Tsukamoto Masaya, Kawasaki Tomoyuki, Umezawa Akihiro, Akutsu Hidenori
Center for Regenerative Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, Japan.
Bio Protoc. 2024 Oct 5;14(19):e5081. doi: 10.21769/BioProtoc.5081.
Induced pluripotent stem cells (iPSCs) hold significant promise for numerous applications in regenerative medicine, disease modeling, and drug discovery. However, the conventional workflow for iPSC generation, with cells grown under two-dimensional conditions, presents several challenges, including the need for specialized scientific skills such as morphologically assessing and picking colonies and removing differentiated cells during the establishment phase. Furthermore, maintaining established iPSCs in three-dimensional culture systems, while offering scalability, necessitates an enzymatic dissociation step for their further growth in a complex and time-consuming protocol. In this study, we introduce a novel approach to address these challenges by reprogramming somatic cells grown under three-dimensional conditions as spheres using a bioreactor, thereby eliminating the need for two-dimensional culture and colony picking. The iPSCs generated in this study were maintained under three-dimensional conditions simply by transferring spheres to the next bioreactor, without the need for an enzymatic dissociation step. This streamlined method simplifies the workflow, reduces technical variability and labor, and paves the way for future advancements in iPSC research and its wider applications. Key features • Establishment of induced pluripotent stem cells in a three-dimensional environment. • Maintenance and cryopreservation of iPSCs without the need for a dissociation step.
诱导多能干细胞(iPSC)在再生医学、疾病建模和药物发现等众多应用中具有巨大潜力。然而,传统的iPSC生成工作流程是在二维条件下培养细胞,这带来了诸多挑战,包括在建立阶段需要形态学评估和挑选集落以及去除分化细胞等专业科学技能。此外,在三维培养系统中维持已建立的iPSC,虽然具有可扩展性,但在复杂且耗时的方案中,其进一步生长需要酶解步骤。在本研究中,我们引入了一种新方法来应对这些挑战,即使用生物反应器将在三维条件下生长为球体的体细胞重编程,从而无需二维培养和集落挑选。本研究中生成的iPSC仅通过将球体转移到下一个生物反应器就可在三维条件下维持,无需酶解步骤。这种简化的方法简化了工作流程,减少了技术变异性和劳动力,并为iPSC研究的未来进展及其更广泛应用铺平了道路。关键特性 • 在三维环境中建立诱导多能干细胞。 • 无需解离步骤即可维持和冷冻保存iPSC。