Nguyen Minh K, Jeon Oju, Krebs Melissa D, Schapira Daniel, Alsberg Eben
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44016, USA.
Chemical and Biological Engineering Department, Colorado School of Mines, 1500 Illinois Street, Golden, Colorado 80401, USA.
Biomaterials. 2014 Aug;35(24):6278-6286. doi: 10.1016/j.biomaterials.2014.04.048. Epub 2014 May 13.
To date, RNA interfering molecules have been used to differentiate stem cells on two-dimensional (2D) substrates that do not mimic three-dimensional (3D) microenvironments in the body. Here, in situ forming poly(ethylene glycol) (PEG) hydrogels were engineered for controlled, localized and sustained delivery of RNA interfering molecules to differentiate stem cells encapsulated within the 3D polymer network. RNA interfering molecules were released from the hydrogels in a sustained and controlled manner over the course of 3-6 weeks, and exhibited high bioactivity. Importantly, it was demonstrated that the delivery of siRNA and/or miRNA from the hydrogel constructs enhanced the osteogenic differentiation of encapsulated stem cells. Prolonged delivery of siRNA and/or miRNA from this polymeric scaffold permitted extended regulation of cell behavior, unlike traditional siRNA experiments performed in vitro. This approach presents a powerful new methodology for controlling cell fate, and is promising for multiple applications in tissue engineering and regenerative medicine.
迄今为止，RNA干扰分子已被用于在二维（2D）基质上分化干细胞，而这种基质无法模拟体内的三维（3D）微环境。在此，原位形成的聚乙二醇（PEG）水凝胶被设计用于将RNA干扰分子可控、局部且持续地递送至包裹在三维聚合物网络中的干细胞，以使其分化。RNA干扰分子在3至6周的时间内以持续且可控的方式从水凝胶中释放出来，并表现出高生物活性。重要的是，已证明从水凝胶构建体中递送小干扰RNA（siRNA）和/或微小RNA（miRNA）可增强包裹的干细胞的成骨分化。与体外进行的传统siRNA实验不同，从这种聚合物支架中长期递送siRNA和/或miRNA可实现对细胞行为的长期调控。这种方法为控制细胞命运提供了一种强大的新方法，在组织工程和再生医学的多种应用中具有广阔前景。
