The antifibrotic adipose-derived stromal cell: Grafted fat enriched with CD74+ adipose-derived stromal cells reduces chronic radiation-induced skin fibrosis
Open Access
- 20 June 2020
- journal article
- research article
- Published by Oxford University Press (OUP) in Stem Cells Translational Medicine
- Vol. 9 (11), 1401-1413
- https://doi.org/10.1002/sctm.19-0317
Abstract
Fat grafting can reduce radiation‐induced fibrosis. Improved outcomes are found when fat grafts are enriched with adipose‐derived stromal cells (ASCs), implicating ASCs as key drivers of soft tissue regeneration. We have identified a subpopulation of ASCs positive for CD74 with enhanced antifibrotic effects. Compared to CD74− and unsorted (US) ASCs, CD74+ ASCs have increased expression of hepatocyte growth factor, fibroblast growth factor 2, and transforming growth factor β3 (TGF‐β3) and decreased levels of TGF‐β1. Dermal fibroblasts incubated with conditioned media from CD74+ ASCs produced less collagen upon stimulation, compared to fibroblasts incubated with media from CD74− or US ASCs. Upon transplantation, fat grafts enriched with CD74+ ASCs reduced the stiffness, dermal thickness, and collagen content of overlying skin, and decreased the relative proportions of more fibrotic dermal fibroblasts. Improvements in several extracellular matrix components were also appreciated on immunofluorescent staining. Together these findings indicate CD74+ ASCs have antifibrotic qualities and may play an important role in future strategies to address fibrotic remodeling following radiation‐induced fibrosis.Keywords
Funding Information
- PSF/MTF Biologics Allograft Tissue Research Grant
- Stinehart-Reed Fund
- Gunn/Olivier Research Fund
- NIH (DE027346, U01 HL099776, R01 GM116892)
- Sarnoff cardiovascular foundation
- California Institute for Regenerative Medicine
- Plastic Surgery Research Foundation
- NIH S10 Shared Instrumentation Grant (1S10OD02349701)
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