Multi-Omics Assessment of Primed Tissue-Specific MSCs-sEV to Unveil Their Regenerative Potential

Area of Science:

• Cell Biology
• Regenerative Medicine
• Biotechnology

Background:

• Small extracellular vesicles (sEVs) are crucial for intercellular communication and hold significant therapeutic promise.
• Mesenchymal stromal cells (MSCs) are a key source of therapeutic sEVs, with bone marrow (BM-MSC) and Wharton's jelly (WJ-MSC) being common sources.
• The composition and function of MSC-sEVs can be influenced by culture conditions, including oxygen availability.

Purpose of the Study:

• To characterize and compare sEVs derived from BM-MSCs and WJ-MSCs cultured under normoxic and hypoxic conditions.
• To elucidate the impact of oxygenation state on the miRNA and protein cargo of MSC-sEVs.
• To identify unique molecular signatures and networks within MSC-sEVs for potential therapeutic applications.

Main Methods:

• High-throughput miRNA sequencing to profile miRNA content.
• Mass spectrometry-based proteomic analysis to identify protein cargo.
• Comparative bioinformatic analyses of miRNA-protein interactions and networks.

Main Results:

• Distinct miRNA and protein profiles were identified between BM-MSC and WJ-MSC sEVs, influenced by both cell source and oxygenation.
• Hypoxic preconditioning significantly altered sEV composition, enriching for miRNAs and proteins associated with angiogenesis, immunomodulation, and tissue regeneration.
• Overlapping and unique miRNA-protein networks were observed, suggesting differential regulatory roles and therapeutic specificities.

Conclusions:

• The cellular microenvironment, particularly oxygen availability, critically influences MSC-sEV composition and functional potential.
• Hypoxia-driven enrichment of specific molecular cargo enhances the regenerative and immunomodulatory capacity of MSC-sEVs.
• These findings provide a basis for rationally designing tailored MSC-sEV-based therapies for regenerative medicine, inflammation, and tissue repair.