Development of novel bone marrow transplantation for treatment of CNS disorders in lysosomal disease.

为了评估骨髓（BM）细胞在治疗神经系统疾病中的作用，我们检测了表达同源盒B4 （HoxB4）基因的BM细胞通过移植治疗异色性脑白质营养不良（MLD）小鼠的有效性。在移植hoxb4转导的骨髓细胞（B4MLD）的MLD小鼠的大脑中，与移植gfp转导的骨髓细胞（MIGMLD）相比，供体细胞数量增加。在该小鼠模型中，移植过表达HoxB4的骨髓细胞似乎可以有效地阻止MLD的进展。这些发现支持了这样一种观点，即用HoxB4表达载体转导的造血干细胞（hsc）可以作为治疗性蛋白的有效载体进入大脑，用于少突胶质细胞的再生，以治疗脱髓鞘疾病，如MLD、Krabbe病和多发性硬化症。

To evaluate the contribution of bone marrow (BM) cells to treat neurological disorders, we examined the effectiveness of BM cells expressing the homeobox B4 (HoxB4) gene to cure mice with metachromatic leukodystrophy (MLD) through transplantation. Increased number of donor cells was observed in brains of the MLD mice transplanted with HoxB4-transduced BM cells (B4MLD) in contrast to those transplanted with control GFP-transduced BM cells (MIGMLD). Transplantation of BM cells overexpressing HoxB4 appears to effectively prevent the progression of MLD in this mouse model. These findings support the idea that hematopoietic stem cells (HSCs) transduced with a HoxB4 expression vector could be useful carriers of therapeutic proteins into the brain for regeneration of oligodendrocytes to treat such demyelinating disorders as MLD, Krabbe disease and multiple sclerosis.