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Updated: Jul 9, 2026
Chemogenetic Regulation in Reprogrammed Stem Cell-derived Precursor Cells in Treating Neurodegenerative Diseases
Published on: May 2, 2025
Mesenchymal stem cells preserve neuronal architecture by reprogramming miRNA-mRNA regulatory networks in experimental
Amrendra Chaudhary1, Indu Sharma1, Reva Sharan Thakur2
1Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India; Division of Immunology, National Institute of Malaria Research, Dwarka, New Delhi, 110077, India.
Abstract:
Cerebral malaria (CM) is associated with disruption of the blood-brain barrier (BBB), neurovascular injury, and high mortality. Although mesenchymal stem cells (MSCs) have demonstrated therapeutic efficacy in experimental cerebral malaria (ECM), the molecular mechanisms underlying these effects remain insufficiently defined. In this study, we investigated how MSC treatment modulates host miRNA networks during ECM using a Plasmodium berghei ANKA infection in C57BL/6 mice. MSC treatment significantly reduced clinical severity, improved survival, and preserved BBB integrity, as indicated by decreased Evans blue extravasation and reduced microvascular sequestration within brain. RNA sequencing identified 64 differentially expressed miRNAs associated with MSC treatment. Pathway enrichment using DIANA-miRPath v4.0 identified 23 miRNAs associated to CM-relevant pathways. Eleven miRNAs with highest pathway interactions were subsequently validated by RT-qPCR, confirming consistent down-regulation of eight miRNAs following MSC treatment. miRNA-mRNA network construction revealed several hub genes, including Rora, Nfia, Nfib, Slc1a2, Tcf4, Pura, and Atxn1, linked to neurological phenotypes relevant to CM pathology. Collectively, these findings suggest that MSCs mitigate ECM pathology by reprogramming miRNA-mRNA regulatory networks governing cerebral and neuronal stability. The identified miRNA-mRNA hubs represent promising candidates for future biomarker studies and may provide a foundation for the development of adjunctive therapeutic strategies against cerebral malaria.
Insights
Mesenchymal stem cells (MSCs) reduce cerebral malaria severity and improve survival by altering microRNA networks. These stem cells reprogram miRNA-mRNA interactions crucial for brain stability, offering potential biomarkers and therapies for cerebral malaria.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Cerebral malaria (CM) causes blood-brain barrier (BBB) disruption and high mortality.
- Mesenchymal stem cells (MSCs) show therapeutic promise in experimental CM (ECM), but mechanisms are unclear.
Purpose of the Study:
- Investigate how MSC treatment affects host miRNA networks in ECM.
- Identify molecular targets for MSC-based therapies against CM.
Main Methods:
- Used Plasmodium berghei ANKA infection in C57BL/6 mice to model ECM.
- Analyzed miRNA expression via RNA sequencing and RT-qPCR.
- Constructed miRNA-mRNA networks to identify key regulatory genes.
Main Results:
- MSC treatment improved survival, reduced clinical severity, and preserved BBB integrity in ECM mice.
- Identified 64 differentially expressed miRNAs, with 8 consistently downregulated post-MSC treatment.
- Revealed key miRNA-mRNA hubs (e.g., Rora, Nfia, Nfib) linked to CM-relevant neurological phenotypes.
Conclusions:
- MSCs mitigate ECM by reprogramming miRNA-mRNA networks governing cerebral and neuronal stability.
- Identified miRNA-mRNA hubs are potential biomarkers and therapeutic targets for cerebral malaria.
