Yao Kevin, Ricardo Sharon D
Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
Nephrology (Carlton). 2016 May;21(5):363-71. doi: 10.1111/nep.12643.
MicroRNAs (miRNAs) are short single strands of RNA responsible for post-transcriptional regulation of gene expression and have been implicated in the pathogenesis of chronic kidney disease (CKD). Emerging evidence reports that miRNAs can reduce kidney fibrosis through regulation of targets associated with collagen and extracellular matrix accumulation. However, the development of miRNA therapies has been hampered by the lack of targeted and sustainable methods of systemic miRNA delivery. Mesenchymal stem cells (MSCs) provide a promising miRNA delivery platform to overcome toxicity, the potential for insertional mutations and the low efficiency of previous methods. MSCs are endogenously immunoprivileged and home to sites of inflammation. They also release trophic growth factors to modulate the immune system, alter the polarization of macrophages and provide renal protection and repair. The potential to engineer MSCs to express or overexpress miRNAs, released by exosomes, may enhance their natural functions. Clinical studies are already being conducted individually for the use of miRNAs in cancer and MSCs in diseases associated with CKD. Hence, the combination of miRNAs and MSCs may provide an unparalleled cell-based therapy for treating CKD.
微小RNA(miRNA)是负责基因表达转录后调控的短单链RNA,并且已被证明与慢性肾脏病(CKD)的发病机制有关。新出现的证据表明,miRNA可通过调控与胶原蛋白和细胞外基质积累相关的靶点来减轻肾脏纤维化。然而,miRNA疗法的发展受到缺乏靶向性和系统性miRNA递送可持续方法的阻碍。间充质干细胞(MSC)为克服毒性、插入突变可能性和以往方法的低效性提供了一个有前景的miRNA递送平台。MSC具有内源性免疫特权,可归巢至炎症部位。它们还释放营养生长因子来调节免疫系统、改变巨噬细胞的极化并提供肾脏保护和修复。通过工程化使MSC表达或过表达由外泌体释放的miRNA的潜力,可能会增强其天然功能。目前已经分别针对miRNA在癌症中的应用以及MSC在与CKD相关疾病中的应用开展了临床研究。因此,miRNA与MSC的联合应用可能为治疗CKD提供一种无与伦比的基于细胞的疗法。