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Induzierte pluripotente Stammzellen

Eine neue Ressource in der modernen Medizin

Induced pluripotent stem cells

A new resource in modern medicine

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Zusammenfassung

Pluripotente Stammzellen besitzen ein unbegrenztes Selbsterneuerungs- und Differenzierungspotenzial zur Gewinnung sämtlicher Zellarten des menschlichen Organismus. Damit stellen sie ein einzigartiges Modell für die Beantwortung entwicklungsbiologischer Fragestellungen wie auch für die Zelltherapie und regenerative Medizin dar. Dem Arzt und Stammzellforscher S. Yamanaka gelang erstmals die Reprogrammierung somatischer Zellen zu sog. induzierten pluripotenten Stammzellen durch die ektope Expression der Transkriptionsfaktoren Oct4 („Octamer-binding transcription factor 4“), Sox2 („sex determining region Y – box 2“), Klf4 („Kruppel-like factor 4“) und c-Myc („v-myc myelocytomatosis viral oncogene homolog“). Damit revolutionierte er die Möglichkeiten in der regenerativen Medizin. Insbesondere eröffneten sich durch die Anwendung dieser Techniken im patienten- bzw. krankheitsspezifischen Kontext neue Möglichkeiten zur Modellierung von Krankheiten und zur individualisierten Testung von Medikamenten. Zudem rückt das sog. therapeutische Klonen einen ganzen Schritt näher. Die vorliegende Übersichtsarbeit soll daher dem klinisch tätigen Arzt einen Überblick über den Stand der Forschung und die klinische Anwendung pluripotenter Stammzellen geben.

Abstract

Pluripotent stem cells possess a remarkable unlimited self-renewal capacity and offer unparalleled in vitro differentiation potential. This provides a unique model system not only to study early human development but also gives renewed hope in terms of developing cell therapies and regenerative medicine. S. Yamanaka, a medical doctor and researcher, reported the possibility of reprogramming somatic cells to so-called induced pluripotent stem cells via the ectopic expression of four transcription factors, namely Oct4, Sox2, Klf4 and c-Myc. This Nobel Prize winning work has since revolutionized stem cell research and paved the way for countless new avenues within regenerative medicine. This includes disease modeling in a patient-specific context with the ultimate aim of individually tailored pharmaceutical therapy. Additionally, genetic correction studies have rapidly increased in basic science and thus there is hope that these can be effectively and efficiently translated into clinical applications. Addressing the medical community this review gives a broad general overview about the state of the research field and possible clinical applications of pluripotent stem cells.

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Literatur

  1. Aasen T, Raya A, Barrero MJ et al (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 26:1276–1284

    Article  PubMed  CAS  Google Scholar 

  2. Amabile G, Welner RS, Nombela-Arrieta C et al (2013) In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells. Blood 121:1255–1264

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  3. Carvajal-Vergara X, Sevilla A, D’Souza SL et al (2010) Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 465:808–812

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Cayo MA, Cai J, Delaforest A et al (2012) JD induced pluripotent stem cell-derived hepatocytes faithfully recapitulate the pathophysiology of familial hypercholesterolemia. Hepatology 56:2163–2171

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Choi SM, Kim Y, Shim JS et al (2013) Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells. Hepatology 57:2458–2468

    Article  PubMed  CAS  Google Scholar 

  6. Egawa N, Kitaoka S, Tsukita K et al (2012) Drug screening for ALS using patient-specific induced pluripotent stem cells. Sci Transl Med 4:145ra104

    PubMed  Google Scholar 

  7. Gordon PH, Moore DH, Miller RG et al (2007) Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol 6:1045–1053

    Article  PubMed  CAS  Google Scholar 

  8. Hanna J, Cheng AW, Saha K et al (2010) Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proc Natl Acad Sci U S A 107:9222–9227

    Article  CAS  Google Scholar 

  9. Hanna J, Wernig M, Markoulaki S et al (2007) Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318:1920–1923

    Article  PubMed  CAS  Google Scholar 

  10. Hoing S, Rudhard Y, Reinhardt P et al (2012) Discovery of inhibitors of microglial neurotoxicity acting through multiple mechanisms using a stem-cell-based phenotypic assay. Cell Stem Cell 11:620–632

    Article  PubMed  CAS  Google Scholar 

  11. Kaufman MH, Robertson EJ, Handyside AH et al (1983) Establishment of pluripotential cell lines from haploid mouse embryos. J Embryol Exp Morphol 73:249–261

    Google Scholar 

  12. Kriks S, Shim JW, Piao J et al (2011) Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature 480:547–551

    PubMed Central  PubMed  CAS  Google Scholar 

  13. Li Y, Tsai YT, Hsu CW et al (2012) Long-term safety and efficacy of human-induced pluripotent stem cell (iPS) grafts in a preclinical model of retinitis pigmentosa. Mol Med 18:1312–1319

    PubMed Central  PubMed  CAS  Google Scholar 

  14. Liang P, Lan F, Lee AS et al (2013) Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity. Circulation 127:1677–1691

    Article  PubMed  CAS  Google Scholar 

  15. Linta L, Stockmann M, Kleinhans KN et al (2012) Rat embryonic fibroblasts improve reprogramming of human keratinocytes into induced pluripotent stem cells. Stem Cells Dev 21:965–976

    Article  PubMed  CAS  Google Scholar 

  16. Loh YH, Agarwal S, Park IH et al (2009) Generation of induced pluripotent stem cells from human blood. Blood 113:5476–5479

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Matsa E, Rajamohan D, Dick E et al (2011) Drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation. Eur Heart J 32:952–962

    Article  CAS  Google Scholar 

  18. Mayshar Y, Ben-David U, Lavon N et al (2010) Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. Cell Stem Cell 7:521–531

    Article  PubMed  CAS  Google Scholar 

  19. Patel M, Yang S (2010) Advances in reprogramming somatic cells to induced pluripotent stem cells. Stem Cell Rev 6:367–380

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  20. Raya A, Rodriguez-Piza I, Guenechea G et al (2009) Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature 460:53–59

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Reinhardt P, Schmid B, Burbulla LF et al (2013) Genetic correction of a LRRK2 mutation in human iPSCs links parkinsonian neurodegeneration to ERK-dependent changes in gene expression. Cell Stem Cell 12:354–367

    Article  PubMed  CAS  Google Scholar 

  22. Si-Tayeb K, Noto FK, Nagaoka M et al (2010) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51:297–305

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Smits AM, Van Laake LW, Den Ouden K et al (2009) Human cardiomyocyte progenitor cell transplantation preserves long-term function of the infarcted mouse myocardium. Cardiovasc Res 83:527–535

    Article  PubMed  CAS  Google Scholar 

  24. Stockmann M, Linta L, Fohr KJ et al (2013) Developmental and functional nature of human iPSC derived motoneurons. Stem Cell Rev 9:475–492

    Article  PubMed  Google Scholar 

  25. Streckfuss-Bomeke K, Wolf F, Azizian A et al (2013) Comparative study of human-induced pluripotent stem cells derived from bone marrow cells, hair keratinocytes, and skin fibroblasts. Eur Heart J 34:2618–2629

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  27. Thomson JA, Itskovitz-Eldor J, Shapiro SS et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  PubMed  CAS  Google Scholar 

  28. Tulpule A, Kelley JM, Lensch MW et al (2013) Pluripotent stem cell models of Shwachman-Diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction. Cell Stem Cell 12:727–736

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Weidgang CE, Russell R, Tata PR et al (2013) TBX3 directs cell-fate decision toward mesendoderm. Stem Cell Reports 1:248–265

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. Wootla B, Denic A, Warrington AE et al (2012) Need for a paradigm shift in therapeutic approaches to CNS injury. Expert Rev Neurother 12:409–420

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  31. Yang YM, Gupta SK, Kim KJ et al (2013) A small molecule screen in stem-cell-derived motor neurons identifies a kinase inhibitor as a candidate therapeutic for ALS. Cell Stem Cell 12:713–726

    Article  PubMed  CAS  Google Scholar 

  32. Yu DX, Marchetto MC, Gage FH (2013) Therapeutic translation of iPSCs for treating neurological disease. Cell Stem Cell 12:678–688

    Article  PubMed  CAS  Google Scholar 

  33. Zou J, Maeder ML, Mali P et al (2009) Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells. Cell Stem Cell 5:97–110

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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Einhaltung ethischer Richtlinien

Interessenkonflikt. S. Liebau, M. Stockmann, A. Illing, T. Seufferlein und A. Kleger geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Correspondence to S. Liebau or A. Kleger.

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S. Liebau und M. Stockmann haben in gleichem Maße zu dieser Arbeit beigetragen.

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Liebau, S., Stockmann, M., Illing, A. et al. Induzierte pluripotente Stammzellen. Internist 55, 460–469 (2014). https://doi.org/10.1007/s00108-013-3397-2

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