DNA damage response manages cell cycle restriction of senile multipotent mesenchymal stromal cells

Area of Science:

• Cell Biology
• Regenerative Medicine
• Genetics

Background:

• Multipotent mesenchymal stromal cells (MMSCs) show therapeutic potential for degenerative and traumatic diseases.
• In vitro expansion of MMSCs is hindered by passage-induced aging, leading to cell cycle arrest and genetic alterations.
• Cellular senescence in MMSCs is primarily driven by DNA damage and executed by the DNA damage response (DDR).

Purpose of the Study:

• To comprehensively review the mechanisms of DNA damage response (DDR) associated cell cycle regulation in MMSC senescence.
• To summarize new findings on proliferation and metabolism pathways involved in DNA damage-induced cell cycle arrest.
• To provide insights for improving the in vitro expansion capacity of MMSCs for clinical applications.

Main Methods:

• Literature review and synthesis of existing research on MMSC senescence.
• Analysis of molecular signaling pathways involved in DNA damage and cell cycle arrest.
• Identification of key genetic and biological changes during MMSC aging.

Main Results:

• DNA damage is a primary cause of MMSC senescence, with DDR acting as the main executor.
• Indelible DNA damage triggers permanent cell cycle arrest in MMSCs.
• Proliferation and metabolism pathways are also implicated in DNA damage-related cell cycle arrest.

Conclusions:

• Understanding DDR and associated pathways is crucial for overcoming MMSC senescence.
• This knowledge can enhance ex vivo expansion of MMSCs, promoting their clinical utility.
• Targeting DDR and related signaling may improve the therapeutic efficacy of MMSCs.