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

• Published in: Scientific reports Vol. 11; no. 1; pp. 16983 - 18
• Main Authors: Kotikalapudi, Nagasuryaprasad, Sampath, Samuel Joshua Pragasam, Sukesh Narayan, Sinha, R., Bhonde, Nemani, Harishankar, Mungamuri, Sathish Kumar, Venkatesan, Vijayalakshmi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.08.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/45/127; 631/45/320; 631/532; 631/532/2074; 631/80/86/2367; Adipocytes; Adipocytes - metabolism; Adipose tissue; Adipose Tissue - metabolism; AKT protein; Animals; Blood glucose; Blood Glucose - metabolism; Cell therapy; Cells, Cultured; Cytokines; Cytokines - metabolism; Diabetes mellitus; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - prevention & control; Diabetes Mellitus, Experimental - therapy; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - etiology; Diabetes Mellitus, Type 2 - prevention & control; Diabetes Mellitus, Type 2 - therapy; Female; Glucose; Glucose Transporter Type 4 - metabolism; Homeostasis; Humanities and Social Sciences; Humans; Insulin; Insulin - metabolism; Insulin resistance; Macrophages - metabolism; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Metabolic disorders; Metabolic syndrome; Models, Biological; multidisciplinary; Obesity - complications; Palmitic acid; Peripheral blood; Phosphatidylinositol 3-Kinases - metabolism; Placenta; Placenta - cytology; Pregnancy; Protein Transport; Proto-Oncogene Proteins c-akt - metabolism; Rats; Risk factors; Science; Science (multidisciplinary); Signal Transduction; Stem cells; Therapeutic applications
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-96121-0

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.