Autologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus: effect on β-cell function and insulin sensitivity

Shobhit Bhansali, Pinaki Dutta, Mukesh Kumar Yadav, Ashish Jain, Sunder Mudaliar, Meredith Hawkins, Anura V Kurpad, Deepak Pahwa, Ashok Kumar Yadav, Ratti Ram Sharma, Vivekanand Jha, Neelam Marwaha, Shipra Bhansali, Anil Bhansali, Shobhit Bhansali, Pinaki Dutta, Mukesh Kumar Yadav, Ashish Jain, Sunder Mudaliar, Meredith Hawkins, Anura V Kurpad, Deepak Pahwa, Ashok Kumar Yadav, Ratti Ram Sharma, Vivekanand Jha, Neelam Marwaha, Shipra Bhansali, Anil Bhansali

Abstract

Background: Insulin resistance and insulin deficiency are the cardinal defects in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite the plethora of anti-diabetic medications, drugs specifically targeting the β-cells are still desired. Stem cell therapy has emerged as a novel therapeutics strategy to target β-cells; however, their mechanism of action has not been well defined. This study aims to examine the efficacy and safety of autologous bone marrow-derived mononuclear cells (ABM-MNCs) transplantation in T2DM, and explores the mechanistic insights into stem cells action through metabolic studies.

Methods: Seven T2DM patients with the duration of disease ≥5 years, receiving triple oral anti-diabetic drugs along with insulin (≥0.4 IU per kg per day) and HbA1c ≤ 7.5% (≤58.0 mmol/mol) were enrolled for ABM-MNCs administration through a targeted approach. The primary end-point was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c < 7.0% (<53.0 mmol/mol) with improvement in insulin secretion, and/or insulin sensitivity after ABM-MNCs transplantation.

Results: Six out of 7 (90%) patients achieved the primary end-point. At 6 months, there was a significant reduction in insulin requirement by 51% as compared to baseline (p < 0.003). This was accompanied by a significant increase in the 2nd phase C-peptide response during hyperglycemic clamp (p = 0.018), whereas there were no significant alterations in insulin sensitivity and glucose disposal rate during hyperinsulinemic-euglycemic clamp relative to the baseline. Other measures of β-cell indices like HOMA-β, and stimulated C-peptide response to glucagon and mixed meal tolerance test were non-contributory.

Conclusion: ABM-MNCs transplantation results in significant reduction in insulin doses and improvement in C-peptide response in patients with T2DM. Metabolic studies may be more useful than conventional indices to predict β-cell function in patients with advanced duration of T2DM. Trial registration-Clinicaltrials.gov NCT01759823.

Keywords: Autologous bone marrow-derived mononuclear cells; Stem cells; T2DM.

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Source: PubMed

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