Intra-bone marrow-bone marrow transplantation slows disease progression and prolongs survival in G93A mutant SOD1 transgenic mice, an animal model mouse for amyotrophic lateral sclerosis.
It has been reported that bone marrow transplantation (BMT) has clinical effects on not only hematopoietic diseases and autoimmune diseases but also solid malignant tumors and metabolic diseases. We have found that intra-bone marrow-bone marrow transplantation (IBM-BMT) is superior to conventional intravenous BMT, since IBM-BMT enables rapid recovery of donor hematopoiesis and reduces the extent of graft-versus-host disease (GVHD). In this experiment, we examined the effects of IBM-BMT on symptomatic G93A mutant SOD1 transgenic mice (mSOD1 Tg mice), a model mouse line for amyotrophic lateral sclerosis (ALS). Symptomatic mSOD1 Tg mice (12 weeks old) were irradiated with 6Gyx2 at a 4-hour interval, one day before IBM-BMT. The mice were transplanted with bone marrow cells (BMCs) from 12-wk-old eGFP-transgenic C57BL/6 mice (eGFP Tg mice) or BMCs from 12-wk-old mSOD1 Tg mice. The ALS model mice transplanted with BMCs from eGFP Tg mice showed longer survival and slower disease progression than those transplanted with BMCs from mSOD1 Tg mice or untreated mSOD1 Tg mice. There was a significantly high number of eGFP(+) cells in the anterior horn of the spinal cord of the mSOD1 Tg mice transplanted with BMCs of eGFP Tg mice, some of which expressed Iba-1, a marker of microglia, although they did not differentiate into neural cells. These results suggest that the replacement with normal hematopoietic cells improved the neural cell environment, thereby slowing the progression of the disease.
Ohnishi
Shizuo
S
Department of Neurology, Kansai Medical University, Moriguchi City, Osaka, Japan.
Ito
Hidefumi
H
Suzuki
Yasuhiro
Y
Adachi
Yasushi
Y
Wate
Reika
R
Zhang
Jianhua
J
Nakano
Satoshi
S
Kusaka
Hirofumi
H
Ikehara
Susumu
S
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000503:physiopathology / Q000601:surgery*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D001842:Bone and Bones / Q000601:surgery*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D020125:Mutation, Missense; D009474:Neurons / Q000502:physiology; D011897:Random Allocation; D013116:Spinal Cord / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013997:Time Factors; D016896:Treatment Outcome
C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1