Human adipose liquid extract induces angiogenesis and adipogenesis: a novel cell-free therapeutic agent

Abstract

Background Taking advantage of cellular paracrine mechanisms, the secretome of adipose-derived stem cells (ADSCs) and adipose tissue has been demonstrated to induce tissue repair and regeneration in various ischemic and impaired conditions. However, these cell-based therapies have been hindered by issues, such as inherent safety and cost-efficiency for clinical applications. In this study, we prepared a liquid cell-free extract from human adipose tissue [adipose liquid extract (ALE)] and evaluated its potential therapeutic efficacy. Methods ALE was prepared from human subcutaneous adipose tissue using a rapid and physical approach, and the protein components in ALE were identified using mass spectrometry analysis. In vivo, the therapeutic effect of this agent was investigated on wound healing in C57BL/6 mice, and wound healing rate, vessel density, and neo-adipocyte formation in wounded skins were measured at days 3, 7, 11, and 14. In vitro, the effect of ALE on the viability of human ADSCs, tube formation of human umbilical vein endothelial cells (HUVECs), and adipogenic differentiation of ADSCs were tested. Results The results demonstrated that ALE contained a variety of growth factors and did not affect cell viability. ALE-treated wounds exhibited accelerated wound healing with increased vessel density and formation of neo-adipocytes compared to that of control wounds. Moreover, when added as a cell culture supplement, ALE effectively induced tube formation of HUVECs and lipid accumulation in ADSCs. ALE-treated ADSCs also exhibited elevated levels of adipogenic gene expression. Conclusions ALE is a novel growth-rich therapeutic agent that is cell-free and easy to produce. Besides, it is also able to induce angiogenesis and adipogenesis both in vitro and in vivo, thus indicating that it could be used for wound repair and soft tissue regeneration.

Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing

“…Inducing microenvironment changes by the overexpression of SDF-1 in DF led to keratinocyte proliferation and ADSC recruitment, providing that a neovascularization has taken place together with the increase of ECM secretion, thus promoting the remodeling phase of healing [29,105,109]. Adipose tissue extract paved the way for ADSCs and accelerated wound healing and improved angiogenesis via the increased vessel density [110].…”

Therapeutic applications of adipose cell-free derivatives: a review

“…Then centrifuge at 2000 g for 5 min and filter with a 0.22-μm syringe filter 6. Or after being frozen and thawed for one cycle and centrifuge at 1200 g for 5 min, then filter with a 0.22μm syringe filter Rich in cytokines, but the source is relatively limited VEGF [23][24][25][26] bFGF [24][25][26][27] BDNF [23,27];GDNF [23,27] TGF-β [23,26,27]; HGF [23,26,27]; PDGF [23,26,27]; IGF-1 [80,85]; KGF [28] dimensional culture, ADSC-CM from three-dimensional culture showed a superior stimulatory effect on the proliferation and migration of fibroblasts and keratinocytes and was more effective in promoting wound healing [32]. This was consistent with the finding that galectin-1 was only detected in ADSC-CM from three-dimensional culture, which was found to be an important factor for the migration of keratinocytes [32], as well as to the higher cytokine secretion [44].…”

“…However, the storage of the three cell-free derivatives is also different, lacking a unified storage method. For example, ATE is generally stored at − 20°C, although some authors have indicated its storage at − 40°C [24]; extracted ADSC-Exo is suspended in PBS or PBS containing Exo and stored at − 80°C, while ADSC-CM is stored at − 20°C or − 80°C. In addition, as far as the method of administration is concerned, these three cell-free derivatives are usually mainly applied topically, and some are given by subcutaneous injection or intravenous injection.…”

“…Then centrifuge at 2000 g for 5 min and filter with a 0.22-μm syringe filter 6. Or after being frozen and thawed for one cycle and centrifuge at 1200 g for 5 min, then filter with a 0.22-μm syringe filter Rich in cytokines, but the source is relatively limited VEGF [ 23 – 26 ] bFGF [ 24 – 27 ] BDNF [ 23 , 27 ];GDNF [ 23 , 27 ] TGF-β [ 23 , 26 , 27 ]; HGF [ 23 , 26 , 27 ]; PDGF [ 23 , 26 , 27 ]; IGF-1 [80, 85]; KGF [ 28 ] …”

Modeling Adipogenesis: Current and Future Perspective

“…From another perspective, a notable novel study underlines the potential of exploiting adipogenesis to regenerate soft tissues and to enhance wound repair. Cell-free human adipose liquid extracts are used to trigger angiogenesis and adipogenesis [ 138 ]. Finally, another recent promising therapy would be the Korean mistletoe-derived polypeptide viscothionin.…”