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Stammzellbasierte In-vitro-Modelle als Ersatz für Tiermodelle bei Toxizitäts- und Wirksamkeitsprüfungen

Stem cell-based in vitro models as alternative methods for toxicity and efficacy tests in animals

  • reaLeitthema: Forschung mit humanen embryonalen Stammzellen
  • Published:
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz Aims and scope

Zusammenfassung

In Bezug auf Toxizitäts- und Wirksamkeitsstudien für pharmakologische Formulierungen, Medikamentenkandidaten und andere chemische Substanzen (REACH) besteht der Bedarf, Ersatzmodelle für Tierversuche auf der Basis kultivierter menschlicher Zellen (In-vitro-Systeme) zu entwickeln. Im vorliegenden Beitrag werden Ergebnisse aus frühen Phasen von Projekten vorgestellt, die das diesbezügliche Potenzial muriner und humaner embryonaler Stammzellmodelle (mESC- bzw. hESC-Modelle) erforschen. Dabei liegt der Fokus auf der Etablierung von ESC-Modellen für neurodegenerative Erkrankungen zur Wirksamkeitstestung entsprechender Pharmaka sowie auf entsprechenden Modellen zur Testung der Embryotoxizität von Substanzen. Es konnte zunächst gezeigt werden, dass aus hESC differenzierte Neurone ein für neuronale Zellen typisches funktionelles Verhalten aufweisen. Zu beobachten war zudem, dass in diesen Zellen Prozesse induziert werden können, die für eine Ischämie oder nach einer exzitotoxischen Neuronenschädigung (z. B. Glutamat-vermittelte Toxizität) charakteristisch sind. Vorgestellt werden weiterhin Möglichkeiten zur Entwicklung genauerer molekularer Endpunkte, die für die Bestimmung der Wirksamkeit von Substanzen in diesen Modellen genutzt werden könnten. Abschließend werden die Ergebnisse aus einem groß angelegten europäischen Projekt zur Embryotoxizität (http://www.reprotect.eu) diskutiert, bei dem auch murine und menschliche ESC-Modelle verwendet wurden.

Abstract

Regarding toxicity and efficacy tests of pharmacological and chemical substances (REACH legislation in Europe), there is a strong need to develop alternative methods for animal in vivo studies, in particular for human in vitro models. Here we present results from early phases of projects exploring the potential of embryonic stem cell models, with a special emphasis on embryo toxicity and neuronal stress.

We have been able to demonstrate key functional read-outs of neural hESC models, in addition to representing mechanistic aspects which are characteristic for ischemia or excitotoxicity. There is agreement that these mechanisms underlie a variety of human neurodegenerative diseases. We discuss the possibilities to develop more precise endpoints on the molecular level and present an example of a protein biomarker signature emerging from a European FP6 project about embryo toxicity (www.reprotect.eu), employing murine and human embryonic stem cell models.

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Authors and Affiliations

  1. ProteoSys AG, Mainz, BRD

    M. Klemm, K. Groebe, V. Šoškić & André Schrattenholz

  2. ProteoSys AG, Carl-Zeiss-Straße 51, 55129, Mainz, BRD

    André Schrattenholz

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  1. M. Klemm
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  2. K. Groebe
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  3. V. Šoškić
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  4. André Schrattenholz
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Correspondence to André Schrattenholz.

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Klemm, M., Groebe, K., Šoškić, V. et al. Stammzellbasierte In-vitro-Modelle als Ersatz für Tiermodelle bei Toxizitäts- und Wirksamkeitsprüfungen. Bundesgesundheitsbl. 51, 1033–1038 (2008). https://doi.org/10.1007/s00103-008-0632-4

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