Cho Yeon-Woo, Jee Seohyeon, Suhito Intan Rosalina, Lee Jeong-Hyeon, Park Chun Gwon, Choi Kyung Min, Kim Tae-Hyung
School of Integrative Engineering, Chung-Ang University, 84 Heukseuk-ro, Dongjak-gu, Seoul 06974, Republic of Korea.
Department of Chemical and Biological Engineering, Sookmyung Women's University, 100 Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea.
Sci Adv. 2022 Apr 22;8(16):eabj7736. doi: 10.1126/sciadv.abj7736. Epub 2022 Apr 20.
Stable and continuous supply of essential biomolecules is critical to mimic in vivo microenvironments wherein spontaneous generation of various cell types occurs. Here, we report a new platform that enables highly efficient neuronal cell generation of neural stem cells using single metal-organic framework (MOF) nanoparticle-embedded nanopit arrays (SMENA). By optimizing the physical parameters of homogeneous periodic nanopatterns, each nanopit can confine single nMOFs (UiO-67) that are specifically designed for long-term storage and release of retinoic acid (RA). The SMENA platform successfully inhibited physical interaction with cells, which contributed to remarkable stability of the nMOF (RA⊂UiO-67) structure without inducing nanoparticle-mediated toxicity issues. Owing to the continuous and long-term supply of RA, the neural stem cells showed enhanced mRNA expressions of various neurogenesis-related activities. The developed SMENA platform can be applied to other stem cell sources and differentiation lineages and is therefore useful for various stem cell-based regenerative therapies.
稳定且持续地供应必需生物分子对于模拟体内发生各种细胞类型自发产生的微环境至关重要。在此，我们报告了一种新平台，该平台利用嵌入单个金属有机框架（MOF）纳米颗粒的纳米坑阵列（SMENA）能够高效地将神经干细胞诱导生成神经元细胞。通过优化均匀周期性纳米图案的物理参数，每个纳米坑能够容纳专门设计用于长期储存和释放视黄酸（RA）的单个纳米金属有机框架（nMOF，UiO - 67）。SMENA平台成功抑制了与细胞的物理相互作用，这有助于nMOF（RA⊂UiO - 67）结构具有显著稳定性，且不会引发纳米颗粒介导的毒性问题。由于RA的持续长期供应，神经干细胞显示出各种神经发生相关活性的mRNA表达增强。所开发的SMENA平台可应用于其他干细胞来源和分化谱系，因此对各种基于干细胞的再生疗法有用。
