Abstract
Human mesenchymal stem cells (hMSCs) are widely used in regenerative medicine. In some applications, they must survive under low nutrient conditions engendered by avascularity. Strategies to improve hMSCs survival may be of high relevance in tissue engineering. Carnitine palmitoyltransferase 1 C (CPT1C) is a pseudoenzyme exclusively expressed in neurons and cancer cells. In the present study, we show that CPT1C is also expressed in hMSCs and protects them against glucose starvation, glycolysis inhibition, and oxygen/glucose deprivation. CPT1C overexpression in hMSCs did not increase fatty acid oxidation capacity, indicating that the role of CPT1C in these cells is different from that described in tumor cells. The increased survival of CPT1C-overexpressing hMSCs observed during glucose deficiency was found to be the result of autophagy enhancement, leading to a greater number of lipid droplets and increased intracellular ATP levels. In fact, inhibition of autophagy or lipolysis was observed to completely block the protective effects of CPT1C. Our results indicate that CPT1C-mediated autophagy enhancement in glucose deprivation conditions allows a greater availability of lipids to be used as fuel substrate for ATP generation, revealing a new role of CPT1C in stem cell adaptation to low nutrient environments.
Highlights
Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into various tissues of mesenchymal origin, including adipocytes, chondrocytes, osteocytes or myocytes, and even transdifferentiate into other embryonic lineage tissues, such as neurons or corneal cells[1,2,3]
To study whether Carnitine palmitoyltransferase 1 C (CPT1C) is expressed in human adult stem cells, we used human adult mesenchymal stem cells (hMSCs) derived from dental pulp kindly provide by the Regenerative Medicine Research Institute (RMI), at UIC24,25. hMSCs were used at 6–9 passages in all the experiments
Taking into account that CPT1C is exclusively present in neurons and not in glial cells[8], and that neurons represent about 10% of brain cells, we can say that the Carnitine palmitoyltransferase 1 (CPT1) expression in hMSC is similar to the one in neurons
Summary
Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into various tissues of mesenchymal origin, including adipocytes, chondrocytes, osteocytes or myocytes, and even transdifferentiate into other embryonic lineage tissues, such as neurons or corneal cells[1,2,3] They are attractive candidates for cell therapies and regenerative medicine because of their minimally invasive isolation procedure, low immunogenicity, low tumorigenic potential, and prevalent homing to injured tissues[4]. In the present study we show for the first time that CPT1C is expressed in human adult mesenchymal stem cells (hMSCs) and located in ER-mitochondria contact sites, and that CPT1C promotes cell survival under glucose deficiency conditions through the enhancement of the autophagic flux and lipid droplet synthesis. This work unravels a new role of CPT1C different from the previous ones described in tumor cells or neurons, and identifies CPT1C as a possible target in strategies aimed to improve the survival of hMSCs in regenerative medicine
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