Abstract

The use of bioactive scaffolds in conjunction with stem cell therapies for cardiac repair after a myocardial infarction shows significant promise for clinical translation. We performed a systematic review and meta-analysis of preclinical trials that investigated the use of bioactive scaffolds to support stem cell-aided cardiac regeneration, in comparison to stem cell treatment alone. Cochrane Library, Medline, Embase, PubMed, Scopus, Web of Science, and grey literature were searched through April 23, 2020 and 60 articles were included in the final analysis. The overall effect size observed in scaffold and stem cell-treated small animals compared to stem cell-treated controls for ejection fraction (EF) was 7.98 [95% confidence interval (CI): 6.36, 9.59] and for fractional shortening (FS) was 5.50 [95% CI: 4.35, 6.65] in small animal models. The largest improvements in EF and FS were observed when hydrogels were used (MD = 8.45 [95% CI: 6.46, 10.45] and MD = 5.76 [95% CI: 4.46, 7.05], respectively). Subgroup analysis revealed that cardiac progenitor cells had the largest effect size for FS, and was significant from pluripotent, mesenchymal and endothelial stem cell types. In large animal studies, the overall improvement of EF favoured the use of stem cell-embedded scaffolds compared to direct injection of cells (MD = 10.49 [95% CI: 6.30, 14.67]). Significant publication bias was present in the small animal trials for EF and FS. This study supports the use of bioactive scaffolds to aid in stem cell-based cardiac regeneration. Hydrogels should be further investigated in larger animal models for clinical translation.

Graphical abstract

中文翻译：

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心肌梗塞干细胞疗法中的生物活性支架：临床前试验的系统评价和荟萃分析

摘要

将生物活性支架与干细胞疗法结合用于心肌梗塞后的心脏修复显示出临床转化的巨大希望。我们对临床前试验进行了系统回顾和荟萃分析，这些试验研究了使用生物活性支架来支持干细胞辅助心脏再生，与单独的干细胞治疗相比。检索到 2020 年 4 月 23 日的 Cochrane Library、Medline、Embase、PubMed、Scopus、Web of Science 和灰色文献，最终分析纳入 60 篇文章。与干细胞处理的对照组相比，支架和干细胞处理的小动物中观察到的射血分数 (EF) 的总体效应大小为 7.98 [95% 置信区间 (CI): 6.36, 9.59]，缩短分数 (FS) 为在小动物模型中为 5.50 [95% CI: 4.35, 6.65]。使用水凝胶时观察到 EF 和 FS 的最大改进（分别为 MD = 8.45 [95% CI: 6.46, 10.45] 和 MD = 5.76 [95% CI: 4.46, 7.05]）。亚组分析显示，心脏祖细胞对 FS 的影响最大，并且在多能、间充质和内皮干细胞类型中具有显着性。在大型动物研究中，与直接注射细胞相比，EF 的整体改善有利于使用干细胞包埋支架（MD = 10.49 [95% CI: 6.30, 14.67]）。在 EF 和 FS 的小动物试验中存在显着的发表偏倚。该研究支持使用生物活性支架来帮助基于干细胞的心脏再生。应在更大的动物模型中进一步研究水凝胶以进行临床转化。

图形概要