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TumorDiagnostik & Therapie 2011; 32(6): 338-344
DOI: 10.1055/s-0031-1281844
Thieme Onkologie aktuell

© Georg Thieme Verlag KG Stuttgart · New York

Pluripotente Stammzellquellen heute

Pluripotent Stem CellsT. Müller1 , R. Blasczyk1
  • 1Institut für Transfusionsmedizin, Medizinische Hochschule Hannover
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Publication History

Publication Date:
12 December 2011 (online)

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Zusammenfassung

Wohl keine andere wissenschaftliche Entdeckung der letzten Jahre hat die regenerative Medizin so beschleunigt und gleichzeitig heftige gesellschaftliche Kontroversen ausgelöst wie die Gewinnung von embryonalen Stammzellen (ESC). Heute, rund ein Jahrzehnt später, werden in kleinem Rahmen diese pluripotenten Zellen in ersten klinischen Studien angewandt. Trotz immunologischer Probleme, ethischer Bedenken und der Gefahr der Teratombildung sind die ESCs nach wie vor wegen ihrer Plastizität und Expansionsfähigkeit ein interessanter Kandidat für die Therapie. Adulte Stammzellen (ASC) werden schon länger therapeutisch sowohl allogen als auch autolog insbesondere in der hämatopoietischen Stammzelltransplantation genutzt, und derzeit gewinnen bei den ASCs besonders mesenchymale Stammzellen durch überlegene Plastizität und Expansion mehr und mehr an Bedeutung. Reprogrammierte Zellen sind speziell in der autologen Anwendung und in Verbindung mit Gentherapie von größtem therapeutischem Interesse, allerdings gibt es trotz erheblicher Fortschritte auch bei der nicht-invasiven Reprogrammierung im Bereich der klinischen Sicherheit in bezug auf Mutationen und Teratombildung noch großen Forschungsbedarf. 

Abstract

No other scientific development in the last years has quickend regenerative medicine and at the same time lead to many controversies as the generation of embryonic stem cells (ESC). Today, one decade later, these cells are utilized in small scale for the first time in clinical studies. Despite immunological problems, ethical concerns and the threat of termatoma formation ESC are due to their high plasticity and propagation capabilities a very interesting candidate for therapy. Adult stem cells (ASC) are already in use for many years, eypecially in allogeneic and autologous hematopoietic stem cell transplantation, and currently, in the field of ACSs, mesenchymal stem cells gain more and more attention due to their superior plasticity and expansion qualities. Reprogrammed cells are of special therapeutic interest for autologous applications and in combination with corrective gene therapy; however, beside tremendous progress in the non-invasive reprogramming technology there is still much work to accomplish to reach with regard to mutations and teratoma formation a safety level acceptable for clinical use. 

Schlüsselwörter

embryonale Stammzellen - adulte Stammzellen - hämatopoietische Stammzelltransplantation - mesenchymale Stammzellen

Key words

embryonic stem cells - adult stem cells - hematopoietic stem cell transplantation - mesenchymal stem cells

Literatur

  • 1 Jaenisch R, Young R. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming.  Cell. 2008;  132 567-582
    Google Scholar
  • 2 Vazin T, Becker K G, Chen J et al. A novel combination of factors, termed SPIE, which promotes dopaminergic neuron differentiation from human embryonic stem cells.  PLoS One. 2009;  4 e6606
    Google Scholar
  • 3 Gilbert S F, Howes-Mischel R. “Show me your original face before you were born”: the convergence of public fetuses and sacred DNA.  Hist Philos Life Sci. 2004;  26 377-394
    Google Scholar
  • 4 Huang J, Wang F, Okuka M et al. Association of telomere length with authentic pluripotency of ES / iPS cells.  Cell Res. 2011;  21 779-792
    Google Scholar
  • 5 Rosler E S, Fisk G J, Ares X et al. Long-term culture of human embryonic stem cells in feeder-free conditions.  Dev Dyn. 2004;  229 259-274
    Google Scholar
  • 6 Hayflick L. The establishment of a line (WISH) of human amnion cells in continuous cultivation.  Exp Cell Res. 1961;  23 14-20
    Google Scholar
  • 7 Baker D E, Harrison N J, Maltby E et al. Adaptation to culture of human embryonic stem cells and oncogenesis in vivo.  Nat Biotechnol. 2007;  25 207-215
    Google Scholar
  • 8 Draper J S, Smith K, Gokhale P et al. Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells.  Nat Biotechnol. 2004;  22 53-54
    Google Scholar
  • 9 Martin G R. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells.  Proc Natl Acad Sci USA. 1981;  78 7634-7638
    Google Scholar
  • 10 Evans M J, Kaufman M H. Establishment in culture of pluripotential cells from mouse embryos.  Nature. 1981;  292 154-156
    Google Scholar
  • 11 Thomson J A, Itskovitz-Eldor J, Shapiro S S et al. Embryonic stem cell lines derived from human blastocysts.  Science. 1998;  282 1145-1147
    Google Scholar
  • 12 Thomson J A, Kalishman J, Golos T G et al. Isolation of a primate embryonic stem cell line.  Proc Natl Acad Sci USA. 1995;  92 7844-7848
    Google Scholar
  • 13 Reubinoff B E, Pera M F, Fong C Y et al. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro.  Nat Biotechnol. 2000;  18 399-404
    Google Scholar
  • 14 Amit M, Carpenter M K, Inokuma M S et al. Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture.  Dev Biol. 2000;  227 271-278
    Google Scholar
  • 15 Fernandes A M, Meletti T, Guimaraes R et al. Worldwide survey of published procedures to culture human embryonic stem cells.  Cell Transplant. 2010;  19 509-523
    Google Scholar
  • 16 Beattie G M, Lopez A D, Bucay N et al. Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers.  Stem Cells. 2005;  23 489-495
    Google Scholar
  • 17 James D, Levine A J, Besser D et al. TGFbeta / activin / nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells.  Development. 2005;  132 1273-1282
    Google Scholar
  • 18 Fraga A M, Souza de Araujo E S, Stabellini R et al. A Survey of Parameters Involved in the Establishment of New Lines of Human Embryonic Stem Cells.  Stem Cell Rev. 2010;  6 234-236
    Google Scholar
  • 19 Fraga A M, Sukoyan M, Rajan P et al. Establishment of a Brazilian line of human embryonic stem cells in defined medium: implications for cell therapy in an ethnically diverse population.  Cell Transplant. 2011;  20 431-440
    Google Scholar
  • 20 Mosher W D, Jones J. Use of contraception in the United States: 1982 – 2008.  Vital Health Stat. 2010;  23 1-44
    Google Scholar
  • 21 Agarwal S, Holton K L, Lanza R. Efficient differentiation of functional hepatocytes from human embryonic stem cells.  Stem Cells. 2008;  26 1117-1127
    Google Scholar
  • 22 Loya K, Eggenschwiler R, Ko K et al. Hepatic differentiation of pluripotent stem cells.  Biol Chem. 2009;  390 1047-1055
    Google Scholar
  • 23 Segev H, Fishman B, Ziskind A et al. Differentiation of human embryonic stem cells into insulin-producing clusters.  Stem Cells. 2004;  22 265-274
    Google Scholar
  • 24 Wen Y, Chen B, Ildstad S T. Stem cell-based strategies for the treatment of type 1 diabetes mellitus.  Expert Opin Biol Ther. 2011;  11 41-53
    Google Scholar
  • 25 Liew C G. Generation of insulin-producing cells from pluripotent stem cells: from the selection of cell sources to the optimization of protocols.  Rev Diabet Stud. 2010;  7 82-92
    Google Scholar
  • 26 Rippon H J, Lane S, Qin M et al. Embryonic stem cells as a source of pulmonary epithelium in vitro and in vivo.  Proc Am Thorac Soc. 2008;  5 717-722
    Google Scholar
  • 27 Samadikuchaksaraei A, Cohen S, Isaac K et al. Derivation of distal airway epithelium from human embryonic stem cells.  Tissue Eng. 2006;  12 867-875
    Google Scholar
  • 28 Barberi T, Willis L M, Socci N D et al. Derivation of multipotent mesenchymal precursors from human embryonic stem cells.  PLoS Med. 2005;  2 e161
    Google Scholar
  • 29 Kensah G, Gruh I, Viering J et al. A novel miniaturized multimodal bioreactor for continuous in situ assessment of bioartificial cardiac tissue during stimulation and maturation.  Tissue Eng Part C Methods. 2011;  17 463-473
    Google Scholar
  • 30 Tandon N, Marsano A, Maidhof R et al. Optimization of electrical stimulation parameters for cardiac tissue engineering.  J Tissue Eng Regen Med. 2011;  5 e115-e125
    Google Scholar
  • 31 Chadwick K, Wang L, Li L et al. Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells.  Blood. 2003;  102 906-915
    Google Scholar
  • 32 Ledran M H, Krassowska A, Armstrong L et al. Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches.  Cell Stem Cell. 2008;  3 85-98
    Google Scholar
  • 33 Aberdam E, Barak E, Rouleau M et al. A pure population of ectodermal cells derived from human embryonic stem cells.  Stem Cells. 2008;  26 440-444
    Google Scholar
  • 34 Yue F, Johkura K, Shirasawa S et al. Differentiation of primate ES cells into retinal cells induced by ES cell-derived pigmented cells.  Biochem Biophys Res Commun. 2010;  394 877-883
    Google Scholar
  • 35 Reubinoff B E, Itsykson P, Turetsky T et al. Neural progenitors from human embryonic stem cells.  Nat Biotechnol. 2001;  19 1134-1140
    Google Scholar
  • 36 Lee S K, Lee B, Ruiz E C et al. Olig2 and Ngn2 function in opposition to modulate gene expression in motor neuron progenitor cells.  Genes Dev. 2005;  19 282-294
    Google Scholar
  • 37 Du Z W, Li X J, Nguyen G D et al. Induced expression of Olig2 is sufficient for oligodendrocyte specification but not for motoneuron specification and astrocyte repression.  Mol Cell Neurosci. 2006;  33 371-380
    Google Scholar
  • 38 Erceg S, Lainez S, Ronaghi M et al. Differentiation of human embryonic stem cells to regional specific neural precursors in chemically defined medium conditions.  PLoS One. 2008;  3 e2122
    Google Scholar
  • 39 Gerrard L, Rodgers L, Cui W. Differentiation of human embryonic stem cells to neural lineages in adherent culture by blocking bone morphogenetic protein signaling.  Stem Cells. 2005;  23 1234-1241
    Google Scholar
  • 40 Zhang Y, Wang J, Chen G et al. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells.  Biochem Biophys Res Commun. 2011;  404 610-614
    Google Scholar
  • 41 Olsen A L, Stachura D L, Weiss M J. Designer blood: creating hematopoietic lineages from embryonic stem cells.  Blood. 2006;  107 1265-1275
    Google Scholar
  • 42 Olivier E N, Qiu C, Velho M et al. Large-scale production of embryonic red blood cells from human embryonic stem cells.  Exp Hematol. 2006;  34 1635-1642
    Google Scholar
  • 43 Lu S J, Li F, Yin H et al. Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice.  Cell Res. 2011;  21 530-545
    Google Scholar
  • 44 Woll P S, Grzywacz B, Tian X et al. Human embryonic stem cells differentiate into a homogeneous population of natural killer cells with potent in vivo antitumor activity.  Blood. 2009;  113 6094-6101
    Google Scholar
  • 45 Karlsson K R, Cowley S, Martinez F O et al. Homogeneous monocytes and macrophages from human embryonic stem cells following coculture-free differentiation in M-CSF and IL-3.  Exp Hematol. 2008;  36 1167-1175
    Google Scholar
  • 46 Mohib K, Allan D, Wang L. Human embryonic stem cell-extracts inhibit the differentiation and function of monocyte-derived dendritic cells.  Stem Cell Rev. 2010;  6 611-621
    Google Scholar
  • 47 Martin C H, Woll P S, Ni Z et al. Differences in lymphocyte developmental potential between human embryonic stem cell and umbilical cord blood-derived hematopoietic progenitor cells.  Blood. 2008;  112 2730-2737
    Google Scholar
  • 48 Galic Z, Kitchen S G, Kacena A et al. T lineage differentiation from human embryonic stem cells.  Proc Natl Acad Sci USA. 2006;  103 11742-11747
    Google Scholar
  • 49 Bretzner F, Gilbert F, Baylis F et al. Target populations for first-in-human embryonic stem cell research in spinal cord injury.  Cell Stem Cell. 2011;  8 468-475
    Google Scholar
  • 50 Matveyenko A V, Georgia S, Bhushan A et al. Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats.  Am J Physiol Endocrinol Metab. 2010;  299 E713-E720
    Google Scholar
  • 51 Gage F H. Mammalian neural stem cells.  Science. 2000;  287 1433-1438
    Google Scholar
  • 52 Takacs L, Toth E, Berta A et al. Stem cells of the adult cornea: from cytometric markers to therapeutic applications.  Cytometry A. 2009;  75 54-66
    Google Scholar
  • 53 Alonso L, Fuchs E. Stem cells in the skin: waste not, Wnt not.  Genes Dev. 2003;  17 1189-1200
    Google Scholar
  • 54 Al Battah F, De Kock J, Ramboer E et al. Evaluation of the multipotent character of human adipose tissue-derived stem cells isolated by Ficoll gradient centrifugation and red blood cell lysis treatment.  Toxicol In Vitro. 2011;  [Epub ahead of print]
    Google Scholar
  • 55 Miki T. Amnion-derived stem cells: in quest of clinical applications.  Stem Cell Res Ther. 2011;  2 25
    Google Scholar
  • 56 Landgren H, Curtis M A. Locating and labeling neural stem cells in the brain.  J Cell Physiol. 2011;  226 1-7
    Google Scholar
  • 57 Bovetti S, Gribaudo S, Puche A C et al. A. From progenitors to integrated neurons: Role of neurotransmitters in adult olfactory neurogenesis.  J Chem Neuroanat. 2011;  [Epub ahead of print]
    Google Scholar
  • 58 Corona R, Larriva-Sahd J, Paredes R G. Paced-mating increases the number of adult new born cells in the internal cellular (granular) layer of the accessory olfactory bulb.  PLoS One. 2011;  6 e19380
    Google Scholar
  • 59 Brennand K, Melton D. Slow and steady is the key to beta-cell replication.  J Cell Mol Med. 2009;  13 472-487
    Google Scholar
  • 60 Docherty K. Pancreatic stellate cells can form new beta-like cells.  Biochem J. 2009;  421 e1-e4
    Google Scholar
  • 61 McCulloch E A, Till J E, Siminovitch L. The role of independent and dependent stem cells in the control of hemopoietic and immunologic responses.  Wistar Inst Symp Monogr. 1965;  4 61-68
    Google Scholar
  • 62 Flomenberg N, DiPersio J, Calandra G. Role of CXCR4 chemokine receptor blockade using AMD3100 for mobilization of autologous hematopoietic progenitor cells.  Acta Haematol. 2005;  114 198-205
    Google Scholar
  • 63 Dzierzak E, Medvinsky A. The discovery of a source of adult hematopoietic cells in the embryo.  Development. 2008;  135 2343-2346
    Google Scholar
  • 64 Barbosa C M, Leon C M, Nogueira-Pedro A et al. Differentiation of hematopoietic stem cell and myeloid populations by ATP is modulated by cytokines.  Cell Death Dis. 2011;  2 e165
    Google Scholar
  • 65 Aguila J R, Liao W, Yang J et al. SALL4 is a robust stimulator for the expansion of hematopoietic stem cells.  Blood. 2011;  [Epub ahead of print]
    Google Scholar
  • 66 Kim J Y, Jeon H B, Yang Y S et al. Application of human umbilical cord blood-derived mesenchymal stem cells in disease models.  World J Stem Cells. 2010;  2 34-38
    Google Scholar
  • 67 Hilfiker A, Kasper C, Hass R et al. Mesenchymal stem cells and progenitor cells in connective tissue engineering and regenerative medicine: is there a future for transplantation?.  Langenbecks Arch Surg. 2011;  396 489-497
    Google Scholar
  • 68 Dominici M, Horwitz E M. Getting beneath the skin to understand MSC complexity.  Cytotherapy. 2010;  12 438-439
    Google Scholar
  • 69 Choong P F, Mok P L, Cheong S K et al. Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro.  Cytotherapy. 2007;  9 170-183
    Google Scholar
  • 70 Xu J, Wang W, Kapila Y et al. Multiple differentiation capacity of STRO-1 + / CD146 +  PDL mesenchymal progenitor cells.  Stem Cells Dev. 2009;  18 487-496
    Google Scholar
  • 71 Phuc P V, Nhung T H, Loan D T et al. Differentiating of banked human umbilical cord blood-derived mesenchymal stem cells into insulin-secreting cells.  In Vitro Cell Dev Biol Anim. 2011;  47 54-63
    Google Scholar
  • 72 Leeb C, Jurga M, McGuckin C et al. Promising new sources for pluripotent stem cells.  Stem Cell Rev. 2010;  6 15-26
    Google Scholar
  • 73 Krampera M, Glennie S, Dyson J et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide.  Blood. 2003;  101 3722-3729
    Google Scholar
  • 74 Le Blanc K, Tammik C, Rosendahl K et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells.  Exp Hematol. 2003;  31 890-896
    Google Scholar
  • 75 Rocha V, Labopin M, Sanz G et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia.  N Engl J Med. 2004;  351 2276-2285
    Google Scholar
  • 76 Lee K H, Lee J H, Lee J H et al. Reduced-intensity conditioning therapy with busulfan, fludarabine, and anti-thymocyte globulin for HLA-haploidentical hematopoietic cell transplantation in acute leukemia and myelodysplastic syndrome.  Blood. 2011;  [Epub ahead of print]
    Google Scholar
  • 77 Porrata L F, Markovic S N. Autograft mediated adoptive immunotherapy of cancer in the context of autologous stem cell transplantation.  World J Clin Oncol. 2010;  1 29-34
    Google Scholar
  • 78 Smits E L, Lee C, Hardwick N et al. Clinical evaluation of cellular immunotherapy in acute myeloid leukaemia.  Cancer Immunol Immunother. 2011;  60 757-769
    Google Scholar
  • 79 Serana F, Sottini A, Chiarini M et al. The different extent of B and T cell immune reconstitution after hematopoietic stem cell transplantation and enzyme replacement therapies in SCID patients with adenosine deaminase deficiency.  J Immunol. 2010;  185 7713-7722
    Google Scholar
  • 80 Allers K, Hutter G, Hofmann J et al. Evidence for the cure of HIV infection by CCR5Delta32 / Delta32 stem cell transplantation.  Blood. 2011;  117 2791-2799
    Google Scholar
  • 81 Eapen M, Le Rademacher J, Antin J H et al. Effect of stem cell source on outcomes after adult unrelated donor transplantation in severe aplastic anemia.  Blood. 2011;  [Epub ahead of print]
    Google Scholar
  • 82 Ayas M, Al-Jefri A, Al-Seraihi A et al. Matched-related allogeneic stem cell transplantation in Saudi patients with Fanconi anemia: 10 year’s experience.  Bone Marrow Transplant. 2008;  42 S45-S48
    Google Scholar
  • 83 Inatomi T, Nakamura T, Koizumi N et al. Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation.  Am J Ophthalmol. 2006;  141 267-275
    Google Scholar
  • 84 Nishida K, Yamato M, Hayashida Y et al. Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium.  N Engl J Med. 2004;  351 1187-1196
    Google Scholar
  • 85 Badiavas E V, Falanga V. Treatment of chronic wounds with bone marrow-derived cells.  Arch Dermatol. 2003;  139 510-516
    Google Scholar
  • 86 Blocklet D, Toungouz M, Berkenboom G et al. Myocardial homing of nonmobilized peripheral-blood CD34 +  cells after intracoronary injection.  Stem Cells. 2006;  24 333-336
    Google Scholar
  • 87 Janssens S, Theunissen K, Boogaerts M et al. Bone marrow cell transfer in acute myocardial infarction.  Nat Clin Pract Cardiovasc Med. 2006;  3 S69-S72
    Google Scholar
  • 88 Stilley C S, Ryan C M, Kondziolka D et al. Changes in cognitive function after neuronal cell transplantation for basal ganglia stroke.  Neurology. 2004;  63 1320-1322
    Google Scholar
  • 89 Bauchet L, Lonjon N, Perrin F E et al. Strategies for spinal cord repair after injury: A review of the literature and information.  Ann Phys Rehabil Med. 2009;  52 330-351
    Google Scholar
  • 90 Terai S, Yamamoto N, Omori K et al. A new cell therapy using bone marrow cells to repair damaged liver.  J Gastroenterol. 2002;  37 162-163
    Google Scholar
  • 91 Ishikawa T, Banas A, Hagiwara K et al. Stem cells for hepatic regeneration: the role of adipose tissue derived mesenchymal stem cells.  Curr Stem Cell Res Ther. 2010;  5 182-189
    Google Scholar
  • 92 Baiguera S, Gonfiotti A, Jaus M et al. Development of bioengineered human larynx.  Biomaterials. 2011;  32 4433-4442
    Google Scholar
  • 93 Roh J D, Sawh-Martinez R, Brennan M P et al. Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling.  Proc Natl Acad Sci USA. 2010;  107 4669-4674
    Google Scholar
  • 94 Koch S, Flanagan T C, Sachweh J S et al. Fibrin-polylactide-based tissue-engineered vascular graft in the arterial circulation.  Biomaterials. 2010;  31 4731-4739
    Google Scholar
  • 95 Haisch A. Ear reconstruction through tissue engineering.  Adv Otorhinolaryngol. 2010;  68 108-119
    Google Scholar
  • 96 Huang S, Xu Y, Wu C et al. In vitro constitution and in vivo implantation of engineered skin constructs with sweat glands.  Biomaterials. 2010;  31 5520-5525
    Google Scholar
  • 97 Lee D Y, Yang J M, Baek M K. A dermal equivalent can be developed from fibroblast culture by means of a high concentration of serum.  Br J Dermatol. 2011;  164 1109-1111
    Google Scholar
  • 98 Gunter K C, Caplan A L, Mason C et al. Cell therapy medical tourism: time for action.  Cytotherapy. 2010;  12 965-968
    Google Scholar
  • 99 Haimes E, Taylor K. Researching the Relationships between Tissue Providers, Clinicians, and Stem Cell Scientists.  Cell Stem Cell. 2011;  8 613-615
    Google Scholar
  • 100 Yamanaka S, Takahashi K. [Induction of pluripotent stem cells from mouse fibroblast cultures].  Tanpakushitsu Kakusan Koso. 2006;  51 2346-2351
    Google Scholar
  • 101 Takahashi K, Tanabe K, Ohnuki M et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors.  Cell. 2007;  131 861-872
    Google Scholar
  • 102 Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.  Cell. 2006;  126 663-676
    Google Scholar
  • 103 Maherali N, Sridharan R, Xie W et al. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution.  Cell Stem Cell. 2007;  1 55-70
    Google Scholar
  • 104 Park I H, Zhao R, West J A et al. Reprogramming of human somatic cells to pluripotency with defined factors.  Nature. 2008;  451 141-146
    Google Scholar
  • 105 Hemberger M, Dean W, Reik W. Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington’s canal.  Nat Rev Mol Cell Biol. 2009;  10 526-537
    Google Scholar
  • 106 Avilion A A, Nicolis S K, Pevny L H et al. Multipotent cell lineages in early mouse development depend on SOX2 function.  Genes Dev. 2003;  17 126-140
    Google Scholar
  • 107 Chambers I, Silva J, Colby D et al. Nanog safeguards pluripotency and mediates germline development.  Nature. 2007;  450 1230-1234
    Google Scholar
  • 108 Sridharan R, Tchieu J, Mason M J et al. Role of the murine reprogramming factors in the induction of pluripotency.  Cell. 2009;  136 364-377
    Google Scholar
  • 109 Stadtfeld M, Nagaya M, Utikal J et al. Induced pluripotent stem cells generated without viral integration.  Science. 2008;  322 945-949
    Google Scholar
  • 110 Yu J, Hu K, Smuga-Otto K et al. Human induced pluripotent stem cells free of vector and transgene sequences.  Science. 2009;  324 797-801
    Google Scholar
  • 111 Kaji K, Norrby K, Paca A et al. Virus-free induction of pluripotency and subsequent excision of reprogramming factors.  Nature. 2009;  458 771-775
    Google Scholar
  • 112 Woltjen K, Michael I P, Mohseni P et al. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells.  Nature. 2009;  458 766-770
    Google Scholar
  • 113 Soldner F, Hockemeyer D, Beard C et al. Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors.  Cell. 2009;  136 964-977
    Google Scholar
  • 114 Lin S L, Chang D C, Lin C H et al. Regulation of somatic cell reprogramming through inducible mir-302 expression.  Nucleic Acids Res. 2011;  39 1054-1065
    Google Scholar
  • 115 Yang C S, Li Z, Rana T M. microRNAs modulate iPS cell generation.  RNA. 2011;  [Epub ahead of print]
    Google Scholar
  • 116 Kim D, Kim C H, Moon J I et al. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins.  Cell Stem Cell. 2009;  4 472-476
    Google Scholar
  • 117 Wang Y, Mah N, Prigione A et al. A transcriptional roadmap to the induction of pluripotency in somatic cells.  Stem Cell Rev. 2010;  6 282-296
    Google Scholar
  • 118 Nishino K, Toyoda M, Yamazaki-Inoue M et al. DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time.  PLoS Genet. 2011;  7 e1002085
    Google Scholar
  • 119 Mikkelsen T S, Hanna J, Zhang X et al. Dissecting direct reprogramming through integrative genomic analysis.  Nature. 2008;  454 49-55
    Google Scholar
  • 120 Huangfu D, Maehr R, Guo W et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds.  Nat Biotechnol. 2008;  26 795-797
    Google Scholar
  • 121 Hacein-Bey-Abina S, Garrigue A, Wang G P et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1.  J Clin Invest. 2008;  118 3132-3142
    Google Scholar
  • 122 Kiskinis E, Eggan K. Progress toward the clinical application of patient-specific pluripotent stem cells.  J Clin Invest. 2010;  120 51-59
    Google Scholar
  • 123 Marchetto M C, Yeo G W, Kainohana O et al. Transcriptional signature and memory retention of human-induced pluripotent stem cells.  PLoS One. 2009;  4 e7076
    Google Scholar
  • 124 Hussein S M, Batada N N, Vuoristo S et al. Copy number variation and selection during reprogramming to pluripotency.  Nature. 2011;  471 58-62
    Google Scholar
  • 125 Gore A, Li Z, Fung H L et al. Somatic coding mutations in human induced pluripotent stem cells.  Nature. 2011;  471 63-67
    Google Scholar
  • 126 Lister R, Pelizzola M, Kida Y S et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells.  Nature. 2011;  471 68-73
    Google Scholar
  • 127 Okita K, Nakagawa M, Hyenjong H et al. Generation of mouse induced pluripotent stem cells without viral vectors.  Science. 2008;  322 949-953
    Google Scholar
  • 128 Hanna J, Wernig M, Markoulaki S et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin.  Science. 2007;  318 1920-1923
    Google Scholar
  • 129 Raya A, Rodriguez-Piza I, Guenechea G et al. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells.  Nature. 2009;  460 53-59
    Google Scholar

T. Müller

Institut für TransfusionsmedizinMedizinische Hochschule Hannover

Carl-Neuberg Straße 1

30625 Hannover

Email: mueller.thomas@mh-hannover.de

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