Related Experiment Video
Updated: Aug 3, 2026
MitoCeption: Transferring Isolated Human MSC Mitochondria to Glioblastoma Stem Cells
Published on: February 22, 2017
The Diurnal Variation in Mitochondrial Gene in Human Type 2 Diabetic Mesenchymal Stem Cell Grafts
Michiko Horiguchi1, Kenichi Yoshihara1, Yoichi Mizukami2
1Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi 756-0884, Japan.
Abstract:
The application of regenerative therapy through stem cell transplantation has emerged as a promising avenue for the treatment of diabetes mellitus (DM). Transplanted tissue homeostasis is affected by disturbances in the clock genes of stem cells. The aim of this study is to investigate the diurnal variation in mitochondrial genes and function after transplantation of adipose-derived mesenchymal stem cells (T2DM-ADSCs) from type 2 diabetic patients into immunodeficient mice. Diurnal variation in mitochondrial genes was assessed by next-generation sequencing. As a result, the diurnal variation in mitochondrial genes showing troughs at ZT10 and ZT22 was observed in the group transplanted with adipose-derived mesenchymal stem cells derived from healthy individuals (N-ADSC). On the other hand, in the group transplanted with T2DM-ADSCs, diurnal variation indicative of troughs was observed at ZT18, with a large phase and amplitude deviation between the two groups. To evaluate the diurnal variation in mitochondrial function, we quantified mitochondrial DNA copy number using the Human mtDNA Monitoring Primer Set, measured mitochondrial membrane potential using JC-1, and evaluated mitophagy staining. The results showed a diurnal variation in mitochondrial DNA copy number, mitophagy, mitochondrial membrane potential, and NF-kB signaling in the N-ADSC transplant group. In contrast, no diurnal variation was observed in T2DM-ADSC transplants. The diurnal variation in mitochondrial function revealed in this study may be a new marker for the efficiency of T2DM-ADSC transplantation.
Insights
Diurnal variations in mitochondrial gene expression and function are disrupted in stem cells from type 2 diabetes patients. This dysfunction may impact the effectiveness of stem cell transplantation for diabetes mellitus treatment.
Area of Science:
- Mitochondrial biology
- Chronobiology
- Stem cell therapy
Background:
- Stem cell transplantation shows promise for diabetes mellitus (DM) treatment.
- Disrupted clock genes in stem cells can affect transplanted tissue homeostasis.
- Understanding diurnal variations in stem cell function is crucial for optimizing regenerative therapies.
Purpose of the Study:
- To investigate diurnal variations in mitochondrial genes and function in adipose-derived mesenchymal stem cells (ADSCs) from type 2 diabetic patients (T2DM-ADSCs) after transplantation into mice.
- To compare these variations with those in ADSCs from healthy individuals (N-ADSCs).
Main Methods:
- Next-generation sequencing to assess diurnal variation in mitochondrial genes.
- Quantification of mitochondrial DNA copy number.
- Measurement of mitochondrial membrane potential using JC-1.
- Mitophagy staining and NF-kB signaling evaluation.
Main Results:
- Healthy N-ADSCs exhibited diurnal variation in mitochondrial genes with troughs at ZT10 and ZT22.
- T2DM-ADSCs showed altered diurnal variation with troughs at ZT18, indicating phase and amplitude deviations.
- N-ADSC transplants displayed diurnal variation in mitochondrial DNA copy number, mitophagy, membrane potential, and NF-kB signaling.
- T2DM-ADSC transplants showed a lack of diurnal variation in these mitochondrial functions.
Conclusions:
- Diurnal variation in mitochondrial function is present in healthy ADSC transplants but absent in T2DM-ADSC transplants.
- Altered diurnal mitochondrial function in T2DM-ADSCs may indicate impaired regenerative potential.
- Diurnal mitochondrial function patterns could serve as a novel biomarker for assessing the efficiency of T2DM-ADSC transplantation.
More Related Videos
08:03Ultrasound-Guided Induced Pluripotent Stem Cell-Derived Cardiomyocyte Implantation in Myocardial Infarcted Mice
Published on: March 30, 2022
06:50Author Spotlight: Bidirectional Mitochondrial Transfer between MSCs and Retinal Pigment Epithelium Cells — Pathways and In Vivo Challenges
Published on: October 4, 2024
