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人脱落乳牙干细胞移植通过减少大鼠神经元凋亡减轻慢性脑缺血所致的认知障碍

Transplantation of Stem Cells from Human Exfoliated Deciduous Teeth Decreases Cognitive Impairment from Chronic Cerebral Ischemia by Reducing Neuronal Apoptosis in Rats.

作者信息

Zhu Shu, Min Dongyu, Zeng Jianhong, Ju Yetao, Liu Yao, Chen Xu

机构信息

Department of Pediatric Dentistry, School of Stomatology, China Medical University, Shenyang 110002, China.

Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110002, China.

出版信息

Stem Cells Int. 2020 Mar 6;2020:6393075. doi: 10.1155/2020/6393075. eCollection 2020.

Abstract

Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population with high self-renewal ability that originates from the cranial neural crest. Since SHED are homologous to the central nervous system, they possess superior capacity to differentiate into neural cells. However, whether and how SHED ameliorate degenerative central nervous disease are unclear. Chronic cerebral ischemia (CCI) is a kind of neurological disease caused by long-term cerebral circulation insufficiency and is characterized by progressive cognitive and behavioral deterioration. In this study, we showed that either systemic transplantation of SHED or SHED infusion into the hippocampus ameliorated cognitive impairment of CCI rats in four weeks after SHED treatment by rescuing the number of neurons in the hippocampus area. Mechanistically, SHED transplantation decreased the apoptosis of neuronal cells in the hippocampus area of CCI rats through downregulation of cleaved caspase-3. In summary, SHED transplantation protected the neuronal function and reduced neuronal apoptosis, resulting in amelioration of cognitive impairment from CCI. Our findings suggest that SHED are a promising stem cell source for cell therapy of neurological diseases in the clinic.

摘要

人乳牙脱落干细胞(SHED)是一种独特的出生后干细胞群体,具有高自我更新能力,起源于颅神经嵴。由于SHED与中枢神经系统同源,它们具有分化为神经细胞的卓越能力。然而,SHED是否以及如何改善退行性中枢神经疾病尚不清楚。慢性脑缺血(CCI)是一种由长期脑循环不足引起的神经疾病,其特征是进行性认知和行为恶化。在本研究中,我们表明,无论是SHED的全身移植还是将SHED注入海马体,在SHED治疗四周后,均可通过挽救海马区神经元数量来改善CCI大鼠的认知障碍。从机制上讲,SHED移植通过下调裂解的半胱天冬酶-3来减少CCI大鼠海马区神经元细胞的凋亡。总之,SHED移植保护了神经元功能并减少了神经元凋亡,从而改善了CCI引起的认知障碍。我们的研究结果表明,SHED是临床上用于神经疾病细胞治疗的一种很有前景的干细胞来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f54/7079222/2d19a45a0862/SCI2020-6393075.001.jpg

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