BMP-2-dependent integration of adult mouse subventricular stem cells into the neural crest of chick and quail embryos

Abstract

Central nervous system (CNS) stem cells isolated from the subventricular zone (SVZ) show a remarkable differentiation potential into neural derivatives. Surprisingly adult SVZ cells can also be induced in vitro to differentiate into neural crest cell fates. This fate switch is dependent on the combination of fibroblast growth factor 2 (FGF2) and bone morphogenetic proteins (BMPs). Here we transplanted adult SVZ stem cells from GFP mice as neurospheres into the trunk neural tube of chick and quail embryos. Only neurospheres pre-exposed to BMP-2 and FGF2 formed close contacts with the dorsal neuroepithelium corresponding to the neural crest area. GFP-positive cells emigrated from the neurosphere and were identified in the roof plate, the dorsal neuroepithelium and among emigrating neural crest cells adjacent to the neural tube. Neurospheres not treated with BMP-2 did not integrate into the neuroepithelium. Our data demonstrate that adult CNS stem cells can be efficiently prepared in vitro for integration into the embryonic neural crest. BMP-2 treatment conveys the necessary morphogenetic capabilities to adult stem cells for future clinical transplantation strategies.

Peripheral Nervous System Progenitors Can Be Reprogrammed to Produce Myelinating Oligodendrocytes and Repair Brain Lesions

“…These findings are in line with the observation that the reverse fate change, the reprogramming of CNS progenitors to Schwann cells, is elicited in brain lesions (Keirstead et al, 1999;Zawadzka et al, 2010). The fate of CNS neural stem cells is also modulated in vitro (Gabay et al, 2003;Hack et al, 2004), which includes the acquisition of NCSC properties under the influence of bone morphogenetic proteins (BMPs) (Gajavelli et al, 2004;Sailer et al, 2005;Busch et al, 2006). Thus, culture and lesion conditions may promote reprogramming and diversity of stem cells that were fate-restricted in vivo by niche signals.…”

Noggin blocks invasive growth of murine B16‐F1 melanoma cells in the optic cup of the chick embryo

“…In contrast to transformed melanoma cells, neural stem cells transplanted into the neural tube of the chick embryo integrate into the neural crest and perform neural crest cell migration only after pretreatment with BMP-2 for 24 hr. 4 This is in line with the observation that in vitro adult neural stem cells from the subventricular zone (SVZ) can be induced to differentiate into neural crest cell fates. This fate switch is dependent on the combination of fibroblast growth factor 2 and BMPs.…”

“…When neural stem cells from the SVZ of adult mice were transplanted into the chick embryo neural tube, integration into the neural crest of the SVZ cells was dependent on exogenous BMP-2 treatment. 4 In contrast, transplanted human and mouse melanoma cells integrated into the neural crest without BMP-2 treatment. 1,2 The explanation for these observations is the constitutive open BMP signalling pathway in melanoma cells.…”

Magnetic resonance imaging of iron-oxide labeled SK-Mel 28 human melanoma cells in the chick embryo using a clinical whole body MRI scanner

“…However, SPIO labeling can be associated with toxic effects, such as induction of apoptosis and inhibition of stem cell differentiation, if the cells are incubated at very high iron concentrations (e.g., ≥500 µg Fe/ml [19]). In our recent publication, we were able to show that SPIO-labeling of subventricular neurosphere stem cells neither affects viability nor morphogenetic properties of the cells after transplantation into the neural tube of chick and quail embryos [20]. Other authors have proposed that SPIO labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis [21].…”