Laboratory of Neuroscience, Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Sackler Faculty of Medicine, Tel Aviv University, Petach Tikva, Israel.
Transl Psychiatry. 2011 Dec 13;1(12):e61. doi: 10.1038/tp.2011.64.
Stem cell-based regenerative therapy is considered a promising cellular therapeutic approach for the patients with incurable brain diseases. Mesenchymal stem cells (MSCs) represent an attractive cell source for regenerative medicine strategies for the treatment of the diseased brain. Previous studies have shown that these cells improve behavioral deficits in animal models of neurological disorders such as Parkinson's and Huntington's diseases. In the current study, we examined the capability of intracerebral human MSCs transplantation (medial pre-frontal cortex) to prevent the social impairment displayed by mice after withdrawal from daily phencyclidine (PCP) administration (10 mg kg(-1) daily for 14 days). Our results show that MSCs transplantation significantly prevented the PCP-induced social deficit, as assessed by the social preference test. In contrast, the PCP-induced social impairment was not modified by daily clozapine treatment. Tissue analysis revealed that the human MSCs survived in the mouse brain throughout the course of the experiment (23 days). Significantly increased cortical brain-derived neurotrophic factor levels were observed in the MSCs-treated group as compared with sham-operated controls. Furthermore, western blot analysis revealed that the ratio of phosphorylated Akt to Akt was significantly elevated in the MSCs-treated mice compared with the sham controls. Our results demonstrate that intracerebral transplantation of MSCs is beneficial in attenuating the social deficits induced by sub-chronic PCP administration. We suggest a novel therapeutic approach for the treatment of schizophrenia-like negative symptoms in animal models of the disorder.
基于干细胞的再生疗法被认为是一种有前途的细胞治疗方法，可用于治疗无法治愈的脑部疾病患者。间充质干细胞（MSCs）是治疗脑部疾病的再生医学策略中一种有吸引力的细胞来源。先前的研究表明，这些细胞可以改善帕金森病和亨廷顿病等神经紊乱动物模型中的行为缺陷。在当前的研究中，我们检查了脑内人 MSCs 移植（额前皮质）的能力，以防止每日苯环己哌啶（PCP）给药后（14 天，每天 10mg/kg）小鼠出现社交障碍。我们的结果表明，MSCs 移植可显著预防 PCP 诱导的社交缺陷，如社交偏好测试所评估的。相比之下，每日氯氮平治疗并不能改变 PCP 诱导的社交障碍。组织分析显示，人 MSCs 在整个实验过程中（23 天）都在小鼠大脑中存活。与假手术对照组相比，在 MSCs 治疗组中观察到皮质脑源性神经营养因子水平显著升高。此外，Western blot 分析显示，与假手术对照组相比，MSCs 治疗的小鼠中磷酸化 Akt 与 Akt 的比值显著升高。我们的结果表明，脑内 MSCs 移植有益于减轻亚慢性 PCP 给药引起的社交缺陷。我们提出了一种治疗该疾病动物模型中类似精神分裂症阴性症状的新治疗方法。
