Fat Therapeutics: The Clinical Capacity of Adipose-Derived Stem Cells and Exosomes for Human Disease and Tissue Regeneration
journal contributionposted on 19.01.2021, 08:08 by L Shukla, Y Yuan, R Shayan, David GreeningDavid Greening, T Karnezis
© Copyright © 2020 Shukla, Yuan, Shayan, Greening and Karnezis. Fat grafting is a well-established surgical technique used in plastic surgery to restore deficient tissue, and more recently, for its putative regenerative properties. Despite more frequent use of fat grafting, however, a scientific understanding of the mechanisms underlying either survival or remedial benefits of grafted fat remain lacking. Clinical use of fat grafts for breast reconstruction in tissues damaged by radiotherapy first provided clues regarding the clinical potential of stem cells to drive tissue regeneration. Healthy fat introduced into irradiated tissues appeared to reverse radiation injury (fibrosis, scarring, contracture and pain) clinically; a phenomenon since validated in several animal studies. In the quest to explain and enhance these therapeutic effects, adipose-derived stem cells (ADSCs) were suggested as playing a key role and techniques to enrich ADSCs in fat, in turn, followed. Stem cells - the body’s rapid response ‘road repair crew’ - are on standby to combat tissue insults. ADSCs may exert influences either by releasing paracrine-signalling factors alone or as cell-free extracellular vesicles (EVs, exosomes). Alternatively, ADSCs may augment vital immune/inflammatory processes; or themselves differentiate into mature adipose cells to provide the ‘building-blocks’ for engineered tissue. Regardless, adipose tissue constitutes an ideal source for mesenchymal stem cells for therapeutic application, due to ease of harvest and processing; and a relative abundance of adipose tissue in most patients. Here, we review the clinical applications of fat grafting, ADSC-enhanced fat graft, fat stem cell therapy; and the latest evolution of EVs and nanoparticles in healing, cancer and neurodegenerative and multiorgan disease.
The authors acknowledge Janna Taylor for her expertise and professionalism in assistance with formatting and figure and table preparations. TK, RS, LS, and YY also thank the Wicking Trust, Stafford Fox Trust and McMullin Family Trust for their ongoing financial support of their work. This work was funded, in part, by the National Health & Medical Research Council of Australia (project grant 1057741 and 1139489 to DG) and Helen Amelia Hanis Fellowship (to DG).
JournalFrontiers in Pharmacology
Pagination23p. (p. 1-23)
PublisherFrontiers Research Foundation
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Science & TechnologyLife Sciences & BiomedicinePharmacology & Pharmacyadiposestem cellexosomeextracellular vesiclesregenerationSTROMAL-VASCULAR FRACTIONBREAST-CANCER CELLSPATTERN SKIN FLAPSMESENCHYMAL STEMEXTRACELLULAR VESICLESSOFT-TISSUEISCHEMIA-REPERFUSIONIN-VITROIMMUNOMODULATORY PROPERTIESAUTOLOGOUS TRANSPLANTATION