However, contrary to these previous reports, most of the grafted cells migrating to tumors with CXCL12 facilitation in the present study were found to differentiate into neurons (Figure 5 and Table 1). Two possible reasons for the contradictory findings are the species from which the NSPCs originated (rat in this study and human or mouse in the aforementioned studies) and the high

levels of CXCL12 used in the present study. Unlike mouse and human NSPCs, which can be maintained for a long period of time in vitro without genetic modifications, rat NSPCs derived selleck screening library from the subventricular zone or hippocampal subgranular zone typically sustain proliferation for only a relatively short time and have a tendency to differentiate [60] and [61]. In addition, local administration of CXCL12 may create a distinct local environment that stimulates NSPCs to differentiate into neurons. CXCL12 was shown to promote neuronal survival and the differentiation of NSPCs to support neural tissues [15] and [62] and to stimulate neurite outgrowth and axonal branching of cultured neuronal cells [63] and [64], indicating its role in controlling neuronal

differentiation. Together, these results indicate that rat NSPCs, which tend to differentiate, may MS-275 order respond to CXCL12 induction and, as a result, differentiate into neurons. It has recently been reported that the expressions of neuronal markers in brain tumors may be associated with a poor outcome [65], [66] and [67]. NeuN was noted to be present in various types of high-grade and recurrent gliomas [65] and [66]. Multiple neuronal immunomarker expressions in glioma were associated with a poor survival rate [67]. We have demonstrated herein that ~ 80% of grafted cells migrating toward tumors with the combined CXCL12-NPSC treatment differentiated into neurons (Figure 4 and Figure 5). The present results show that the increased number of neurons in tumors was associated Methane monooxygenase with increased tumor volume. However, the roles of such an increased number of tumor neurons remain unclear. The strategy of using exogenous CXCL12 to promote

NSPC migration in brain tumors was found in the present study to be associated with a higher rate of tumor growth and an increase in intratumoral hemorrhage. These grafted NSPCs that migrated toward the tumors tended to differentiate into neurons due to the known differentiation potential of rat NSPCs and induction by CXCL12. In conclusion, the results of the present study are especially important in that they illustrate possible effects of stem cell therapies on brain tumors. That is, the strategy of further promoting targeted NSPC migration by CXCL12 may lead to adverse effects. “
“Nearly all human genes undergo alternative splicing, substantially increasing diversity in protein structure and function [1].