Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 416

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study

Open access
Kalladka, Dheeraj, Sinden, John, Pollock, Kenneth, Haig, Caroline, McLean, John, Smith, Wilma, McConnachie, Alex, Santosh, Celestine, Bath, Philip M, Dunn, Laurence, Muir, Keith W·2016·The Lancet
DOI 10.1016/s0140-6736(16)30513-x
Open this paper in CoChat — free account

Abstract

BACKGROUND CTX0E03 is an immortalised human neural stem-cell line from which a drug product (CTX-DP) was developed for allogeneic therapy. Dose-dependent improvement in sensorimotor function in rats implanted with CTX-DP 4 weeks after middle cerebral artery occlusion stroke prompted investigation of the safety and tolerability of this treatment in stroke patients. METHODS We did an open-label, single-site, dose-escalation study. Men aged 60 years or older with stable disability (National Institutes of Health Stroke Scale [NIHSS] score ≥6 and modified Rankin Scale score 2-4) 6-60 months after ischaemic stroke were implanted with single doses of 2 million, 5 million, 10 million, or 20 million cells by stereotactic ipsilateral putamen injection. Clinical and brain imaging data were collected over 2 years. The primary endpoint was safety (adverse events and neurological change). This trial is registered with ClinicalTrials.gov, number NCT01151124. FINDINGS 13 men were recruited between September, 2010, and January, 2013, of whom 11 (mean age 69 years, range 60-82) received CTX-DP. Median NIHSS score before implantation was 7 (IQR 6-8) and the mean time from stroke was 29 (SD 14) months. Three men had subcortical infarcts only and seven had right-hemisphere infarcts. No immunological or cell-related adverse events were seen. Other adverse events were related to the procedure or comorbidities. Hyperintensity around the injection tracts on T2-weighted fluid-attenuation inversion recovery MRI was seen in five patients. At 2 years, improvement in NIHSS score ranged from 0 to 5 (median 2) points. INTERPRETATION Single intracerebral doses of CTX-DP up to 20 million cells induced no adverse events and were associated with improved neurological function. Our observations support further investigation of CTX-DP in stroke patients. FUNDING ReNeuron Limited.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(16)30513-x

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 4 references

Research works printed but not linked: 30

  1. Saka, 2009, Cost of stroke in the United Kingdom, Age Ageing, 38, 27, 10.1093/ageing/afn281 · DOI · Paper page
  2. Ullberg, 2015, Changes in functional outcome over the first year after stroke: an observational study from the Swedish stroke register, Stroke, 46, 389, 10.1161/STROKEAHA.114.006538 · DOI · Paper page
  3. Magalhaes, 2014, Functional status three months after the first ischemic stroke is associated with long-term outcome: data from a community-based cohort, Cerebrovasc Dis, 38, 46, 10.1159/000364938 · DOI
  4. Pollock, 2014, Physical rehabilitation approaches for the recovery of function and mobility following stroke, Cochrane Database Syst Rev, 4, 10.1002/14651858.CD001920.pub3 · DOI · Paper page
  5. Chollet, 2014, Pharmacological therapies in post stroke recovery: recommendations for future clinical trials, J Neurol, 261, 1461, 10.1007/s00415-013-7172-z · DOI
  6. Kalladka, 2014, Brain repair: cell therapy in stroke, Stem Cells Cloning, 7, 31
  7. Stroemer, 2009, The neural stem cell line CTX0E03 promotes behavioral recovery and endogenous neurogenesis after experimental stroke in a dose-dependent fashion, Neurorehabil Neural Repair, 23, 895, 10.1177/1545968309335978 · DOI
  8. Smith, 2012, Implantation site and lesion topology determine efficacy of a human neural stem cell line in a rat model of chronic stroke, Stem Cells, 30, 785, 10.1002/stem.1024 · DOI
  9. Pendharkar, 2010, Biodistribution of neural stem cells after intravascular therapy for hypoxic-ischemia, Stroke, 41, 2064, 10.1161/STROKEAHA.109.575993 · DOI · Paper page
  10. Hicks, 2013, In vivo and in vitro characterization of the angiogenic effect of CTX0E03 human neural stem cells, Cell Transplant, 22, 1541, 10.3727/096368912X657936 · DOI
  11. Hassani, 2012, Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke, PLoS One, 7, e50444, 10.1371/journal.pone.0050444 · DOI
  12. Brott, 1989, Measurements of acute cerebral infarction: a clinical examination scale, Stroke, 20, 864, 10.1161/01.STR.20.7.864 · DOI · Paper page
  13. Quinn, 2007, Initial experience of a digital training resource for modified Rankin scale assessment in clinical trials, Stroke, 38, 2257, 10.1161/STROKEAHA.106.480723 · DOI
  14. Jones, 2013, A regulatory perspective of clinical trial applications for biological products with particular emphasis on advanced therapy medicinal products (ATMPs), Br J Clin Pharmacol, 76, 203, 10.1111/bcp.12057 · DOI
  15. Bohannon, 1987, Interrater reliability of a modified Ashworth scale of muscle spasticity, Phys Ther, 67, 206, 10.1093/ptj/67.2.206 · DOI · Paper page
  16. Mahoney, 1965, Functional evaluation: the Barthel Index, Md State Med J, 14, 61
  17. Pollock, 2006, A conditionally immortal clonal stem cell line from human cortical neuroepithelium for the treatment of ischemic stroke, Exp Neurol, 199, 143, 10.1016/j.expneurol.2005.12.011 · DOI · Paper page
  18. Thomas, 2009, Automated, serum-free production of CTX0E03: a therapeutic clinical grade human neural stem cell line, Biotechnol Lett, 31, 1167, 10.1007/s10529-009-9989-1 · DOI
  19. Kondziolka, 2004, Evaluation of surgical techniques for neuronal cell transplantation used in patients with stroke, Cell Transpl, 13, 749, 10.3727/000000004783983350 · doi:10.3727/000000004783983350
  20. Favre, 2002, An analysis of the respective risks of hematoma formation in 361 consecutive morphological and functional stereotactic procedures, Neurosurgery, 50, 48
  21. Kondziolka, 2005, Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial, J Neurosurg, 103, 38, 10.3171/jns.2005.103.1.0038 · DOI · Paper page
  22. Kondziolka, 2000, Transplantation of cultured human neuronal cells for patients with stroke, Neurology, 55, 565, 10.1212/WNL.55.4.565 · DOI · Paper page
  23. Savitz, 2005, Neurotransplantation of fetal porcine cells in patients with basal ganglia infarcts: a preliminary safety and feasibility study, Cerebrovasc Dis, 20, 101, 10.1159/000086518 · DOI · Paper page
  24. Garbe, 2002, The New American Joint Committee on Cancer staging system for cutaneous melanoma: a critical analysis based on data of the German Central Malignant Melanoma Registry, Cancer, 94, 2305, 10.1002/cncr.10468 · doi:10.1002/cncr.10468
  25. Menotti, 2001, Prevalence of morbidity and multimorbidity in elderly male populations and their impact on 10-year all-cause mortality: the FINE study (Finland, Italy, Netherlands, Elderly), J Clin Epidemiol, 54, 680, 10.1016/S0895-4356(00)00368-1 · DOI · Paper page
  26. Uchida, 2012, Human neural stem cells induce functional myelination in mice with severe dysmyelination, Sci Transl Med, 4, 155ra136, 10.1126/scitranslmed.3004371 · DOI
  27. Gupta, 2012, Neural stem cell engraftment and myelination in the human brain, Sci Transl Med, 4, 155ra137, 10.1126/scitranslmed.3004373 · DOI · Paper page
  28. Acosta, 2015, Intravenous bone marrow stem cell grafts preferentially migrate to spleen and abrogate chronic inflammation in stroke, Stroke, 46, 2616, 10.1161/STROKEAHA.115.009854 · DOI · Paper page
  29. Stevanato, 2009, c-MycERTAM transgene silencing in a genetically modified human neural stem cell line implanted into MCAo rodent brain, BMC Neurosci, 10, 86, 10.1186/1471-2202-10-86 · DOI
  30. Cohen, 2012, Sham neurosurgical procedures: the patients' perspective, Lancet Neurol, 11, 1022, 10.1016/S1474-4422(12)70277-6 · doi:10.1016/s1474-4422(12)70277-6

Cited by

See all 416

Metadata

Authors
Kalladka, D., Sinden, J., Pollock, K., Haig, C., McLean, J., Smith, W., McConnachie, A., Santosh, C., Bath, P. M., Dunn, L., & Muir, K. W.
Venue
The Lancet
Publisher
Elsevier BV
Published
2016-08
Volume
388
Issue
10046
Pages
787-796
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(16)30513-x
OpenAlex
W2490585184
Cited by
416
References
4
FWCI
29.90
Type
journal article
Language
en
Open access
green
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study. https://app.cochat.ai/papers/10.1016/s0140-6736(16)30513-x
The paper
Kalladka, D., Sinden, J., Pollock, K., Haig, C., McLean, J., Smith, W., McConnachie, A., Santosh, C., Bath, P. M., Dunn, L., & Muir, K. W. (2016). Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study. The Lancet. https://doi.org/10.1016/s0140-6736(16)30513-x

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.