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Active Magnesium Boride/Alginate Hydrogels Rejuvenate Senescent Cells
Yingchao Han1,2, Dandan Zheng1, Yucheng Ji1
1Department of Spine Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P. R. China.
ACS Nano
|August 15, 2024
Summary
Magnesium boride-alginate hydrogels rejuvenate senescent cells in age-related diseases by creating a mild alkaline environment. This strategy promotes cell proliferation and reduces oxidative stress, offering a novel approach for treating conditions like intervertebral disc degeneration.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Cell Biology
Background:
- Senescent cell clearance can harm low cell density diseases like intervertebral disc degeneration (IVDD).
- Rejuvenating senescent cells is challenging for age-related diseases.
- Current strategies may not effectively address senescent cell accumulation in degenerative conditions.
Purpose of the Study:
- To investigate a mild-alkalization strategy using magnesium boride-alginate (MB-ALG) hydrogels for senescent cell rejuvenation.
- To explore the potential of MB-ALG hydrogels in treating age-related diseases characterized by cellular senescence.
- To elucidate the mechanisms underlying senescent cell rejuvenation induced by mild alkalization.
Main Methods:
- Development and characterization of MB-ALG hydrogels with surface roughness for ensnaring senescent cells.
- Induction of mild alkalization (pH ~ 8.0) from an acidic microenvironment (pH ~ 6.2) via MB-ALG hydrolysis.
- Investigation of cellular pathways involved, including PI3K/Akt/mTOR, ROS clearance, Ca2+ influx, and sirt1-p53 signaling.
- In vitro and in vivo studies using rat intervertebral discs to assess antisenescence and rejuvenation effects.
Main Results:
- MB-ALG hydrogels effectively ensnared senescent cells.
- Mild alkalization promoted senescent cell proliferation through PI3K/Akt/mTOR pathway activation.
- Hydrogen (H2) aided in reactive oxygen species (ROS) clearance, reducing oxidative stress.
- Magnesium ions (Mg2+) rejuvenated cells by inhibiting Ca2+ influx and modulating sirt1-p53 pathways.
- Sustained antisenescence and rejuvenation effects were observed in vivo for up to 12 weeks.
Conclusions:
- Mild alkalization is a viable strategy for dictating cellular destiny and rejuvenating senescent cells.
- MB-ALG hydrogels demonstrate sustained efficacy in combating senescence and promoting cell rejuvenation.
- This approach offers promising insights for developing therapeutic interventions for age-related diseases like IVDD.
