Brain Research Institute, School of Medicine and Health Sciences, Monash University, Sunway Campus, Selangor 47500, Malaysia.
Anatomy Unit, Faculty of Medicine, AIMST University, Semeling, Bedong, Kedah 08100, Malaysia.
Int J Mol Sci. 2019 Jan 29;20(3):568. doi: 10.3390/ijms20030568.
Parkinson's disease (PD) is a neurodegenerative disorder defined by progressive deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Dental pulp stem cells (DPSCs) have been proposed to replace the degenerated dopaminergic neurons due to its inherent neurogenic and regenerative potential. However, the effective delivery and homing of DPSCs within the lesioned brain has been one of the many obstacles faced in cell-based therapy of neurodegenerative disorders. We hypothesized that DPSCs, delivered intranasally, could circumvent these challenges. In the present study, we investigated the therapeutic efficacy of intranasally administered DPSCs in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Human deciduous DPSCs were cultured, pre-labelled with PKH 26, and intranasally delivered into PD mice following MPTP treatment. Behavioural analyses were performed to measure olfactory function and sensorimotor coordination, while tyrosine hydroxylase (TH) immunofluorescence was used to evaluate MPTP neurotoxicity in SNpc neurons. Upon intranasal delivery, degenerated TH-positive neurons were ameliorated, while deterioration in behavioural performances was significantly enhanced. Thus, the intranasal approach enriched cell delivery to the brain, optimizing its therapeutic potential through its efficacious delivery and protection against dopaminergic neuron degeneration.
帕金森病(PD)是一种神经退行性疾病,其特征是黑质致密部(SNpc)中的多巴胺能神经元进行性恶化。牙髓干细胞(DPSCs)因其固有的神经发生和再生潜力而被提议替代退化的多巴胺能神经元。然而,在神经退行性疾病的基于细胞的治疗中,DPSCs 在病变大脑内的有效传递和归巢一直是面临的众多挑战之一。我们假设,经鼻内给药的 DPSCs 可以规避这些挑战。在本研究中,我们研究了经鼻内给予 DPSCs 在 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的 PD 小鼠模型中的治疗效果。培养人乳牙 DPSCs,用 PKH26 预先标记,然后在 MPTP 处理后经鼻内递送至 PD 小鼠。进行行为分析以测量嗅觉功能和感觉运动协调,同时使用酪氨酸羟化酶(TH)免疫荧光评估 SNpc 神经元中的 MPTP 神经毒性。经鼻内给药后,退化的 TH 阳性神经元得到改善,而行为表现的恶化则显著增强。因此,经鼻途径富集了细胞向大脑的传递,通过有效的传递和防止多巴胺能神经元退化来优化其治疗潜力。