PMID- 21926447
OWN - NLM
STAT- MEDLINE
DCOM- 20120501
LR  - 20211020
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 2
IP  - 9
DP  - 2011 Sep
TI  - Human amniotic fluid stem cells as a model for functional studies of genes 
      involved in human genetic diseases or oncogenesis.
PG  - 705-12
AB  - 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.
FAU - Rosner, Margit
AU  - Rosner M
AD  - Medical Genetics, Medical University of Vienna, Austria.
FAU - Dolznig, Helmut
AU  - Dolznig H
FAU - Schipany, Katharina
AU  - Schipany K
FAU - Mikula, Mario
AU  - Mikula M
FAU - Brandau, Oliver
AU  - Brandau O
FAU - Hengstschlager, Markus
AU  - Hengstschlager M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
SB  - IM
MH  - Amniotic Fluid/*cytology/metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Transformation, Neoplastic/*genetics/metabolism
MH  - Disease Models, Animal
MH  - Humans
MH  - Mice
MH  - Neoplastic Stem Cells/*cytology/metabolism
MH  - Stem Cells/*cytology/metabolism
PMC - PMC3248217
EDAT- 2011/09/20 06:00
MHDA- 2012/05/02 06:00
PMCR- 2011/09/01
CRDT- 2011/09/20 06:00
PHST- 2011/09/20 06:00 [entrez]
PHST- 2011/09/20 06:00 [pubmed]
PHST- 2012/05/02 06:00 [medline]
PHST- 2011/09/01 00:00 [pmc-release]
AID - 328 [pii]
AID - 10.18632/oncotarget.328 [doi]
PST - ppublish
SO  - Oncotarget. 2011 Sep;2(9):705-12. doi: 10.18632/oncotarget.328.