Journal de recherche et de thérapie en toxicomanie

Abstrait

Preparation and Characterization of Microglia-Like Cells Derived from Rat, Mouse, and Human Bone Marrow Cells for Therapeutic Strategy of Alzheimer's Disease

Kazuyuki Takata, Tetsuya Takada, Hironori Tatsuda, Tomomi Tsuruno, Kaneyasu Nishimura, Shun Shimohama and Yoshihisa Kitamura

Dementia-associated neuropsychiatric symptoms, such as depression and apathy, are core features of Alzheimer’s disease (AD). Pathological hallmarks of AD include senile plaques, neurofibrillary tangles (NFTs), and neurodegeneration. Senile plaques are composed of amyloid-β (Aβ) and are surrounded by microglia, an immune effector cells in brains. Studies on responsible genes of familial AD have suggested that Aβ accumulation is a primary event that influences other AD pathologies, and the reduction of brain Aβ has been proposed as a therapeutic target for AD. On the other hand, microglial phagocytosis has been noted as an Aβ clearance system in the brain. In this context, the transplantation of microglia prepared from bone marrow cells may contribute to the clearance of Aβ in vivo brain. As a first step for this cell therapeutic strategy, we examined the preparation of microglia-like cells from mouse, rat, and human bone marrow cells by the treatment with macrophage colony-stimulating factor (M-CSF) and analyzed their phagocytic ability. In the cultivation of bone marrow cells collected from mouse, rat, and human, adherent cells on the culture dish were markedly increased by the treatment with human M-CSF. In addition, the adherent cells from mouse bone marrow cells were more sensitive to human M-CSF than that from rat bone marrow cells and more effectively expressed microglial makers, such as cluster of differentiation (CD) 11b, Iba1, and CD68. Furthermore, we demonstrated that a part of adherent cells derived from mouse and human bone marrow cells have phagocytic abilities of iron particles and Aβ peptides, and the treatment with human M-CSF significantly increased the number of phagocytic cells. Thus, we positively suggest that the microglia-like cells prepared from bone marrow cells by the treatment with human M-CSF could be a source for the cell therapeutic strategy for AD.