Skyler Jay S, Fonseca Vivian A, Segal Karen R, Rosenstock Julio
Diabetes Research Institute, University of Miami, Miami, FL
Tulane University Health Sciences Center, New Orleans, LA.
Diabetes Care. 2015 Sep;38(9):1742-9. doi: 10.2337/dc14-2830. Epub 2015 Jul 7.
To assess the safety, tolerability, and feasibility of adult allogeneic bone marrow-derived mesenchymal precursor cells (MPCs) in type 2 diabetes inadequately controlled with metformin either alone or with one additional oral antidiabetic agent.
The study was a dose-escalating randomized placebo-controlled trial assessing one intravenous (IV) infusion of MPCs (rexlemestrocel-L; Mesoblast Inc.) 0.3 × 10(6)/kg (n = 15), 1.0 × 10(6)/kg (n = 15), or 2.0 × 10(6)/kg (n = 15) or placebo (n = 16). Study duration was 12 weeks.
Subjects (21 women, 40 men) with a mean ± SD baseline HbA1c 8.3 ± 1.0% (67 ± 10.9 mmol/mol), BMI 33.5 ± 5.5 kg/m(2), and diabetes duration 10.1 ± 6.0 years were enrolled at 18 U.S. sites. No acute adverse events (AEs) were associated with infusion. No serious AEs, serious hypoglycemia AEs, or discontinuations due to AEs over 12 weeks were found. No subjects developed donor-specific anti-HLA antibodies or became sensitized. The safety profile was comparable among treatment groups. Compared with placebo, a single IV infusion of rexlemestrocel-L reduced HbA1c at all time points after week 1. The adjusted least squares mean ± SE dose-related differences in HbA1c from placebo in the rexlemestrocel-L groups ranged from -0.1 ± 0.2% (-1.1 ± 2.2 mmol/mol) to -0.4 ± 0.2% (4.4 ± 2.2 mmol/mol) at 8 weeks and from 0.0 ± 0.25% to -0.3 ± 0.25% (-3.3 ± -2.7 mmol/mol) at 12 weeks (P < 0.05 for 2.0 × 10(6)/kg dose at 8 weeks). The clinical target HbA1c <7% (53 mmol/mol) was achieved by 33% (5 of 15) of the subjects who received the 2.0 × 10(6)/kg dose vs. 0% of those who received placebo (P < 0.05).
This short-term study demonstrates the safety and feasibility of up to 246 million MPCs in subjects with type 2 diabetes.
评估成人同种异体骨髓间充质前体细胞（MPCs）用于二甲双胍单药治疗或联合一种其他口服抗糖尿病药物血糖控制不佳的2型糖尿病患者的安全性、耐受性和可行性。
本研究为剂量递增的随机安慰剂对照试验，评估单次静脉输注MPCs（rexlemestrocel-L；Mesoblast公司），剂量分别为0.3×10⁶/kg（n = 15）、1.0×10⁶/kg（n = 15）或2.0×10⁶/kg（n = 15），或安慰剂（n = 16）。研究持续时间为12周。
在美国18个研究点招募了平均±标准差基线糖化血红蛋白（HbA1c）为8.3±1.0%（67±10.9 mmol/mol）、体重指数（BMI）为33.5±5.5 kg/m²、糖尿病病程为10.1±6.0年的受试者（21名女性，40名男性）。输注未引发急性不良事件（AE）。未发现严重AE、严重低血糖AE或12周内因AE导致的停药情况。无受试者产生供体特异性抗人白细胞抗原（HLA）抗体或致敏。各治疗组的安全性概况相当。与安慰剂相比，单次静脉输注rexlemestrocel-L在第1周后的所有时间点均降低了HbA1c。在rexlemestrocel-L组中，与安慰剂相比，调整后的HbA1c最小二乘均值±标准误剂量相关差异在第8周时为-0.1±0.2%（-1.1±2.2 mmol/mol）至-0.4±0.2%（4.4±2.2 mmol/mol），在第12周时为0.0±0.25%至-0.3±0.25%（-3.3± -2.7 mmol/mol）（2.0×10⁶/kg剂量在第8周时P<0.05）。接受2.0×10⁶/kg剂量的受试者中有33%（15名中的5名）达到临床目标HbA1c<7%（53 mmol/mol），而接受安慰剂的受试者中这一比例为0%（P<0.05）。
这项短期研究证明了高达2.46亿个MPCs用于2型糖尿病患者的安全性和可行性。
