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Engineered Neural Tissue Made Using Clinical-Grade Human Neural Stem Cells Supports Regeneration in a Long Gap Peripheral Nerve Injury Model

33 Pages Posted: 13 May 2021 Publication Status: Under Review

See all articles by Melissa Lucy Doreen Rayner

Melissa Lucy Doreen Rayner

University College London - School of Pharmacy

Adam GE Day

University College London - School of Pharmacy

Kulraj S. Bhangra

University College London - School of Pharmacy

John Sinden

University College London - School of Pharmacy

James B. Phillips

University College London - School of Pharmacy

Abstract

A surgical autograft remains the clinical gold-standard therapy for gap repair following peripheral nerve injury, however, challenges remain with achieving full recovery and reducing donor-site morbidity. Engineered neural tissue (EngNT) manufactured using differentiated CTX0E03 human stem cells (EngNT-CTX) has been developed as a potential ‘off the shelf’ allogeneic autograft replacement. Ensheathed within a collagen membrane developed to facilitate biomechanical integration, EngNT-CTX was used to bridge a critical-length (15 mm) sciatic nerve gap injury in athymic nude rats. The effectiveness of EngNT-CTX was compared to an autograft using outcome measures that assessed neuronal regeneration and functional recovery at 8 and 16 weeks. At both time points EngNT-CTX restored electrophysiological nerve conduction and functional reinnervation of downstream muscles to the same extent as the autograft. Histological analysis confirmed that more motor neurons had successfully regenerated through the repair in EngNT-CTX in comparison to the autograft at 8 weeks, which was consistent with the electrophysiology, with the number of motor neurons similar in both groups by 16 weeks. The total number of neurons (motor + sensory) was greater in autografts than EngNT-CTX at 8 weeks, indicating that more sensory fibres may have sprouted in those animals at this time point. In conclusion, this study provides evidence to support the effectiveness of EngNT-CTX as a replacement for the nerve autograft, as the functional regeneration assessed through histological and electrophysiological outcome measures demonstrated equivalent performance.

Keywords: Nerve regeneration; Functional recovery; Tissue engineering; Stem cells

Suggested Citation

Rayner, Melissa Lucy Doreen and Day, Adam GE and Bhangra, Kulraj S. and Sinden, John and Phillips, James B., Engineered Neural Tissue Made Using Clinical-Grade Human Neural Stem Cells Supports Regeneration in a Long Gap Peripheral Nerve Injury Model. Available at SSRN: https://ssrn.com/abstract=3845714 or http://dx.doi.org/10.2139/ssrn.3845714

Melissa Lucy Doreen Rayner (Contact Author)

University College London - School of Pharmacy ( email )

London, WC1N 1AX
United Kingdom

Adam GE Day

University College London - School of Pharmacy ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Kulraj S. Bhangra

University College London - School of Pharmacy ( email )

Gower Street
London, WC1E 6BT
United Kingdom

John Sinden

University College London - School of Pharmacy ( email )

Gower Street
London, WC1E 6BT
United Kingdom

James B. Phillips

University College London - School of Pharmacy ( email )

Gower Street
London, WC1E 6BT
United Kingdom

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