School of Biological Sciences, University of Auckland, 1150 Auckland, New Zealand.
Maurice Wilkins Centre, University of Auckland, 1150 Auckland, New Zealand.
Int J Mol Sci. 2020 Feb 21;21(4):1492. doi: 10.3390/ijms21041492.
There is clinical interest in using human adipose tissue-derived mesenchymal stromal cells (ASC) to treat a range of inflammatory and regenerative conditions. Aspects of ASC biology, including their regenerative potential and paracrine effect, are likely to be modulated, in part, by microRNAs, small RNA molecules that are embedded as regulators of gene-expression in most biological pathways. However, the effect of standard isolation and expansion protocols on microRNA expression in ASC is not well explored. Here, by using an untouched and enriched population of primary human ASC, we demonstrate that there are rapid and significant changes in microRNA expression when ASC are subjected to standard isolation and expansion methods. Functional studies focusing on miR-378 indicate that these changes in expression may have an impact on phenotype and function. Specifically, we found that increased levels of miR-378 significantly promoted adipogenesis in late passage ASC. These results are informative to maximizing the potential of ASC for use in various clinical applications, and they have implications for targeting microRNAs as a therapeutic strategy for obesity or metabolic disease.
人们对利用人脂肪组织来源的间充质基质细胞（ASC）治疗一系列炎症和再生性疾病很感兴趣。ASC 生物学的各个方面，包括其再生潜力和旁分泌作用，可能部分受到 microRNA 的调节，microRNA 是一种小 RNA 分子，作为大多数生物途径中基因表达的调节剂嵌入其中。然而，标准分离和扩增方案对 ASC 中 microRNA 表达的影响尚未得到很好的探索。在这里，我们使用未受干扰且富含原发性人 ASC 的群体，证明了当 ASC 经历标准分离和扩增方法时，microRNA 表达会发生快速而显著的变化。专注于 miR-378 的功能研究表明，这些表达变化可能会对表型和功能产生影响。具体而言，我们发现 miR-378 的水平升高可显著促进晚期传代 ASC 的脂肪生成。这些结果对于最大限度地发挥 ASC 在各种临床应用中的潜力具有重要意义，并且对于将 microRNA 作为肥胖或代谢性疾病的治疗策略具有重要意义。
