Placental mesenchymal stem cells restore glucose and energy homeostasis in obesogenic adipocytes.

Obesity (Ob) depicts a state of energy imbalance(s) being characterized by the accumulation of excessive fat and which predisposes to several metabolic diseases. Mesenchymal stem cells (MSCs) represent a promising option for addressing obesity and its associated metabolic co-morbidities. The present study aims at assessing the beneficial effects of human placental MSCs (P-MSCs) in mitigating Ob-associated insulin resistance (IR) and mitochondrial dysfunction both in vivo and in vitro. Under obesogenic milieu, adipocytes showed a significant reduction in glucose uptake, and impaired insulin signaling with decreased expression of UCP1 and PGC1α, suggestive of dysregulated non-shivering thermogenesis vis-a-vis mitochondrial biogenesis respectively. Furthermore, obesogenic adipocytes demonstrated impaired mitochondrial respiration and energy homeostasis evidenced by reduced oxygen consumption rate (OCR) and blunted ATP/NAD+/NADP+ production respectively. Interestingly, co-culturing adipocytes with P-MSCs activated PI3K-Akt signaling, improved glucose uptake, diminished ROS production, enhanced mitochondrial OCR, improved ATP/NAD+/NADP+ production, and promoted beiging of adipocytes evidenced by upregulated expression of PRDM16, UCP1, and PGC1α expression. In vivo, P-MSCs administration increased the peripheral blood glucose uptake and clearance, and improved insulin sensitivity and lipid profile with a coordinated increase in the ratio of ATP/ADP and NAD+ and NADP+ in the white adipose tissue (WAT), exemplified in WNIN/GR-Ob obese mutant rats. In line with in vitro findings, there was a significant reduction in adipocyte hypertrophy, increased mitochondrial staining, and thermogenesis. Our findings advocate for a therapeutic application of P-MSCs for improving glucose and energy homeostasis, i.e., probably restoring non-shivering thermogenesis towards obesity management.

The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems.

Obesity (Ob) poses a significant risk factor for the onset of metabolic syndrome with associated complications, wherein the Mesenchymal Stem Cell (MSC) therapy shows pre-clinical success. Here, we explore the therapeutic applications of human Placental MSCs (P-MSCs) to address Ob-associated Insulin Resistance (IR) and its complications. In the present study, we show that intramuscular injection of P-MSCs homed more towards the visceral site, restored HOMA-IR and glucose homeostasis in the WNIN/GR-Ob (Ob-T2D) rats. P-MSC therapy was effective in re-establishing the dysregulated cytokines. We report that the P-MSCs activates PI3K-Akt signaling and regulates the Glut4-dependant glucose uptake and its utilization in WNIN/GR-Ob (Ob-T2D) rats compared to its control. Our data reinstates P-MSC treatment's potent application to alleviate IR and restores peripheral blood glucose clearance evidenced in stromal vascular fraction (SVF) derived from white adipose tissue (WAT) of the WNIN/GR-Ob rats. Gaining insights, we show the activation of the PI3K-Akt pathway by P-MSCs both in vivo and in vitro (palmitate primed 3T3-L1 cells) to restore the insulin sensitivity dysregulated adipocytes. Our findings suggest a potent application of P-MSCs in  pre-clinical/Ob-T2D management.

Polyvaccine: joining the links in the cascade of type 1 diabetes

The incidence of type 1 diabetes mellitus (T1DM), an autoimmune disorder, has ascended considerably with around 98,200 and 15,900 incidents in children below 15 years of age, globally and in India, respectively. This is typically due to environmental changes leading to genetic modifications. Also, T1DM encompasses the presence of autoantigens and many other etiologies which can be targeted by proper immunization. In this paper, we consciously discuss and collate various candidate triggers of islet autoimmunity and other factors expected to promote progression of T1DM. This paper bridges all the mechanisms caused by these factors and linking them with each other. We have also highlighted on the novel corona virus as a trigger for T1DM. Finally, we suggest that an amalgamated model of polyvaccine can batter the condition by inducing protection against various triggers of T1DM.