Evidence map›Paper›PMID 42469204›Full record

ReviewCell death & disease2026

From neural loss to regeneration: modulating cell death to enhance pluripotent stem cell graft survival and integration.

Ouye Chen, Kelvin K Hui, Fabian Raudzus, Jeffrey T Henderson

Abstract readReview
In one paragraph

Review in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Ouye ChenGraduate Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Kelvin K HuiCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.ORCID http://orcid.org/0000-0003-2699-4536
Fabian RaudzusCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan. fabian.raudzus@cira.kyoto-u.ac.jp.ORCID http://orcid.org/0000-0001-8327-2076
Jeffrey T HendersonGraduate Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada. jeff.henderson@utoronto.ca.ORCID http://orcid.org/0000-0001-7636-2604

Funding

Kyoto University ISHIZUE 2025MEXT | Japan Society for the Promotion of Science (JSPS) 22K06430University of Toronto (UofT) Connaught New Innovations Award
6 · The paper itself

Abstract

Cerebrovascular and neurodegenerative diseases rank among the leading causes of death worldwide and represent an increasing socioeconomic burden, particularly in aging populations. Pluripotent stem cell (PSC)-based therapies have emerged as promising strategies for replacing lost neurons and restoring neural circuits in disorders of the central nervous system (CNS). However, major barriers remain, including poor survival, limited integration, and variable functional maturation of transplanted cells. These challenges currently limit the reproducibility and clinical translation of PSC-based therapies. Here, we examine these barriers with a particular focus on ischemic stroke and Parkinson's disease, two conditions that represent complementary models of acute and chronic neuronal loss and are among the most advanced indications for PSC-based transplantation. We discuss how programmed cell death signaling contributes not only to neuronal loss in these disorders but also to the limited survival of transplanted PSC-derived grafts. Building on this mechanistic framework, we highlight strategies that may improve graft survival and functional integration. Specifically, we propose an integrated approach that combines modulation of programmed cell death pathways, targeted activation of RAS signaling, optimization of mitochondrial health, and use of biocompatible scaffolds to support neuronal maturation and network integration. Together, these strategies provide a conceptual framework for improving the reliability and therapeutic efficacy of PSC-based cell transplantation therapies and accelerating their translation toward clinical application. Overview of strategies to enhance PSC-derived neural graft survival and integration through modulation of cell death pathways, RAS signaling, mitochondrial function, and extracellular scaffolds. Created in BioRender. Raudzus, F. (2026) https://BioRender.com/blr0ycj .

Indexed as

Graft SurvivalNeuronsPluripotent Stem CellsStem Cell TransplantationAnimalsCell DeathHumansParkinson DiseaseSignal Transduction

Identifiers

PMID42469204
PMCPMC13658219

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.