Targeting efferocytosis for tissue regeneration: From microenvironment reprogramming to clinical translation

Area of Science:

• Cell Biology
• Immunology
• Regenerative Medicine

Background:

• Efferocytosis, the clearance of apoptotic cells (ACs), is vital for tissue homeostasis, inflammation resolution, and regeneration.
• It prevents secondary necrosis and dampens damage-associated molecular patterns (DAMPs), reprogramming phagocytes to a pro-reparative state.
• The process involves distinct stages: signal-mediated recruitment, AC recognition, internalization, and degradation.

Purpose of the Study:

• To review the biological process of efferocytosis and its role in tissue repair.
• To highlight the mechanisms by which efferocytosis promotes regeneration and resolves inflammation.
• To discuss challenges and future directions in therapeutic strategies targeting efferocytosis.

Main Methods:

• Literature review of efferocytosis mechanisms and functions.
• Analysis of efferocytosis's role in various tissue repair contexts (wound healing, organ injury).
• Examination of therapeutic approaches and their clinical translation challenges.

Main Results:

• Efferocytosis is essential for resolving inflammation and coordinating tissue repair through multiple mechanisms.
• Dysfunctional efferocytosis contributes to chronic pathologies like diabetic ulcers and fibrosis due to AC accumulation.
• Therapeutic strategies, including pharmaceuticals and biomaterials, are being developed but face spatiotemporal control and translation hurdles.

Conclusions:

• Efferocytosis is a critical regulator of tissue repair and inflammation resolution.
• Targeting efferocytosis offers therapeutic potential for chronic diseases.
• Future research should focus on multi-omics and smart biomaterials for dynamic efferocytosis modulation.