Abstract
Mesenchymal stem cells (MSCs) represent a promising cell population for cell therapy and regenerative medicine applications. However, how variations in glucose are perceived by MSC pool is still unclear. Since, glucose metabolism is cell type and tissue dependent, this must be considered when MSCs are derived from alternative sources such as the heart. The zinc finger transcription factor Egr-1 is an important early response gene, likely to play a key role in the glucose-induced response. Our aim was to investigate how short-term changes in in vitro glucose concentrations affect multipotent cardiac tissue-derived MSCs (cMSCs) in a mouse model of Egr-1 KO (Egr-1−/−). Results showed that loss of Egr-1 does not significantly influence cMSC proliferation. In contrast, responses to glucose variations were observed in wt but not in Egr-1−/− cMSCs by clonogenic assay. Phenotype analysis by RT-PCR showed that cMSCs Egr-1−/− lost the ability to regulate the glucose transporters GLUT-1 and GLUT-4 and, as expected, the Egr-1 target genes VEGF, TGFβ-1, and p300. Acetylated protein levels of H3 histone were impaired in Egr-1−/− compared to wt cMSCs. We propose that Egr-1 acts as immediate glucose biological sensor in cMSCs after a short period of stimuli, likely inducing epigenetic modifications.
Highlights
Mesenchymal stem cells (MSCs) are widely distributed in the body and are an important source of tissue formation and regeneration
Proliferation Responses to Glucose Administrations. cardiac tissue-derived MSCs (cMSCs) derived from wt and Egr-1−/− mice were firstly isolated and phenotypically analyzed by cytofluorimetry according to the expression of differentiation antigens on the surface of murine cardiac stromal cells as previously reported [28]
We show that increased concentrations of glucose decrease the number of clones generated by wt but not by Egr-1−/− cMSCs, where the role of Egr-1 gene as biological glucose sensor is not preserved
Summary
Mesenchymal stem cells (MSCs) are widely distributed in the body and are an important source of tissue formation and regeneration. Glucose is the main fuel source for MSCs, whose pool and metabolism are influenced in both physiological and pathological conditions [3, 4]. The way in which glucose variations in MSCs exert their effects on stem cell pool is a highly interesting issue. Elevated concentrations of glucose have been demonstrated to impair original important cellular functions, such as apoptosis, cell viability, and proliferation as well as colony forming ability both in vitro and in vivo of MSCs regardless of their tissue of origin [3, 5, 6]. Glucose reduction improves all the aforementioned properties, due to the overall beneficial effects of caloric restriction reported in MSCs such as a decrease in cell death, senescence, and aging [7]
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