Skip to main content

Use of Human Embryonic Stem Cells in Therapy

  • Chapter
  • First Online:
Book cover Stem Cells and Cell Therapy

Part of the book series: Cell Engineering ((CEEN,volume 8))

Abstract

Pluripotent stem cells (PSCs) are defined by their potential of unlimited self-renewal and the ability to differentiate – both in vitro and in vivo – into all cell types of endodermal, mesodermal and ectodermal origins, rendering them a promising applicability in cell replacement therapies. These characteristics also make PSCs powerful tools for studying the molecular mechanisms underlying cellular differentiation, as well as for accessing the biological effects of pharmaceutical compounds on the normal embryo development, and also on virtually any differentiated cell type. PSCs can be obtained from early stage embryos – usually from the inner cell mass of blastocysts – and adapted for propagation in culture in the laboratory, thus resulting in the establishment of an Embryonic Stem Cell (ESC) line. They can also be artificially obtained in the laboratory through the use of techniques that induce the reprogramming of somatic, differentiated cell types (i.e. dermal fibroblasts) into undifferentiated, pluripotent stem cells (Induced Pluripotent Stem Cells – iPSCs). In this chapter we discuss the potential advantages and disadvantages of the use of these two PSC types in regenerative medicine, and give an overview of the current status of cell therapy studies and clinical trials in humans. We also comment on a more recently developed alternative source of cells for use in therapy – the direct reprogrammed cells – and finally, we discuss the potential applications of PSCs and directly reprogrammed cells in drug screening assays.

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

  • Baker DE, Harrison NJ, Maltby E, Smith K, Moore HD, Shaw PJ, Heath PR, Holden H, Andrews PW (2007) Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. Nat Biotechnol 25(2):207–215

    Article  PubMed  CAS  Google Scholar 

  • Banerjee ER, Laflamme MA, Papayannopoulou T, Kahn M, Murry CE, Henderson WR Jr (2012) Human embryonic stem cells differentiated to lung lineage-specific cells ameliorate pulmonary fibrosis in a xenograft transplant mouse model. PLoS One 7(3):e33165

    Article  PubMed  CAS  Google Scholar 

  • Bosnali M, Edenhofer F (2008) Generation of transducible versions of transcription factors Oct4 and Sox2. Biol Chem 389(7):851–861

    Article  PubMed  CAS  Google Scholar 

  • Brimble SN, Zeng X, Weiler DA, Luo Y, Liu Y, Lyons IG, Freed WJ, Robins AJ, Rao MS, Schulz TC (2004) Karyotypic stability, genotyping, differentiation, feeder-free maintenance, and gene expression sampling in three human embryonic stem cell lines derived prior to August 9, 2001. Stem Cells Dev 13:585–597

    Article  PubMed  CAS  Google Scholar 

  • Burra P, Bizzaro D, Ciccocioppo R, Marra F, Piscaglia AC, Porretti L, Gasbarrini A, Russo FP (2011) Therapeutic application of stem cells in gastroenterology: an up-date. World J Gastroenterol 17(34):3870–3880

    Article  PubMed  Google Scholar 

  • Callera F, do Nascimento RX (2006) Delivery of autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique in patients with spinal cord injury: a preliminary safety study. Exp Hematol 34(2):130–131

    Article  PubMed  Google Scholar 

  • Caspi O, Itzhaki I, Kehat I, Gepstein A, Arbel G, Huber I, Satin J, Gepstein L (2009) In vitro electrophysiological drug testing using human embryonic stem cell derived cardiomyocytes. Stem Cells Dev 18(1):161–172

    Article  PubMed  CAS  Google Scholar 

  • Chin MH, Mason MJ, Xie W, Volinia S, Singer M, Peterson C, Ambartsumyan G, Aimiuwu O, Richter L, Zhang J, Khvorostov I, Ott V, Grunstein M, Lavon N, Benvenisty N, Croce CM, Clark AT, Baxter T, Pyle AD, Teitell MA, Pelegrini M, Plath K, Lowry WE (2009) Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 5:111–123

    Article  PubMed  CAS  Google Scholar 

  • Cho YM, Lim JM, Yoo DH, Kim JH, Chung SS, Park SG, Kim TH, Oh SK, Choi YM, Moon SY, Park KS, Lee HK (2008) Betacellulin and nicotinamide sustain PDX1 expression and induce pancreatic beta-cell differentiation in human embryonic stem cells. Biochem Biophys Res Commun 366(1):129–134

    Article  PubMed  CAS  Google Scholar 

  • Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, Du MQ, Luan SL, Altmann DR, Thompson AJ, Compston A, Scott MA, Miller DH, Chandran S (2012) Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol 11(2):150–156

    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(11):1392–1401

    Article  PubMed  CAS  Google Scholar 

  • Deng J, Shoemaker R, Xie B, Gore A, LeProust EM, Antosiewicz-Bourget J, Egli D, Maherali N, Park IH, Yu J, Daley GQ, Eggan K, Hochedlinger K, Thomson J, Wang W, Gao Y, Zhang K (2009) Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming. Nat Biotechnol 27:353–360

    Article  PubMed  CAS  Google Scholar 

  • Draper JS, Smith K, Gokhale P, Moore HD, Maltby E, Johnson J, Meisner L, Zwaka TP, Thomson JA, Andrews PW (2003) Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat Biotechnol 22:53–54

    Article  PubMed  CAS  Google Scholar 

  • Drukker M, Katz G, Urbach A, Schuldiner M, Markel G, Itskovitz-Eldor J, Reubinoff B, Mandelboim O, Benvenisty N (2002) Characterization of the expression of MHC proteins in human embryonic stem cells. Proc Natl Acad Sci USA 99:9864–9869

    Article  PubMed  CAS  Google Scholar 

  • Erdö F, Bührle C, Blunk J, Hoehn M, Xia Y, Fleischmann B, Föcking M, Küstermann E, Kolossov E, Hescheler J, Hossmann KA, Trapp T (2003) Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke. J Cereb Blood Flow Metab 23(7):780–785

    PubMed  Google Scholar 

  • Feng B, Jiang J, Kraus P, Ng JH, Heng JC, Chan YS, Yaw LP, Zhang W, Loh YH, Han J, Vega VB, Cacheux-Rataboul V, Lim B, Lufkin T, Ng H-H (2009) Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat Cell Biol 11:197–203

    Article  PubMed  CAS  Google Scholar 

  • Fleischhauer K, Shaw BE, Gooley T, Malkki M, Bardy P, Bignon JD, Dubois V, Horowitz MM, Madrigal JA, Morishima Y, Oudshoorn M, Ringden O, Spellman S, Velardi A, Zino E, Petersdorf EW, on behalf of the International Histocompatibility Working Group in Hematopoietic Cell Transplantation (2012) Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study. Lancet Oncol 13(4):366–374

    Article  PubMed  CAS  Google Scholar 

  • Fraga AM, Araújo ESS, Stabellini R, Vergani N, Pereira LV (2011a) A Survey of Parameters Involved in the Establishment of New Lines of Human Embryonic Stem Cells. Stem Cell Rev 7(4):775–781

    Article  PubMed  Google Scholar 

  • Fraga AM, Sukoyan M, Rajan P, Braga DP, Iaconelli A Jr, Franco JG Jr, Borges E Jr, Pereira LV (2011b) Establishment of a Brazilian line of human embryonic stem cells in defined medium: implications for cell therapy in an ethnically diverse population. Cell Transplant 20(3):431–440

    Article  PubMed  Google Scholar 

  • Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M (2009) Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc Jpn Acad Ser B Phys Biol Sci 85:348–362

    Article  PubMed  CAS  Google Scholar 

  • Grskovic M, Javaherian A, Strulovici B, Daley GQ (2011) Induced pluripotent stem cells – opportunities for disease modelling and drug discovery. Nat Rev Drug Discov 10(12):915–929

    PubMed  CAS  Google Scholar 

  • Guenou H, Nissan X, Larcher F, Feteira J, Lemaitre G, Saidani M, Del Rio M, Barrault CC, Bernard FX, Peschanski M, Baldeschi C, Waksman G (2009) Human embryonic stem-cell derivatives for full reconstruction of the pluristratified epidermis: a preclinical study. Lancet 374(9703):1745–1753

    Article  PubMed  CAS  Google Scholar 

  • Heile A, Brinker T (2011) Clinical translation of stem cell therapy in traumatic brain injury: the potential of encapsulated mesenchymal cell biodelivery of glucagon-like peptide-1. Dialogues Clin Neurosci 13(3):279–286

    PubMed  Google Scholar 

  • Hochedlinger K, Yamada Y, Beard C, Jaenisch R (2005) Ectopic expression ofOct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 121:465–477

    Article  PubMed  CAS  Google Scholar 

  • Hyun I (2010) The bioethics of stem cell research and therapy. J Clin Invest 120(1):71–75

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  • International Stem Cell Initiative (2011) Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage. Nat Biotechnol 29(12):1132–1144

    Article  CAS  Google Scholar 

  • Jiang R, Han Z, Zhuo G, Qu X, Li X, Wang X, Shao Y, Yang S, Han ZC (2011) Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Front Med 5(1):94–100

    Article  PubMed  Google Scholar 

  • Kadereit S, Trounson A (2011) In vitro immunogenicity of undifferentiated pluripotent stem cells (PSC) and derived lineages. Semin Immunopathol 33:551–562

    Article  PubMed  CAS  Google Scholar 

  • Keirstead HS, Nistor G, Bernal G, Totoiu M, Cloutier F, Sharp K, Steward O (2005) Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci 25(19):4694–4705

    Article  PubMed  CAS  Google Scholar 

  • Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472–476

    Article  PubMed  CAS  Google Scholar 

  • Knoller N, Auerbach G, Fulga V, Zelig G, Attias J, Bakimer R, Marder JB, Yoles E, Belkin M, Schwartz M, Hadani M (2005) Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine 3(3):173–181

    Article  PubMed  Google Scholar 

  • Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, Homma S, Edwards NM, Itescu S (2001) Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 7:430–436

    Article  PubMed  CAS  Google Scholar 

  • Kofidis T, Lebl DR, Swijnenburg RJ, Greeve JM, Klima U, Robbins RC (2006) Allopurinol/uricase and ibuprofen enhance engraftment of cardiomyocyte-enriched human embryonic stem cells and improve cardiac function following myocardial injury. Circulation 111(1):11–20

    Google Scholar 

  • Krawetz R, Rancourt DE (2012) Suspension bioreactor expansion of undifferentiated human embryonic stem cells. Methods Mol Biol 873:227–235

    Article  PubMed  CAS  Google Scholar 

  • Kriks S, Shim JW, Piao J, Ganat YM, Wakeman DR, Xie Z, Carrillo-Reid L, Auyeung G, Antonacci C, Buch A, Yang L, Beal MF, Surmeier DJ, Kordower JH, Tabar V, Studer L (2011) Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. Nature 480(7378):547–551

    PubMed  CAS  Google Scholar 

  • Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG, Eliazer S, Young H, Richardson M, Smart NG, Cunningham J, Agulnick AD, D'Amour KA, Carpenter MK, Baetge EE (2008) Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 26(4):443–452

    Article  PubMed  CAS  Google Scholar 

  • Kuznetsov SA, Cherman N, Robey PG (2011) In vivo bone formation by progeny of human embryonic stem cells. Stem Cells Dev 20(2):269–287

    Article  PubMed  CAS  Google Scholar 

  • Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA, Dupras SK, Reinecke H, Xu C, Hassanipour M, Police S, O’Sullivan C, Collins L, Chen Y, Minami E, Gill EA, Ueno S, Yuan C, Gold J, Murry CE (2007) Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 25(9):1015–1024

    Article  PubMed  CAS  Google Scholar 

  • Laurent LC, Nievergelt CM, Lynch C, Fakunle E, Harness JV, Schmidt U, Galat V, Laslett AL, Otonkoski T, Keirstead HS, Schork A, Park HS, Loring JF (2010) Restricted ethnic diversity in human embryonic stem cell lines. Nat Methods 7(1):6–7

    Article  PubMed  CAS  Google Scholar 

  • Lee JE, Kang MS, Park MH, Shim SH, Yoon TK, Chung HM, Lee DR (2010) Evaluation of 28 human embryonic stem cell lines for use as unrelated donors in stem cell therapy: implications of HLA and ABO genotypes. Cell Transplant 19(11):1383–1395

    Article  PubMed  Google Scholar 

  • Lefort N, Feyeux M, Bas C, Féraud O, Bennaceur-Griscelli A, Tachdjian G, Peschanski M, Perrier AL (2008) Human embryonic stem cells reveal recurrent genomic instability at 20q11.21. Nat Biotechnol 26:1364–1366

    Article  PubMed  CAS  Google Scholar 

  • Lima C, Pratas-Vital J, Escada P, Hasse-Ferreira A, Capucho C, Peduzzi JD (2006) Olfactory mucosa autografts in human spinal cord injury: a pilot clinical study. J Spinal Cord Med 29(3):191–203

    PubMed  Google Scholar 

  • Lin G, Xie Y, Ouyang Q, Qian X, Xie P, Zhou X, Xiong B, Tan Y, Li W, Deng L, Zhou J, Zhou D, Du L, Cheng D, Liao Y, Gu Y, Zhang S, Liu T, Sun Y, Lu G (2009) HLA-matching potential of an established human embryonic stem cell bank in China. Cell Stem Cell 5(5):461–465

    Article  PubMed  CAS  Google Scholar 

  • Lu B, Malcuit C, Wang S, Girman S, Francis P, Lemieux L, Lanza R, Lund R (2009) Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Stem Cells 27(9):2126–2135

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lui KO, Waldmann H, Fairchild PJ (2009) Embryonic stem cells: overcoming the immunological barriers to cell replacement therapy. Curr Stem Cell Res Ther 4(1):70–80

    Article  PubMed  CAS  Google Scholar 

  • Lund RD, Wang S, Klimanskaya I, Holmes T, Ramos-Kelsey R, Lu B, Girman S, Bischoff N, Sauvé Y, Lanza R (2006) Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Cloning Stem Cells 8(3):189–199

    Article  PubMed  CAS  Google Scholar 

  • Markoulaki S, Hanna J, Beard C, Carey BW, Cheng AW, Lengner CJ, Dausman JA, Fu D, Gao Q, Wu S (2009) Transgenic mice with defined combinations of drug-inducible reprogramming factors. Nat Biotechnol 27:169–171

    Article  PubMed  CAS  Google Scholar 

  • Martin MJ, Muotri A, Gage F, Varki A (2005) Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med 11(2):228–232

    Article  PubMed  CAS  Google Scholar 

  • Mateizel I, De Temmerman N, Ullmann U, Cauffman G, Sermon K, Van de Velde H, De Rycke M, Degreef E, Devroey P, Liebaers I, Van Steirteghem A (2006) Derivation of human embryonic stem cell lines from embryos obtained after IVF and after PGD for monogenic disorders. Hum Reprod 21(2):503–511

    Article  PubMed  CAS  Google Scholar 

  • Maury Y, Gauthier M, Peschanski M, Martinat C (2012) Human pluripotent stem cells for disease modelling and drug screening. Bioessays 34(1):61–71

    Article  PubMed  CAS  Google Scholar 

  • Mazzini L, Mareschi K, Ferrero I, Miglioretti M, Stecco A, Servo S, Carriero A, Monaco F, Fagioli F (2012) Mesenchymal stromal cell transplantation in amyotrophic lateral sclerosis: a long-term safety study. Cytotherapy 14(1):56–60

    Article  PubMed  Google Scholar 

  • Menasche P (2007) Skeletal myoblasts as a therapeutic agent. Prog Cardiovasc Dis 50(1):7–17

    Article  PubMed  Google Scholar 

  • Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, Hecker H, Schaefer A, Arseniev L, Hertenstein B, Ganser A, Drexler H (2006) Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months’ follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation 113(10):1287–1294

    Article  PubMed  Google Scholar 

  • Mfopou JK, Chen B, Mateizel I, Sermon K, Bouwens L (2010) Noggin, retinoids, and fibroblast growth factor regulate hepatic or pancreatic fate of human embryonic stem cells. Gastroenterology 138(7):2233–2245

    Article  PubMed  CAS  Google Scholar 

  • Mitalipova MM, Rao RR, Hoyer DM, Johnson JA, Meisner LF, Jones KL, Dalton S, Stice SL (2005) Preserving the genetic integrity of human embryonic stem cells. Nat Biotechnol 23:19–20

    Article  PubMed  CAS  Google Scholar 

  • Mosher JT, Pemberton TJ, Harter K, Wang C, Buzbas EO, Dvorak P, Simón C, Morrison SJ, Rosenberg NA (2010) Lack of population diversity in commonly used human embryonic stem-cell lines. N Engl J Med 362(2):183–185

    Article  PubMed  CAS  Google Scholar 

  • Moviglia GA, Fernandez Viña R, Brizuela JA, Saslavsky J, Vrsalovic F, Varela G, Bastos F, Farina P, Etchegaray G, Barbieri M, Martinez G, Picasso F, Schmidt Y, Brizuela P, Gaeta CA, Costanzo H, Moviglia Brandolino MT, Merino S, Pes ME, Veloso MJ, Rugilo C, Tamer I, Shuster GS (2006) Combined protocol of cell therapy for chronic spinal cord injury. Report on the electrical and functional recovery of two patients. Cytotherapy 8(3):202–209

    Article  PubMed  CAS  Google Scholar 

  • Muro M, López-Álvarez MR, Campillo JA, Marin L, Moya-Quiles MR, Bolarín JM, Botella C, Salgado G, Martínez P, Sánchez-Bueno F, López-Hernández R, Boix F, Bosch A, Martínez H, de la Peña-Moral JM, Pérez N, Robles R, García-Alonso AM, Minguela A, Miras M, Alvarez-López MR (2012) Influence of human leukocyte antigen mismatching on rejection development and allograft survival in liver transplantation: is the relevance of HLA-A locus matching being underestimated? Transpl Immunol 26(2–3):88–93

    Article  PubMed  CAS  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(4):983–985

    Article  PubMed  CAS  Google Scholar 

  • Niclis JC, Trounson AO, Dottori M, Ellisdon AM, Bottomley SP, Verlinsky Y, Cram DS (2009) Human embryonic stem cell models of Huntington disease. Reprod Biomed Online 19(1):106–113

    Article  PubMed  CAS  Google Scholar 

  • Nistor GI, Totoiu MO, Haque N, Carpenter MK, Keirstead HS (2005) Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 49(3):385–396

    Article  PubMed  Google Scholar 

  • Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448:313–317

    Article  PubMed  CAS  Google Scholar 

  • Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322:949–953

    Article  PubMed  CAS  Google Scholar 

  • Pennings G (2003) New Belgian law on research on human embryos: trust in progress through medical science. J Assist Reprod Genet 20(8):343–346

    Article  PubMed  CAS  Google Scholar 

  • Ramirez JM, Bai Q, Dijon-Grinand M, Assou S, Gerbal-Chaloin S, Hamamah S, De Vos J (2010) Human pluripotent stem cells: from biology to cell therapy. World J Stem Cells 2(2):24–33

    Article  PubMed  Google Scholar 

  • Rosenthal N, Brown S (2007) The mouse ascending: perspectives for human-disease models. Nat Cell Biol 9(9):993–999

    Article  PubMed  CAS  Google Scholar 

  • Savitz SI (2012) Stem cells and stroke: are we further away than anyone is willing to admit? Int J Stroke 7(1):34–35

    Article  PubMed  Google Scholar 

  • Schofield PN, Sundberg JP, Hoehndorf R, Gkoutos GV (2011) New approaches to the representation and analysis of phenotype knowledge in human diseases and their animal models. Brief Funct Genomics 10(5):258–265

    Article  PubMed  Google Scholar 

  • Schuleri KH, Boyle AJ, Hare JM (2007) Mesenchymal stem cells for cardiac regenerative therapy. Handb Exp Pharmacol 180:195–218

    Article  PubMed  CAS  Google Scholar 

  • Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, Lanza R (2012) Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 379(9817):713–720

    Article  PubMed  CAS  Google Scholar 

  • Sermon K, Van Steirteghem A, Liebaers I (2004) Preimplantation genetic diagnosis. Lancet 363(9421):1633–1641

    Article  PubMed  Google Scholar 

  • Sharp J, Frame J, Siegenthaler M, Nistor G, Keirstead HS (2010) Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury. Stem Cells 28(1):152–163

    PubMed  CAS  Google Scholar 

  • Silk KM, Tseng SY, Nishimoto KP, Lebkowski J, Reddy A, Fairchild PJ (2011) Differentiation of dendritic cells from human embryonic stem cells. Methods Mol Biol 767:449–461

    Article  PubMed  CAS  Google Scholar 

  • Snyder EY, Loring JF (2006) Beyond fraud – stem-cell research continues. N Engl J Med 354(4):321–324

    Article  PubMed  CAS  Google Scholar 

  • Son EY, Ichida JK, Wainger BJ, Toma JS, Rafuse VF, Woolf CJ, Kevin Eggan K (2011) Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell Stem Cell 9(3):205–218

    Article  PubMed  CAS  Google Scholar 

  • Song M, Paul S, Lim H, Dayem AA, Cho SG (2012) Induced pluripotent stem cell research: a revolutionary approach to face the challenges in drug screening. Arch Pharm Res 35(2):245–260

    Article  PubMed  CAS  Google Scholar 

  • Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K (2008) Induced pluripotent stem cells generated without viral integration. Science 322:945–949

    Article  PubMed  CAS  Google Scholar 

  • Stern JH, Temple S (2011) Stem cells for retinal replacement therapy. Neurotherapeutics 8(4):736–743

    Article  PubMed  Google Scholar 

  • Strauer BE, Schannwell CM, Brehm M (2009) Therapeutic potentials of stem cells in cardiac diseases. Minerva Cardioangiol 57(2):249–267

    PubMed  CAS  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676

    Article  PubMed  CAS  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(5):861–872

    Article  PubMed  CAS  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(9502):2019–2025

    Article  PubMed  Google Scholar 

  • Thomas KE, Moon LD (2011) Will stem cell therapies be safe and effective for treating spinal cord injuries? Br Med Bull 98:127–142

    Article  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  PubMed  CAS  Google Scholar 

  • Titomanlio L, Kavelaars A, Dalous J, Mani S, El Ghouzzi V, Heijnen C, Baud O, Gressens P (2011) Stem cell therapy for neonatal brain injury: perspectives and challenges. Ann Neurol 70(5):698–712

    Article  PubMed  Google Scholar 

  • Trounson A (2006) The production and directed differentiation of human embryonic stem cells. Endocr Rev 27(2):208–219

    Article  PubMed  Google Scholar 

  • Uccelli A, Benvenuto F, Laroni A, Giunti D (2011) Neuroprotective features of mesenchymal stem cells. Best Pract Res Clin Haematol 24(1):59–64

    Article  PubMed  CAS  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(1):R48–R53

    Article  PubMed  CAS  Google Scholar 

  • Urbach A, Bar-Nur O, Daley GQ, Benvenisty N (2010) Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell 6(5):407–411

    Article  PubMed  CAS  Google Scholar 

  • Vilquin JT, Catelain C, Vauchez K (2011) Cell therapy for muscular dystrophies: advances and challenges. Curr Opin Organ Transplant 16(6):640–649

    Article  PubMed  CAS  Google Scholar 

  • Wang S, Qu X, Zhao RC (2012) Clinical applications of mesenchymal stem cells. J Hematol Oncol 5(1):19

    Article  PubMed  CAS  Google Scholar 

  • Wollert KC, Drexler H (2005) Mesenchymal stem cells for myocardial infarction: promises and pitfalls. Circulation 112(2):151–153

    Article  PubMed  Google Scholar 

  • Woo DH, Kim SK, Lim HJ, Heo J, Park HS, Kang GY, Kim SE, You HJ, Hoeppner DJ, Kim Y, Kwon H, Choi TH, Lee JH, Hong SH, Song KW, Ahn EK, Chenoweth JG, Tesar PJ, McKay RD, Kim JH (2012) Direct and indirect contribution of human embryonic stem cell-derived hepatocyte-like cells to liver repair in mice. Gastroenterology 142(3):602–611

    Article  PubMed  CAS  Google Scholar 

  • Wood KJ, Goto R (2012) Mechanisms of rejection: current perspectives. Transplantation 93(1):1–10

    Article  PubMed  Google Scholar 

  • Xue T, Cho HC, Akar FG, Tsang SY, Jones SP, Marbán E, Tomaselli GF, Li RA (2005) Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: insights into the development of cell-based pacemakers. Circulation 111(1):11–20

    Article  PubMed  Google Scholar 

  • Yahata N, Asai M, Kitaoka S, Takahashi K, Asaka I, Hioki H, Kaneko T, Maruyama K, Saido TC, Nakahata T, Asada T, Yamanaka S, Iwata N, Inoue H (2011) Anti-Aβ drug screening platform using human iPS cell-derived neurons for the treatment of Alzheimer’s disease. PLoS One 6(9):e25788

    Article  PubMed  CAS  Google Scholar 

  • Yoon SH, Shim YS, Park YH, Chung JK, Nam JH, Kim MO, Park HC, Park SR, Min BH, Kim EY, Choi BH, Park H, Ha Y (2007) Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: phase I/II clinical trial. Stem Cells 25(8):2066–2073

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II, Thomson JA (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324:797–801

    Article  PubMed  CAS  Google Scholar 

  • Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, Trauger S, Bien G, Yao S, Zhu Y, Siuzdak G, Scholer HR, Duan L, Ding S (2009) Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4:381–384

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lygia V. Pereira .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Fraga, A.M., de Araújo, É.S.S., Vergani, N., Fonseca, S.A.S., Pereira, L.V. (2014). Use of Human Embryonic Stem Cells in Therapy. In: Al-Rubeai, M., Naciri, M. (eds) Stem Cells and Cell Therapy. Cell Engineering, vol 8. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7196-3_1

Download citation

Publish with us

Policies and ethics