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Received Apr 29, 2017; Revised Jun 13, 2017; Accepted Jun 15, 2017
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1. Introduction
Wound healing is a highly complex process that remains a major challenge in modern medicine. Among the factors contributing to these nonhealing conditions, impairment of cytokine production and reduced vascularization play crucial roles [1]. Mesenchymal stem cells- (MSCs-) based cytotherapy is an attractive approach in wound healing due to the differentiation potential, immunomodulating properties, and paracrine effects of MSCs [2–5]. Among the available MSCs, adipose-derived stem cells (ASCs) are promising candidates for cytotherapy because they can be easily harvested from adipose tissue and are abundant in number [6, 7]. However, isolation of ASCs still requires enzymatic digestion, which increases the risk of biological contamination. Additionally, in vitro culture and expansion of ASCs require specific laboratory experience and can take days to weeks. Moreover, in most studies, ASCs suspensions are injected separately without the protection of extracellular matrix (ECM) components, leading to rapid elimination of ASCs by the immune system and subsequent poor cell retention at recipient sites [8–10]. All of these factors weaken the therapeutic effects and applications of ASCs-based cytotherapy.
We have recently described a novel adipose-tissue-derived injectable extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) [11]. Taking advantage of shearing force (mechanical emulsification of adipose tissue by shifting between two 10 mL syringes connected by a female-to-female Luer-Lok connector) to selectively break mature adipocytes, the ECM/SVF-gel eliminates most of the lipids and other unwanted components (such as tumescent fluid) of Coleman fat. The shear force causes more damage to adipocytes than to stromal vascular fraction (SVF) cells components due to the large size and fragility of the cells, leaving only the extracellular matrix (ECM) and SVF cells and greatly improving ASCs density. According to our previous results, standard Coleman fat mechanically processed for 1 min...