–716

    Article  PubMed  Google Scholar 

  • Brett S, Livie M, Thomas G, McConnell A, Rajkhowa M (2009) Report on the donation of supernumerary embryos from fresh IVF and ICSI treatment cycles for human stem cell research. Hum Fertil (Camb) 12:34–39

    Article  CAS  Google Scholar 

  • Bruin JE, Erener S, Vela J, Hu X, Johnson JD, Kurata HT, Lynn FC, Piret JM, Asadi A, Rezania A et al (2014) Characterization of polyhormonal insulin-producing cells derived in vitro from human embryonic stem cells. Stem Cell Res 12:194–208

    Article  CAS  PubMed  Google Scholar 

  • Cai L, Johnstone BH, Cook TG, Liang Z, Traktuev D, Cornetta K, Ingram DA, Rosen ED, March KL (2007) Suppression of hepatocyte growth factor production impairs the ability of adipose-derived stem cells to promote ischemic tissue revascularization. Stem Cells 25:3234–3243

    Article  CAS  PubMed  Google Scholar 

  • Caisander G, Park H, Frej K, Lindqvist J, Bergh C, Lundin K, Hanson C (2006) Chromosomal integrity maintained in five human embryonic stem cell lines after prolonged in vitro culture. Chromosome Res 14:131–137

    Article  CAS  PubMed  Google Scholar 

  • Caspi O, Huber I, Kehat I, Habib M, Arbel G, Gepstein A, Yankelson L, Aronson D, Beyar R, Gepstein L (2007) Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol 50:1884–1893

    Article  PubMed  Google Scholar 

  • Catalina P, Montes R, Ligero G, Sanchez L, de la Cueva T, Bueno C, Leone PE, Menendez P (2008) Human ESCs predisposition to karyotypic instability: is a matter of culture adaptation or differential vulnerability among hESC lines due to inherent properties? Mol Cancer 7:76

    Article  PubMed  PubMed Central  Google Scholar 

  • Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113:643–655

    Article  CAS  PubMed  Google Scholar 

  • Chen AE, Egli D, Niakan K, Deng J, Akutsu H, Yamaki M, Cowan C, Fitz-Gerald C, Zhang K, Melton DA et al (2009) Optimal timing of inner cell mass isolation increases the efficiency of human embryonic stem cell derivation and allows generation of sibling cell lines. Cell Stem Cell 4:103–106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Civin CI, Rao MS (2006) How many human embryonic stem cell lines are sufficient? A U.S. perspective. Stem Cells 24:800–803

    Article  PubMed  Google Scholar 

  • Crook JM, Peura TT, Kravets L, Bosman AG, Buzzard JJ, Horne R, Hentze H, Dunn NR, Zweigerdt R, Chua F et al (2007) The generation of six clinical-grade human embryonic stem cell lines. Cell Stem Cell 1:490–494

    Article  CAS  PubMed  Google Scholar 

  • Crook JM, Hei D, Stacey G (2010) The International Stem Cell Banking Initiative (ISCBI): raising standards to bank on. In Vitro Cell Dev Biol Anim 46(3–4):169–172. Epub 2010 Mar 3. Review

    Article  PubMed  Google Scholar 

  • D’Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE (2006) Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 24:1392–1401

    Article  PubMed  Google Scholar 

  • Daley GQ, Scadden DT (2008) Prospects for stem cell-based therapy. Cell 132:544–548

    Article  CAS  PubMed  Google Scholar 

  • Dalgetty DM, Medine CN, Iredale JP, Hay DC (2009) Progress and future challenges in stem cell-derived liver technologies. Am J Physiol Gastrointest Liver Physiol 297:G241–G248

    Article  CAS  PubMed  Google Scholar 

  • Desai N, Rambhia P, Gishto A (2015) Human embryonic stem cell cultivation: historical perspective and evolution of xeno-free culture systems. Reprod Biol Endocrinol 13(1):9

    Article  PubMed  PubMed Central  Google Scholar 

  • Desbordes SC, Placantonakis DG, Ciro A, Socci ND, Lee G, Djaballah H, Studer L (2008) High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells. Cell Stem Cell 2:602–612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dokras A, Sargent IL, Barlow DH (1993) Human blastocyst grading: an indicator of developmental potential? Hum Reprod 8:2119–2127

    CAS  PubMed  Google Scholar 

  • Draper JS, Smith K, Gokhale P, Moore HD, Maltby E, Johnson J, Meisner L, Zwaka TP, Thomson JA, Andrews PW (2004) Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat Biotechnol 22:53–54

    Article  CAS  PubMed  Google Scholar 

  • Ellerstrom C, Strehl R, Moya K, Andersson K, Bergh C, Lundin K, Hyllner J, Semb H (2006) Derivation of a xeno-free human embryonic stem cell line. Stem Cells 24:2170–2176

    Article  PubMed  Google Scholar 

  • Ellerstrom C, Strehl R, Noaksson K, Hyllner J, Semb H (2007) Facilitated expansion of human embryonic stem cells by single-cell enzymatic dissociation. Stem Cells 25:1690–1696

    Article  PubMed  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 

  • Feki A, Bosman A, Dubuisson JB, Irion O, Dahoun S, Pelte MF, Hovatta O, Jaconi ME (2008) Derivation of the first Swiss human embryonic stem cell line from a single blastomere of an arrested four-cell stage embryo. Swiss Med Wkly 138:540–550

    CAS  PubMed  Google Scholar 

  • Gavrilov S, Prosser RW, Khalid I, MacDonald J, Sauer MV, Landry DW, Papaioannou VE (2009) Non-viable human embryos as a source of viable cells for embryonic stem cell derivation. Reprod Biomed Online 18(2):301–308

    Article  PubMed  Google Scholar 

  • Geens M, Mateizel I, Sermon K, De Rycke M, Spits C, Cauffman G, Devroey P, Tournaye H, Liebaers I, Van de Velde H (2009) Human embryonic stem cell lines derived from single blastomeres of two 4-cell stage embryos. Hum Reprod 24:2709–2717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geron (2009) Geron receives FDA clearance to begin world’s first human clinical trial of embryonic stem cell-based therapy. http://ir.geron.com/phoenix.zhtml?c=67323&p=irol-newsArticle&ID=1636192. Press release

  • Guguen-Guillouzo C, Corlu A, Guillouzo A (2010) Stem cell-derived hepatocytes and their use in toxicology. Toxicology 270(1):3–9. Epub 2009 Oct 6

    Article  CAS  PubMed  Google Scholar 

  • Heins N, Englund MC, Sjoblom C, Dahl U, Tonning A, Bergh C, Lindahl A, Hanson C, Semb H (2004) Derivation, characterization, and differentiation of human embryonic stem cells. Stem Cells 22:367–376

    Article  PubMed  Google Scholar 

  • Heiskanen A, Satomaa T, Tiitinen S, Laitinen A, Mannelin S, Impola U, Mikkola M, Olsson C, Miller-Podraza H, Blomqvist M et al (2007) N-glycolylneuraminic acid xenoantigen contamination of human embryonic and mesenchymal stem cells is substantially reversible. Stem Cells 25:197–202

    Article  CAS  PubMed  Google Scholar 

  • Ilic D, Stephenson E, Wood V, Jacquet L, Stevenson D, Petrova A, Kadeva N, Codognotto S, Patel H, Semple M, Cornwell G, Ogilvie C, Braude P (2012) Derivation and feeder-free propagation of human embryonic stem cells under xeno-free conditions. Cytotherapy 14(1):122–128. Epub 2011 Oct 27

    Article  CAS  PubMed  Google Scholar 

  • Itskovitz-Eldor J, Schuldiner M, Karsenti D, Eden A, Yanuka O, Amit M, Soreq H, Benvenisty N (2000) Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med 6:88–95

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jensen J, Hyllner J, Bjorquist P (2009) Human embryonic stem cell technologies and drug discovery. J Cell Physiol 219:513–519

    Article  CAS  PubMed  Google Scholar 

  • Kehat I, Kenyagin-Karsenti D, Snir M, Segev H, Amit M, Gepstein A, Livne E, Binah O, Itskovitz-Eldor J, Gepstein L (2001) Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 108:407–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SU, de Vellis J (2009) Stem cell-based cell therapy in neurological diseases: a review. J Neurosci Res 87:2183–2200

    Article  CAS  PubMed  Google Scholar 

  • Klimanskaya I, Chung Y, Becker S, Lu SJ, Lanza R (2006) Human embryonic stem cell lines derived from single blastomeres. Nature 444:481–485

    Article  CAS  PubMed  Google Scholar 

  • Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA, Dupras SK, Reinecke H, Xu C, Hassanipour M, Police S et al (2007) Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 25:1015–1024

    Article  CAS  PubMed  Google Scholar 

  • Leor J, Gerecht S, Cohen S, Miller L, Holbova R, Ziskind A, Shachar M, Feinberg MS, Guetta E, Itskovitz-Eldor J (2007) Human embryonic stem cell transplantation to repair the infarcted myocardium. Heart 93:1278–1284

    Article  PubMed  PubMed Central  Google Scholar 

  • Lerou PH, Yabuuchi A, Huo H, Miller JD, Boyer LF, Schlaeger TM, Daley GQ (2008a) Derivation and maintenance of human embryonic stem cells from poor-quality in vitro fertilization embryos. Nat Protoc 3:923–933

    Article  CAS  PubMed  Google Scholar 

  • Lerou PH, Yabuuchi A, Huo H, Takeuchi A, Shea J, Cimini T, Ince TA, Ginsburg E, Racowsky C, Daley GQ (2008b) Human embryonic stem cell derivation from poor-quality embryos. Nat Biotechnol 26:212–214

    Article  CAS  PubMed  Google Scholar 

  • Li X, Krawetz R, Liu S, Meng G, Rancourt DE (2009) ROCK inhibitor improves survival of cryopreserved serum/feeder-free single human embryonic stem cells. Hum Reprod 24:580–589

    Article  CAS  PubMed  Google Scholar 

  • Li M, Suzuki K, Kim NY, Liu GH, Izpisua Belmonte JC (2014) A cut above the rest: targeted genome editing technologies in human pluripotent stem cells. J Biol Chem 289(8):4594–4599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim JW, Bodnar A (2002) Proteome analysis of conditioned medium from mouse embryonic fibroblast feeder layers which support the growth of human embryonic stem cells. Proteomics 2(9):1187–1203

    Article  CAS  PubMed  Google Scholar 

  • Loser P, Schirm J, Guhr A, Wobus AM, Kurtz A (2010) Human embryonic stem cell lines and their use in international research. Stem Cells 28:240–246

    PubMed  PubMed Central  Google Scholar 

  • Ludwig TE, Levenstein ME, Jones JM, Berggren WT, Mitchen ER, Frane JL, Crandall LJ, Daigh CA, Conard KR, Piekarczyk MS et al (2006) Derivation of human embryonic stem cells in defined conditions. Nat Biotechnol 24:185–187

    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 MJ, Muotri A, Gage F, Varki A (2005) Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med 11:228–232

    Article  CAS  PubMed  Google Scholar 

  • Medine CN, Lucendo-Villarin B, Zhou W, West CC, Hay DC (2011) Robust generation of hepatocyte-like cells from human embryonic stem cell populations. J Vis Exp 2011:e2969. doi:10.3791/2969

    Google Scholar 

  • Menasché P, Vanneaux V, Fabreguettes JR, Bel A, Tosca L, Garcia S, Bellamy V, Farouz Y, Pouly J, Damour O, Périer MC, Desnos M, Hagège A, Agbulut O, Bruneval P, Tachdjian G, Trouvin JH, Larghero J (2015) Towards a clinical use of human embryonic stem cell-derived cardiac progenitors: a translational experience. Eur Heart J 36(12):743–750. Epub 2014 May 16

    Article  PubMed  Google Scholar 

  • Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S (2003) The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113:631–642

    Article  CAS  PubMed  Google Scholar 

  • Mummery C, Ward-van Oostwaard D, Doevendans P, Spijker R, van den Brink S, Hassink R, van der Heyden M, Opthof T, Pera M, de la Riviere AB et al (2003) Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells. Circulation 107:2733–2740

    Article  CAS  PubMed  Google Scholar 

  • Murdoch A, Braude P, Courtney A, Brison D, Hunt C, Lawford-Davies J, Moore H, Stacey G, Sethe S (2012) For the procurement Working Group of the National Clinical hESC Forum. The procurement of cells for the derivation of human embryonic stem cell lines for therapeutic use: recommendations for good practice. Stem Cell Rev 8(1):91–99

    Article  PubMed  Google Scholar 

  • Nakajima F, Tokunaga K, Nakatsuji N (2007) Human leukocyte antigen matching estimations in a hypothetical bank of human embryonic stem cell lines in the Japanese population for use in cell transplantation therapy. Stem Cells 25:983–985

    Article  CAS  PubMed  Google Scholar 

  • Nasonkin IO, Koliatsos VE (2006) Nonhuman sialic acid Neu5Gc is very low in human embryonic stem cell-derived neural precursors differentiated with B27/N2 and noggin: implications for transplantation. Exp Neurol 201:525–529

    Article  CAS  PubMed  Google Scholar 

  • Pagliuca FW, Millman JR, Gürtler M, Segel M, Van Dervort A, Ryu JH, Peterson QP, Greiner D, Melton DA (2014) Generation of functional human pancreatic β cells in vitro. Cell 159(2):428–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parsons XH, Teng YD, Parsons JF, Snyder EY, Smotrich DB, Moore DA (2011) Efficient derivation of human cardiac precursors and cardiomyocytes from pluripotent human embryonic stem cells with small molecule induction. J Vis Exp 2011(57):e3274. doi:10.3791/3274

    Google Scholar 

  • Passier R, Mummery C (2005) Cardiomyocyte differentiation from embryonic and adult stem cells. Curr Opin Biotechnol 16:498–502

    Article  CAS  PubMed  Google Scholar 

  • Prowse AB, McQuade LR, Bryant KJ, Van Dyk DD, Tuch BE, Gray PP (2005) A proteome analysis of conditioned media from human neonatal fibroblasts used in the maintenance of human embryonic stem cells. Proteomics 5(4):978–989

    Article  CAS  PubMed  Google Scholar 

  • Rajala K, Hakala H, Panula S, Aivio S, Pihlajamaki H, Suuronen R, Hovatta O, Skottman H (2007) Testing of nine different xeno-free culture media for human embryonic stem cell cultures. Hum Reprod 22:1231–1238

    Article  CAS  PubMed  Google Scholar 

  • Rambhatla L, Chiu CP, Kundu P, Peng Y, Carpenter MK (2003) Generation of hepatocyte-like cells from human embryonic stem cells. Cell Transplant 12:1–11

    Article  PubMed  Google Scholar 

  • Rho JY, Yu K, Han JS, Chae JI, Koo DB, Yoon HS, Moon SY, Lee KK, Han YM (2006) Transcriptional profiling of the developmentally important signalling pathways in human embryonic stem cells. Hum Reprod 21:405–412

    Article  CAS  PubMed  Google Scholar 

  • Richards M, Bongso A (2006) Propagation of human embryonic stem cells on human feeder cells. Methods Mol Biol 331:23–41

    PubMed  Google Scholar 

  • Richards M, Fong CY, Tan S, Chan WK, Bongso A (2004) An efficient and safe xeno-free cryopreservation method for the storage of human embryonic stem cells. Stem Cells 22:779–789

    Article  PubMed  Google Scholar 

  • Rodin S, Antonsson L, Hovatta O, Tryggvason K (2014) Monolayer culturing and cloning of human pluripotent stem cells on laminin-521-based matrices under xeno-free and chemically defined conditions. Nat Protoc 9(10):2354–2368. Epub 2014 Sep 11

    Article  CAS  PubMed  Google Scholar 

  • Schwartz SD, Regillo CD, Lam BL, Eliott D, Rosenfeld PJ, Gregori NZ, Hubschman JP, Davis JL, Heilwell G, Spirn M, Maguire J, Gay R, Bateman J, Ostrick RM, Morris D, Vincent M, Anglade E, Del Priore LV, Lanza R (2015) Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet 385(9967):509–516. doi:10.1016/S0140-6736(14)61376-3. Epub 2014 Oct 15

    Article  PubMed  Google Scholar 

  • Sjogren A, Hardarson T, Andersson K, Caisander G, Lundquist M, Wikland M, Semb H, Hamberger L (2004) Human blastocysts for the development of embryonic stem cells. Reprod Biomed Online 9:326–329

    Article  PubMed  Google Scholar 

  • Sjogren-Jansson E, Zetterstrom M, Moya K, Lindqvist J, Strehl R, Eriksson PS (2005) Large-scale propagation of four undifferentiated human embryonic stem cell lines in a feeder-free culture system. Dev Dyn 233:1304–1314

    Article  PubMed  Google Scholar 

  • Snykers S, De Kock J, Rogiers V, Vanhaecke T (2009) In vitro differentiation of embryonic and adult stem cells into hepatocytes: state of the art. Stem Cells 27:577–605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stephenson EL, Braude PR, Mason C (2007) International community consensus standard for reporting derivation of human embryonic stem cell lines. Regen Med 2:349–362

    Article  PubMed  Google Scholar 

  • Strelchenko N, Verlinsky O, Kukharenko V, Verlinsky Y (2004) Morula-derived human embryonic stem cells. Reprod Biomed Online 9:623–629

    Article  PubMed  Google Scholar 

  • Suemori H, Yasuchika K, Hasegawa K, Fujioka T, Tsuneyoshi N, Nakatsuji N (2006) Efficient establishment of human embryonic stem cell lines and long-term maintenance with stable karyotype by enzymatic bulk passage. Biochem Biophys Res Commun 345:926–932

    Article  CAS  PubMed  Google Scholar 

  • Synnergren J, Akesson K, Dahlenborg K, Vidarsson H, Ameen C, Steel D, Lindahl A, Olsson B, Sartipy P (2008) Molecular signature of cardiomyocyte clusters derived from human embryonic stem cells. Stem Cells 26:1831–1840

    Article  CAS  PubMed  Google Scholar 

  • Taylor CJ, Bolton EM, Pocock S, Sharples LD, Pedersen RA, Bradley JA (2005) Banking on human embryonic stem cells: estimating the number of donor cell lines needed for HLA matching. Lancet 366:2019–2025

    Article  PubMed  Google Scholar 

  • Thomas RJ, Anderson D, Chandra A, Smith NM, Young LE, Williams D, Denning C (2009) Automated, scalable culture of human embryonic stem cells in feeder-free conditions. Biotechnol Bioeng 102:1636–1644

    Article  CAS  PubMed  Google Scholar 

  • Thomson JA, Kalishman J, Golos TG, Durning M, Harris CP, Becker RA, Hearn JP (1995) Isolation of a primate embryonic stem cell line. Proc Natl Acad Sci U S A 92:7844–7848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomson JA, Kalishman J, Golos TG, Durning M, Harris CP, Hearn JP (1996) Pluripotent cell lines derived from common marmoset (Callithrix jacchus) blastocysts. Biol Reprod 55:254–259

    Article  CAS  PubMed  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 

  • Unger C, Skottman H, Blomberg P, Dilber MS, Hovatta O (2008) Good manufacturing practice and clinical-grade human embryonic stem cell lines. Hum Mol Genet 17:R48–R53

    Article  CAS  PubMed  Google Scholar 

  • Uosaki H, Fukushima H, Takeuchi A, Matsuoka S, Nakatsuji N, Yamanaka S, Yamashita JK (2011) Efficient and scalable purification of cardiomyocytes from human embryonic and induced pluripotent stem cells by VCAM1 surface expression. PLoS One 6(8):e23657. Epub 2011 Aug 18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Laake LW, Passier R, Monshouwer-Kloots J, Verkleij AJ, Lips DJ, Freund C, den Ouden K, Ward-van Oostwaard D, Korving J, Tertoolen LG et al (2007) Human embryonic stem cell-derived cardiomyocytes survive and mature in the mouse heart and transiently improve function after myocardial infarction. Stem Cell Res 1:9–24

    Article  PubMed  Google Scholar 

  • van Laake LW, Passier R, den Ouden K, Schreurs C, Monshouwer-Kloots J, Ward-van Oostwaard D, van Echteld CJ, Doevendans PA, Mummery CL (2009) Improvement of mouse cardiac function by hESC-derived cardiomyocytes correlates with vascularity but not graft size. Stem Cell Res 3:106–112

    Article  PubMed  Google Scholar 

  • van Laake LW, van Donselaar EG, Monshouwer-Kloots J, Schreurs C, Passier R, Humbel BM, Doevendans PA, Sonnenberg A, Verkleij AJ, Mummery CL (2010) Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes. Cell Mol Life Sci 67(2):277–290. Epub 2009 Oct 22

    Article  PubMed  PubMed Central  Google Scholar 

  • Watanabe K, Ueno M, Kamiya D, Nishiyama A, Matsumura M, Wataya T, Takahashi JB, Nishikawa S, Muguruma K, Sasai Y (2007) A ROCK inhibitor permits survival of dissociated human embryonic stem cells. Nat Biotechnol 25:681–686

    Article  CAS  PubMed  Google Scholar 

  • Xu RH, Chen X, Li DS, Li R, Addicks GC, Glennon C, Zwaka TP, Thomson JA (2002) BMP4 initiates human embryonic stem cell differentiation to trophoblast. Nat Biotechnol 20:1261–1264

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Soonpaa MH, Adler ED, Roepke TK, Kattman SJ, Kennedy M, Henckaerts E, Bonham K, Abbott GW, Linden RM et al (2008) Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature 453:524–528

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Stojkovic P, Przyborski S, Cooke M, Armstrong L, Lako M, Stojkovic M (2006) Derivation of human embryonic stem cells from developing and arrested embryos. Stem Cells 24:2669–2676

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Miss Claire Balfour for providing images for the figures.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Terri Gaskell .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Gaskell, T., Englund, M.C.O., Hyllner, J. (2016). Human Embryonic Stem Cells. In: Steinhoff, G. (eds) Regenerative Medicine - from Protocol to Patient. Springer, Cham. https://doi.org/10.1007/978-3-319-27610-6_2

Download citation

Publish with us

Policies and ethics