Mouse epidermal growth factor-responsive neural precursor cells increase the survival and functional capacity of embryonic rat dopamine neurons in vitro

Abstract

We have grown expanded populations of epidermal growth factor (EGF)-responsive mouse striatal precursor cells and subsequently co-cultured these with primary E14 rat ventral mesencephalon. The aim of these experiments was to induce dopaminergic (DA) neuronal phenotypes from the murine precursors. While no precursor cell-derived neurons were induced to express tyrosine hydroxylase (TH), there was a dramatic 30-fold increase in the survival of rat-derived TH-positive neurons in the co-cultures. The effect was not explicable solely in terms of total plating density, and was accompanied by a significantly enhanced capacity for [3H]dopamine uptake in the co-cultures compared to rat alone cultures. The present data show that, although primary rat E14 mesencephalic cells are incapable of inducing the development of DA neurons from EGF-responsive mouse neural precursor cells, such precursors will differentiate into cells capable of enhancing the survival and overall functional efficacy of primary embryonic dopamine neurons.

Directing the differentiation of embryonic stem cells to neural stem cells

“…This finding, although surprising, is consistent with the observation that NSCs isolated from the neonatal mouse subventricular zone also secrete Sonic Hedgehog (Shh; Rafuse et al, 2005). These Shh-secreting NSCs support the survival of dopaminergic neurons when co-cultured with ventral midbrain tissue (Rafuse et al, 2005) and when transplanted into a mouse model of Parkinson's disease (Ostenfeld et al, 1999). Shh may also provide a survival advantage to NSCs over ESCs under serum-free, low density conditions.…”

Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates

“…This suggests a protective effect from secreted factors produced by the hNPC (Po0.001; Figure 2a and c) and supports our earlier observations that neural stem cells alone can increase the survival of primary dopamine neurons. 35 Supernatant from hNPC-GDNF had effects on overall dopamine neuron number comparable to that produced from wild-type hNPC ( Figure 2c). In contrast, conditioned supernatant from hNPC-GDNF significantly increased both dopamine neuron neurite outgrowth and cell body area when compared with supernatant from wild-type hNPC (Po0.001; Figure 2b, d and e).…”

Elimination of serotonergic cells induces a marked increase in generation of dopaminergic neurons from mesencephalic precursors

“…Administration of FGF‐8 and Shh together induces DA neuron differentiation in the dorsal diencephalon, suggesting that both are necessary and sufficient for early specification of DA neurons from progenitors in many regions anterior to the mid–hindbrain boundary (Ye et al ., 1998; Hynes & Rosenthal, 1999). However, it has been observed that administration of Shh and FGF‐8 to cell aggregates of human or rodent mesencephalic precursors has no effect on induction of DA phenotypes (Ostenfeld et al ., 1999; Svendsen et al ., 1999). This suggests that both of these molecules may be endogenously produced in the aggregates and therefore that their absence is not responsible for the poor spontaneous differentiation of DA neurons from mesencephalic precursors.…”