Human placental mesenchymal stromal cell therapy restores the cytokine efflux and insulin signaling in the skeletal muscle of obesity-induced type 2 diabetes rat model

Nagasuryaprasad Kotikalapudi, Samuel Joshua Pragasam Sampath, Sukesh Narayan Sinha, R. Bhonde, Sathish Kumar Mungamuri, Vijayalakshmi Venkatesan

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Obesity poses a significant risk factor for the onset of metabolic syndrome with allied complications, wherein mesenchymal stem cell therapy is seen as a promising treatment for obesity-induced metabolic syndrome. In the present study, we aim to explore the beneficial effects of the human placental mesenchymal stromal cells (P-MSCs) on obesity-associated insulin resistance (IR) including inflammation. To understand this, we have analyzed the peripheral blood glucose, serum insulin levels by ELISA, and the glucose uptake capacity of skeletal muscle by a 2-NBDG assay using flow cytometry in WNIN/GR-Ob rats treated with and without P-MSCs. Also, we have studied insulin signaling and cytokine profile in the skeletal muscle by western blotting, dot blotting, and Multiplex-ELISA techniques. The skeletal muscle of WNIN/GR-Ob rats demonstrates dysregulation of cytokines, altered glucose uptake vis-a-vis insulin signaling. However, P-MSCs’ treatment was effective in WNIN/GR-Ob rats as compared to its control, to restore HOMA-IR, re-establishes dysregulated cytokines and PI3K-Akt pathway in addition to enhanced Glut4 expression and glucose uptake studied in skeletal muscle. Overall, our data advocate the beneficial effects of P-MSCs to ameliorate inflammatory milieu, improve insulin sensitivity, and normalize glucose homeostasis underlining the Ob-T2D conditions, and we attribute for immunomodulatory, paracrine, autocrine, and multipotent functions of P-MSCs.

Original languageEnglish
Pages (from-to)557-571
Number of pages15
JournalHuman Cell
Volume35
Issue number2
DOIs
StatePublished - Mar 2022
Externally publishedYes

Keywords

  • Cytokines
  • Glut4
  • Human placental mesenchymal stromal cells
  • Insulin signaling
  • Skeletal muscle tissue
  • WNIN/GR-Ob rats

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