Neural stem cell delivery via porous collagen scaffolds promotes neuronal differentiation and locomotion recovery in spinal cord injury

Alexandra Kourgiantaki; Dimitrios S Tzeranis; Kanelina Karali; Konstantina Georgelou; Efstathia Bampoula; Sotirios Psilodimitrakopoulos; Ioannis V Yannas; Emmanuel Stratakis; Kyriaki Sidiropoulou; Ioannis Charalampopoulos; Achille Gravanis

doi:10.1038/s41536-020-0097-0

Neural stem cell delivery via porous collagen scaffolds promotes neuronal differentiation and locomotion recovery in spinal cord injury

NPJ Regen Med. 2020 Jun 15:5:12. doi: 10.1038/s41536-020-0097-0. eCollection 2020.

Authors

Alexandra Kourgiantaki^#^{1

2}, Dimitrios S Tzeranis^#^{2

3}, Kanelina Karali^#^{1

2}, Konstantina Georgelou^{1

2}, Efstathia Bampoula⁴, Sotirios Psilodimitrakopoulos⁵, Ioannis V Yannas³, Emmanuel Stratakis⁵, Kyriaki Sidiropoulou^{2

4}, Ioannis Charalampopoulos^{1

2}, Achille Gravanis^{1

2}

Affiliations

¹ Department of Pharmacology, School of Medicine, University of Crete, Heraklion, 71003 Greece.
² Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, 71003 Greece.
³ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 USA.
⁴ Department of Biology, University of Crete, Heraklion, 71003 Greece.
⁵ Institute of Electronic Structure and Laser, Foundation for Research and Technology-Hellas, Heraklion, 71003 Greece.

^# Contributed equally.

Abstract

Neural stem cell (NSC) grafts have demonstrated significant effects in animal models of spinal cord injury (SCI), yet their clinical translation remains challenging. Significant evidence suggests that the supporting matrix of NSC grafts has a crucial role in regulating NSC effects. Here we demonstrate that grafts based on porous collagen-based scaffolds (PCSs), similar to biomaterials utilized clinically in induced regeneration, can deliver and protect embryonic NSCs at SCI sites, leading to significant improvement in locomotion recovery in an experimental mouse SCI model, so that 12 weeks post-injury locomotion performance of implanted animals does not statistically differ from that of uninjured control animals. NSC-seeded PCS grafts can modulate key processes required to induce regeneration in SCI lesions including enhancing NSC neuronal differentiation and functional integration in vivo, enabling robust axonal elongation, and reducing astrogliosis. Our findings suggest that the efficacy and translational potential of emerging NSC-based SCI therapies could be enhanced by delivering NSC via scaffolds derived from well-characterized clinically proven PCS.

Keywords: Neural stem cells; Spinal cord injury; Translational research.