The circadian rhythms of mitochondrial function after transplantation of mesenchymal stem cells

Abstract

Regenerative therapy involving stem cell transplantation has become an option for the radical treatment of diabetes mellitus. Disruption in the clock genes of stem cells affects the homeostasis of transplanted tissues. This is possibly the first study to examine the circadian rhythm of genes in transplanted adipose-derived mesenchymal stem cells derived from a patient with type 2 diabetes mellitus (T2DM-ADSC). The clock genes (PER2, CLOCK1, CRY1, and ARNTL[BMAL1]) exhibited similar daily fluctuations in phase and amplitude between a group transplanted with adipose-derived mesenchymal stem cells derived from a healthy individual (N-ADSC) and a group transplanted with T2DM-ADSC. The findings demonstrated that clock genes in stem cells are synchronized with those in living organisms. Moreover, mitochondrial genes and functions showed daily fluctuations in the N-ADSC group. However, such fluctuations were not noted in the T2DM-ADSC group. In the T2DM-ADSC group, daily fluctuations in MTATP8P1 and NDUFA7_2 genes disappeared. In the N-ADSC transplant, the results showed the circadian rhythm in the number of mitochondrial DNA copies, Mitophagy, the mitochondrial membrane potential and NF-kB signaling. In contrast, no daily fluctuations were observed in the T2DM-ADSC transplant. The circadian rhythms of mitochondrial function and NF-kB signaling revealed in this study may be a new marker for the efficiency of stem cell transplantation in patients with diabetes.