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Updated: May 8, 2026
Isolation and Identification of Mesenchymal Stem Cells Derived from Adipose Tissue of Sprague Dawley Rats
Published on: April 7, 2023
Biological characteristics and transcriptomic profile of adipose-derived mesenchymal stem cells isolated from
Mohammed Zayed1,2,3, Yong-Chan Kim4,5, Byung-Hoon Jeong6,7
1Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, 54531, Republic of Korea.
Background:
Prion diseases are characterized by accumulation of misfolded host prion proteins (PrPSc) that produce aggregates in brain tissue. Mesenchymal stem cells (MSCs) have been identified as potential therapeutic candidates for prion diseases. However, it has been demonstrated that MSCs maintained and expressed PrPSc levels following inoculation, raising concerns regarding their safe and effective use in medical applications. Prion infectivity has been reported in fat tissues, thus the response of adipose-derived MSCs (AdMSCs) to prion infection needs to be fully studied.
Methods:
For this study, we analyzed the properties of AdMSCs isolated from mice infected with the ME7 scrapie strain and compared them with negative controls. We investigated morphology, viability, immunophenotyping, markers of inflammation, migration activity, and neurotrophic factors. RNA sequencing (RNA-Seq) was performed to identify transcriptome profile changes.
Results:
AdMSCs derived from ME7-infected mice displayed immunophenotypes similar to cells from negative controls, but they were larger with lower viability (p < 0.05). ME7 infection caused higher expression of inflammatory mediators CCL5, TNF-α, C3, and IL6 (p < 0.05 and p < 0.01) and low expression of the stem cell marker, CXCR4 (p < 0.05) which was confirmed by immunofluorescence staining. The results showed decreased migration activity and wound closure ability of AdMSCs isolated from ME7-infected mice as confirmed by Transwell migration and scratch wound assays (p < 0.05 and p < 0.001), respectively. The RNA-Seq results detected 367 differentially expressed genes between AdMSCs from ME7-infected mice and those from the negative controls, and negative regulation of locomotion, extracellular matrix (ECM) organization, collagen-containing ECM, and extracellular structure organization genes were common in AdMSCs from ME7-infected mice. Transcriptomic analysis revealed that pathways enriched in AdMSCs from ME7-infected mice included those involved in the PI3K-Akt signaling pathway, cell adhesion, protein digestion and absorption, and cytokine-cytokine receptor interactions. Interestingly, genes related to the regulation of iron storage, such as Hp and hepcidin, were upregulated in AdMSCs isolated from ME7-infected mice.
Conclusions:
Based on these data, therapeutic strategies for AdMSCs in prion disease should be further investigated.
Insights
Adipose-derived mesenchymal stem cells (AdMSCs) from prion-infected mice showed reduced viability and impaired function. Further research is needed to explore therapeutic strategies using AdMSCs for prion diseases.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Infectious Diseases
Background:
- Prion diseases involve misfolded prion protein aggregates in the brain.
- Mesenchymal stem cells (MSCs) are explored for prion disease therapy.
- Adipose-derived MSCs (AdMSCs) response to prion infection requires study due to prion presence in fat tissue.
Purpose of the Study:
- To analyze the properties of AdMSCs from prion-infected mice.
- To compare AdMSCs from infected and control mice.
- To assess the impact of prion infection on AdMSC characteristics and gene expression.
Main Methods:
- AdMSCs were isolated from ME7 scrapie strain-infected mice and controls.
- Evaluated morphology, viability, immunophenotype, inflammation markers, migration, and neurotrophic factors.
- RNA sequencing (RNA-Seq) was used for transcriptome profiling.
Main Results:
- Infected AdMSCs were larger with lower viability and altered immunophenotype (reduced CXCR4).
- Increased expression of inflammatory mediators (CCL5, TNF-α, C3, IL6) and decreased migration activity were observed.
- RNA-Seq revealed differentially expressed genes, enriched pathways (PI3K-Akt, cell adhesion), and upregulated iron storage genes (Hp, hepcidin).
Conclusions:
- Prion infection significantly alters AdMSC properties, including viability, migration, and gene expression.
- These findings suggest potential risks and limitations for AdMSC-based prion disease therapies.
- Further investigation into therapeutic strategies involving AdMSCs for prion diseases is warranted.
