Physiology Department, Parkinson's Disease and Sleep Neurophysiology Lab, Universidade Federal do Paraná (UFPR), Curitiba, Brazil.
Core for Cell Technology, School of Medicine and Life Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil.
Cytotherapy. 2024 Sep;26(9):1052-1061. doi: 10.1016/j.jcyt.2024.04.068. Epub 2024 Apr 27.
In recent years, dental pulp stromal cells (DPSCs) have emerged as a promising therapeutic approach for Parkinson's disease (PD), owing to their inherent neurogenic potential and the lack of neuroprotective treatments for this condition. However, uncertainties persist regarding the efficacy of these cells in an undifferentiated state versus a neuronally-induced state. This study aims to delineate the distinct therapeutic potential of uninduced and neuronally-induced DPSCs in a rodent model of PD induced by 6-Hydroxydopamine (6-OHDA).
DPSCs were isolated from human teeth, characterized as mesenchymal stromal cells, and induced to neuronal differentiation. Neuronal markers were assessed before and after induction. DPSCs were transplanted into the substantia nigra pars compacta (SNpc) of rats 7 days following the 6-OHDA lesion. In vivo tracking of the cells, evaluation of locomotor behavior, dopaminergic neuron survival, and the expression of essential proteins within the dopaminergic system were conducted 7 days postgrafting.
Isolated DPSCs exhibited typical characteristics of mesenchymal stromal cells and maintained a normal karyotype. DPSCs consistently expressed neuronal markers, exhibiting elevated expression of βIII-tubulin following neuronal induction. Results from the animal model showed that both DPSC types promoted substantial recovery in dopaminergic neurons, correlating with enhanced locomotion. Additionally, neuronally-induced DPSCs prevented GFAP elevation, while altering DARPP-32 phosphorylation states. Conversely, uninduced DPSCs reduced JUN levels. Both DPSC types mitigated the elevation of glycosylated DAT.
Our results suggested that uninduced DPSCs and neuronally-induced DPSCs exhibit potential in reducing dopaminergic neuron loss and improving locomotor behavior, but their underlying mechanisms differ.
近年来，牙髓基质细胞（DPSCs）作为治疗帕金森病（PD）的一种有前途的治疗方法而出现，这是由于其内在的神经发生潜力以及缺乏针对这种疾病的神经保护治疗。然而，对于这些细胞在未分化状态与神经元诱导状态下的疗效仍存在不确定性。本研究旨在阐明未诱导和神经元诱导的 DPSCs 在 6-羟多巴胺（6-OHDA）诱导的 PD 啮齿动物模型中的不同治疗潜力。
从人牙中分离 DPSCs，鉴定为间充质基质细胞，并诱导其向神经元分化。在诱导前后评估神经元标志物。在 6-OHDA 损伤后 7 天，将 DPSCs 移植到大鼠的黑质致密部（SNpc）中。在移植后 7 天，对细胞进行体内追踪，评估运动行为，多巴胺能神经元存活以及多巴胺能系统内关键蛋白的表达。
分离的 DPSCs 表现出间充质基质细胞的典型特征，并保持正常核型。DPSCs 始终表达神经元标志物，在神经元诱导后βIII-微管蛋白表达升高。动物模型的结果表明，两种类型的 DPSCs 均促进多巴胺能神经元的大量恢复，与运动增强相关。此外，神经元诱导的 DPSCs 可防止 GFAP 升高，同时改变 DARPP-32 磷酸化状态。相反，未诱导的 DPSCs 可降低 JUN 水平。两种类型的 DPSCs 均可减轻糖基化 DAT 的升高。
我们的结果表明，未诱导的 DPSCs 和神经元诱导的 DPSCs 在减少多巴胺能神经元丢失和改善运动行为方面具有潜力，但它们的潜在机制不同。
