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

作者：Cai, Jinquan; Wu, Zhixian; Xu, Xiumin; Liao, Lianming; Chen, Jin; Huang, Lianghu; Wu, Weizhen; Luo, Fang; Wu, Chenguang; Pugliese, Alberto; Pileggi, Antonello; Ricordi, Camillo; Tan, Jianming^*

来源：Diabetes Care, 2016, 39(1): 149-157.

DOI：10.2337/dc15-0171

• STEM-CELLS
• KIDNEY-TRANSPLANTS
• CHINESE PATIENTS
• C-PEPTIDE
• NEW-ONSET
• THERAPY
• MELLITUS
• MICE
• ASSOCIATION
• TRIALS

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.

• 出版日期2016-1
• 单位中国人民解放军南京军区福州总医院; 厦门大学