Abstract
In neuronal diseases, it is difficult to provide the satisfactory outcome only by stem cell transplantation because their pathogenesis is complex. Therefore, it should be developed a novel therapy considering the pathophysiology. We focused on migration of bone marrow-derived cell (BMDC)s to pathological lesion step by step with disease progression. We devised to apply this phenomenon, namely cell migration and targeting, to therapeutic strategy.
As application of cell migration, bone marrow transplantation was performed for the treatment of ALS mice. BMDCs migrated to the spinal cord and delayed disease progression, and this effect was enhanced by stem cell factor. Furthermore, we show other strategies with mesenchymal stem cells expressing growth factors transduced by human artificial chromosome vectors and with BMDCs as gene delivery carrier to target tissues.
As application of cell targeting, we have identified tissue specific peptides for dorsal root ganglion, microglia or astrocytes. And their peptides were incorporated into viral vectors or the complexes with therapeutic oligonucleotides to develop a novel therapy.
The combination of cell migration and targeting is a very useful tool for novel molecular therapy of neuronal diseases. This strategy is expected to have high therapeutic potential because therapeutic genes are targeted to specific cells and rescue cells gradually accumulate in pathological lesion as much as diseases progress.
