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Dll4 Inhibition Promotes Graft Retention in Fat Grafting Enriched with Adipose-Derived Stem Cells
Choong-Kun Lee1, Bo-Yoon Park2, Taehee Jo3
1Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Stem Cells Translational Medicine
|May 17, 2022
Summary
Blocking Delta-like ligand 4 (Dll4) enhances fat graft retention by promoting angiogenesis. Combining Dll4 inhibition with adipose-derived stem cell (ASC) supplementation offers synergistic benefits for soft-tissue restoration.
Area of Science:
- Regenerative Medicine
- Vascular Biology
- Tissue Engineering
Background:
- Autologous fat grafting is a common procedure for soft-tissue restoration.
- Improving fat graft retention remains a challenge.
- Adipose-derived stem cells (ASCs) are explored to enhance fat graft outcomes.
Purpose of the Study:
- To investigate the role of Delta-like ligand 4 (Dll4) in fat graft angiogenesis and retention.
- To evaluate the effect of Dll4 inhibition on ASC-supplemented fat grafts.
- To elucidate the mechanisms underlying Dll4's influence on graft survival.
Main Methods:
- Murine fat graft model to assess Dll4 expression, graft volume, vascularity, and perfusion.
- Treatment with Dll4-blocking antibody, ASC supplementation, or combination therapy.
- Transcriptome analysis to explore underlying molecular mechanisms.
Main Results:
- Dll4 is highly expressed in endothelial cells (ECs) within fat grafts.
- Dll4 blockade significantly increased angiogenesis, graft volume, and perfusion.
- Combined Dll4 inhibition and ASC supplementation showed synergistic improvement in graft retention.
- Dll4 inhibition upregulated junctional proteins in ECs and downregulated inflammation.
Conclusions:
- Dll4 inhibition promotes angiogenesis and enhances fat graft retention.
- Concomitant ASC supplementation synergizes with Dll4 inhibition for improved graft survival.
- Targeting Dll4 presents a potential therapeutic strategy for cell-assisted fat grafting.
