Abstract
Stem cell therapy has long been considered a promising mode of treatment for many incurable diseases. Human mesenchymal stem cells (hMSCs) have provided the most promising results to date for regenerative medicine. Nevertheless, due to several obstacles such as difficulty in sourcing and characterizing hMSCs, they remain largely unavailable for clinical use. The signaling requirements for maintaining stem cell function have been studied widely, but little is known about how metabolism contributes to stem cell function. hMSCs have been shown to promote therapeutic efficacy in hypoxic conditions through metabolic conversion. According to published studies, certain metabolites are able to convert stem cell metabolism from oxidative phosphorylation to glycolysis. In this study, we selected several metabolites (fructose-1,6-bisphosphate (FBP), Phosphoenolpyruvic acid (PEP) and sodium oxalate (OXA)) to examine the relation between metabolites and stem cell functions. In addition, we investigated the ability of selected metabolites to induce rapid expansion of this cell population. Our results indicate that selected metabolites stimulate stem cell proliferation by induce glycolytic metabolism via AKT/STAT signaling.
Highlights
The current excitement regarding the potential for stem cell therapy to improve patient outcomes is understandable
We first examined the effect of hypoxic conditions on Human mesenchymal stem cells (hMSCs) metabolism
The number of hMSCs at the end of the culture period was greater under hypoxic conditions compared to normoxic conditions (Fig. 1a)
Summary
The current excitement regarding the potential for stem cell therapy to improve patient outcomes is understandable. Mesenchymal stem cells (MSCs) have been shown to promote therapeutic efficacy via a mechanism that is potentiated by hypoxic conditions (low O2)[3]. Certain metabolites are able to convert stem cell metabolism from oxidative phosphorylation to glycolysis. Among these metabolites, fructose-1,6-bisphosphate (FBP), 3-phosphoglyceric acid (3PG), Phosphoenolpyruvic acid (PEP), 2-deoxyglucose (2DG), indoleacetic acid (IAA), and sodium oxalate (OXA) have been shown to have promising effects in vitro in several cancer and progenitor cell line models[5,6,7,8]. We investigated the molecular effects and relationship between hypoxic condition and metabolites on hMSCs. Our results will improve the understanding of the underlying mechanisms of metabolites www.nature.com/scientificreports/. Our results may increase the feasibility of stem cell therapy
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