Park Seul-Ki, Lee Jung Shin, Choi Eun Kyung, You Dalsan, Kim Choung-Soo, Suh Nayoung
Asan Institute for Life Sciences, Asan Medical Center; Department of Medicine, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Institute for Innovative Cancer Research; Department of Internal Medicine, University of Ulsan College of Medicine, Seoul 138-736, Korea.
BMB Rep. 2014 Aug;47(8):469-74. doi: 10.5483/bmbrep.2014.47.8.106.
Cell therapies utilizing mesenchymal stem cells (MSCs) have a great potential in many research and clinical settings. The mechanisms underlying the therapeutic effects of MSCs have been studied previously and the paracrine effects elicited by their production of various growth factors and cytokines were recognized as being crucial. However, the molecular controls that govern these paracrine effects remain poorly understood. To elucidate the molecular regulators of this process, we performed a global knockdown of microRNAs (miRNAs) in human adipose-derived mesenchymal stem cells (hADSCs) by inhibiting DGCR8, a key protein in miRNA biogenesis. Global disruption of miRNA biogenesis in hADSCs caused dramatic changes in the expression of subsets of growth factors and cytokines. By performing an extensive bioinformatic analysis, we were able to associate numerous putative miRNAs with these genes. Taken together, our results strongly suggest that miRNAs are essential for the production of growth factors and cytokines in hADSCs.
利用间充质干细胞（MSCs）的细胞疗法在许多研究和临床环境中具有巨大潜力。此前已对MSCs治疗效果的潜在机制进行了研究，并且其产生的各种生长因子和细胞因子所引发的旁分泌效应被认为至关重要。然而，对这些旁分泌效应的分子调控仍知之甚少。为了阐明这一过程的分子调节因子，我们通过抑制DGCR8（miRNA生物合成中的关键蛋白）在人脂肪来源的间充质干细胞（hADSCs）中对微小RNA（miRNAs）进行了全面敲低。hADSCs中miRNA生物合成的全面破坏导致生长因子和细胞因子亚群的表达发生显著变化。通过进行广泛的生物信息学分析，我们能够将众多假定的miRNAs与这些基因联系起来。综上所述，我们的结果强烈表明，miRNAs对于hADSCs中生长因子和细胞因子的产生至关重要。
