Vascularization of iNSC spheroid in a 3D spheroid‐on‐a‐chip platform enhances neural maturation

• Published in: Biotechnology and bioengineering 2022-02, Vol.119 (2), p.566-574
• Main Authors: Shin, Nari, Kim, Youngtaek, Ko, Jihoon, Choi, Soon Won, Hyung, Sujin, Lee, Seung‐Eun, Park, Seunghyuk, Song, Jiyoung, Jeon, Noo Li, Kang, Kyung‐Sun
• Format: Article
• Language: English
• Subjects: 3D spheroid; Apoptosis; Apoptosis - physiology; Blood vessels; Blood Vessels - physiology; Brain; Brain stem; Cell Differentiation - physiology; Coculture Techniques - methods; Differentiation; Gene expression; Humans; induced neural stem cell; Lab-On-A-Chip Devices; Maturation; microfluidic; Microfluidics; Neovascularization, Physiologic - physiology; Neural stem cells; Neural Stem Cells - cytology; Organoids; Spheroids; Spheroids, Cellular - cytology; spheroid‐on‐a‐chip; Stem cells; Structure-function relationships; Three dimensional models; Tissue Engineering; Vascularization
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.27978

In vitro platforms for studying the human brain have been developed, and brain organoids derived from stem cells have been studied. However, current organoid models lack three‐dimensional (3D) vascular networks, limiting organoid proliferation, differentiation, and apoptosis. In this study, we created a 3D model of vascularized spheroid cells using an injection‐molded microfluidic chip. We cocultured spheroids derived from induced neural stem cells (iNSCs) with perfusable blood vessels. Gene expression analysis and immunostaining revealed that the vascular network greatly enhanced spheroid differentiation and reduced apoptosis. This platform can be used to further study the functional and structural interactions between blood vessels and neural spheroids, and ultimately to simulate brain development and disease. Current organoid models lack 3D vascular networks, limiting proliferation and differentiation of organoid. In this study, we developed a 3D model of vascularized iNSC spheroids using an injection‐molded microfluidic chip. The vascular network in chip was perfusable and in contact with neural spheroid. Furthermore, vascularized neural spheroids showed enhanced differentiation and reduced apoptosis. We suggest that this model could be applied to the organoids‐on‐a‐chip model, and it would be a powerful tool for understanding of developmental biology and human diseases.