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Extracellular Vesicles from Human Induced Pluripotent Stem Cells Exhibit a Unique MicroRNA and CircRNA Signature.
Mario Barilani1, Valeria Peli1, Paolo Manzini1
1Unit of Cell and Gene Therapies, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
International Journal of Biological Sciences
|December 12, 2024
Summary
Human induced pluripotent stem cells (hiPSC) derived from cord blood mesenchymal stem cells offer a scalable source for therapeutic extracellular vesicles (EV). These hiPSC-derived EVs show potential for regenerative medicine applications.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Extracellular Vesicles
Background:
- Primary cell-derived extracellular vesicles (EVs) face manufacturing challenges for clinical use, including senescence and donor variability.
- Human induced pluripotent stem cells (hiPSC) present a potential solution due to their inexhaustible supply and potential as an EV source.
- Mesenchymal stem/stromal cells (MSCs) from cord blood are a viable starting material for hiPSC generation.
Purpose of the Study:
- To generate and characterize extracellular vesicles (EVs) derived from hiPSC sourced from cord blood MSCs.
- To evaluate the therapeutic potential of these hiPSC-derived EVs, focusing on their cargo and biological effects.
- To establish hiPSC as a scalable and reliable source for cell-free therapeutics.
Main Methods:
- Reprogramming of cord blood MSCs into hiPSC.
- Comprehensive characterization of hiPSC-derived small EVs (sEVs) following MISEV2023 guidelines.
- Analysis of sEV non-coding RNA cargo (miRNA, circRNA) and assessment of release kinetics and cellular uptake.
- Evaluation of ex vivo tissue-protective properties and bioinformatics analysis of ncRNA cargo functions.
Main Results:
- hiPSC-derived EVs exhibited physical characteristics consistent with sEVs, with confirmed identity and purity.
- The non-coding RNA landscape of sEVs was detailed, including miRNA and circRNA cargo.
- Robust production and consistent neuronal uptake of hiPSC-sEVs were observed.
- hiPSC-sEVs demonstrated ex vivo cell tissue-protective effects, with ncRNA cargo implicated in biological activity.
Conclusions:
- Cord blood MSC-derived hiPSC represent a promising and scalable source for therapeutic sEV production.
- hiPSC-derived sEVs possess characteristics and functions suitable for regenerative medicine applications.
- This study advances the understanding of pluripotent stem cell-derived EVs for therapeutic development.
Keywords:
circRNAcord bloodexosomesextracellular vesicleshuman-induced pluripotent stem cellsmiRNAnanoparticlesMore Related Videos
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