Construction of a novel inducing system with multi-layered alginate microcapsules to regulate differentiation of neural precursor cells from bone mesenchymal stem cells

Abstract

Neural precursor cells (NPCs) are a promising cell source for the treatment of nervous system diseases; however, they are limited in their applications due to source-related ethical considerations or legislations. Therefore, a novel approach is necessary to obtain sufficient NPCs. Recently, the usage of bone marrow-derived mesenchymal stem cells (BMSCs) differentiated into neural cells has become a potential method to obtain NPCs. Moreover, growth factors (GFs) are emerging as inducers to evoke the differentiation of BMSCs into NPCs. For example, GFs may activate various signaling pathways related to neural differentiation, such as phosphatidylinositol 3 kinase/protein kinase B, cyclic adenosine monophosphate/protein kinase A, and Janus kinase/signal transducer activator of transcription. However, the utilization of growth factors still has some limitations such as high costs and low rates of neural differentiation. Neuroblastoma cells have been characterized as a potential pool for growth factors. Additionally, basic fibroblast growth factor (bFGF), a type of growth factor, has been demonstrated to be able to increase the differentiation and survival rate of NPCs. For better use of neuroblastoma cells and bFGF, we established a novel system involving multi-layered alginate-polylysine-alginate (APA) microcapsules to encapsulate neuroblastoma cells and bFGF, which may not only provide sufficient growth factors in a sustained manner but also avoid the carcinogenicity caused by neuroblastoma cells. Above all, we hypothesized that neuroblastoma cells and bFGF encapsulated in multilayered alginate microcapsules may efficiently induce the differentiation of BMSCs into NPCs.