Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion

OBJECTIVE To determine the safety and effects on insulin secretion of umbilical cord (UC) mesenchymal stromal cells (MSCs) plus autologous bone marrow mononuclear cell (aBM-MNC) stem cell transplantation (SCT) without immunotherapy in established type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Between January 2009 and December 2010, 42 patients with T1D were randomized (n = 21/group) to either SCT (1.1 x 10(6)/kg UC-MSC, 106.8 x 10(6)/kg aBM-MNC through supraselective pancreatic artery cannulation) or standard care (control). Patients were followed for 1 year at 3-month intervals. The primary end point was C-peptide area under the curve (AUC(C-Pep)) during an oral glucose tolerance test at 1 year. Additional end points were safety and tolerability of the procedure, metabolic control, and quality of life. RESULTS The treatment was well tolerated. At 1 year, metabolic measures improved in treated patients: AUCC-Pep increased 105.7% (6.6 +/- 6.1 to 13.6 +/- 8.1 pmol/mL/180 min, P = 0.00012) in 20 of 21 responders, whereas it decreased 7.7% in control subjects (8.4 +/- 6.8 to 7.7 +/- 4.5 pmol/mL/180 min, P = 0.013 vs. SCT); insulin area under the curve increased 49.3% (1,477.8 +/- 1,012.8 to 2,205.5 +/- 1,194.0 mmol/mL/180 min, P = 0.01), whereas it decreased 5.7% in control subjects (1,517.7 +/- 630.2 to 1,431.7 +/- 441.6 mmol/mL/180 min, P = 0.027 vs. SCT). HbA(1c) decreased 12.6% (8.6 +/- 0.81% [70.0 +/- 7.1 mmol/mol] to 7.5 +/- 1.0% [58.0 +/- 8.6 mmol/mol], P < 0.01) in the treated group, whereas it increased 1.2% in the control group (8.7 +/- 0.9% [72.0 +/- 7.5 mmol/mol] to 8.8 +/- 0.9% [73 +/- 7.5 mmol/mol], P < 0.01 vs. SCT). Fasting glycemia decreased 24.4% (200.0 +/- 51.1 to 151.2 +/- 22.1 mg/dL, P < 0.002) and 4.3% in control subjects (192.4 +/- 35.3 to 184.2 +/- 34.3 mg/dL, P < 0.042). Daily insulin requirements decreased 29.2% in only the treated group (0.9 +/- 0.2 to 0.660.2 IU/day/kg, P = 0.001), with no change found in control subjects (0.9 +/- 0.2 to 0.9 +/- 0.2 IU/day/kg, P < 0.01 vs. SCT). CONCLUSIONS Transplantation of UC-MSC and aBM-MNC was safe and associated with moderate improvement of metabolic measures in patients with established T1D.