Obese-derived ASCs show impaired migration and angiogenesis properties

Abstract

Efficient delivery of stem cells to target tissues is a major problem in regenerative medicine. Adipose derived stem cells have been proposed as important tools in cell therapy for recovering tissues after damage. Nevertheless, the ability of these ASCs to migrate or invade in order to reach the tissue of interest has not been tested so far. In this study we present evidence that the ASCs derived from obese subjects present a detrimental ability to migrate and invade in comparison with ASCs derived from control subjects. Besides, obese-derived ASCs are unable to respond to certain stimuli and to form enough capillaries after stimulation. We propose that the use of specific cytokines could overcome these deficiencies of the obese environment, offering a tool to optimize cell therapy.

Insight into the development of obesity: functional alterations of adipose‐derived mesenchymal stem cells

“…In fact, ASCs derived from human morbid obese patients showed an impaired angiogenic potential . This observation is further supported by another study showing that, compared with non‐obese ASCs, this angiogenic potential was reduced in human obese ASCs and in a mouse model . Interestingly, when phorbol 12‐myristate 13‐acetate, an angiogenic stimulus, was added to the cultures, obese ASCs were not responsive to this stimulus, whereas ASCs from non‐obese donors increased their capacity to form tubule‐like structures .…”

“…Interestingly, an increased recruitment of ASCs to the tumour has been also observed in obese patients, resulting in an increase in the number of circulating ASCs . These observations suggest that the mobility is enhanced in obese ASCs, which seems contradictory to the finding by Perez and colleagues . This discrepancy could result from different experimental settings such as the presence or absence of chemokine attractants, which affect directly the motility and directionality of ASCs.…”

“…During differentiation to mature adipocytes, mouse and human non‐obese ASCs increased their insulin sensitivity and inhibited lipolysis, whereas obese‐derived ASCs were insulin resistant, showing impaired insulin‐stimulated glucose uptake and resistance to the anti‐lipolytic effect of insulin . Interestingly, the insulin sensitivity on glucose and lipid metabolism could be restored after the cytosolic transfer from control ASCs into obese ASCs, likely due to the restoration of the Lin28/Let 7 pathway involved in a feedback loop with NF‐κB and TNF‐α , indicating a connection between inflammation and cellular insulin resistance in ASCs. Moreover, it was shown that the mitochondrial content and function were impaired in ASCs from obese mouse and human adipose tissue .…”

Unhealthy Stem Cells: When Health Conditions Upset Stem Cell Properties

“…Subcutaneous adipose tissue from obese patients has a diminished reservoir of functionally active stem cells [85]. Moreover, metabolism and maturation of APCs are arrested in an obese environment [17], and their ability to migrate or invade a tissue is impaired [86, 87]. Mechanistically, obesity causes a short circuit in the stemness gene network [88], promoting an imbalance in metabolism and a reduction in stemness properties [89].…”

Obesity reshapes stem cell extracellular vesicles

“…It has been shown that ASCs derived from obese animals and humans have reduced proliferative and migratory abilities and an impaired angiogenic capacity whereas they often commit to adipocyte differentiation when compared to those from non-obese subjects (1,2). MSCs have shown promise for regenerative cell therapy.…”