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

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

Research output: Contribution to journalArticle

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Abstract

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 (1.13106/kg UC-MSC, 106.83106/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 (AUCC-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 treatmentwaswell tolerated. At 1 year,metabolicmeasures 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 (1,517.76630.2 to 1,431.76 441.6 mmol/mL/180 min, P = 0.027 vs. SCT). HbA1c decreased 12.6% (8.6 ± 0.81% [70.067.1mmol/mol] to 7.561.0% [58.068.6mmol/mol], P <0.01) in the treated group, whereas it increased 1.2% in the control group (8.7 ± 0.9% [72.0 6 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 (0.96 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 associatedwithmoderate improvement of metabolic measures in patients with established T1D.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalDiabetes Care
Volume39
Issue number1
DOIs
StatePublished - Jan 1 2016

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Umbilical Cord
Stem Cell Transplantation
Bone Marrow Transplantation
Mesenchymal Stromal Cells
Type 1 Diabetes Mellitus
Insulin
Safety
Bone Marrow Cells
Area Under Curve
C-Peptide
Glucose Tolerance Test
Catheterization
Immunotherapy
Clinical Studies
Fasting
Research Design
Arteries
Transplantation
Quality of Life
Control Groups

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

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. / 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.

In: Diabetes Care, Vol. 39, No. 1, 01.01.2016, p. 149-157.

Research output: Contribution to journalArticle

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. / 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. In: Diabetes Care. 2016 ; Vol. 39, No. 1. pp. 149-157.
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abstract = "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 (1.13106/kg UC-MSC, 106.83106/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 (AUCC-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 treatmentwaswell tolerated. At 1 year,metabolicmeasures 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 (1,517.76630.2 to 1,431.76 441.6 mmol/mL/180 min, P = 0.027 vs. SCT). HbA1c decreased 12.6{\%} (8.6 ± 0.81{\%} [70.067.1mmol/mol] to 7.561.0{\%} [58.068.6mmol/mol], P <0.01) in the treated group, whereas it increased 1.2{\%} in the control group (8.7 ± 0.9{\%} [72.0 6 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 (0.96 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 associatedwithmoderate improvement of metabolic measures in patients with established T1D.",
author = "Jinquan Cai and Zhixian Wu and Xiumin Xu and Lianming Liao and Jin Chen and Lianghu Huang and Weizhen Wu and Fang Luo and Chenguang Wu and Alberto Pugliese and Antonello Pileggi and Camillo Ricordi and Jianming Tan",
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TY - JOUR

T1 - Umbilical Cord Mesenchymal Stromal Cell with Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes

T2 - A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion

AU - Cai, Jinquan

AU - Wu, Zhixian

AU - Xu, Xiumin

AU - Liao, Lianming

AU - Chen, Jin

AU - Huang, Lianghu

AU - Wu, Weizhen

AU - Luo, Fang

AU - Wu, Chenguang

AU - Pugliese, Alberto

AU - Pileggi, Antonello

AU - Ricordi, Camillo

AU - Tan, Jianming

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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 (1.13106/kg UC-MSC, 106.83106/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 (AUCC-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 treatmentwaswell tolerated. At 1 year,metabolicmeasures 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 (1,517.76630.2 to 1,431.76 441.6 mmol/mL/180 min, P = 0.027 vs. SCT). HbA1c decreased 12.6% (8.6 ± 0.81% [70.067.1mmol/mol] to 7.561.0% [58.068.6mmol/mol], P <0.01) in the treated group, whereas it increased 1.2% in the control group (8.7 ± 0.9% [72.0 6 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 (0.96 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 associatedwithmoderate improvement of metabolic measures in patients with established T1D.

AB - 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 (1.13106/kg UC-MSC, 106.83106/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 (AUCC-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 treatmentwaswell tolerated. At 1 year,metabolicmeasures 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 (1,517.76630.2 to 1,431.76 441.6 mmol/mL/180 min, P = 0.027 vs. SCT). HbA1c decreased 12.6% (8.6 ± 0.81% [70.067.1mmol/mol] to 7.561.0% [58.068.6mmol/mol], P <0.01) in the treated group, whereas it increased 1.2% in the control group (8.7 ± 0.9% [72.0 6 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 (0.96 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 associatedwithmoderate improvement of metabolic measures in patients with established T1D.

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