Fabrication of homotypic neural ribbons as a multiplex platform optimized for spinal cord delivery

• Published in: Scientific reports 2020-07, Vol.10 (1), p.12939-12939, Article 12939
• Main Authors: Olmsted, Zachary T., Stigliano, Cinzia, Badri, Abinaya, Zhang, Fuming, Williams, Asher, Koffas, Mattheos A. G., Xie, Yubing, Linhardt, Robert J., Cibelli, Jose, Horner, Philip J., Paluh, Janet L.
• Format: Article
• Language: English
• Subjects: 631/136; 631/136/142; 631/136/2091; 631/136/2139; 631/136/2444; 631/136/334; 631/136/334/1874; 631/136/368; 631/136/532; 631/136/756; 631/136/83; 631/1647; 631/1647/245; 631/1647/328; 631/1647/334; 631/1647/48; 631/1647/767; 631/378; 631/378/1934; 631/378/1959; 631/378/2183; 631/378/2596; 631/378/371; 631/532; 631/532/1360; 631/532/2182; 631/61; 631/61/54/2295; 631/61/54/993; 631/80; 631/80/128; 631/80/221; 631/80/2373; 631/80/641; 631/80/79; 631/80/82; 631/80/86; 631/92; 631/92/221; 631/92/607; Alginic acid; Animals; Axons; Cell therapy; Chondroitin ABC lyase; Chondroitin ABC Lyase - pharmacology; Contusions; Disease Models, Animal; Extracellular matrix; Fabrication; Female; Humanities and Social Sciences; Humans; multidisciplinary; Neural stem cells; Neural Stem Cells - metabolism; Neural Stem Cells - pathology; Neural Stem Cells - transplantation; Rats, Long-Evans; Recovery of Function; Retention; Science; Science (multidisciplinary); Spinal cord; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal cord injuries; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Spinal Cord Injuries - therapy; Stem cell transplantation; Stem Cell Transplantation - instrumentation; Stem Cell Transplantation - methods; Stem cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-69274-7

Cell therapy for the injured spinal cord will rely on combined advances in human stem cell technologies and delivery strategies. Here we encapsulate homotypic spinal cord neural stem cells (scNSCs) in an alginate-based neural ribbon delivery platform. We perform a comprehensive in vitro analysis and qualitatively demonstrate graft survival and injury site retention using a rat C4 hemi-contusion model. Pre-configured neural ribbons are transport-stable modules that enable site-ready injection, and can support scNSC survival and retention in vivo. Neural ribbons offer multifunctionality in vitro including co-encapsulation of the injury site extracellular matrix modifier chondroitinase ABC (chABC), tested here in glial scar models, and ability of cervically-patterned scNSCs to differentiate within neural ribbons and project axons for integration with 3-D external matrices. This is the first extensive in vitro characterization of neural ribbon technology, and constitutes a plausible method for reproducible delivery, placement, and retention of viable neural cells in vivo.