title: 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.
abstract: 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).
  
  
  METHODS
  Between January 2009 and December 2010, 42 patients with T1D were randomized (n = 21/group) to either SCT (1.1 × 10(6)/kg UC-MSC, 106.8 × 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). HbA1c 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 0.6 ± 0.2 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.
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, Xiamen University, Fuzhou, China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cai
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, Xiamen University, Fuzhou, China.
authors.forename: Zhixian
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Diabetes Research Institute, Cell Transplant Center, University of Miami, Miami, FL Diabetes Research Institute Federation, Hollywood, FL The Cure Alliance, Miami, FL Department of Surgery, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Xiumin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, Xiamen University, Fuzhou, China.
authors.forename: Lianming
authors.initials: L
authors.lastname: Liao
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, Xiamen University, Fuzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, Xiamen University, Fuzhou, China.
authors.forename: Lianghu
authors.initials: L
authors.lastname: Huang
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, Xiamen University, Fuzhou, China.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Wu
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, Xiamen University, Fuzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Luo
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, Xiamen University, Fuzhou, China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wu
authors.affiliation: Diabetes Research Institute, Cell Transplant Center, University of Miami, Miami, FL Department of Medicine, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pugliese
authors.affiliation: Diabetes Research Institute, Cell Transplant Center, University of Miami, Miami, FL Diabetes Research Institute Federation, Hollywood, FL The Cure Alliance, Miami, FL Department of Surgery, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Antonello
authors.identifier: http://orcid.org/0000-0001-7819-2813
authors.initials: A
authors.lastname: Pileggi
authors.affiliation: Diabetes Research Institute, Cell Transplant Center, University of Miami, Miami, FL Diabetes Research Institute Federation, Hollywood, FL The Cure Alliance, Miami, FL Department of Surgery, University of Miami Miller School of Medicine, Miami, FL Department of Medicine, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Camillo
authors.identifier: http://orcid.org/0000-0001-8092-7153
authors.initials: C
authors.lastname: Ricordi
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, Xiamen University, Fuzhou, China Diabetes Research Institute Federation, Hollywood, FL The Cure Alliance, Miami, FL tanjm156@xmu.edu.cn.
authors.forename: Jianming
authors.initials: J
authors.lastname: Tan
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002096:C-Peptide / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000628:therapy*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use; D000078790:Insulin Secretion; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D010865:Pilot Projects; D011788:Quality of Life; D014182:Transplantation, Autologous; D014470:Umbilical Cord / Q000166:cytology; D055815:Young Adult
chemical_list: D002096:C-Peptide; D007328:Insulin