Fat grafting rescues radiation-induced joint contracture

Abstract

The aim of this study was to explore the therapeutic effects of fat grafting on radiation‐induced hind limb contracture. Radiation therapy (RT) is used to palliate and/or cure a range of malignancies but causes inevitable and progressive fibrosis of surrounding soft tissue. Pathological fibrosis may lead to painful contractures which limit movement and negatively impact quality of life. Fat grafting is able to reduce and/or reverse radiation‐induced soft tissue fibrosis. We explored whether fat grafting could improve extensibility in irradiated and contracted hind limbs of mice. Right hind limbs of female 60‐day‐old CD‐1 nude mice were irradiated. Chronic skin fibrosis and limb contracture developed. After 4 weeks, irradiated hind limbs were then injected with (a) fat enriched with stromal vascular cells (SVCs), (b) fat only, (c) saline, or (d) nothing (n = 10/group). Limb extension was measured at baseline and every 2 weeks for 12 weeks. Hind limb skin then underwent histological analysis and biomechanical strength testing. Irradiation significantly reduced limb extension but was progressively rescued by fat grafting. Fat grafting also reduced skin stiffness and reversed the radiation‐induced histological changes in the skin. The greatest benefits were found in mice injected with fat enriched with SVCs. Hind limb radiation induces contracture in our mouse model which can be improved with fat grafting. Enriching fat with SVCs enhances these beneficial effects. These results underscore an attractive approach to address challenging soft tissue fibrosis in patients following RT.

Human Adipocyte Conditioned Medium Promotes In Vitro Fibroblast Conversion to Myofibroblasts

“…Clinically, autologous fat grafting has been adopted widely in reconstructive surgery because of its utility in tissue reconstruction and augmentation 25,26,56 . More recently, lipoaspirate, processed to retain different components of the stromal vascular fraction (SVF), has been promoted for its potential to improve healing and reverse scarring from traumatic injury 23 , burns 21,22 , and radiation 25,26 . There is, however, uncertainty regarding the efficacy of this procedure, and the underlying biological processes involved remain largely unknown.…”

“…Adipocytes may also be involved in the matrix formation stages of wound healing, as they are closely associated with angiogenesis and production of collagen type VI in tissue from obese patients [17][18][19] . In addition, a growing number of clinicians have advocated for the use of fat autografts to reduce scarring and improve healing [20][21][22][23][24][25][26] . Other adipocyte-related cells, such as their precursors (i.e., pre-adipocytes and adipose derived stem cells (ASCs)), may also influence the healing process 20, [27][28][29][30] .…”

Prophylactic treatment with transdermal deferoxamine mitigates radiation-induced skin fibrosis

“…Images of Picrosirius Red-stained slides were captured at 40 × and then color deconvoluted, converted to gray scale, binarized, and skeletonized using a novel algorithm run in MATLAB with Image Processing Toolbox (R2018b, MathWorks, Natick, MA) 41 . From the skeletonized images, 13 parameters of red collagen fibers were extracted (brightness, number, length, width, persistence, angle, branchpoints, euler number, extent, perimeter, solidity, eccentricity, equivalent diameter), measured using the regionprops command 42 , and underwent dimensionality reduction to generate 2 dimensional t-Distributed Stochastic Neighbor Embedding (TSNE) plots to visualize collective differences in the collagen fiber network patterns between groups. Geometric shapes were drawn to approximate the distribution of each cluster.…”

Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model

“…Borrelli et al showed that fat grafting decreased dermal thickness and collagen production in a radiation-induced fibrotic skin mouse model. 66 Therefore, injecting ASCs immediately post-isolation will determine if soft priming is necessary for this cell type to elicit an improved healing response. Finally, while translationally relevant, our model of elbow contracture is a highly specific wound environment.…”