Apoptotic vesicles are required to repair DNA damage and suppress premature cellular senescence

Area of Science:

• Cellular Biology
• Molecular Biology
• Genetics

Background:

• DNA damage is a known inducer of apoptosis.
• The role of apoptosis and its products in DNA repair remains largely unexplored.

Purpose of the Study:

• To investigate the role of apoptotic vesicles (apoVs) in DNA repair.
• To determine if apoVs can mitigate DNA damage and cellular senescence.
• To explore the therapeutic potential of stem cell-derived apoVs for DNA damage repair.

Main Methods:

• Utilized apoptosis-deficient mice (Fasmut and Bim-/-) to assess DNA damage and senescence.
• Administered mesenchymal stromal cell (MSC)-derived 16,000g apoVs to rescue DNA damage.
• Exposed mice to radiation and evaluated survival and body weight changes.
• Investigated the mechanism of DNA repair enzyme transfer via apoVs.
• Assessed the DNA repair capacity of embryonic stem cell-derived apoVs in irradiated mice.

Main Results:

• Apoptosis-deficient mice exhibited elevated DNA damage, premature senescence, and reduced apoVs.
• MSC-derived apoVs rescued DNA damage and senescence in these mice.
• MSC-apoV infusion ameliorated radiation-induced DNA damage, reduced mortality, and restored body weight.
• Apoptosis assembles nuclear DNA repair enzymes into apoVs, which are transferred to recipient cells.
• Embryonic stem cell-derived apoVs demonstrated superior DNA repair capacity in rescuing lethally irradiated mice.

Conclusions:

• Apoptotic vesicles play a crucial role in safeguarding tissues against DNA damage.
• ApoVs transfer DNA repair components to recipient cells, facilitating DNA repair and eliminating senescent cells.
• Stem cell-derived apoVs represent a promising therapeutic strategy for ameliorating irradiation-induced DNA damage.