Functional dopaminergic neurons derived from human chorionic mesenchymal stem cells ameliorate striatal atrophy and improve behavioral deficits in Parkinsonian rat model

Abstract

Human chorionic mesenchymal stem cells (HCMSCs) have been recognized as a desirable choice for cell therapy in neurological disorders such as Parkinson's disease (PD). Due to invaluable features of HCMSCs including their immunomodulatory and immunosuppressive properties, easily accessible and less differentiated compared to other types of MSCs, HCMSCs provide a great hope for regenerative medicine. Thus, the purpose of this study was to determine the in vitro and in vivo efficacy of HCMSCs‐derived dopaminergic (DA) neuron‐like cells with regard to PD. Initially, HCMSCs were isolated and underwent a 2‐week DA differentiation, followed by in vitro assessments, using quantitative real‐time polymerase chain reaction, immunocytochemistry, patch clamp recording, and high‐performance liquid chromatography. In addition, the effects of implanted HCMSCs‐derived DA neuron‐like cells on the motor coordination along with stereological alterations in the striatum of rat models of PD were investigated. Our results showed that under neuronal induction, HCMSCs revealed neuron‐like morphology, and expressed neuronal and DA‐specific genes, together with DA release. Furthermore, transplantation of HCMSCs‐derived DA neurons into the striatum of rat models of PD, augmented performance. Besides, it prevented reduction of striatal volume, dendritic length, and the total number of neurons, coupled with a diminished level of cleaved caspase‐3. Altogether, these findings suggest that HCMSCs could be considered as an attractive strategy for cell‐based therapies in PD.

Autonomic behavioral impairment induced by simazine exposure during early life of male mouse is mediated by Lmx1a/Wnt1 pathway

“…Many studies related to neurodegenerative diseases have reported that the damaged morphology and function of dopaminergic neuron eventually led to autonomic behavioral impairment. 43,44 Herein, abnormal development of the dopaminergic nervous system during the embryonic and lactation periods resulted in autonomic behavioral impairment in weaned male offspring. In the open-field test, we found that the autonomic exploring behavior of the simazinetreated male offspring was significantly lower than the solvent control group, and no significant change was found in simazine-treated female offspring, indicating that simazine exposure gender-specifically impaired the ability of the male offspring to explore and perceive their surrounding environment at this stage of life.…”

Comparative study between bone marrow mesenchymal stem cell and their conditioned medium in the treatment of rat model of Parkinsonism

“…Mesenchymal stem cells (MSCs) are multipotent cells that are capable of differentiating into functional dopaminergic neurons, which have been effective in regenerating the structure and function of the substantia nigra (Ebrahimi et al, 2019; Sarkaki, Farbood, Dolatshahi, Mansouri, & Khodadadi, 2016; Zhu et al, 2017).…”