Human adipose-derived stem cells partially rescue the stroke syndromes by promoting spatial learning and memory in mouse middle cerebral artery occlusion model.
Human adipose-derived stem cells partially rescue the stroke syndromes by promoting spatial learning and memory in mouse middle cerebral artery occlusion model.
复制标题
人类脂肪干细胞通过促进小鼠大脑中动脉闭塞模型的空间学习和记忆来部分挽救中风综合征
DOI：
10.1186/s13287-015-0078-1
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发表时间：
2015-05-09
影响因子：
7.5
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Zhou F;Gao S;Wang L;Sun C;Chen L;Yuan P;Zhao H;Yi Y;Qin Y;Dong Z;Cao L;Ren H;Zhu L;Li Q;Lu B;Liang A;Xu GT;Zhu H;Gao Z;Ma J;Xu J;Chen X
前言越来越多的证据使干细胞治疗作为治疗中风的新的有希望的方法走到了前列。在所有候选种子细胞中，脂肪干细胞(ADSCs)被认为是最适合治疗中风的细胞之一。然而，以往的实验数据对ADSC移植治疗卒中蛋白的疗效及其机制尚不能达成一致，这阻碍了其在临床上的进一步翻译应用。方法用表达FG12慢病毒的增强型绿色荧光蛋白标记hADSC，并将其原位注射到MCAO小鼠脑梗死区，以探讨hADSC对神经损伤的存活机制。用Rogers评分系统评定神经功能，用Morris测验测定空间学习记忆能力。用2，3，5-三苯基四氮唑氯化铵比较各组间的脑梗塞面积。组织免疫染色跟踪注射的hADSCs在移行、转分化和与内源性神经元回路的整合过程中的情况。通过对MBP、MAP2、GFAP、Iba1的小胶质细胞标志物进行qRT-PCR分析。结果hADSCs对MCAO小鼠的空间学习记忆能力有促进作用。GFP和MAP2在整个大脑皮质中共同定位，对侧皮质的比例显著高于同侧皮质(P<；0.01)。GFP和GFAP共定位细胞在整个皮质的比例较低。同时，hADSC对Iba1+小胶质细胞和GFAP+星形胶质细胞有明显的抑制作用(P<；0.05)。结论hADSC可以在体内转分化为神经元样细胞(MAP2+)，有望作为替代干细胞治疗卒中的种子细胞。此外，还发现了显著的免疫调节作用。同时，hADSCs对内源性神经元存活有明显的保护作用。本研究表明，hADSC对MCAO小鼠的干预可通过直接细胞替代、增强免疫抑制和提高内源性神经元的活性来明显改善卒中症状。
IntroductionGrowing evidence has brought stem cell therapy to the forefront as new promising approaches towards stroke treatment. Of all candidate seeding cells, adipose-derived stem cells (ADSCs) are considered as one of the most appropriate for stroke treatment. However, previous experimental data could not reach to an agreement on the efficacy of ADSC transplantation for treating strokein vivoas well as its mechanism which hinders their further clinical translational application.MethodsTo explore theirin vivomechanism of hADSC administration on neurological injury, hADSC were labeled with Enhanced Green Fluorescence Protein expressing FG12 lentivirus and injected into MCAO mouse infarct area byin situway. Neurological function was evaluated by Rogers Scaling System and their spatial learning and memory was determined by Morris Test. 2,3,5-triphenyltetrazolium chloride was carried out to compare the infarct area among groups. Histoimmunostaining was used to track the injected hADSCs for theirin vivomigration, transdifferentiation and integration with the endogenous neuronal circuitry. To better address the underlying rescuing mechanism, qRT-PCR was performed on neural markers of MBP, MAP2, GFAP, microglia marker of Iba1.ResultsIt was found that hADSCs could promote both spatial learning and memory of MCAO mice. Co-localization of GFP and MAP2 were found in the whole cortex with significantly (P<0.01) higher percentage at the contralateral cortex compared with the ipsilateral cortex. Low percentage of GFP and GFAP co-localized cells were found at whole cortex. Meanwhile, Iba1+microglia and GFAP+astrocyte cells were significantly (P<0.05) suppressed by hADSC injection.ConclusionshADSCs could transdifferentiate into neuron like cells (MAP2+)in vivoand probably used as seeding cells for replacement based stem cell therapy of stroke. Also, significant immunomodulation was found. Meanwhile hADSCs could significantly protect the endogenous neuron survival. This study demonstrated that hADSC intervention with MCAO mice could apparently ameliorate stroke symptoms by direct cell replacement, enhanced immnunosuppression and increasing the viability of endogenous neurons.
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影响因子：
2.7
作者：
Gimble JM;Bunnell BA;Guilak F
通讯作者：
Guilak F
影响因子：
7.5
作者：
Gutiérrez-Fernández M;Rodríguez-Frutos B;Ramos-Cejudo J;Teresa Vallejo-Cremades M;Fuentes B;Cerdán S;Díez-Tejedor E
通讯作者：
Díez-Tejedor E
影响因子：
5.2
作者：
Mitchell, James B.;McIntosh, Kevin;Gimble, Jeffrey M.
通讯作者：
Gimble, Jeffrey M.
影响因子：
5.2
作者：
Kern, Susanne;Eichler, Hermann;Bieback, Karen
通讯作者：
Bieback, Karen
影响因子：
4.5
作者：
Ikegame, Yuka;Yamashita, Kentaro;Iwama, Toru
通讯作者：
Iwama, Toru