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

Cytotherapy. 2015 Jul;17(7):940-7. doi: 10.1016/j.jcyt.2015.03.608. Epub 2015 Apr 11.

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 × 10(4) 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 × 10(4) 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.

Keywords: C-peptide; glycosylated hemoglobin; insulin requirement; insulin-secreting cells; mesenchymal stromal cells; stem cell therapy; type 1 diabetes mellitus.

Publication types

  • Clinical Trial

MeSH terms

  • Adipose Tissue / cytology
  • Adult
  • Blood Glucose / metabolism
  • Bone Marrow Cells / cytology
  • C-Peptide / blood
  • Cell- and Tissue-Based Therapy / methods*
  • Diabetes Mellitus, Type 1 / therapy*
  • Female
  • Glycated Hemoglobin A / analysis
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Leukocyte Common Antigens / blood
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Obesity / therapy
  • Prospective Studies
  • Subcutaneous Fat / metabolism
  • Young Adult

Substances

  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A
  • Insulin
  • Leukocyte Common Antigens
  • PTPRC protein, human