One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study

Stem Cell Research & Therapy

Bin Wang¹  Yan Bi²  Shan-mei Shen²  Duo-duo Qu²  Wei Zhang²  Da-long Zhu²  Qing Ling²  Jing Lu²  Li-rong Li³ 

[1] Clinical Stem Cell Center, Drum Tower Hospital Affiliated to Nanjing University Medical School, No 321, Zhongshan Road, 210008, Nanjing, Jiangsu, China;Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, No 321, Zhongshan Road, 210008, Nanjing, Jiangsu, China;School of Clinical Medicine and Nursing, Suzhou Vocational Health College, No 28, Kehua Road, Suzhou International Education Park, 215151, Suzhou, Jiangsu, China;

关键词: Mesenchymal stromal cells;    Type 1 diabetes;    Transplantation;    β cell function;   

DOI  :  10.1186/s13287-021-02417-3

来源: Springer

【 摘 要 】

BackgroundThe preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D.MethodsThis was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses.ResultsAfter 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed.ConclusionOne repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone.Trial registrationChiCTR2100045434. Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/

【 授权许可】

CC BY