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Published on: October 4, 2024
Inhibition and Rescue of Hyperglycemia-Induced Cellular Senescence by Mitochondrial Transfer from Enucleated
Zixuan Dong1, Xiaobing Liu1, Shichun Li1
1School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, P. R. China.
Abstract:
The aberrant cellular senescence in chronic wounds presents a significant barrier to healing. Mitochondrial dysfunction is critical in initiating and maintaining cellular senescence, underscoring therapeutic potential in restoring mitochondrial function by delivering healthy mitochondria to wound cells. However, approaches for delivering mitochondria to achieve optimized wound repair remain lacking. Herein, enucleated MSCs-derived microvesicles containing functional mitochondria (Mito@euMVs) via simple extrusion are developed. By controlling the size of microvesicles within a small micron-scale range, the mitochondrial encapsulation efficiency is optimized. Mito@euMVs effectively delivered mitochondria into fibroblasts and HUVECs, inhibiting and rejuvenating hyperglycemia-induced cellular senescence. To enhance the clinical applicability, soluble PVA microneedle patches for the transdermal Mito@euMVs delivery are utilized. In diabetic rats with pressure sores, the senescence-inhibiting and -rescuing properties of Mito@euMVs are further validated, along with their therapeutic efficacy, demonstrating their potential for chronic wound repair. Moreover, as a versatile delivery vehicle for mitochondria, Mito@euMVs hold promising for treating mitochondrial dysfunction and aging-related conditions.
Insights
Researchers developed microvesicles carrying healthy mitochondria (Mito@euMVs) to combat cellular senescence in chronic wounds. This novel approach effectively rejuvenates aged cells and promotes wound healing, offering potential for age-related conditions.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Cellular Biology
Background:
- Aberrant cellular senescence impedes chronic wound healing.
- Mitochondrial dysfunction is a key driver of cellular senescence.
- Effective delivery of functional mitochondria to wound cells is needed for therapeutic intervention.
Purpose of the Study:
- To develop a novel method for delivering functional mitochondria to chronic wound cells.
- To investigate the potential of mitochondria-loaded microvesicles for cellular senescence inhibition and rejuvenation.
- To evaluate the therapeutic efficacy of this approach in a preclinical wound healing model.
Main Methods:
- Enucleated MSCs-derived microvesicles containing functional mitochondria (Mito@euMVs) were generated via extrusion.
- Microvesicle size was controlled to optimize mitochondrial encapsulation.
- Mito@euMVs were delivered transdermally using soluble PVA microneedle patches.
- In vitro and in vivo studies were conducted using fibroblasts, HUVECs, and diabetic rats with pressure sores.
Main Results:
- Mito@euMVs successfully delivered functional mitochondria into fibroblasts and HUVECs.
- Hyperglycemia-induced cellular senescence was inhibited and rejuvenated by Mito@euMVs.
- Transdermal delivery via microneedles enhanced clinical applicability.
- Therapeutic efficacy was validated in diabetic rats, showing senescence inhibition and improved wound repair.
Conclusions:
- Mito@euMVs represent a promising strategy for delivering mitochondria to combat cellular senescence in chronic wounds.
- This approach demonstrates significant potential for promoting wound healing and treating aging-related conditions.
- The developed microneedle patch system offers a viable transdermal delivery method for Mito@euMVs.
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