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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

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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.

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Acknowledgements

The authors would like to acknowledge Dr. R. Hemalatha, Director, ICMR-NIN, for providing the necessary infrastructure to conduct the current research and sanction intramural funding. We wish to thank the Animal Facility for all its support in carrying out these experiments. We also thank ICMR for the SRF manpower support.

Funding

The present study has been supported by ICMR-NIN intramural fundings (15-BS03 and 18-BS10) to Dr. VV, KN received a Senior Research Fellowship (5/3/8/31/ITR-F/2018-ITR) from ICMR for the present study.

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Author notes

  1. R. Bhonde

    Present address: Dr D. Y. Patil Vidyapeeth, Pune, 411018, India

Authors and Affiliations

  1. Division of Cell and Molecular Biology, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India

    Nagasuryaprasad Kotikalapudi, Samuel Joshua Pragasam Sampath & Vijayalakshmi Venkatesan

  2. Division of Food Safety, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India

    Sukesh Narayan Sinha & Sathish Kumar Mungamuri

  3. Department of Regenerative Medicine, Manipal Institute of Regenerative Medicine, GKVK Post, Bellary Road, Allalasandra, Yelahanka, Bangalore, 560065, India

    R. Bhonde

Authors
  1. Nagasuryaprasad Kotikalapudi
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  2. Samuel Joshua Pragasam Sampath
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  3. Sukesh Narayan Sinha
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  4. R. Bhonde
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  5. Sathish Kumar Mungamuri
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  6. Vijayalakshmi Venkatesan
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Contributions

KN carried out most of the animal experimentation, cell, and molecular work including characterization and injection of P-MSCs. SJPS was also associated in preparation, characterization, and injection of P-MSCs into rats. SNS and SKM were involved in designing some experiments, configuration of figures, and preparation of the manuscript. RRB was involved in human placenta collection, human ethical approval, as well as isolation of P-MSCs. VV coordinated the overall team, including project design and manuscript preparation.

Corresponding author

Correspondence to Vijayalakshmi Venkatesan.

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Kotikalapudi, N., Sampath, S.J.P., Sinha, S.N. et al. 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. Human Cell 35, 557–571 (2022). https://doi.org/10.1007/s13577-021-00664-3

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