Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea.
Stem Cells. 2010 Feb;28(2):329-43. doi: 10.1002/stem.277.
Alzheimer's disease (AD) is characterized by the deposition of amyloid-beta peptide (Abeta) and the formation of neurofibrillary tangles. Transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) has been suggested as a potential therapeutic approach to prevent various neurodegenerative disorders, including AD. However, the actual therapeutic impact of BM-MSCs and their mechanism of action in AD have not yet been ascertained. The aim of this study was therefore to evaluate the therapeutic effect of BM-MSC transplantation on the neuropathology and memory deficits in amyloid precursor protein (APP) and presenilin one (PS1) double-transgenic mice. Here we show that intracerebral transplantation of BM-MSCs into APP/PS1 mice significantly reduced amyloid beta-peptide (Abeta) deposition. Interestingly, these effects were associated with restoration of defective microglial function, as evidenced by increased Abeta-degrading factors, decreased inflammatory responses, and elevation of alternatively activated microglial markers. Furthermore, APP/PS1 mice treated with BM-MSCs had decreased tau hyperphosphorylation and improved cognitive function. In conclusion, BM-MSCs can modulate immune/inflammatory responses in AD mice, ameliorate their pathophysiology, and improve the cognitive decline associated with Abeta deposits. These results demonstrate that BM-MSCs are a potential new therapeutic agent for AD.
阿尔茨海默病（AD）的特征是淀粉样β肽（Abeta）的沉积和神经原纤维缠结的形成。骨髓间充质干细胞（BM-MSCs）的移植已被提议作为预防各种神经退行性疾病，包括 AD 的潜在治疗方法。然而，BM-MSCs 的实际治疗效果及其在 AD 中的作用机制尚未确定。因此，本研究旨在评估 BM-MSC 移植对 APP 和早老素 1（PS1）双转基因小鼠神经病理学和记忆缺陷的治疗效果。在这里，我们表明，将 BM-MSCs 脑内移植到 APP/PS1 小鼠中可显著减少淀粉样β肽（Abeta）的沉积。有趣的是，这些效果与受损小胶质细胞功能的恢复有关，这表现为 Abeta 降解因子的增加、炎症反应的减少和替代激活的小胶质细胞标志物的升高。此外，用 BM-MSCs 治疗的 APP/PS1 小鼠 tau 过度磷酸化减少，认知功能改善。总之，BM-MSCs 可以调节 AD 小鼠的免疫/炎症反应，改善其病理生理学，并改善与 Abeta 沉积相关的认知下降。这些结果表明，BM-MSCs 是 AD 的一种有潜力的新治疗剂。
