Olfactory mucosa stem cells delivery via nasal route: a simple way for the treatment of Parkinson disease

Author(s):  
Sara Simorgh ◽  
Rafieh Alizadeh ◽  
Ronk Shabani ◽  
Fariba Karimzadeh ◽  
Elham Seidkhani ◽  
...  
2017 ◽  
Vol 26 (8) ◽  
pp. 1452-1461 ◽  
Author(s):  
Yi Zhuo ◽  
Lei Wang ◽  
Lite Ge ◽  
Xuan Li ◽  
Da Duan ◽  
...  

Olfactory mucosa mesenchymal stem cells (OM-MSCs) display significant clonogenic activity and may be easily propagated for Parkinson’s disease therapies. Methods of inducing OM-MSCs to differentiate into dopaminergic (DAergic) neurons using olfactory ensheathing cells (OECs) are thus an attractive topic of research. We designed a hypoxic induction protocol to generate DAergic neurons from OM-MSCs using a physiological oxygen (O2) level of 3% and OEC-conditioned medium (OCM; HI group). The normal induction (NI) group was cultured in O2 at ambient air level (21%). The role of hypoxia-inducible factor-1α (HIF-1α) in the differentiation of OM-MSCs under hypoxia was investigated by treating cells with an HIF-1α inhibitor before induction (HIR group). The proportions of β-tubulin- and tyrosine hydroxylase (TH)-positive cells were significantly increased in the HI group compared with the NI and HIR groups, as shown by immunocytochemistry and Western blotting. Furthermore, the level of dopamine was significantly increased in the HI group. A slow outward potassium current was recorded in differentiated cells after 21 d of induction using whole-cell voltage-clamp tests. A hypoxic environment thus promotes OM-MSCs to differentiate into DAergic neurons by increasing the expression of HIF-1α and by activating downstream target gene TH. This study indicated that OCM under hypoxic conditions could significantly upregulate key transcriptional factors involved in the development of DAergic neurons from OM-MSCs, mediated by HIF-1α. Hypoxia promotes DAergic neuronal differentiation of OM-MSCs, and HIF-1α may play an important role in hypoxia-inducible pathways during DAergic lineage specification and differentiation in vitro.


2010 ◽  
Vol 10 ◽  
pp. 422-433 ◽  
Author(s):  
Cameron McDonald ◽  
Alan Mackay-Sim ◽  
Denis Crane ◽  
Wayne Murrell

This study examines the hypothesis that multipotent olfactory mucosal stem cells could provide a basis for the development of autologous cell transplant therapy for the treatment of heart attack. In humans, these cells are easily obtained by simple biopsy. Neural stem cells from the olfactory mucosa are multipotent, with the capacity to differentiate into developmental fates other than neurons and glia, with evidence of cardiomyocyte differentiationin vitroand after transplantation into the chick embryo. Olfactory stem cells were grown from rat olfactory mucosa. These cells are propagated as neurosphere cultures, similar to other neural stem cells. Olfactory neurospheres were grownin vitro, dissociated into single cell suspensions, and transplanted into the infarcted hearts of congeneic rats. Transplanted cells were genetically engineered to express green fluorescent protein (GFP) in order to allow them to be identified after transplantation. Functional assessment was attempted using echocardiography in three groups of rats: control, unoperated; infarct only; infarcted and transplanted. Transplantation of neurosphere-derived cells from adult rat olfactory mucosa appeared to restore heart rate with other trends towards improvement in other measures of ventricular function indicated. Importantly, donor-derived cells engrafted in the transplanted cardiac ventricle and expressed cardiac contractile proteins.


Life Sciences ◽  
2021 ◽  
Vol 265 ◽  
pp. 118861
Author(s):  
Jialin He ◽  
Yan Huang ◽  
Jianyang Liu ◽  
Lite Ge ◽  
Xiangqi Tang ◽  
...  

2004 ◽  
Vol 10 (3) ◽  
pp. 224-225 ◽  
Author(s):  
Clive N Svendsen ◽  
J William Langston
Keyword(s):  

2010 ◽  
Vol 38 (2) ◽  
pp. 257-266 ◽  
Author(s):  
Bernard Lo ◽  
Lindsay Parham

Stem cells derived from pluripotent cells offer the hope of new treatments for diseases for which current therapy is inadequate. Clinical trials are essential in developing effective and safe stem cell therapies and fulfilling this promise. However, such clinical trials raise ethical issues that are more complex than those raised in clinical trials using drugs, cord blood stem cells, or adult stem cells. Several clinical trials are now being carried out with stem cells derived from pluripotent cells, and many more can be expected in light of the rapid scientific progress in the field.Degenerative neurological diseases are desirable targets for stem cell clinical trials. The FDA has approved Phase 1 clinical trials of neural stem cell transplantation for Batten Disease, Pelizaeus-Merzbacher Disease, and spinal cord injury. In Parkinson Disease (PD), stem cell transplantation could correct the primary pathophysiological defect — inadequate levels of the neurotransmitter dopamine. Current treatment is unsatisfactory in late-stage PD.


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