Brain repair
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Hydrogel supports iPSC-derived brain repair in Parkinson’s disease
Regenerative therapies based on transplantation of induced pluripotent stem cells (iPSC) have a great potential to treat neuronal cell loss in a variety of neurological disorders including Parkinson’s disease (PD). Despite their considerable benefits, treatment effects are often limited by poor graft survival and maturation of target neurons.?
Irish researchers have now identified a creative solution to this problem – the gel method. In a recent preclinical study, they looked at whether embedding neuronal precursor cells in a collagen hydrogel might improve cell survival and maturation.
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What they uncovered
For the study, the investigators differentiated iPSCs into dopaminergic progenitor cells (iPSC-DAPs, n=300,000). These cells were grafted in the striatum of female athymic nude rats who previously underwent lesion surgery to map dopaminergic cell loss. Four experimental conditions were chosen: transplantation with (1) or without the collagen hydrogel (2), and with (3) or without the neurotrophic factors GDNF and BDNF (4).
Results indicate that the collagen hydrogel may provide continuous neurotrophic support to the grafted cells. Survival and maturation of the iPSC-derived dopaminergic precursor cells embedded in the neurotrophin-enriched hydrogel were significantly better compared to cells without the biomaterial.??
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Not so fast
Replacing cells to combat neuronal loss seems to be such a natural, pragmatic idea. However, there are certain factors to keep in mind before starting clinical testing, such as:
1.???? Does the hydrogel affect the ability of the mature, iPSC-derived neurons to release dopamine?
2.???? What happens if the study is repeated in immunocompetent rats?
Future research focusing on the functionality of the iPSC-derived dopaminergic neurons and immunological responses is required to provide answers to these questions. ?The results will help investigators decide if the experimental protocols for collagen hydrogel and iPSC culture production are ready to be used in clinical settings.
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Why does it matter?????
In the future, neurodegenerative disorders such as PD will become a major burden for our healthcare systems. Most treatment options for PD are symptomatic as the cause of the disease is still poorly understood. Stem-cell based therapies might potentially delay or even shift the progression of the disease. Enhancing the safety and efficacy of cell transplants is of utmost importance to enable personalised treatment strategies for patients with PD.
Take home messages
1.???? iPSC-based transplants hold great potential for replenishing neuronal cell levels.
2.???? Neurotrophin-enriched hydrogel boosts survival and maturation of iPSC-derived transplants.
3.???? Clinical translation of cell-based therapies is often hampered by poor graft survival, maturation or immune rejection.
?Guest author: Andrea Huschens, MSc.
This article was written as part of a series of 'journal club' summaries for Scientific Writers Ltd., and is based on the following publication:??
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?First Author: Giulia Comini et al.
Journal: Journal of Neural Engineering,?Volume 21,?Number 2
Date online: 25 March 2024
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Other references: