Recent works show that stem cells reside within defined localities known as stem cell niches. It is postulated that neural stem cells exist in different tissues, but with different degrees of abundance.
We previously generated F1B-Tag transgenic mice in which promoter 1B of FGF1 gene dictates the brain-specific expression of SV40 T antigen. We already showed that F1B-Tag tumor cells are multipotent neural stem cells capable of differentiating into all three neural progeny lineages. We further showed that GFP-positive cells isolated from mouse and human brain tissues that have been transfected with F1B-GFP are also multipotent neural stem cells, capable of differentiating into all three neural progeny lineages.
In a separate study, we showed that GFP-positive cells isolated from developing (E14.5, E17.5 and P1) mouse brains are more potent in their differentiation capability than those from adult brains. The GFP-positive mouse neural cells were tested for their functionality in treating rats with sciatic nerve injury. GFP-positive mouse neural stem cells were injected into the micropatterned conduit before implantation. The peripheral nerve recovery was assessed weekly by walking track analysis and evaluated using sciatic functional index and immunohistochemistry. Rats treated with GFP-positive mouse neural stem cells regain the activity to use their injured legs within one week. In contrast, those that were treated using conduits without neural stem cells could not re-use their hind legs even after three weeks.
These results suggest that our F1B-GFP transfected cells not only have the self-renewal capacity of neural stem cells but, upon introduction into the conduits sutured together with severed sciatic nerve, are capable of rehabilitating these crippled rats.
The clinical applications of GFP-tagged human adult and fetal neural stem cells would be immense. Since neural stem cells usually reside in the brain and are difficult to access for autologous grafting, we propose in the future to identify and isolate neural stem cells from sources that are more easily accessible, such as cord blood, bone marrow, adipose tissues, and placenta. A facile means to identify and isolate neural stem cells could lead to developing strategies for stem cell-based therapies for neurodegenerative disorders and traumatic diseases. Based on his accomplishments, Dr. Chiu was elected to the Fellow of American Association for the Advancement of Science this year for his “contributions to the field of FGF signaling, particularly in developing neural stem cells and micropatterned conduits to repair sciatic nerve injury.”