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Evaluation of Injury-induced Senescence and In Vivo Reprogramming in the Skeletal Muscle
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Partial Reprogramming Exerts a Rejuvenating Effect on Human Mesenchymal Stem Cells That Underwent Replicative
Julia Ivanova1, Mariia Shorokhova1, Natalia Pugovkina1
1Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Tikhoretskii pr. 4, St. Petersburg 194064, Russia.
International Journal of Molecular Sciences
|December 17, 2024
Summary
Partial reprogramming rejuvenates senescent human mesenchymal stem/stromal cells (MSCs), restoring youthful characteristics and enhancing therapeutic potential. However, virus-free methods are crucial for safe application in regenerative medicine.
Area of Science:
- Stem Cell Biology
- Regenerative Medicine
- Cellular Senescence
Background:
- Mesenchymal stem/stromal cells (MSCs) are vital for biomedical applications.
- Long-term culture of MSCs leads to replicative senescence, limiting their therapeutic use.
- Partial reprogramming offers a potential solution for cell rejuvenation.
Purpose of the Study:
- To investigate the efficacy of partial reprogramming in rejuvenating senescent human endometrial MSCs.
- To assess the therapeutic potential of partially reprogrammed MSCs.
- To evaluate the biosafety of the reprogramming method.
Main Methods:
- Senescent human endometrial MSCs were subjected to partial reprogramming using Sendai virus vectors encoding Yamanaka factors (Oct4, Sox2, Klf4, c-Myc).
- Characterization included assessing senescence markers (morphology, β-galactosidase, DNA breaks), proliferation, and DNA damage response.
- Therapeutic activity was evaluated using an in vitro wound-healing assay, and biosafety was tested for viral components.
Main Results:
- Partial reprogramming restored youthful morphology, reduced senescence markers, and enhanced proliferation and DNA damage response in MSCs.
- Conditioned medium from reprogrammed MSCs exhibited increased therapeutic activity compared to senescent cells.
- Viral components were detected in conditioned medium, causing erythrocyte agglutination, indicating a biosafety concern.
Conclusions:
- Partial reprogramming is a promising strategy for rejuvenating late-passage cultured MSCs.
- The use of virus-free protocols is essential for the safe clinical application of this rejuvenation technique.
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