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Calcium Folate Nanoparticles as Dual-Functional Neural Inducing Factors to Promote the Differentiation of Neural Stem Cells into Cholinergic Neurons
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2023-03-27 , DOI: 10.1002/adfm.202208835 Liang Wang 1 , Wenjuan Zhou 2 , Hongru Yang 1 , Feng Liu 1 , Ying Kong 1 , Wenhan Wang 1 , Hang Zhao 1 , Wenjun Ma 1 , Yuanhua Sang 1 , Fan Yi 3 , Hong Liu 1, 4 , Chao Liu 5 , Aijun Hao 2 , Jichuan Qiu 1
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2023-03-27 , DOI: 10.1002/adfm.202208835 Liang Wang 1 , Wenjuan Zhou 2 , Hongru Yang 1 , Feng Liu 1 , Ying Kong 1 , Wenhan Wang 1 , Hang Zhao 1 , Wenjun Ma 1 , Yuanhua Sang 1 , Fan Yi 3 , Hong Liu 1, 4 , Chao Liu 5 , Aijun Hao 2 , Jichuan Qiu 1
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Alzheimer's disease (AD) features the loss of cholinergic neurons in the mesopontine area. There is no available approach to repair the damaged cholinergic neurons. Neural stem cell (NSC)-based therapy is a promising strategy for the treatment of AD. However, it is a challenge to direct the NSCs to specifically differentiate into cholinergic neurons. Herein, calcium folate (CaFO) nanoparticles are synthesized through a facile nanoprecipitation approach for promoting the differentiation of NSCs into functional cholinergic neurons. After uptake by NSCs, the CaFO nanoparticles are distributed in the lysosomes (pH< 5.5) and can be decomposed into Ca2+ and folic acid in the acidic environment. The Ca2+ can accelerate the differentiation rate of NSCs while the folic acid can direct the NSCs to differentiate into cholinergic neurons. The in vitro experiments demonstrate that under the stimulation of CaFO nanoparticles, the NSCs differentiate into functional cholinergic neurons within 5 d. Animal experiments prove that the CaFO nanoparticles also promote the neuronal differentiation of NSCs in vivo, leading to the improvement in the cognitive memory ability of AD mice. This study provides a new strategy to induce the quick differentiation of NSCs into functional cholinergic neurons, which is promising for the treatment of AD.
中文翻译：
Calcium Folate Nanoparticles as Dual-Functional Neural Inducing Factors to Promote the Differentiation of Neural Stem Cells into Cholinergic Neurons,叶酸钙纳米颗粒作为双功能神经诱导因子促进神经干细胞分化为胆碱能神经元
Alzheimer's disease (AD) features the loss of cholinergic neurons in the mesopontine area. There is no available approach to repair the damaged cholinergic neurons. Neural stem cell (NSC)-based therapy is a promising strategy for the treatment of AD. However, it is a challenge to direct the NSCs to specifically differentiate into cholinergic neurons. Herein, calcium folate (CaFO) nanoparticles are synthesized through a facile nanoprecipitation approach for promoting the differentiation of NSCs into functional cholinergic neurons. After uptake by NSCs, the CaFO nanoparticles are distributed in the lysosomes (pH< 5.5) and can be decomposed into Ca2+ and folic acid in the acidic environment. The Ca2+ can accelerate the differentiation rate of NSCs while the folic acid can direct the NSCs to differentiate into cholinergic neurons. The in vitro experiments demonstrate that under the stimulation of CaFO nanoparticles, the NSCs differentiate into functional cholinergic neurons within 5 d. Animal experiments prove that the CaFO nanoparticles also promote the neuronal differentiation of NSCs in vivo, leading to the improvement in the cognitive memory ability of AD mice. This study provides a new strategy to induce the quick differentiation of NSCs into functional cholinergic neurons, which is promising for the treatment of AD.,阿尔茨海默病 (AD) 的特点是中脑桥区域胆碱能神经元的丧失。没有可用的方法来修复受损的胆碱能神经元。基于神经干细胞（NSC）的疗法是治疗 AD 的一种有前途的策略。然而，引导 NSC 特异性分化为胆碱能神经元是一个挑战。在此，通过简单的纳米沉淀方法合成了叶酸钙（CaFO）纳米颗粒，用于促进 NSC 分化为功能性胆碱能神经元。CaFO纳米颗粒被NSCs摄取后分布在溶酶体（pH<5.5）中，在酸性环境中可分解为Ca 2+和叶酸。钙2+叶酸可以加速NSCs的分化速度，而叶酸可以指导NSCs分化为胆碱能神经元。体外实验表明，在CaFO纳米颗粒的刺激下，NSCs在5 d内分化为功能性胆碱能神经元。动物实验证明，CaFO纳米颗粒还能促进体内NSCs的神经元分化，从而改善AD小鼠的认知记忆能力。该研究提供了诱导NSCs快速分化为功能性胆碱能神经元的新策略，有望用于治疗AD。
更新日期：2023-03-27
中文翻译：
Calcium Folate Nanoparticles as Dual-Functional Neural Inducing Factors to Promote the Differentiation of Neural Stem Cells into Cholinergic Neurons,叶酸钙纳米颗粒作为双功能神经诱导因子促进神经干细胞分化为胆碱能神经元
Alzheimer's disease (AD) features the loss of cholinergic neurons in the mesopontine area. There is no available approach to repair the damaged cholinergic neurons. Neural stem cell (NSC)-based therapy is a promising strategy for the treatment of AD. However, it is a challenge to direct the NSCs to specifically differentiate into cholinergic neurons. Herein, calcium folate (CaFO) nanoparticles are synthesized through a facile nanoprecipitation approach for promoting the differentiation of NSCs into functional cholinergic neurons. After uptake by NSCs, the CaFO nanoparticles are distributed in the lysosomes (pH< 5.5) and can be decomposed into Ca2+ and folic acid in the acidic environment. The Ca2+ can accelerate the differentiation rate of NSCs while the folic acid can direct the NSCs to differentiate into cholinergic neurons. The in vitro experiments demonstrate that under the stimulation of CaFO nanoparticles, the NSCs differentiate into functional cholinergic neurons within 5 d. Animal experiments prove that the CaFO nanoparticles also promote the neuronal differentiation of NSCs in vivo, leading to the improvement in the cognitive memory ability of AD mice. This study provides a new strategy to induce the quick differentiation of NSCs into functional cholinergic neurons, which is promising for the treatment of AD.,阿尔茨海默病 (AD) 的特点是中脑桥区域胆碱能神经元的丧失。没有可用的方法来修复受损的胆碱能神经元。基于神经干细胞（NSC）的疗法是治疗 AD 的一种有前途的策略。然而，引导 NSC 特异性分化为胆碱能神经元是一个挑战。在此，通过简单的纳米沉淀方法合成了叶酸钙（CaFO）纳米颗粒，用于促进 NSC 分化为功能性胆碱能神经元。CaFO纳米颗粒被NSCs摄取后分布在溶酶体（pH<5.5）中，在酸性环境中可分解为Ca 2+和叶酸。钙2+叶酸可以加速NSCs的分化速度，而叶酸可以指导NSCs分化为胆碱能神经元。体外实验表明，在CaFO纳米颗粒的刺激下，NSCs在5 d内分化为功能性胆碱能神经元。动物实验证明，CaFO纳米颗粒还能促进体内NSCs的神经元分化，从而改善AD小鼠的认知记忆能力。该研究提供了诱导NSCs快速分化为功能性胆碱能神经元的新策略，有望用于治疗AD。
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