Summary: Exercise enhances the effectiveness of stem cell-derived neuron transplants in a Parkinson’s disease (PD) rat model. Transplanted neurons alone improved basic motor functions, but when combined with voluntary exercise, the rats displayed significantly better agility and paw control.
The researchers found that exercise helped transplanted neurons mature and form stronger connections with host brain cells, likely due to an increase in beneficial brain proteins. These findings suggest that exercise could be a simple, non-invasive way to boost outcomes in future PD stem cell therapies.
Key Facts:
- Therapy Synergy: Exercise enhanced the function of stem cell-derived neuron transplants in PD rats.
- Better Integration: Exercise promoted transplant maturation and connectivity with host neurons.
- Clinical Potential: Suggests a safe, accessible way to improve outcomes in human PD trials.
Source: International Society for Stem Cell Research
Parkinson’s disease (PD) is a disabling neurodegenerative disease that affects approximately 10 million people worldwide, with numbers steadily increasing.
Symptoms include tremors, difficulties with movement and speech, as well mental health issues and dementia.
Although PD can be managed by medication and lifestyle adjustments, the efficacy of these interventions varies between patients and cannot stop or reverse disease progression.
PD is caused by progressive loss of a certain type of neurons in the brain which produce dopamine, a chemical substance required to control movement, etc.
Encouragingly, studies dating back to the eighties have shown that replacing lost dopaminergic neurons with donated fetal tissue-derived neurons can improve symptoms in PD patients.
Since then, researchers have made progress in generating a replenishable source of dopaminergic neurons from pluripotent stem cells in the lab and achieved promising results when transplanting these cells in animal models of PD.
Currently, clinical trials are ongoing to test the safety and efficacy of transplanting such stem cell-derived neurons in PD patients. A key to success in patients will be the successful integration and maturation of the transplanted cells within the brain.
To address this, a research team led by Clare Parish from The Florey Institute of Neuroscience and Mental Health (in Melbourne) and Lachlan Thompson from the University of Sydney, Australia has now tested whether exercise enhances transplant function in PD rats.
In their study, rats received a stem cell-derived transplant to replace lost dopaminergic neurons and some of the rats were given free access to a running wheel.
Their work was recently published in Stem Cell Reports.
While the neural grafts improved gross motor function, combined with exercise saw paw movements and agility improved significantly.
Their research found that voluntary exercise improved the maturation of the transplant and the establishment of connections between the transplant and the rat neurons.
A likely cause for this was the enhanced secretion of certain beneficial proteins in the brains of exercising rats which promoted transplant survival and integration.
In conclusion, exercise may be a non-invasive and easily implemented strategy to enhance treatment outcomes in PD patients in combination with stem cell-derived transplants, warranting further testing in upcoming clinical trials.
About this Parkinson’s disease and genetics research news
Author: Kym Kilbourne
Source: International Society for Stem Cell Research
Contact: Kym Kilbourne – International Society for Stem Cell Research
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Exercise promotes the functional integration of human stem cell-derived neural grafts in a rodent model of Parkinson’s disease” by Clare Parish et al. Stem Cell Reports
Abstract
Exercise promotes the functional integration of human stem cell-derived neural grafts in a rodent model of Parkinson’s disease
Human pluripotent stem cell (hPSC)-derived dopamine neurons can functionally integrate and reverse motor symptoms in Parkinson’s disease models, motivating current clinical trials.
However, dopamine neuron proportions remain low and their plasticity inferior to fetal tissue grafts.
Evidence shows exercise can enhance neuron survival and plasticity, warranting investigation for hPSC-derived neural grafts.
We show voluntary exercise (wheel running) significantly increases graft plasticity, accelerating motor recovery in animals receiving ectopic, but not homotopic, placed grafts, suggestive of threshold requirements.
Plasticity was accompanied by increased phosphorylated extracellular signal-regulated kinase (ERK+) cells in the graft (and host), reflective of mitogen-activated protein kinase (MAPK)-ERK signaling, a downstream target of glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), proteins that were also elevated. Verifying improved graft integration was the increase in cFos+ postsynaptic striatal neurons.
These findings have direct implications for the adoption of physical therapy-based approaches to enhance neural transplantation outcomes in future Parkinson’s disease clinical trials.
Get the source article here
