Research Perspectives:

Human amniotic fluid stem cells as a model for functional studies of genes involved in human genetic diseases or oncogenesis

Margit Rosner, Helmut Dolznig, Katharina Schipany, Mario Mikula, Oliver Brandau and Markus Hengstschläger _

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Oncotarget. 2011; 2:705-712. https://doi.org/10.18632/oncotarget.328

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Margit Rosner, Helmut Dolznig, Katharina Schipany, Mario Mikula, Oliver Brandau, and Markus Hengstschläger

1Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090 Vienna, Austria

Received: September 12, 2011; Accepted: September 14, 2011; Published: September 14, 2011;

Keywords: stem cells, human genetics, oncogenesis, amniocentesis, RNA interference, mTOR


Markus Hengstschläger, email:


Besides their putative usage for therapies, stem cells are a promising tool for functional studies of genes involved in human genetic diseases or oncogenesis. For this purpose induced pluripotent stem (iPS) cells can be derived from patients harbouring specific mutations. In contrast to adult stem cells, iPS cells are pluripotent and can efficiently be grown in culture. However, iPS cells are modulated due to the ectopic induction of pluripotency, harbour other somatic mutations accumulated during the life span of the source cells, exhibit only imperfectly cleared epigenetic memory of the source cell, and are often genomically instable. In addition, iPS cells from patients only allow the investigation of mutations, which are not prenatally lethal. Embryonic stem (ES) cells have a high proliferation and differentiation potential, but raise ethical issues. Human embryos, which are not transferred in the course of in vitro fertilization, because of preimplantation genetic diagnosis of a genetic defect, are still rarely donated for the establishment of ES cell lines. In addition, their usage for studies on gene functions for oncogenesis is hampered by the fact the ES cells are already tumorigenic per se. In 2003 amniotic fluid stem (AFS) cells have been discovered, which meanwhile have been demonstrated to harbour the potential to differentiate into cells of all three germ layers. Monoclonal human AFS cell lines derived from amniocenteses have a high proliferative potential, are genomically stable and are not associated with ethical controversies. Worldwide amniocenteses are performed for routine human genetic diagnosis. We here discuss how generation and banking of monoclonal human AFS cell lines with specific chromosomal aberrations or monogenic disease mutations would allow to study the functional consequences of disease causing mutations. In addition, recently a protocol for efficient and highly reproducible siRNA-mediated long-term knockdown of endogenous gene functions in AFS cells was established. Since AFS cells are not tumorigenic, gene modulations not only allow to investigate the role of endogenous genes involved in human genetic diseases but also may help to reveal putative oncogenic gene functions in different biological models, both in vitro and in vivo. This concept is discussed and a “proof of principle”, already obtained via modulating genes involved in the mammalian target of rapamycin (mTOR) pathway in AFS cells, is presented.

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