I23 Tracking transplanted human foetal cells using bioluminescence imaging in a huntington's disease model. (September 2018)

• Record Type: Journal Article
• Authors: Abdulla, Mutwakil; Jathoul, Amit; Vinh, Ngoc-Nga; Zhu, Ying; Williams, David; Messaritaki, Eirini; Murray, Jim; Rosser, Anne; Gray, William
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 89(2018)Supplement 1
• Page Start: A96
• Page End: A97
• Publication Date: 2018-09
• Subjects: Human foetal cells -- bioluminescence -- in vivo -- cell tracking -- transplantation -- MRI -- imaging; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2018-EHDN.259
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background: Efforts in cell replacement therapy for Huntington's disease (HD) are hindered by uncertainty of graft fate after transplantation. Current cell tracking methods fall short to either: 1) Detect labelled transplanted cells, or 2) Differentiate between live and dead cells, or 3) Provide long term tracking of growing grafts. Bioluminescence imaging (BLI) addresses these problems and could provide a cheaper, more reliable and less inconvenient alternative to currently used intracerebral cell tracking techniques. Aim: We aimed to describe methods for long term tracking of transplanted Human Foetal Cells (HFC) using BLI in a HD rat model. Methods: In-vitro: We have developed protocols to transduce Human Embryonic Kidney cells, Medium Spiny Neuron Progenitors and eventually HFCs with a lentivirus carrying a firefly luciferase gene. In-vivo: Using quinolinic acid lesioned adult female Sprague-Dawley rats as a HD model, 4 animals underwent transduced-cells transplantation followed immediately by BLI using intracerebral (IC) luciferin injection. These animals had pre and post-operative MRI for comparison. Five animals underwent BLI with IC luciferin at 12 weeks. Eight animals underwent acute BLI after transplantation using intraperitoneal (IP) Luciferin alternatives, namely: AkaLumin, D-Luciferin, D-Luciferin packaged in a nano vector and InfraLuciferin. Results: In-vitro: All tested cell types were reliably transduced with a viral vector to express engineered luciferase. HFC viability inversely correlated with duration of incubation with the virus. In-vivo: HFC grafts were detected using BLI acutely and at 12 weeks after transplantation. D-Luciferin packaged in a nano vector showed promising results after IP injection, however signal is considerably weaker than IC injection. Conclusion: BLI reliably and conveniently tracks transplanted HFC in small animals. This technique has great potentials in studying graft fate in terms of localization, viability, growth and integration.