Abstract
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.
Highlights
Adipose dysregulation is fundamental to several important human disease states, such as obesity, chronic lymphedema and lipedema
As multipotent adipose derived stem cell (ADSC) can differentiate into various cell types of the tri-germ lineages, including osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic b-cells, and hepatocytes; the use of fat/ADSCs and their cell products represents a paradigm of tissue regeneration and cell restoration
We review the treatment of human diseases using adipose tissue from its origins as the humble fat graft, through attempts to enrich the concentration of ADSCs within the grafts; to selective attempts to harness the potential paracrine effects of the ADSC secretome, and to the most recent evolution – the targeted use of ADSC exosomes
Summary
Adipose dysregulation is fundamental to several important human disease states, such as obesity, chronic lymphedema and lipedema. The addition of components to enhance ADSC efficiency—such as collagenase processing—created the impression that the fat has been significantly altered and ceases to be an autologous tissue transfer, but more a modified therapeutic product (Raposio and Ciliberti, 2017) The first of these reservations was addressed when it was contested that, despite in-vitro data that suggesting that introducing stem cells might promote cell proliferation, there was no equivalent definitive evidence in-vivo to that effect (Ross et al, 2014; Shukla et al, 2015; Simonacci et al, 2016). These findings suggest that ADSCs are a potential therapeutic tool for promoting wound healing
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