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Increased deep grey matter functional connectivity of poststroke hNSC implanted ipsilesional putamen
  1. Dheeraj Kalladka1,2,
  2. John Sinden3,
  3. John McLean4,
  4. Fiona Catherine Moreton1,5,
  5. Xuya Huang1,
  6. Keith W Muir1
  1. 1 Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, UK
  2. 2 Department of Stroke and Neurosciences, Imperial College Healthcare NHS Trust, London, UK
  3. 3 ReNeuron Ltd, Bridgend, UK
  4. 4 Department of Neuroradiology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK
  5. 5 Department of Neurology, Western General Hospital, Edinburgh, UK
  1. Correspondence to Dr Dheeraj Kalladka, Department of Stroke and Neurosciences, Imperial College Healthcare NHS Trust, London W6 8RF, UK; dheeraj.kalladka{at}nhs.net

http://dx.doi.org/10.1136/jnnp-2018-319022

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    Although stroke results in focal brain tissue loss, remote effects consequent to the disruption of structural and functional networks are recognised. Resting-state functional connectivity MRI has the ability to image subjects with a broad range of impairments following stroke without the interpretive confound of variable task performance seen in task-based paradigms. Significant proportion of stroke survivors has permanent residual disability, indicating limited endogenous recovery capacity. In rat middle cerebral artery occlusion models (MCAo), CTX0E03 human neural stem cell (hNSCs) (clonally derived from human foetal cortical epithelium) injected to the striatum adjacent to the infarct 4 weeks after MCAo showed improvement in behavioural outcome measures along with histological evidence of increased host angiogenesis and neurogenesis.1 We examined the effects of intracerebral hNSC implantation in the putamen on functional networks assessed by longitudinal resting-state functional connectivity and explored associations with clinical measures.

    Patients for this study were from the Pilot Investigation of Stem Cells in Stroke (PISCES) trial2 a phase I, open-label study of intracerebral stereotactic implantation of CTX0E03 hNSCs to the ipsilateral putamen in patients with chronic ischaemic stroke. Eleven patients (National Institutes of Health Stroke Scale (NIHSS) ≥6, modified Rankin Scale (mRS)=2–4) with a first ischaemic stroke 6 months to 5 years previously were recruited. Cells were implanted under general anaesthesia and patients followed up over 2 years. Assessments covered neurological impairment (NIHSS), disability (mRS), spasticity (modified Ashworth scale) and activities of daily living (Barthel Index (BI)).

    Brain MRI was performed on three occasions, baseline (1 month prior), M1 (1 month after) and M12 (1 year after implantation) on a 3T GE Signa-Excite-HDxt scanner. Acquisition parameters included T1W (time to echo …

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    Footnotes

    • Contributors DK contributed to acquiring the data, imaging analysis, drafting and revising the manuscript for intellectual content and final approval. JS funded the trial and provided the stem cells. JM contributed to imaging data acquisition. FM and XH contributed to clinical reviews and data acquisition. KWM contributed to study design, critically revising the manuscript and final approval.

    • Funding ReNeuron Ltd. funded the PISCES study.

    • Competing interests DK has received Jim Gatheral and MacRobertson travel scholarship and Guarantors of Brain travel scholarships. JS is an employee and stock holder of ReNeuron Ltd. KWM has received trial funding from ReNeuron for PISCES and PISCES-2 stroke stem cell trial.

    • Patient consent for publication Not required.

    • Ethics approval National Research Ethics Committee (Formerly Gene Therapy Advisory Committee, UK).

    • Provenance and peer review Not commissioned; externally peer reviewed.