Human Amniotic Epithelial Cells Alleviate a Mouse Model of Parkinson's Disease Mainly by Neuroprotective, Anti-Oxidative and Anti-Inflammatory Factors.
Jiaofei ZhangHui LiHao YangJianhua LinYou WangQianjun ZhangWei-Qiang GaoHuiming XuPublished in: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology (2020)
Human amniotic epithelial cells (hAECs) have been reported to have neuroprotective roles in Parkinson's disease (PD) animal models. However, the molecular mechanism is not fully understood. The present study was designed to explore the possible mechanism by which hAECs ameliorate PD symptoms and the important paracrine factors produced by hAECs that attribute to the recovery of dopaminergic neurons. Thus, we performed in vivo and in vitro experiments with hAECs in PD models or lesioned dopaminergic neurons, respectively. First, hAECs were transplanted into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and motor deficits were significantly attenuated. Second, the grafts prevented the loss of nigral dopaminergic neurons and promoted the outgrowth of neurites and striatal axon fibers in PD mice. In addition, decreased microglial activation, inflammatory factor levels and MPTP-induced excessive reactive oxygen species (ROS) levels were also observed in hAEC-treated PD mice. In vitro, we found that the conditioned medium (CM) from hAECs promoted the survival of mesencephalic dopaminergic neurons stimulated with 1-methyl-4-phenylpyridine (MPP+) and induced neurite outgrowth. Next, analysis of hAEC-CM with an antibody array of 507 soluble target proteins revealed that the levels of many neurotrophic factors, growth factors, neuronal cell adhesion molecule (NrCAM) and anti-inflammatory factors were evidently high. In addition, antibody neutralization experiments showed that many of these factors contributed to the survival and growth of dopaminergic neurons and neurite outgrowth. More importantly, we found that the anti-inflammatory factor interleukin-1 receptor antagonist (IL-1ra) also augmented the survival of dopaminergic neurons, demonstrating for the first time an anti-oxidative and anti-inflammatory role of hAECs in PD mice, which represents a novel molecular mechanism of hAECs in the treatment of PD. The molecular mechanism of hAECs recovering lesioned dopaminergic neurons and attenuating PD symptoms. First, hAECs secret many neurotrophic factors, growth factors, and neuronal cell adhesion molecule (NrCAM) which promote the growth of the damaged dopaminergic neurons and their neurites. Second, hAECs produce many anti-inflammatory factors and other factors contributing to reducing the activation of microglia and suppressing the neuroinflammation. Third, hAECs reduce the excessive ROS levels by upregulating some anti-oxidative signals.
Keyphrases
- anti inflammatory
- spinal cord
- cell adhesion
- reactive oxygen species
- dna damage
- mouse model
- cell death
- depressive symptoms
- high fat diet induced
- oxidative stress
- inflammatory response
- diabetic rats
- cerebral ischemia
- high throughput
- lipopolysaccharide induced
- skeletal muscle
- systemic lupus erythematosus
- mesenchymal stem cells
- weight loss
- lps induced
- adipose tissue
- induced pluripotent stem cells
- brain injury
- combination therapy
- wild type
- deep brain stimulation