title: Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer's disease.
abstract: Stem cell transplantation therapy is currently in clinical trials for the treatment of ischemic stroke, and several beneficial aspects have been reported. Similarly, in Alzheimer's disease (AD), stem cell therapy is expected to provide an efficient therapeutic approach. Indeed, the intracerebral transplantation of stem cells reduced amyloid-β (Aβ) deposition and rescued memory deficits in AD model mice. Here, we show that intravenous transplantation of bone marrow-derived mononuclear cells (BMMCs) improves cognitive function in two different AD mouse models, DAL and APP mice, and prevents neurodegeneration. GFP-positive BMMCs were isolated from tibiae and femurs of 4-week-old mice and then transplanted intravenously into DAL and APP mice. Transplantation of BMMCs suppressed neuronal loss and restored memory impairment of DAL mice to almost the same level as in wild-type mice. Transplantation of BMMCs to APP mice reduced Aβ deposition in the brain. APP mice treated with BMMCs performed significantly better on behavioral tests than vehicle-injected mice. Moreover, the effects were observed even with transplantation after the onset of cognitive impairment in DAL mice. Together, our results indicate that intravenous transplantation of BMMCs has preventive effects against the cognitive decline in AD model mice and suggest a potential therapeutic effect of BMMC transplantation therapy.
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki-shi, Kanagawa 211-8533, Japan; Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kanamaru
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki-shi, Kanagawa 211-8533, Japan. Electronic address: nanakash@nms.ac.jp.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamimura
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki-shi, Kanagawa 211-8533, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokota
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki-shi, Kanagawa 211-8533, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nishimaki
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki-shi, Kanagawa 211-8533, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Iuchi
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki-shi, Kanagawa 211-8533, Japan.
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Pharmacology Research Laboratories, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi , Ibaraki 305-8585, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Takami
authors.affiliation: Pharmacology Research Laboratories, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi , Ibaraki 305-8585, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Akashiba
authors.affiliation: Pharmacology Research Laboratories, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi , Ibaraki 305-8585, Japan.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Shitaka
authors.affiliation: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Katsura
authors.affiliation: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki-shi, Kanagawa 211-8533, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohta
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000523:psychology / Q000628:therapy*; D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000379:methods*; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D058225:Plaque, Amyloid / Q000378:metabolism
keywords: Alzheimer’s disease; Amyloid-β; Intravenous transplantation; Mononuclear cell; Neurodegeneration