Neurogenic differentiation of amniotic fluid stem cells

Abstract

In 2003, human amniotic fluid has been shown to contain stem cells expressing Oct-4, a marker for pluripotency. This finding initiated a rapidly growing and very promising new stem cell research field. Since then, amniotic fluid stem (AFS) cells have been demonstrated to harbour the potential to differentiate into any of the three germ layers and to form three-dimensional aggregates, so-called embryoid bodies, known as the principal step in the differentiation of pluripotent stem cells. Marker selection and minimal dilution approaches allow the establishment of monoclonal AFS cell lineages with high proliferation potential. AFS cells have a lower risk for tumour development and do not raise the ethical issues of embryonic stem cells. Compared to induced pluripotent stem cells, AFS cells do not need exogenic treatment to induce pluripotency, are chromosomal stable and do not harbour the epigenetic memory and accumulated somatic mutations of specific differentiated source cells. Compared to adult stem cells, AFS can be grown in larger quantities and show higher differentiation potential. Accordingly, in the recent past, AFS became increasingly accepted as an optimal tool for basic research and probably also for specific cell-based therapies. Here, we review the current knowledge on the neurogenic differentiation potential of AFS cells.

Rat full term amniotic fluid harbors highly potent stem cells

“…Many research groups have found that AFSCs are highly neurogenic which can be a good candidate for neuronal regenerative purposes (Prusa et al, 2004;Rosner et al, 2012). However, no study has investigated the effect of monolayer differentiation on AFSCs.…”

Proliferation potential of human amniotic fluid stem cells differently responds to mercury and lead exposure

“…Stem cells in amniotic fluid are of fetal origin but the in vivo function of AFS cells in amniotic fluid is still unclear (Rosner et al 2011). Importantly, it remains to be explored whether pluripotent AFS cells are limited in their differentiation potential in a way that has been already described for murine neural stem cells exposed to a very low MeHg concentration (0.0025 lM).…”

“…Similar findings were reported for human embryonic stem cells (hESC), i.e., MeHg seems to inhibit hESC neuronal precursor differentiation by mechanisms different from general cytotoxicity and the differentiation of neuronal precursor-like cells is more sensitive to MeHg exposure than their maturation into neuron-like cells (Stummann et al 2009). This might be highly relevant also for AFS cells that harbor the potential to differentiate into neurogenic, osteogenic, chondrogenic, adipogenic, hepatic, myogenic, renal, and hematopoietic lineages (Rosner et al 2011). …”

“…AFS cells are regarded as an intermediate stage between embryonic stem cells and lineage-restricted adult progenitor cells and have many advantages over embryonic stem cells (e.g., tumor development and ethics) and adult stem cells (e.g., low proliferation rate and lineage-restricted potential). Due to their potential to differentiate into many different cell types, including neuronal cells (Rosner et al 2011), monoclonal primary human AFS cells are an excellent model to study the cell biological effects of mercury and lead toxicity.…”

Spatial consequences of blocking mTOR/S6K: Relevance for therapy

“…Both inhibitors block p70 S6K1 kinase activity to phosphorylate S6 without affecting the S6 nucleocytoplasmic distribution, but, whereas rapamycin inhibits p70 S6K1 T389 phosphorylation and thus nuclear localization, PF-4708671 strongly induces p70 S6K1 T389 phosphorylation and nuclear localization. 12 Since different mTOR/S6K inhibitors can mediate such different, even opposite, effects on the spatial regulation of their targets, which themselves again have distinct cytoplasmic and nuclear substrates, we want to point out that it is of intriguing relevance for their therapeutic usage to provide a detailed molecular investigation of the tumor, including the spatial regulation of both the drug targets and their substrates, causatively involved in the transformation process. The hypothesis is that the usage of such inhibitors could, for example, block substrate A but could simultaneously trigger spatial deregulation of substrate B, which might have adverse effects, even tumor-promoting consequences.…”