Vaka Ramana, Parent Sandrine, Risha Yousef, Khan Saad, Courtman David, Stewart Duncan J, Davis Darryl R
University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine, University of Ottawa, Ottawa, ON K1Y4W7, Canada.
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H8M5, Canada.
Mol Ther Nucleic Acids. 2023 Mar 9;32:80-93. doi: 10.1016/j.omtn.2023.03.001. eCollection 2023 Jun 13.
The cell origin-specific payloads within extracellular vesicles (EVs) mediate therapeutic bioactivity for a wide variety of stem cell types. In this study, we profiled the microRNA (miRNA) and protein cargos found within EVs produced by three clinical-grade stem cell products of different ontogenies being considered for clinical application, namely bone marrow-derived mesenchymal stromal cells (BM-MSCs), heart-derived cells (HDCs), and umbilical cord-derived MSCs (UC-MSCs). Although several miRNAs (757) and proteins (420) were found in common, each producer cell type expressed unique miRNA profiles when the most highly expressed transcripts were compared. Differential expression analysis revealed that BM-MSCs and HDCs were quite similar, while UC-MSCs had the greatest number of unique miRNAs and proteins. Despite these differences, all three EVs promoted cell adhesion/migration, immune response, platelet aggregation, protein translation/stabilization, and RNA processing. EVs from BM-MSCs were implicated in apoptosis, cell-cycle progression, collagen formation, heme pigment synthesis, and smooth muscle differentiation, while HDC and UC-MSC EVs were found to regulate complement activation, endopeptidase activity, and matrix metallopeptidases. Overall, miRNA and protein profiling reveal functional differences between three leading stem cell products. These findings provide a framework for mechanistic exploration of candidate therapeutic molecules driving the salutary effects of EVs.
细胞外囊泡（EVs）中细胞起源特异性的有效载荷介导了多种干细胞类型的治疗生物活性。在本研究中，我们分析了三种不同来源、正考虑用于临床应用的临床级干细胞产品所产生的细胞外囊泡中发现的微小RNA（miRNA）和蛋白质载荷，即骨髓间充质基质细胞（BM-MSCs）、心脏来源细胞（HDCs）和脐带间充质干细胞（UC-MSCs）。虽然发现了几种共同的miRNA（757种）和蛋白质（420种），但当比较表达量最高的转录本时，每种产生细胞类型都表达独特的miRNA谱。差异表达分析显示，BM-MSCs和HDCs非常相似，而UC-MSCs具有最多数量的独特miRNA和蛋白质。尽管存在这些差异，但所有三种细胞外囊泡都促进细胞黏附/迁移、免疫反应、血小板聚集、蛋白质翻译/稳定和RNA加工。来自BM-MSCs的细胞外囊泡与细胞凋亡、细胞周期进程、胶原蛋白形成、血红素色素合成和平滑肌分化有关，而HDC和UC-MSC细胞外囊泡则被发现可调节补体激活、内肽酶活性和基质金属肽酶。总体而言，miRNA和蛋白质分析揭示了三种主要干细胞产品之间的功能差异。这些发现为驱动细胞外囊泡有益作用的候选治疗分子的机制探索提供了一个框架。
