Acellular Adipose Tissue promotes anti-fibrotic remodeling in Phase II Study.

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Acellular Adipose Tissue (AAT) is a cadaveric, adipose-derived extracellular matrix biomaterial for soft tissue reconstruction.
• Preclinical studies and a Phase I trial established AAT's safety, biocompatibility, and ability to promote angiogenesis and adipogenesis.

Purpose of the Study:

• To evaluate the efficacy and biological effects of AAT in the Phase II study for permanent soft tissue defect reconstruction.
• To investigate the cellular and molecular mechanisms underlying AAT's regenerative potential.

Main Methods:

• Analysis of tissue samples from ten patients in a Phase II clinical study of AAT.
• Multiplex immunofluorescence staining using the PhenoCycler imaging platform.
• Nanostring GEOMx spatial transcriptomic analysis.

Main Results:

• AAT induced the infiltration and activity of macrophages, CD3+ T cells, and CD34+ progenitor cells.
• AAT facilitated the formation of tertiary lymphoid structures (TLS) and upregulated key genes (EGR1, MCL1, NR4A1) involved in angiogenesis, anti-apoptosis, and anti-inflammation.
• AAT promoted anti-fibrotic adipose-derived stromal cells, indicating reduced scarring.

Conclusions:

• Acellular Adipose Tissue (AAT) effectively promotes angiogenesis, adipogenesis, and anti-fibrotic remodeling in soft tissue reconstruction.
• The findings support AAT's potential as a regenerative biomaterial for diverse clinical applications.
• AAT's mechanism involves modulating the local immune microenvironment and promoting beneficial cellular activities.