Micro-fragmented fat injection reduces sepsis-induced acute inflammatory response in a mouse model

Area of Science:

• Immunology
• Regenerative Medicine
• Sepsis Research

Background:

• Severe sepsis presents a significant mortality challenge.
• Human mesenchymal stem cells, especially from adipose tissue, show promise in modulating sepsis-related inflammation.
• Adipose tissue's stromal vascular niche may retain crucial immunomodulatory properties.

Purpose of the Study:

• To investigate if micro-fragmented human fat attenuates inflammation and improves outcomes in a murine sepsis model.
• To assess the therapeutic potential of minimally altered adipose tissue in sepsis.

Main Methods:

• Mice underwent caecal ligation and puncture (CLP) to induce sepsis.
• Micro-fragmented fat, lipoaspirate, or saline was administered intraperitoneally 2 hours post-CLP.
• Primary endpoint was the inflammatory score; secondary endpoints included survival and physiological, histological, and biological parameters.

Main Results:

• Micro-fragmented fat significantly decreased the inflammatory score in CLP mice compared to saline treatment (P=0.006).
• Survival and other secondary endpoints were significantly improved in the micro-fragmented fat group.
• The anti-inflammatory effects were diminished by clodronate (macrophage depletion) and NS-398 (COX-2 inhibitor), but not SC-560 (COX-1 inhibitor).

Conclusions:

• Micro-fragmented fat effectively improved early inflammatory status and outcomes in a murine model of severe sepsis.
• The therapeutic benefits appear to be mediated, at least partly, through a cyclo-oxygenase-2-dependent mechanism.
• Further research is warranted to explore the therapeutic value of micro-fragmented fat for severe sepsis.