Adipose tissue-derived extracellular fraction characterization: biological and clinical considerations in regenerative medicine

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.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0956-4) contains supplementary material, which is available to authorized users.

Extracellular fraction of adipose tissue as an innovative regenerative approach for vitiligo treatment

“…Numerous studies in recent years have demonstrated that adipose tissue has a significant impact on the cellular microenvironment by the secretion of a wide range of bioactive factors with pleiotropic functions. We previously demonstrated that adipose tissue extracellular fraction, easily isolated from lipoaspirate during intra‐operatory time, exhibits significant potential in skin repair . Here, consistent with the idea that stress‐related modification of the entire skin may be responsible for melanocytes loss and failure in repigmentation, we propose an innovative approach based on AT‐Ex to target most of the recognized defects of vitiligo skin.…”

“…Levels of bFGF, SCF, ET‐1, α‐MSH and GM‐CSF are lower in vitiligo lesion in comparison with healthy control . We have recently demonstrated that SCF, α‐MSH, GM‐CSF bFGF, keratinocyte growth factor (KGF) and nerve growth factor important regulators of melanocyte biology are abundantly present in the extracellular fraction of lipoaspirates . Altogether, the AT‐Ex profile proved that it is an enriched mixture of growth factors usable in skin regeneration.…”

“…Normal human skin samples matched for anatomic site were taken from seventeen healthy subjects (seven men and ten women, age range: 26‐66 years) who underwent plastic surgery. Primary cultures of dermal fibroblasts and melanocytes were isolated and grown as previously described . All experiments were performed employing cells from short‐term cultures (2‐10 cell culture passage for both melanocytes and fibroblasts).…”

“…Our previous data demonstrated that AT‐Ex has a harmful effect in counteracting oxidative damage in normal dermal and epidermal cells . Since increased ROS levels have been proved to be a key player during vitiligo initiation and progression, we further investigated in vitiligo cell cultures.…”

“…However, adipose tissue also includes endothelial cells, preadipocytes, immune system cells and adipose‐resident macrophages which in addition to ADSCs, compose the stromal vascular fraction and the associated secretome . Recently, we demonstrated that due to the elevated concentration of growth factors, extracellular components of whole adipose tissue could be used as an innovative cell‐free therapy for application requiring functional or structural tissue regeneration but minimal soft tissue augmentation such as skin repair . In line with that idea, we have focused on the paracrine effects of adipose tissue secretome (AT‐Ex) evaluating the possible application of this innovative tool in vitiligo skin as a cell‐free therapy or as an adjuvant therapy in combination with cell suspension transplantation.…”