Amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease with complex pathophysiology, for which no effective curative treatment has yet been found. In ALS mouse models, it has been demonstrated that a subset of bone marrow-derived cells (BMDCs) accumulates at the lesion site in the spinal cord after bone marrow transplantation (BMT). Bone marrow cells, especially stem cells, have the inherent ability to migrate to damaged neural tissues and have the potential to be promising carriers for delivering therapeutic genes to the target. Therefore, bone marrow cells can be used as a regenerative therapy and as a carrier to deliver the therapeutic genes, and can be utilized as a new treatment for ALS. Glutamate transporter 1 (GLT1), which plays an important role in maintaining glutamate homeostasis, has been reported to have the effect of delaying the progression of several neurodegenerative diseases. Based on these findings, we have developed a new therapeutic strategy for ALS that utilizes induced migration of bone marrow dendritic cells (BMDCs) as gene carriers for cell-based gene therapy. This method is likely to be applicable for other therapeutic gene delivery therapies. In this chapter, we will explain a cell-based gene delivery method that combines bone marrow cells and gene therapy by introducing a gene delivery system that takes advantage of the accumulation of bone marrow-derived cells at the lesion site in ALS mice.

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Bone Marrow-Derived Cells with GLT1 Gene Delivery for Amyotrophic Lateral Sclerosis

  • Natsuko Ohashi,
  • Tomoya Terashima

摘要

Amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease with complex pathophysiology, for which no effective curative treatment has yet been found. In ALS mouse models, it has been demonstrated that a subset of bone marrow-derived cells (BMDCs) accumulates at the lesion site in the spinal cord after bone marrow transplantation (BMT). Bone marrow cells, especially stem cells, have the inherent ability to migrate to damaged neural tissues and have the potential to be promising carriers for delivering therapeutic genes to the target. Therefore, bone marrow cells can be used as a regenerative therapy and as a carrier to deliver the therapeutic genes, and can be utilized as a new treatment for ALS. Glutamate transporter 1 (GLT1), which plays an important role in maintaining glutamate homeostasis, has been reported to have the effect of delaying the progression of several neurodegenerative diseases. Based on these findings, we have developed a new therapeutic strategy for ALS that utilizes induced migration of bone marrow dendritic cells (BMDCs) as gene carriers for cell-based gene therapy. This method is likely to be applicable for other therapeutic gene delivery therapies. In this chapter, we will explain a cell-based gene delivery method that combines bone marrow cells and gene therapy by introducing a gene delivery system that takes advantage of the accumulation of bone marrow-derived cells at the lesion site in ALS mice.