Bone marrow-derived mesenchymal stem cells reduce brain amyloid-beta deposition and accelerate the activation of microglia in an acutely induced Alzheimer's disease mouse model.
The therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) has recently been explored in various pathological conditions of the central nervous system (CNS). However, the application of BM-MSCs in acutely induced Alzheimer's disease (AD) has not yet been reported. Herein the feasibility of using the BM-MSCs, as a therapeutic agent for AD has been tested. To assess this possibility, an acutely induced AD model induced by injecting amyloid-beta (Abeta) into the dentate gyrus (DG) of hippocampus of C57BL/6 mice was used. Intracerebral transplantation of BM-MSCs into the brain of an induced AD model reduced their Abeta levels when compared to sham-transplanted animals. The diminution of Abeta deposits was accompanied by the activation of microglia. In addition, the activated microglia was located near the Abeta deposits, and their morphology was changed from ramified to ameboid as a sign of microglial phagocytosis. This study provides evidence that BM-MSCs can promote the reduction of Abeta through the microglial activation in this acutely induced AD brain, suggesting a potential therapeutic agent against AD.
Lee
Jong Kil
JK
Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, South Korea.
Jin
Hee Kyung
HK
Bae
Jae-Sung
JS
D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology* / Q000601:surgery*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism*
C100745:Aif1 protein, rat; D016229:Amyloid beta-Peptides; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins