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Updated: Aug 1, 2025
Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Development of new non-viral systems for genetic modification of senescent cells
Junquera López-Seijas1, Diego Miranda-Balbuena1, Alba Iglesias-Fente1
1Gene and Cell Therapy Research Group (G-CEL), Centro Interdisciplinar de Química e Bioloxía - CICA, Universidade da Coruña, 15071 A Coruña, Spain.
Abstract:
Senescence is a process characterized by a prolonged irreversible cell-cycle arrest. The accumulation of senescent cells in tissues is related to aging and to the development of age-related diseases. Recently, gene therapy has emerged as a powerful tool for treating age-associated diseases by the transference of specific genes into the target cell population. However, the high sensitivity of senescent cells significantly precludes their genetic modification via classical viral and non-viral systems. Niosomes are self-assembled non-viral nanocarriers that exhibit important advantages due to their elevated cytocompatibility, versatility, and cost-efficiency, arising as a new alternative for genetic modification of senescent cells. In this work, we explore for the first time the use of niosomes for genetic modification of senescent umbilical cord-derived mesenchymal stem cells. We report that niosome composition greatly affected transfection efficiency; those formulations prepared in medium with sucrose and containing cholesterol as helper lipid being the most suitable to transfect senescent cells. Moreover, resulting niosome formulations exhibited a superior transfection efficiency with a markedly less cytotoxicity than the commercial reagent Lipofectamine. These findings highlight the potentiality of niosomes as effective vectors for genetic modification of senescent cells, providing new tools for the prevention and/or treatment of age-related diseases.
Insights
Niosomes effectively modify senescent cells, offering a promising gene therapy approach for age-related diseases. This novel non-viral nanocarrier system overcomes challenges in senescent cell genetic modification.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Regenerative Medicine
Background:
- Cellular senescence, a state of irreversible cell-cycle arrest, contributes to aging and age-related diseases.
- Gene therapy shows potential for treating age-associated conditions, but senescent cells are difficult to genetically modify.
- Classical viral and non-viral gene delivery systems face limitations with senescent cells due to their sensitivity.
Purpose of the Study:
- To investigate niosomes as non-viral nanocarriers for the genetic modification of senescent cells.
- To evaluate the impact of niosome composition on transfection efficiency in senescent cells.
- To compare the efficacy and safety of niosomes against a commercial transfection reagent.
Main Methods:
- Utilized niosomes, self-assembled non-viral nanocarriers, for gene delivery.
- Explored various niosome formulations, varying composition (e.g., sucrose, cholesterol) to optimize transfection.
- Tested niosome formulations on senescent umbilical cord-derived mesenchymal stem cells.
- Assessed transfection efficiency and cytotoxicity compared to Lipofectamine.
Main Results:
- Niosome composition significantly influences transfection efficiency in senescent cells.
- Formulations with sucrose and cholesterol as a helper lipid demonstrated superior suitability for senescent cell transfection.
- Niosomes achieved higher transfection efficiency with significantly lower cytotoxicity than Lipofectamine.
- Demonstrated the potential of niosomes for effective and safe genetic modification of senescent cells.
Conclusions:
- Niosomes represent a promising and effective non-viral vector for the genetic modification of senescent cells.
- Optimized niosome formulations offer a viable alternative to current gene delivery methods for senescent cells.
- This research provides novel tools for the prevention and treatment of age-related diseases through senescent cell targeting.
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