干细胞移植(SCT)为自身免疫性疾病的治疗铺平了道路。SCT已在1型糖尿病(T1DM)中作为一种基于自身免疫的疾病进行了研究,但以往的研究并未对其治疗T1DM的效果提出全面的看法。
本系统评价和荟萃分析在PROSPERO注册后,根据Cochrane的临床试验评估指南进行了搜索,以寻找符合资格的临床试验,这些临床试验调查了PubMed的SCT对T1DM的影响(基于ADA®诊断标准),WebofScience,Scopus,etc,以及2000年1月1日至2019年9月31日的临床试验注册。使用MeSH和EM树项设计了搜索策略。主要结果包括胰岛素总日剂量(TDD)(U/kg)水平的变化,次要结局包括HbA1c的变化,c-肽,并调整HbA1c水平。进行QCochrane检验和I2统计量以评估主要临床试验中的异质性及其严重程度。CochraneROB用于确定偏倚风险,和《Cochrane干预措施系统审查手册》用于全文论文。荟萃分析在STATA软件中完成,结果显示在他们的森林地块上。通过元回归检验对混杂因素进行评估。
共有9452项研究进行了电子筛选,共纳入35篇论文进行数据提取。这项回顾研究的结果表明,173(26.5%)糖尿病患者经历了无胰岛素期(1至80个月),445(68%)显示SCT后胰岛素的TDD减少。造血干细胞(HSC)与间充质干细胞(MSC)移植的联合与TDD的改善显着相关(SMD:-0.586,95%CI:-1.204/-0.509,I2:0%),HbA1c(SMD:-0.736,95%CI:-1.107/-0.365,I2:0%),调整后的HbA1c(SMD:-2.041,95%CI:-2.648/-1.434,I2:38.4%),和c肽(SMD:1.917,95%CI:0.192/3.641,I2:92.5%)在随访的第3个月,而其相关性在移植后3至12个月有增长趋势。考虑到严重的不良事件,HSC移植伴随调理不能被认为是一种安全的治疗方法。
T1DM的SCT临床试验大多为单臂。虽然荟萃分析显示SCT与T1DM改善相关,需要精心设计的随机临床试验来阐明其疗效.
根据这项荟萃分析的结果,MSC及其与HSC的组合可被视为T1DM中SCT的“安全小区”。此外,为了评估SCT的疗效,胰岛素TDD的计算(U/kg/天),c肽的AUC,和调整HbA1c是强烈建议。
Stem cell transplantation (SCT) has paved the way for treatment of autoimmune diseases. SCT has been investigated in type 1 diabetes mellitus (T1DM) as an autoimmune-based disorder, but previous studies have not presented a comprehensive view of its effect on treatment of T1DM.
After registration of the present systematic
review and meta-analysis in the PROSPERO, a search was done according to the Cochrane guidelines for evaluation of clinical trials to find eligible clinical trials that investigated the effect of SCT on T1DM (based on ADA® diagnostic criteria) from PubMed, Web of science, Scopus, etc, as well as registries of clinical trials from January 1, 2000, to September 31, 2019. A search strategy was designed using MeSH and EM-tree terms. Primary outcome included the changes in the insulin total daily dose (TDD) (U/kg) level, and secondary outcomes included the changes in the HbA1c, c-peptide, and adjusted HbA1c levels. The Q Cochrane test and I2 statistic were performed to assess the heterogeneity and its severity in primary clinical trials. The Cochrane ROB was used to determine risk of bias, and Cochrane Handbook for Systematic Reviews of Interventions was used in the full text papers. The meta-analysis was accomplished in the STATA software, and the results were shown on their forest plots. Confounders were evaluated by the meta-regression test.
A total of 9452 studies were electronically screened, and 35 papers were included for data extraction. The results of this
review study showed that 173 (26.5%) diabetic patients experienced insulin-free period (from 1 to 80 months), and 445 (68%) showed reduction in TDD of insulin after the SCT. Combination of
hematopoietic stem cell (HSC) with mesenchymal stem cell (MSC) transplantation were significantly associated with improvement of the TDD (SMD: - 0.586, 95% CI: - 1.204/- 0.509, I2: 0%), HbA1c (SMD: - 0.736, 95% CI: - 1.107/- 0.365, I2: 0%), adjusted HbA1c (SMD: - 2.041, 95% CI: - 2.648/- 1.434, I2: 38.4%), and c-peptide (SMD: 1.917, 95% CI: 0.192/3.641, I2: 92.5%) on month 3 of follow-up, while its association had a growing trend from 3 to 12 months after the transplantation. Considering severe adverse events, HSC transplantation accompanied with conditioning could not be suggested as a safe treatment.
Most of the clinical trials of SCT in T1DM were single arm. Although meta-analysis illustrated the SCT is associated with T1DM improvement, well-designed randomized clinical trials are needed to clarify its efficacy.
Based on the results of this meta-analysis, the MSC and its combination with HSC could be considered as \"Safe Cell\" for SCT in T1DM. Furthermore, to evaluate the SCT efficacy, calculation of insulin TDD (U/kg/day), AUC of c-peptide, and adjusted HbA1c are highly recommended.