Abstract
Transplantation of exogenous dopaminergic (DA) neurons is an alternative strategy to replenish DA neurons that have lost along the course of Parkinson’s disease (PD). From the perspective of ethical acceptation, the source limitations, and the intrinsic features of PD pathology, astrocytes (AS) and mesenchymal stem cells (MSCs) are the two promising candidates of DA induction. In the present study, we induced AS or MSCs primary culture by the combination of the classical transcription-factor cocktails Mash1, Lmx1a, and Nurr1 (MLN), the chemical cocktails (S/C/D), and the morphogens SHH, FGF8, and FGF2 (S/F8/F2); the efficiency of induction into DA neurons was further analyzed by using immunostaining against the DA neuronal markers. AS could be efficiently converted into the DA neurons in vitro by the transcriptional regulation of MLN, and the combination with S/C/D or S/F8/F2 further increased the conversion efficiency. In contrast, MSCs from umbilical cord (UC-MSCs) or adipose tissue (AD-MSCs) showed moderate TH immunoreactivity after the induction with S/F8/F2 instead of with MLN or S/C/D. Our data demonstrated that AS and MSCs held lineage-specific molecular codes on the induction into DA neurons and highlighted the unique superiority of AS in the potential of cell replacement therapy for PD.
Highlights
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, and the core pathology is characterized by the selective degeneration of dopaminergic (DA) neurons in the midbrain [1,2]
Sci. 2021, 22, x FOR PEEfiRbRrEiVllIaErWy acidic protein (GFAP), and s100 calcium binding protein β (S100β), only le4sosf t2h1an 5% of cells were positive for the markers of neural progenitors, i.e., Nestin and paired box-6 (PAX6)
This study is the first of its kind, where we have directly compared the molecular codes between AS and mesenchymal stem cells (MSCs) induction into DA neurons
Summary
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, and the core pathology is characterized by the selective degeneration of dopaminergic (DA) neurons in the midbrain [1,2]. Over the last few decades, the mainstay of clinical therapy focused on dopaminergic agents, which facilitated the dopamine restoration and rejuvenation of motor functions. These medications failed to promote the recovery of the lost DA neurons; some undesirable side effects in the later stage of treatment often occur, such as dyskinesia [3]. Replenishment of the dopamineproducing cells is considered to be a plausible strategy that improves focal dopamine levels, accompanied by the restoration of the nigrostriatal function, and the prerequisite for the DA neurons candidate is the easy access, safety as well as the capacity of inducting into DA neurons. A series of studies have been reported that MSCs were able to rescue nigrostriatal circuits and improve behavioral performance in the PD models [12], which were considered as one of the ideal donor cells for PD treatment [13]
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