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

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: 2012-003482-1

Intracranial delivery of stem cells

The method of delivery of stem cells is a major factor to consider in the design of clinical trials of cell therapy. Different methods of delivery will be associated with different risks to the patient, and may also be associated with different potential for benefit. Current approaches are partly informed by the routes selected for study in animal models of focal ischaemia and CNS transplantation, but there has been little work comparing the efficacy of different routes of administration. Direct intraparenchymal delivery of cells has been employed in several preliminary clinical trials, and data on the safety of this approach are reviewe

Stem cells in stroke treatment: the promise and the challenges

Stroke, for some years now the neglected major indication in the pharmaceutical development cupboard, has recently become one of the hot areas for stem cell therapy development. This is driven by better understanding of potential therapeutic opportunities both in the acute and chronic phases and the launch of a series of new early phase clinical trials in a number of countries, driven by positive data in relevant animal models. In addition, the impetus for stem cell product development is motivated by patient demand, with thousands of victims seeking unproven treatments abroad. This article looks at the many challenges facing the development of a stem cell therapy for stroke. These range from product characterization and banking, through nonclinical safety and efficacy to the regulatory requirements for starting patient trials and beyond to maximizing value from carefully designed efficacy trials