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

Yunfan He,Jing Xia,Chengliang Deng,Hsinkai Chen,Feng Lu,Liangyue Wang

doi:10.1186/s13287-019-1356-0

Yunfan He, Jing Xia + Show 4 more

Open Access

https://doi.org/10.1186/s13287-019-1356-0

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Abstract

BackgroundTaking 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.MethodsALE 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.ResultsThe 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.ConclusionsALE 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.

Highlights

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
A secretome extract harvested from cultured adipose tissue was shown to contain various angiogenic and adipogenic factors that were able to induce angiogenesis and adipogenesis in vitro [11]
Ingenuity Pathway Analysis (IPA) analysis showed that the majority of adipose liquid extract (ALE) proteins were from the cytoplasm, followed by the nucleus, and from the extracellular space and plasma membrane (Fig. 2b, c)

Summary

Introduction

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. These cell-based therapies have been hindered by issues, such as inherent safety and cost-efficiency for clinical applications. Taking advantage of paracrine secretory function of cells, developments in growth factors therapies have been reported to make use of cell-derived secretome, which is the complex set of biomolecules secreted He et al Stem Cell Research & Therapy (2019) 10:252 during short-term culture in vitro [6]. Examples of these drawbacks include isolation of cells using enzymatic digestion that increases the risk of biological contamination, the secretome harvested from cultured cells/tissues requires considerable cell expansion, specific laboratory equipment, and good manufacturing practice, which in turn increase the financial burden [12]

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Conclusion