Rathnam Christopher, Yang Letao, Castro-Pedrido Sofia, Luo Jeffrey, Cai Li, Lee Ki-Bum
Department of Chemistry and Chemical Biology Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Department of Biomedical Engineering Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Sci Adv. 2021 Oct;7(40):eabj2281. doi: 10.1126/sciadv.abj2281. Epub 2021 Sep 29.
Although stem cell therapy holds enormous potential for treating debilitating injuries and diseases in the central nervous system, low survival and inefficient differentiation have restricted its clinical applications. Recently, 3D cell culture methods, such as stem cell–based spheroids and organoids, have demonstrated advantages by incorporating tissue-mimetic 3D cell-cell interactions. However, a lack of drug and nutrient diffusion, insufficient cell-matrix interactions, and tedious fabrication procedures have compromised their therapeutic effects in vivo. To address these issues, we developed a biodegradable nanomaterial-templated 3D cell assembly method that enables the formation of hybrid stem cell spheroids with deep drug delivery capabilities and homogeneous incorporation of 3D cell-matrix interactions. Hence, high survival rates, controlled differentiation, and functional recovery were demonstrated in a spinal cord injury animal model. Overall, our hybrid stem cell spheroids represent a substantial development of material-facilitated 3D cell culture systems and can pave the way for stem cell–based treatment of CNS injuries.
尽管干细胞疗法在治疗中枢神经系统的衰弱性损伤和疾病方面具有巨大潜力，但细胞存活率低和分化效率低下限制了其临床应用。最近，基于干细胞的球体和类器官等3D细胞培养方法，通过纳入模拟组织的3D细胞-细胞相互作用展现出了优势。然而，药物和营养物质扩散不足、细胞-基质相互作用不够以及制备过程繁琐，削弱了它们在体内的治疗效果。为了解决这些问题，我们开发了一种可生物降解的纳米材料模板化3D细胞组装方法，该方法能够形成具有深度药物递送能力和均匀整合3D细胞-基质相互作用的混合干细胞球体。因此，在脊髓损伤动物模型中证明了高存活率、可控分化和功能恢复。总体而言，我们的混合干细胞球体代表了材料辅助3D细胞培养系统的重大发展，并可为基于干细胞的中枢神经系统损伤治疗铺平道路。
