Increase of glandular epithelial cell clusters by an external volume expansion device promotes adipose tissue regeneration by recruiting macrophages

Background: There is a clinical need for the use of engineered adipose tissue in place of surgical reconstruction. We previously found that the external volume expansion (EVE) device increased special cell clusters in well-vascularized connective stroma during adipose regeneration. However, the origin of these cell clusters and their role in adipose tissue regeneration remain unknown. Aim: In the present study, we evaluated EVE in the construction of expanded prefabricated adipose tissue (EPAT) in a rat model. Methods: Rats were randomized into an EVE suction group and a control group, with 24 rats in each group. The structure and origin of the special cell clusters were determined by hematoxylin and eosin staining, and immunohistochemistry; their role in adipose tissue regeneration was investigated by immunohistochemistry and Western blot analyses. Results: Special cell clusters began to increase at week 1 with a peak at week 4, and then receded from weeks 8 to 12. Clusters were identified as glandular epithelial cells as determined by their gland-like structure and expression of specific markers. The cell clusters induced significant infiltration of macrophage antigen-2 (Mac-2) positive macrophages by secreting monocyte chemoattractant protein-1 (MCP-1) at the early stage of suction. Subsequently, these infiltrated macrophages expressed massive vascular endothelial growth factor (VEGF) to promoted angiogenesis. Conclusion: EVE generated glandular epithelial cell clusters, which recruited macrophages to promote angiogenesis and subsequent adipose tissue regeneration. These findings shed light on the mechanisms underlying the effects of EVE devices on adipose tissue regeneration.