Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice.

Autor: Jin Y; Department of Chemistry, University of Oxford, Oxford, OX1 3TA, UK., Mikhailova E; Department of Chemistry, University of Oxford, Oxford, OX1 3TA, UK., Lei M; Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK., Cowley SA; James and Lillian Martin Centre for Stem Cell Research, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK., Sun T; Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK., Yang X; Department of Chemistry, University of Oxford, Oxford, OX1 3TA, UK., Zhang Y; Department of Chemistry, University of Oxford, Oxford, OX1 3TA, UK., Liu K; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK., Catarino da Silva D; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK., Campos Soares L; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK., Bandiera S; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK., Szele FG; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK. francis.szele@dpag.ox.ac.uk., Molnár Z; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK. zoltan.molnar@dpag.ox.ac.uk., Zhou L; Department of Chemistry, University of Oxford, Oxford, OX1 3TA, UK. linna.zhou@chem.ox.ac.uk.; Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK. linna.zhou@chem.ox.ac.uk., Bayley H; Department of Chemistry, University of Oxford, Oxford, OX1 3TA, UK. hagan.bayley@chem.ox.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Oct 04; Vol. 14 (1), pp. 5986. Date of Electronic Publication: 2023 Oct 04.
DOI: 10.1038/s41467-023-41356-w
Abstrakt: Engineering 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 Ca 2+ 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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE