Article Text

Download PDFPDF
FM2-6 Cell delivery for intracerebral cell transplantation
  1. MAH Abdulla1,2,
  2. AP Jathoul2,
  3. AE Rosser1,2,
  4. WP Gray1,2
  1. 1University Hospital of Wales, Cardiff, UK
  2. 2Cardiff University, Cardiff, UK

Abstract

Objectives Clinical trials of intracerebral cell replacement therapy (CRT) yield inconsistent results owing to poor graft survival and ectopic graft placement. A paucity of available CE marked specialised delivery systems and a lack of reliable delivery protocols could be major contributing factors to both phenomena. Here, we aimed to investigate current needle delivery strategies in-vitro and in a large animal model in pigs.

Design In-vitro laboratory and in-vivo pigs experiments.

In-vitro Agarose gel In-vivo: 4 white Landracer pigs.

Methods In-vitro: Human Embryonic Kidney cells expressing luciferase and 0.6% agarose gel were used to test 3 delivery strategies:

  1. Bracelet deposit,

  2. Large deposit in a pre–formed tract,

  3. Multiple deposits in a pre–formed tract.

In-vivo: Pigs underwent MRI- guided Human Foetal Luciferase-transduced cell transplantation into the putamen and thalamus. Post-operative MRI, Bioluminescence imaging (BLI) and histology were used to identify graft location and viability.

Results Using a commercially available needle delivery system, significant reflux of deposits was noted in all 3 delivery strategies during in-vitro testing. Depositing into a preformed tract yielded the best delivery, and was therefore used for in-vivo testing. Studies in pigs using MRI and BLI confirmed significant reflux and ectopic deposition of grafts.

Conclusions Simple needle delivery systems appear to suffer from significant reflux and ectopic cell deposition. This may adversely affect the outcomes of CRT trials in humans.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.