Neuroprotective Effects of Microfluidic Encapsulated Induced Conjunctival Mesenchymal Stem Cells Through Autophagy Modulation in a Parkinsonian Model
Abstract Background and Aim: Parkinson's disease (PD) is a progressive neurodegenerative disorder in which cause is attributed to the alpha-synuclein (α-Syn) accumulation due to the decreases rated of autophagy. According to recent studies, cell therapy has been attracted much attention for PD treatment. Due to the many advantages mesenchymal stem cells (MSCs) have proposed, they have been considered a valuable resource for PD cell therapy. The present study aimed to investigate the therapeutic effect of Conjunctival MSCs (CJ-MSCs) on the autophagy manner and the expression of Mammalian target of rapamycin (mTOR), TH, and α-Syn in the parkinsonian rat model.Materials and Methods: our investigation has been performed using the Parkinson's model of rats. Stereotaxic 6-hydroxy dopamine (6-OHDA) was injected directly into the medial forebrain bundle (MFB) to induce Parkinson's disease. An apomorphine-induced rotation test was used to confirm the model establishment. CJ-MSCs were encapsulated in alginate microgel using a microfluidic system. The green fluorescent protein (GFP) labeled CJ-MSCs both encapsulated and free cells were transplanted into the rats' right striatum. Behavioral and molecular analyses have been carried out to evaluate the potency of CJ-MSCs (both encapsulated and free cells) on PD rats. The Rotation, Rotarod Open field test was recruited as the behavioral tests. Immunohistochemistry was used to determine the tyrosine hydroxylase (TH), and Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) has been performed for investigating the α-Syn and mTOR gene expression.Results: Our obtained results indicated that transplantation of CJ-MSCs leads to a decrease in the number of rotations while raising the balance and motor abilities. Immunohistochemistry analysis revealed an increase in the number of TH+ cells compared to the control group. The gene expression evaluation showed a significant reduction in mTOR and α-Syn mRNA levels than the control group. Our results also represented a significant difference between rats receiving encapsulated CJ-MSCs compared to the group received free CJ-MSCs.Conclusion: It seems that CJ-MSCs can promote the degradation of intracellular α-Syn by reducing mTOR and thus increase TH expression that led improve the motor functions of rats. Our results indicated the CJ-MSCs as a suitable source of MSCs to reduce PD complications.