Insulin-secreting adipose-derived mesenchymal stromal cells with bone marrow–derived hematopoietic stem cells from autologous and allogenic sources for type 1 diabetes mellitus

• Published in: Cytotherapy (Oxford, England) Vol. 17; no. 7; pp. 940 - 947
• Main Authors: Thakkar, Umang G, Trivedi, Hargovind L, Vanikar, Aruna V, Dave, Shruti D
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.07.2015
• Subjects: Adipose Tissue - cytology; Adult; Advanced Basic Science; Blood Glucose - metabolism; Bone Marrow Cells - cytology; C-peptide; C-Peptide - blood; Cell- and Tissue-Based Therapy - methods; Diabetes Mellitus, Type 1 - therapy; Female; Glycated Hemoglobin A - analysis; glycosylated hemoglobin; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Humans; Insulin - metabolism; insulin requirement; Insulin Secretion; insulin-secreting cells; Leukocyte Common Antigens - blood; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; mesenchymal stromal cells; Obesity - therapy; Other; Prospective Studies; stem cell therapy; Subcutaneous Fat - metabolism; type 1 diabetes mellitus; Young Adult; insulin requirement; insulin-secreting cells; type 1 diabetes mellitus; C-peptide; stem cell therapy; mesenchymal stromal cells; glycosylated hemoglobin
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2015.03.608

Abstract Background aims Stem cell therapy (SCT) is now the up-coming therapeutic modality for treatment of type 1 diabetes mellitus (T1DM). Methods Our study was a prospective, open-labeled, two-armed trial for 10 T1DM patients in each arm of allogenic and autologous adipose–derived insulin-secreting mesenchymal stromal cells (IS-AD-MSC)+bone marrow–derived hematopoietic stem cell (BM-HSC) infusion. Group 1 received autologous SCT: nine male patients and one female patient; mean age, 20.2 years, disease duration 8.1 years; group 2 received allogenic SCT: six male patients and four female patients, mean age, 19.7 years and disease duration, 7.9 years. Glycosylated hemoglobin (HbA1c) was 10.99%; serum (S.) C-peptide, 0.22 ng/mL and insulin requirement, 63.9 IU/day in group 1; HbA1c was 11.93%, S.C-peptide, 0.028 ng/mL and insulin requirement, 57.55 IU/day in group 2. SCs were infused into the portal+thymic circulation and subcutaneous tissue under non-myelo-ablative conditioning. Patients were monitored for blood sugar, S.C-peptide, glutamic acid decarboxylase antibodies and HbA1c at 3-month intervals. Results Group 1 received mean SCs 103.14 mL with 2.65 ± 0.8 × 104 ISCs/kg body wt, CD34+ 0.81% and CD45−/90+/73+, 81.55%. Group 2 received mean SCs 95.33 mL with 2.07 ± 0.67 × 104 ISCs/kg body wt, CD34+ 0.32% and CD45−/90+/73+ 54.04%. No untoward effect was observed with sustained improvement in HbA1c and S.C-peptide in both groups with a decrease in glutamic acid decarboxylase antibodies and reduction in mean insulin requirement. Conclusions SCT is a safe and viable treatment option for T1DM. Autologous IS-AD-MSC+ BM-HSC co-infusion offers better long-term control of hyperglycemia as compared with allogenic SCT.