Abstract
Adipose-derived stromal/stem cells (ASCs) have been shown to exert regenerative functions, which are mainly attributed to the secretion of trophic factors. Upon transplantation, ASCs are facing an ischemic environment characterized by oxygen and nutrient deprivation. However, current knowledge on the secretion capacity of ASCs under such conditions is limited. Thus, the present study focused on the secretory function of ASCs under glucose and oxygen deprivation as major components of ischemia. After exposure to glucose/oxygen deprivation, ASCs maintained distinct viability, but the metabolic activity was greatly reduced by glucose limitation. ASCs were able to secrete a broad panel of factors under glucose/oxygen deprivation as revealed by a cytokine antibody array. Quantification of selected factors by ELISA demonstrated that glucose deprivation in combination with hypoxia led to markedly higher secretion levels of the angiogenic and anti-apoptotic factors IL-6, VEGF, and stanniocalcin-1 as compared to the hypoxic condition alone. A conditioned medium of glucose/oxygen-deprived ASCs promoted the viability and tube formation of endothelial cells, and the proliferation and migration of fibroblasts. These findings indicate that ASCs are stimulated by ischemia-like stress conditions to secrete trophic factors and would be able to exert their beneficial function in an ischemic environment.
Highlights
Adipose tissue-derived stromal/stem cells (ASCs) represent a valuable tool for cell-based therapies because of their widely acknowledged capacity to exert beneficial functions in tissue regeneration or in tissue repair [1,2,3,4,5,6]
We further investigated the impact of conditioned medium of ischemia-challenged Adipose-derived stromal/stem cells (ASCs) on the viability and tube formation of endothelial cells, and the proliferation and migration of fibroblasts
The results of this study suggest that ASCs can maintain their secretory function and exert regenerative effects even under ischemia-like stress conditions
Summary
Adipose tissue-derived stromal/stem cells (ASCs) represent a valuable tool for cell-based therapies because of their widely acknowledged capacity to exert beneficial functions in tissue regeneration or in tissue repair [1,2,3,4,5,6] This has been demonstrated for example for cell-assisted lipotransfer, where autologous ASCs added to lipografts have been shown to enhance vascularity, to improve the survival rate of grafts, and to reduce postoperative atrophy [7,8,9]. In regenerative approaches such as tissue engineering or cell-assisted lipotransfer, the implanted cell-laden construct or lipograft is at least initially impaired by a lack of blood supply [18,19] This leads to an ischemic environment that is characterized by the deprivation of nutrients, oxygen, and growth factors. It has been shown that depletion of oxygen and nutrients, in particular glucose, significantly affects cell survival and function, as they are both critically required for energy-related pathways [20,21,22]
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