Deconstructing Fat to Reverse Radiation Induced Soft Tissue Fibrosis

Abstract

Adipose tissue is composed of a collection of cells with valuable structural and regenerative function. Taken as an autologous graft, these cells can be used to address soft tissue defects and irregularities, while also providing a reparative effect on the surrounding tissues. Adipose-derived stem or stromal cells are primarily responsible for this regenerative effect through direct differentiation into native cells and via secretion of numerous growth factors and cytokines that stimulate angiogenesis and disrupt pro-inflammatory pathways. Separating adipose tissue into its component parts, i.e., cells, scaffolds and proteins, has provided new regenerative therapies for skin and soft tissue pathology, including that resulting from radiation. Recent studies in both animal models and clinical trials have demonstrated the ability of autologous fat grafting to reverse radiation induced skin fibrosis. An improved understanding of the complex pathologic mechanism of RIF has allowed researchers to harness the specific function of the ASCs to engineer enriched fat graft constructs to improve the therapeutic effect of AFG.

The integration of surgical and dermatological techniques in the treatment of cutaneous aging: multidisciplinary approaches and clinical outcomes - a comprehensive systematic review of current literature

“…These cells and the stromal vascular fraction (SVF) stimulate angiogenesis and disrupt pro-inflammatory pathways, offering a regenerative effect on the damaged tissues. 10…”

A Review of Radiation-Induced Vascular Injury and Clinical Impact

“…Most importantly, ADSCs have been shown to increase vascular density in previously irradiated tissue fields. 46 While the exact mechanism by which these cells induce changes in the microvasculature remains unclear, studies have proposed that ADSCs orchestrate endothelial sprouting via secretion of proangiogenic factors such as VE growth factor. 47 Likewise, Nie et al 48 observed direct differentiation of ADSCs into angiogenic cell lineages to promote neovascularization.…”

“…Although there are currently no specific therapeutics available to overcome it, the advent of cell-based therapies, notably augmentation of fat grafts with adipose-derived stromal cells (ADSCs), has shown promising results. Most importantly, ADSCs have been shown to increase vascular density in previously irradiated tissue fields 46 . While the exact mechanism by which these cells induce changes in the microvasculature remains unclear, studies have proposed that ADSCs orchestrate endothelial sprouting via secretion of proangiogenic factors such as VE growth factor 47 .…”