Mechanisms and research progress of mesenchymal stem cells in improving postoperative cognitive dysfunction

doi:10.3877/cma.j.issn.2095-1221.2026.01.006

Abstract

Abstract:

Postoperative cognitive dysfunction (POCD) is a common central nervous system complication in elderly patients following surgery, primarily characterized by cognitive impairments such as memory decline, inattention, and reduced executive function. Currently, there is a lack of effective clinical strategies for its prevention and treatment. Mesenchymal stem cells (MSCs) have garnered widespread attention in the intervention of neurodegenerative and injury-related neurological diseases due to their multi-lineage differentiation potential and significant paracrine effects. This review systematically elucidates the core mechanisms by which MSCs prevent and treat POCD, with a focus on summarizing their therapeutic potential through multiple pathways including immunomodulation, neurotrophic support, alleviation of oxidative stress, and repair of the blood-brain barrier. It also analyzes the selection of MSCs sources, administration strategies, and preclinical research evidence. Furthermore, the review outlines future directions, such as optimization through cellular engineering techniques, to advance MSCs as a novel and effective therapeutic approach for POCD prevention and treatment.

Key words: Mesenchymal stem cells, Postoperative cognitive dysfunction, Therapy, Clinical research

Lizheng Huang, Yuqian Wang, Jinlan Jiang, Fanglei Han. Mechanisms and research progress of mesenchymal stem cells in improving postoperative cognitive dysfunction[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2026, 16(01): 45-51.

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References 74

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模型	MSCs类型	给药途径	主要效果	参考文献
体外循环的大鼠	AMSCs	尾静脉	通过TLR2/4信号激动剂干预，外泌体组大鼠的游泳距离和停留时间有所改善（P < 0.05）。且在CPB组大鼠中TLR2、TLR4、MyD88和NF-κB的mRNA和蛋白质表达增加（P < 0.05），AMSCs的外泌体补充剂则抑制这一增长，来改善CPB大鼠的认知功能	Yang等^[66]
肝左叶切除术的小鼠	MSCs-CM	尾静脉	MSCs-CM治疗可以逆转对照组中脑IL-1β、IL-6、TNF-α、丙二醛水平升高和BDNF表达减少等变化（P < 0.05），进而改善小鼠认知功能	Jiang等^[48]
AD大鼠	BUMSC-CM	腹腔注射	BUMSC-CM具有神经保护潜力，通过上调BDNF和NGF，同时下调IL-1β和TNF-α，使AD大鼠接受治疗后的海马区神经元数量增加，进而降低神经退行性疾病的发病风险	Wihadmadyatami等^[67]
AD小鼠	BMSC	尾静脉	MSCs可以提高内皮型一氧化氮合酶（eNOS）水平，且eNOS及炎症标志物酶联免疫吸附测定（ELISA）结果显示，治疗组与未治疗组之间差异有统计学意义（P < 0.01），证实MSCs减轻血管性痴呆的积极作用	Lee等^[68]
AD小鼠	iPSC-MSC-sEVs	小脑延髓池注射	小鼠大脑皮层及海马区神经元数量较假手术组明显减少，而iPSC-MSC-sEVs可通过抑制链脲佐菌素诱导的散发性小鼠模型（sAD）中NLRP3/GSDMD相关的神经炎症，减少淀粉样蛋白沉积与神经元细胞凋亡（P < 0.05）从而减轻认知损伤	Lin等^[69]
肝损伤的大鼠	AdMSC	静脉注射	MSC-EVs治疗大鼠通过小胶质细胞激活以及提升TNF-α和IL-1β水平，增强了物体位置记忆，在径向迷宫中提升了工作记忆和学习指数，与对照组差异有统计学意义（P < 0.05）。同时也可以使轻度肝损伤大鼠的NR2B膜表达正常化，改善工作记忆障碍	Mincheva等^[70]
SAE小鼠	MSCs-exo	尾静脉	MSCs-exo可以提高脂多糖诱导的细胞中的谷胱甘肽水平，同时其介导的miR-140-3p递送可通过调控HMGB1及S-乳酰谷胱甘肽代谢途径（P < 0.05），改善SAE小鼠的认知功能障碍	Ma等^[71]

模型	MSCs类型	给药途径	主要效果	参考文献
体外循环的大鼠	AMSCs	尾静脉	通过TLR2/4信号激动剂干预，外泌体组大鼠的游泳距离和停留时间有所改善（P < 0.05）。且在CPB组大鼠中TLR2、TLR4、MyD88和NF-κB的mRNA和蛋白质表达增加（P < 0.05），AMSCs的外泌体补充剂则抑制这一增长，来改善CPB大鼠的认知功能	Yang等^[66]
肝左叶切除术的小鼠	MSCs-CM	尾静脉	MSCs-CM治疗可以逆转对照组中脑IL-1β、IL-6、TNF-α、丙二醛水平升高和BDNF表达减少等变化（P < 0.05），进而改善小鼠认知功能	Jiang等^[48]
AD大鼠	BUMSC-CM	腹腔注射	BUMSC-CM具有神经保护潜力，通过上调BDNF和NGF，同时下调IL-1β和TNF-α，使AD大鼠接受治疗后的海马区神经元数量增加，进而降低神经退行性疾病的发病风险	Wihadmadyatami等^[67]
AD小鼠	BMSC	尾静脉	MSCs可以提高内皮型一氧化氮合酶（eNOS）水平，且eNOS及炎症标志物酶联免疫吸附测定（ELISA）结果显示，治疗组与未治疗组之间差异有统计学意义（P < 0.01），证实MSCs减轻血管性痴呆的积极作用	Lee等^[68]
AD小鼠	iPSC-MSC-sEVs	小脑延髓池注射	小鼠大脑皮层及海马区神经元数量较假手术组明显减少，而iPSC-MSC-sEVs可通过抑制链脲佐菌素诱导的散发性小鼠模型（sAD）中NLRP3/GSDMD相关的神经炎症，减少淀粉样蛋白沉积与神经元细胞凋亡（P < 0.05）从而减轻认知损伤	Lin等^[69]
肝损伤的大鼠	AdMSC	静脉注射	MSC-EVs治疗大鼠通过小胶质细胞激活以及提升TNF-α和IL-1β水平，增强了物体位置记忆，在径向迷宫中提升了工作记忆和学习指数，与对照组差异有统计学意义（P < 0.05）。同时也可以使轻度肝损伤大鼠的NR2B膜表达正常化，改善工作记忆障碍	Mincheva等^[70]
SAE小鼠	MSCs-exo	尾静脉	MSCs-exo可以提高脂多糖诱导的细胞中的谷胱甘肽水平，同时其介导的miR-140-3p递送可通过调控HMGB1及S-乳酰谷胱甘肽代谢途径（P < 0.05），改善SAE小鼠的认知功能障碍	Ma等^[71]

NCT号码	日期	疾病	机制	干预/治疗	来源	主要指标	地点
NCT01309061	2008.03	进行性半侧萎缩症	利用AdMSC的"归巢"特性，通过肌肉注射进行细胞治疗	自体AdMSC移植	脂肪	脂肪层的体积变化、脂肪吸收率	韩国，首尔
NCT02497443	2011.04	癫痫	注射自体MSCs，利用其免疫调节和神经保护等作用来干预和改善难治性癫痫的疾病进程	自体MSCs注射	骨髓	临床观察和脑电图测量	白俄罗斯
NCT02987413	2015.04	肌萎缩侧索硬化症	鞘内注射递增剂量的自体MSCs，利用MSCs的治疗可塑性，来治疗肌萎缩侧索硬化症	自体MSCs鞘内输注	自体	ALS功能评定量表	巴西，圣保罗
NCT02611167	2017.11	特发性帕金森病	静脉输注不同剂量的同种异体BMSC，利用其神经保护、抗炎和免疫调节功能评估其对延缓特发性帕金森病患者疾病进展的安全性和初步有效性	不同剂量的同种异体BMSC静脉输注	骨髓	帕金森病评定量表总分评估	美国，休斯敦
NCT04388982	2020.07	阿尔茨海默病	利用同种异体脂肪间充质干细胞源外泌体，通过其内含的生物活性物质，调节阿尔茨海默病的病理过程	不同剂量的脂肪间充质干细胞源外泌体用于鼻滴漏	脂肪	阿尔茨海默病评估量表、磁共振成像神经影像学评估	中国，上海
NCT05284604	2023.01	年龄相关的衰弱	补充因衰老而耗竭的干细胞，利用MSCs的归巢和旁分泌功能来修复组织损伤和调节炎症，从而改善与年龄相关的虚弱状态	自体MSCs静脉输注	骨髓	改良体能测试，6 min步行测试	美国，休斯敦
NCT07084012	2025.08	急性缺血性中风	利用hUC-MSCs的免疫调节和组织修复功能，治疗急性缺血性中风的继发性损伤，并促进神经功能恢复	不同剂量的hUC-MSCs输注	脐带	Rankin量表评分、美国国立卫生研究院卒中量表评分	中国，北京

NCT号码	日期	疾病	机制	干预/治疗	来源	主要指标	地点
NCT01309061	2008.03	进行性半侧萎缩症	利用AdMSC的"归巢"特性，通过肌肉注射进行细胞治疗	自体AdMSC移植	脂肪	脂肪层的体积变化、脂肪吸收率	韩国，首尔
NCT02497443	2011.04	癫痫	注射自体MSCs，利用其免疫调节和神经保护等作用来干预和改善难治性癫痫的疾病进程	自体MSCs注射	骨髓	临床观察和脑电图测量	白俄罗斯
NCT02987413	2015.04	肌萎缩侧索硬化症	鞘内注射递增剂量的自体MSCs，利用MSCs的治疗可塑性，来治疗肌萎缩侧索硬化症	自体MSCs鞘内输注	自体	ALS功能评定量表	巴西，圣保罗
NCT02611167	2017.11	特发性帕金森病	静脉输注不同剂量的同种异体BMSC，利用其神经保护、抗炎和免疫调节功能评估其对延缓特发性帕金森病患者疾病进展的安全性和初步有效性	不同剂量的同种异体BMSC静脉输注	骨髓	帕金森病评定量表总分评估	美国，休斯敦
NCT04388982	2020.07	阿尔茨海默病	利用同种异体脂肪间充质干细胞源外泌体，通过其内含的生物活性物质，调节阿尔茨海默病的病理过程	不同剂量的脂肪间充质干细胞源外泌体用于鼻滴漏	脂肪	阿尔茨海默病评估量表、磁共振成像神经影像学评估	中国，上海
NCT05284604	2023.01	年龄相关的衰弱	补充因衰老而耗竭的干细胞，利用MSCs的归巢和旁分泌功能来修复组织损伤和调节炎症，从而改善与年龄相关的虚弱状态	自体MSCs静脉输注	骨髓	改良体能测试，6 min步行测试	美国，休斯敦
NCT07084012	2025.08	急性缺血性中风	利用hUC-MSCs的免疫调节和组织修复功能，治疗急性缺血性中风的继发性损伤，并促进神经功能恢复	不同剂量的hUC-MSCs输注	脐带	Rankin量表评分、美国国立卫生研究院卒中量表评分	中国，北京

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