Data_Sheet_1_Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment.DOCX

Human mesenchymal stem cells gather special interest as a universal and feasible add-on therapy for myocardial infarction (MI). In particular, human umbilical cord matrix-derived mesenchymal stromal cells (UCM-MSC) are advantageous since can be easily obtained and display high expansion potential. Using isolation protocols compliant with cell therapy, we previously showed UCM-MSC preserved cardiac function and attenuated remodeling 2 weeks after MI. In this study, UCM-MSC from two umbilical cords, UC-A and UC-B, were transplanted in a murine MI model to investigate consistency and durability of the therapeutic benefits. Both cellular products improved cardiac function and limited adverse cardiac remodeling 12 weeks post-ischemic injury, supporting sustained and long-term beneficial therapeutic effect. Donor associated variability was found in the modulation of cardiac remodeling and activation of the Akt-mTOR-GSK3β survival pathway. In vitro, the two cell products displayed similar ability to induce the formation of vessel-like structures and comparable transcriptome in normoxia and hypoxia, apart from UCM-MSCs proliferation and expression differences in a small subset of genes associated with MHC Class I. These findings support that UCM-MSC are strong candidates to assist the treatment of MI whilst calling for the discussion on methodologies to characterize and select best performing UCM-MSC before clinical application.

人间充质干细胞（human mesenchymal stem cells）作为一种通用且可行的心肌梗死（myocardial infarction, MI）辅助治疗手段，受到了广泛关注。尤为值得注意的是，人脐带基质来源间充质基质细胞（human umbilical cord matrix-derived mesenchymal stromal cells, UCM-MSC）具有易于获取且扩增潜能优异的优势。本团队此前采用符合细胞治疗规范的分离培养方案，证实UCM-MSC可在心肌梗死造模后2周内维持心脏功能并减轻心肌重构。本研究将来自两份脐带（UC-A与UC-B）的UCM-MSC移植至小鼠心肌梗死模型中，以探究其治疗效益的一致性与持久性。两种细胞制剂均可改善缺血损伤后12周的心脏功能，并抑制不良心肌重构，证实其治疗效益具有持续长效性。研究发现供体差异会影响心肌重构的调控以及Akt-mTOR-GSK3β生存通路的激活。体外实验中，两份细胞制剂在常氧与低氧条件下的诱导血管样结构形成能力与转录组特征均较为相似，仅在UCM-MSC的增殖能力以及少量与主要组织相容性复合体I类（major histocompatibility complex class I, MHC Class I）相关的基因表达上存在差异。本研究结果证实UCM-MSC是心肌梗死辅助治疗的优质候选方案，同时也呼吁学界探讨在临床应用前，如何通过标准化方法表征并筛选出疗效最优的UCM-MSC。