Abstract
AbstractEngineering human tissue with diverse cell types and architectures remains challenging. The cerebral cortex, which has a layered cellular architecture composed of layer-specific neurons organised into vertical columns, delivers higher cognition through intricately wired neural circuits. However, current tissue engineering approaches cannot produce such structures. Here, we use a droplet printing technique to fabricate tissues comprising simplified cerebral cortical columns. Human induced pluripotent stem cells are differentiated into upper- and deep-layer neural progenitors, which are then printed to form cerebral cortical tissues with a two-layer organization. The tissues show layer-specific biomarker expression and develop a structurally integrated network of processes. Implantation of the printed cortical tissues into ex vivo mouse brain explants results in substantial structural implant-host integration across the tissue boundaries as demonstrated by the projection of processes and the migration of neurons, and leads to the appearance of correlated Ca2+ oscillations across the interface. The presented approach might be used for the evaluation of drugs and nutrients that promote tissue integration. Importantly, our methodology offers a technical reservoir for future personalized implantation treatments that use 3D tissues derived from a patient’s own induced pluripotent stem cells.
Funder
Oxford University | Oxford Martin School, University of Oxford
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference72 articles.
1. Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).
2. Morizane, A. et al. Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate. Stem Cell Rep. 1, 283–292 (2013).
3. Iaccarino, C., Carretta, A., Nicolosi, F. & Morselli, C. Epidemiology of severe traumatic brain injury. J. Neurosurg. Sci. 62, 535–541 (2018).
4. Frost, S., Barbay, S., Friel, K., Plautz, E. & Nudo, R. Reorganization of remote cortical regions after ischemic brain injury: a potential substrate for stroke recovery. J. Neurophysiol. 89, 3205–3214 (2003).
5. Hatiboglu, M. A., Wildrick, D. M. & Sawaya, R. The role of surgical resection in patients with brain metastases. Ecancermedicalscience 7, 308 (2013).
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献