Major impacts of Type 2 Diabetes Mellitus on potency and metabolism of bone marrow derived mesenchymal stem cells
A research on Major impacts of Type 2 Diabetes Mellitus on potency and metabolism of bone marrow derived mesenchymal stem cells has been done by Researchers from Cellular Manufacturing Department, Vinmec Research Institute of Stem cell and Gene Technology. Results have been presented and discussed at the 3th Vinmec International Conference on Cell and Gene Therapy (VCGT-2019), on 31/10/2019 in Hanoi.
Minh Duc Hoang1, Ai Xuan Hoang1, Lan Anh Ngo1, Trung Duong Tri1, Hue Hong Bui1, Nhung Trinh Thi Hong1, Liem Nguyen Thanh1.
1: Cellular Manufacturing Department, Vinmec Research Institute of Stem cell and Gene Technology, 458 Minh Khai St., Hanoi, Vietnam.
Corresponding author: v.duchm3@vinmec.com
ABSTRACT
Diabetes mellitus (DM) is a major health problem and leading cause of dead in the modern word, characterizing by progressive obesity, insulin resistance, abnormal cholesterol or triglyceride levels, and uncontrollable blood glucose level.
In Vietnam, by the end of 2015, more than 60,000 cases of DM were recorded, representing 5.6% Vietnamese population. This estimate was projected to rise to 85,000 cases by 2040. Many approaches have been recently developed to prevent the health-related consequences of T2DM with the major goal is to protecting patients from the long-term complications of the disease.
These involve new drug deployment, such as Pramlintide, alpha-glucosidase inhibitiors, sulfonylureas, meglitinides, GLP1/DPP-IV-inhibitors, Metformin, Thiazolidinediones, but also gastric manipulations, nutrition-related therapy, and finally mesenchymal stem/stromal cell (MSC) therapy. Recently, stem cell therapy, especially autologous bone marrow derived mesenchymal stem cells (aBM-MSCs) emerged as a novel therapeutic approach for T2DM and has been conducted at Vinmec Research Institute of Stem cell and Gene technology (clinicaltrials.gov ID: NCT03343782).
In this project, it has been noted that the changes in stem cell proliferation occurred in patients with prolong diagnosed T2DM compared to that of control groups (Group 1). To investigate the effects of T2DM on the BM-MSC biology and metabolic activities, our group focused on evaluation of BM-MSCs obtained from three groups of patients who has been diagnosed T2DM for 5 years (Group 2), 10 years (Group 3), and over 15 years (Group 4).
Biological evaluation of BM-MSCs analyzing morphology, MSC marker, and karyotype showed no significant differences between groups. Interestingly, the population doubling times of group 3 and group 4 were significantly slower compared to that of Group 1 and Group 2. Further analysis using Seahorse XF Cell Mito Stress Test Kit and Seahorse XF Glycolysis Stress Test Kit also revealed the differences in mitochondrial activities and glycolysis functions between T2DM patients with the control group, respectively. Our finding support the hypothesis that prolonged T2DM that impairment in proliferation and bioenergetic metabolism of autologous BM-MSCs may be a key mechanism compromising the effectiveness of these cells in the treatment of T2DM.