Cellavita Pesquisas Científicas Ltda., Valinhos 13271-650, SP, Brazil.
Genetics Laboratory, Instituto Butantan, São Paulo 05503-900, SP, Brazil.
Cells. 2022 May 17;11(10):1664. doi: 10.3390/cells11101664.
Huntington's disease (HD) is a neurodegenerative inherited genetic disorder, which leads to the onset of motor, neuropsychiatric and cognitive disturbances. HD is characterized by the loss of gamma-aminobutyric acid (GABA)ergic medium spiny neurons (MSNs). To date, there is no treatment for HD. Mesenchymal stem cells (MSCs) provide a substantial therapeutic opportunity for the HD treatment. Herein, we investigated the therapeutic potential of human immature dental pulp stem cells (hIDPSC), a special type of MSC originated from the neural crest, for HD treatment. Two different doses of hIDPSC were intravenously administrated in a subacute 3-nitropropionic acid (3NP)-induced rat model. We demonstrated hIDPSC homing in the striatum, cortex and subventricular zone using specific markers for human cells. Thirty days after hIDPSC administration, the cells found in the brain are still express hallmarks of undifferentiated MSC. Immunohistochemistry quantities analysis revealed a significant increase in the number of BDNF, DARPP32 and D2R positive stained cells in the striatum and cortex in the groups that received hIDPSC. The differences were more expressive in animals that received only one administration of hIDPSC. Altogether, these data suggest that the intravenous administration of hIDPSCs can restore the BDNF, DARPP32 and D2R expression, promoting neuroprotection and neurogenesis.
亨廷顿病(HD)是一种神经退行性遗传疾病,会导致运动、神经精神和认知障碍。HD 的特征是γ-氨基丁酸(GABA)能中间神经元(MSNs)的丧失。迄今为止,尚无治疗 HD 的方法。间充质干细胞(MSCs)为 HD 治疗提供了重要的治疗机会。在此,我们研究了来源于神经嵴的特殊 MSC 类型——人未成熟牙髓干细胞(hIDPSC)治疗 HD 的潜力。两种不同剂量的 hIDPSC 通过静脉注射入亚急性 3-硝基丙酸(3NP)诱导的大鼠模型中。我们使用人类细胞的特异性标记物证明了 hIDPSC 归巢到纹状体、皮质和侧脑室下区。hIDPSC 给药 30 天后,在大脑中发现的细胞仍表达未分化 MSC 的特征。免疫组织化学数量分析显示,在接受 hIDPSC 治疗的组中,纹状体和皮质中 BDNF、DARPP32 和 D2R 阳性染色细胞的数量显著增加。仅接受一次 hIDPSC 给药的动物差异更明显。总的来说,这些数据表明静脉内给予 hIDPSCs 可以恢复 BDNF、DARPP32 和 D2R 的表达,从而促进神经保护和神经发生。