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Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2)

Muir, Keith W; Bulters, Diederik; Willmot, Mark; Sprigg, Nikola; Dixit, Anand; Ward, Nick; Tyrrell, Pippa; Majid, Arshad; Dunn, Laurence; Bath, Philip M; Howell, Julian; Stroemer, Paul; Pollock, Kenneth; Sinden, John


Keith W Muir

Diederik Bulters

Mark Willmot

Professor of Stroke Medicine

Anand Dixit

Nick Ward

Pippa Tyrrell

Arshad Majid

Laurence Dunn

Stroke Association Professor of Stroke Medicine

Julian Howell

Paul Stroemer

Kenneth Pollock

John Sinden



Human neural stem cell implantation may offer improved recovery from stroke. We investigated the feasibility of intracerebral implantation of the allogeneic human neural stem cell line CTX0E03 in the subacute—chronic recovery phase of stroke and potential measures of therapeutic response in a multicentre study.


We undertook a prospective, multicentre, single-arm, open-label study in adults aged >40 years with significant upper limb motor deficits 2–13 months after ischaemic stroke. 20 million cells were implanted by stereotaxic injection to the putamen ipsilateral to the cerebral infarct. The primary outcome was improvement by 2 or more points on the Action Research Arm Test (ARAT) subtest 2 at 3 months after implantation.


Twenty-three patients underwent cell implantation at eight UK hospitals a median of 7 months after stroke. One of 23 participants improved by the prespecified ARAT subtest level at 3 months, and three participants at 6 and 12 months. Improvement in ARAT was seen only in those with residual upper limb movement at baseline. Transient procedural adverse effects were seen, but no cell-related adverse events occurred up to 12 months of follow-up. Two deaths were unrelated to trial procedures.


Administration of human neural stem cells by intracerebral implantation is feasible in a multicentre study. Improvements in upper limb function occurred at 3, 6 and 12 months, but not in those with absent upper limb movement at baseline, suggesting a possible target population for future controlled trials.


ReNeuron, Innovate UK (application no 32074-222145).

Trial registration number

EudraCT Number: 2012-003482-18


Muir, K. W., Bulters, D., Willmot, M., Sprigg, N., Dixit, A., Ward, N., …Sinden, J. (2020). Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2). Journal of Neurology, Neurosurgery and Psychiatry, 91(4), 396-401.

Journal Article Type Article
Acceptance Date Jan 8, 2020
Online Publication Date Feb 10, 2020
Publication Date 2020-04
Deposit Date Jan 13, 2020
Publicly Available Date Jan 13, 2020
Journal Journal of Neurology, Neurosurgery and Psychiatry
Print ISSN 0022-3050
Electronic ISSN 1468-330X
Publisher BMJ Publishing Group
Peer Reviewed Peer Reviewed
Volume 91
Issue 4
Pages 396-401
Keywords stroke; stem cells; human neural stem cells; surgery; psychiatry and mental health; clinical neurology
Public URL
Publisher URL
Additional Information This article has been accepted for publication in Journal of Neurology, Neurosurgery & Psychiatry, 2020 following peer review, and the Version of Record can be accessed online at
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.


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