Abstract
BackgroundAdipose tissue-derived stem cells are considered to be a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using adipose tissue or purified stem cells, intercellular molecule exchange by the adipose tissue complex, a vast array of bioactive secretory factors, demonstrated beneficial effects by reducing tissue damage and stimulation of endogenous repair. However, for therapeutic purposes, the use of secretome derivatives, such as full conditioned media or purified exosomes generated in vitro, may present considerable disadvantages for cell manufacturing, storage, product safety, and their potential as a ready-to-go therapeutic product.MethodsIn this study, the effect of a liquid fraction of lipoaspirates isolated intraoperatively from 28 healthy donors was evaluated for their protective effect against oxidative stress and senescence, proliferation, and migration in vitro on normal human melanocytes, keratinocytes, and fibroblasts. Immunoenzymatic quantification of several growth factors and important signal molecules was used to define the biological profile of physiological adipose tissue secretome.ResultsAdipose tissue extracellular fraction (AT-Ex), isolated from lipoaspirate, exhibited significant potential for skin repair. AT-Ex augmented dermal and epidermal cell proliferation in a dose-dependent manner without promoting cancer cell growth. Moreover, migration of dermal fibroblasts, an important phenomenon implicated in endogenous repair, was enhanced by AT-Ex treatment. AT-Ex has a positive impact on oxidative stress damage when cells are exposed to extrinsic hostile factors and prevent a fibroblast senescence phenotype including paracrine functions associated with skin aging.ConclusionsCollectively, our findings propose natural systems carrying the physiological balance of in-vivo produced secretome that could improve cutaneous wound healing and tissue repair. This approach, representing an innovative perspective and therapeutic strategy in regenerative medicine, could also be combined with autologous stem cell grafts to treat chronic nonhealing wounds, stable vitiligo, severe burns, and post-oncological scarring.
Highlights
Adipose tissue-derived stem cells are considered to be a promising source in the field of cell therapy and regenerative medicine
Adipose-derived extracellular fluid promotes cell proliferation To characterize the effects of adipose tissue lipoaspirate extracellular fraction (AT-Ex) on dermal and epidermal cell proliferation we examined the responses of normal human keratinocyte (NHK), melanocyte (NHM), and fibroblast (NHF) cell cultures in a set of dose-dependent experiments
Lipoaspirate extracellular fraction stimulates cell migration and extracellular tissue remodeling To test the chemotactic activity of different AT-Ex, we investigated the migration ability of human fibroblasts and keratinocytes, the two major cell types involved in the wound healing process
Summary
Adipose tissue-derived stem cells are considered to be a promising source in the field of cell therapy and regenerative medicine. For therapeutic purposes, the use of secretome derivatives, such as full conditioned media or purified exosomes generated in vitro, may present considerable disadvantages for cell manufacturing, storage, product safety, and their potential as a ready-to-go therapeutic product. Adipose tissue is a multifunctional organ that contains various cellular types, such as mature adipocytes and the stromal vascular fraction (SVF), a source of adipose-derived stem cells (ADSCs), endothelial progenitor cells, pre-adipocytes, lymphocytes, mast cells, pericytes, and adipose-resident macrophages with repair and regenerative potential [1,2,3]. It is necessary to take into consideration that the secretory profile of SVF cells, adipocytes, or adherent adipose-derived mesenchymal stem cells cultured in vitro, alone or in combination as a mixed population, will never be truly compliant with the in-vivo conditions where the multiple cell types that comprise adipose tissue are in close proximity to each other. AT-Ex enhances the proliferation rate of adipose-derived mesenchymal stem cells, increasing the therapeutic potential of autologous grafts
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