The Effect of Mesoporous Silica Particles on Stem Cell Differentiation

Abstract

Stem cell transplantation is an attractive strategy to counteract the progression of neurodegenerative disorders and to replace lost neuronal cells. Despite successful generation of neuronal cell types in vitro, stem cell technology typically fails when applied in vivo. One of the reasons is the lack of control over the differentiation process of transplanted stem cells. Presently used differentiation protocols make use of external growth factors to guide differentiation of stem cells into the desired cell types. These protocols work for differentiation of stem cells in vitro, but are not readily transferable to in vivo application, where how to deliver these factors and control their dosage are major challenges. We recently showed that mesoporous silica particles (MSPs) provide a useful system to transport and deliver a chosen mixture of biomimetic growth factors over a given period of time, allowing precise control of stem cell differentiation, independent of the local recipient surroundings. However, the effect of unloaded MSPs on the differentiation of stem cells and on immune cell response in vivo has not been examined. Here we show that unloaded MSPs, as prepared here, have no adverse effect on the formation of neurospheres from boundary cap neural crest stem cells, and that neuronal differentiation in vitro actually is even enhanced. After in vivo implantation MSPs are present during 1 month after implantation, i.e. well within the time period when mimetics are expected to be released from the particles. After implantation to injured dorsal roots, but not after injection into the intact spinal cord, some MSPs were taken up by microglia/macrophages. These findings suggest that MSPs, used in this study, can be safely used for the delivery of trophic factors in vitro without effecting the early differentiation of cultured stem cells as well as in vivo for the delivery of factors for several weeks without being taken up by local immune cells.