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胎盘来源的间充质样贴壁基质细胞作为大鼠模型中可卡因成瘾的有效细胞疗法

Placenta-Derived Mesenchymal-like Adherent Stromal Cells as an Effective Cell Therapy for Cocaine Addiction in a Rat Model.

作者信息

Pe'er-Nissan Hilla, Ahdoot-Levi Hadas, Betzer Oshra, Itzhak Pnina Shirel, Shraga-Heled Niva, Gispan Iris, Motiei Menachem, Doroshev Arthur, Anker Yaakov, Popovtzer Rachela, Ofir Racheli, Yadid Gal

机构信息

Neuropharmacology Laboratory, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.

The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan 5290002, Israel.

出版信息

Pharmaceutics. 2022 Jun 21;14(7):1311. doi: 10.3390/pharmaceutics14071311.

Abstract

Recent research points to mesenchymal stem cells' potential for treating neurological disorders, especially drug addiction. We examined the longitudinal effect of placenta-derived mesenchymal stromal-like cells (PLX-PAD) in a rat model for cocaine addiction. Sprague-Dawley male rats were trained to self-administer cocaine or saline daily until stable maintenance. Before the extinction phase, PLX-PAD cells were administered by intracerebroventricular or intranasal routes. Neurogenesis was evaluated, as was behavioral monitoring for craving. We labeled the PLX-PAD cells with gold nanoparticles and followed their longitudinal migration in the brain parallel to their infiltration of essential peripheral organs both by micro-CT and by inductively coupled plasma-optical emission spectrometry. Cell locations in the brain were confirmed by immunohistochemistry. We found that PLX-PAD cells attenuated cocaine-seeking behavior through their capacity to migrate to specific mesolimbic regions, homed on the parenchyma in the dentate gyrus of the hippocampus, and restored neurogenesis. We believe that intranasal cell therapy is a safe and effective approach to treating addiction and may offer a novel and efficient approach to rehabilitation.

摘要

近期研究表明间充质干细胞在治疗神经疾病,尤其是药物成瘾方面具有潜力。我们在大鼠可卡因成瘾模型中研究了胎盘来源的间充质基质样细胞(PLX-PAD)的长期效应。将斯普拉格-道利雄性大鼠训练至每日自行注射可卡因或生理盐水,直至稳定维持状态。在消退期前,通过脑室内或鼻内途径给予PLX-PAD细胞。评估神经发生情况,并对渴望进行行为监测。我们用金纳米颗粒标记PLX-PAD细胞,并通过微型计算机断层扫描(micro-CT)和电感耦合等离子体发射光谱法跟踪它们在大脑中的长期迁移及其向重要外周器官的浸润情况。通过免疫组织化学确定细胞在大脑中的位置。我们发现,PLX-PAD细胞通过迁移至特定的中脑边缘区域、归巢于海马齿状回的实质组织并恢复神经发生的能力,减弱了对可卡因的寻求行为。我们认为,鼻内细胞疗法是一种安全有效的成瘾治疗方法,可能为康复提供一种新颖且高效的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b59c/9324501/7ddb3b2fb90c/pharmaceutics-14-01311-g003a.jpg

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