The antifibrotic adipose-derived stromal cell: Grafted fat enriched with CD74+ adipose-derived stromal cells reduces chronic radiation-induced skin fibrosis.
Stem cells translational medicine
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 ?3 (TGF-?3) and decreased levels of TGF-?1. 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.
View details for DOI 10.1002/sctm.19-0317
View details for PubMedID 32563212
CD34+CD146+ adipose-derived stromal cells enhance engraftment of transplanted fat.
Stem cells translational medicine
Fat grafting is a surgical technique able to reconstruct and regenerate soft tissue. The adipose-derived stromal cells (ASCs) within the stromal vascular fraction are believed to drive these beneficial effects. ASCs are increasingly recognized to be a heterogeneous group, comprised of multiple stem and progenitor subpopulations with distinct functions. We hypothesized the existence of an ASC subpopulation with enhanced angiogenic potential. Human ASCs that were CD34+CD146+, CD34+CD146-, or CD34+ unfractionated (UF) were isolated by flow cytometry for comparison of expression of proangiogenic factors and endothelial tube-forming potential. Next, lipoaspirate was enriched with either CD34+CD146+, CD34+CD146-, CD34+ UF ASCs, or was not enriched, and grafted beneath the scalp skin of immunodeficient CD-1 Nude mice (10?000?cells/200??L/graft). Fat retention was monitored radiographically more than 8?weeks and fat grafts were harvested for histological assessment of quality and vascularization. The CD34+CD146+ subpopulation comprised ~30% of ASCs, and exhibited increased expression of vascular endothelial growth factor and angiopoietin-1 compared to CD34+CD146- and CD34+ UF ASCs, and increased expression of fibroblast growth factor-2 compared to CD34+CD146- ASCs. The CD34+CD146+ subpopulation exhibited enhanced induction of tube-formation compared to CD34+CD146- ASCs. Upon transplantation, fat enriched CD34+CD146+ ASCs underwent less resorption and had improved histologic quality and vascularization. We have identified a subpopulation of CD34+ ASCs with enhanced angiogenic effects in?vitro and in?vivo, likely mediated by increased expression of potent proangiogenic factors. These findings suggest that enriching lipoaspirate with CD34+CD146+ ASCs may enhance fat graft vascularization and retention in the clinical setting.
View details for DOI 10.1002/sctm.19-0195
View details for PubMedID 32543083
Outcomes of Fat Grafting in Irradiated Tissue Are Improved by Pre-Treatment with Transdermal Deferoxamine
ELSEVIER SCIENCE INC. 2019: E216
View details for Web of Science ID 000492749600518
CD74+Adipose-Derived Stromal Cells Have Anti-Fibrotic Effects in Grafted Fat in the Irradiated and Non-Irradiated Setting
ELSEVIER SCIENCE INC. 2019: E214
View details for Web of Science ID 000492749600512
Fat Chance: The Rejuvenation of Irradiated Skin
PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN
2019; 7 (2): e2092
Radiotherapy (RT) helps cure and palliate thousands of patients with a range of malignant diseases. A major drawback, however, is the collateral damage done to tissues surrounding the tumor in the radiation field. The skin and subcutaneous tissue are among the most severely affected regions. Immediately following RT, the skin may be inflamed, hyperemic, and can form ulcers. With time, the dermis becomes progressively indurated. These acute and chronic changes cause substantial patient morbidity, yet there are few effective treatment modalities able to reduce radiodermatitis. Fat grafting is increasingly recognized as a tool able to reverse the fibrotic skin changes and rejuvenate the irradiated skin. This review outlines the current progress toward describing and understanding the cellular and molecular effects of fat grafting in irradiated skin. Identification of the key factors involved in the pathophysiology of fibrosis following RT will inform therapeutic interventions to enhance its beneficial effects.
View details for PubMedID 30881833
- Method of Isolating and Transplanting the Hematopoietic Stem Cell with Its Microenvironment Which Improves Functional Hematopoietic Engraftment ELSEVIER SCIENCE INC. 2018: E224