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

J Neurol Neurosurg Psychiatry. 2020 Apr;91(4):396-401. doi: 10.1136/jnnp-2019-322515. Epub 2020 Feb 10.

Abstract

Background: 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.

Methods: 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.

Findings: 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.

Interpretation: 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.

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

Trial registration number: EudraCT Number: 2012-003482-18.

Keywords: human neural stem cells; stem cells; stroke.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain Ischemia / physiopathology
  • Brain Ischemia / therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neural Stem Cells / transplantation*
  • Prospective Studies
  • Recovery of Function / physiology*
  • Stem Cell Transplantation / methods*
  • Stroke / physiopathology
  • Stroke / therapy*
  • Stroke Rehabilitation
  • Treatment Outcome
  • Upper Extremity / physiopathology

Associated data

  • EudraCT/2012-003482-18