title: Efficacy of Autologous Bone Marrow-Derived Mesenchymal Stem Cell and Mononuclear Cell Transplantation in Type 2 Diabetes Mellitus: A Randomized, Placebo-Controlled Comparative Study.
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.
authors.affiliation: 1 Department of Endocrinology, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Shobhit
authors.initials: S
authors.lastname: Bhansali
authors.affiliation: 1 Department of Endocrinology, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Pinaki
authors.initials: P
authors.lastname: Dutta
authors.affiliation: 2 Department of Nephrology/Translational and Regenerative Medicine, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.affiliation: 3 Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Mukesh Kumar
authors.initials: MK
authors.lastname: Yadav
authors.affiliation: 4 Department of Transfusion Medicine, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Ashish
authors.initials: A
authors.lastname: Jain
authors.affiliation: 5 Department of Medicine, University of California , San Diego, La Jolla, California.
authors.forename: Sunder
authors.initials: S
authors.lastname: Mudaliar
authors.affiliation: 6 Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Shipra
authors.initials: S
authors.lastname: Bhansali
authors.affiliation: 4 Department of Transfusion Medicine, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Ratti Ram
authors.initials: RR
authors.lastname: Sharma
authors.affiliation: 2 Department of Nephrology/Translational and Regenerative Medicine, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Vivekanand
authors.initials: V
authors.lastname: Jha
authors.affiliation: 4 Department of Transfusion Medicine, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Neelam
authors.initials: N
authors.lastname: Marwaha
authors.affiliation: 3 Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Niranjan
authors.initials: N
authors.lastname: Khandelwal
authors.affiliation: 7 Department of Pharmacology, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Anand
authors.initials: A
authors.lastname: Srinivasan
authors.affiliation: 1 Department of Endocrinology, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Naresh
authors.initials: N
authors.lastname: Sachdeva
authors.affiliation: 8 Division of Endocrinology and Diabetes Research and Training Center , Department of Medicine, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Meredith
authors.initials: M
authors.lastname: Hawkins
authors.affiliation: 1 Department of Endocrinology, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Anil
authors.initials: A
authors.lastname: Bhansali
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000628:therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D014182:Transplantation, Autologous / Q000379:methods
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: T2DM; insulin sensitivity; stem cells; β-cells