Efficacy of Autologous Bone Marrow-Derived Mesenchymal Stem Cell and Mononuclear Cell Transplantation in Type 2 Diabetes Mellitus: A Randomized, Placebo-Controlled Comparative Study

Shobhit Bhansali, Pinaki Dutta, Vinod Kumar, Mukesh Kumar Yadav, Ashish Jain, Sunder Mudaliar, Shipra Bhansali, Ratti Ram Sharma, Vivekanand Jha, Neelam Marwaha, Niranjan Khandelwal, Anand Srinivasan, Naresh Sachdeva, Meredith A. Hawkins, Anil Bhansali

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Drugs targeting β-cells have provided new options in the management of T2DM; however, their role in β-cell regeneration remains elusive. The recent emergence of cell-based therapies such as autologous bone marrow-derived mesenchymal stem cells (ABM-MSCs) and mononuclear cells (ABM-MNCs) seems to offer a pragmatic approach to augment β-cell function/mass. This study aims to examine the efficacy and safety of ABM-MSC and ABM-MNC transplantation in T2DM and explores alterations in glucose-insulin homeostasis by metabolic studies. Thirty patients of T2DM with duration of disease ≥5 years, receiving triple oral antidiabetic drugs along with insulin (≥0.4 IU/Kg/day) with HbA1c ≤7.5%(≤58.0 mmol/mol), were randomized to receive ABM-MSCs or ABM-MNCs through targeted approach and a sham procedure (n = 10 each). The primary endpoint was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c <7.0% (<53.0 mmol/mol) during 1-year follow-up. Six of 10 (60%) patients in both the ABM-MSC and ABM-MNC groups, but none in the control group, achieved the primary endpoint. At 12 months, there was a significant reduction in insulin requirement in ABM-MSC (P < 0.05) and ABM-MNC groups (P < 0.05), but not in controls (P = 0.447). There was a significant increase in second-phase C-peptide response during hyperglycemic clamp in the ABM-MNC (P < 0.05) group, whereas a significant improvement in insulin sensitivity index (P < 0.05) accompanied with an increase in insulin receptor substrate-1 gene expression was observed in the ABM-MSC group. In conclusion, both ABM-MSCs and ABM-MNCs result in sustained reduction in insulin doses in T2DM. Improvement in insulin sensitivity with MSCs and increase in C-peptide response with MNCs provide newer insights in cell-based therapies.

Original languageEnglish (US)
Pages (from-to)471-481
Number of pages11
JournalStem Cells and Development
Volume26
Issue number7
DOIs
StatePublished - Apr 1 2017

Keywords

  • insulin sensitivity
  • stem cells
  • T2DM
  • β-cells

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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    Bhansali, S., Dutta, P., Kumar, V., Yadav, M. K., Jain, A., Mudaliar, S., Bhansali, S., Sharma, R. R., Jha, V., Marwaha, N., Khandelwal, N., Srinivasan, A., Sachdeva, N., Hawkins, M. A., & Bhansali, A. (2017). Efficacy of Autologous Bone Marrow-Derived Mesenchymal Stem Cell and Mononuclear Cell Transplantation in Type 2 Diabetes Mellitus: A Randomized, Placebo-Controlled Comparative Study. Stem Cells and Development, 26(7), 471-481. https://doi.org/10.1089/scd.2016.0275