ArticleProceedings of the National Academy of Sciences of the United States of America2020
Activity in grafted human iPS cell-derived cortical neurons integrated in stroke-injured rat brain regulates motor behavior.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 99 citations in OpenAlex.
- A novel mWGA-TYR PET reporter gene system for in vivo visualization of whole brain-level neural circuit.European journal of nuclear medicine and molecular imaging · 2026Article
- PET molecular imaging of in vivo brain metabolism, synaptic density and glial reactivity changes after neural stem cell transplantation on a rat model of ischemic stroke.European journal of nuclear medicine and molecular imaging · 2026Article
- Animal stroke models and outcome evaluation: A review.Animal models and experimental medicine · 2026Review
- Co-Delivery of Sustained Release Chondroitinase ABC-37 With Human iPSC-Derived Neural Progenitors Promotes Transplant Survival and Functional Recovery in a Rodent Model of Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pathophysiological roles of neural stem cells in neuropsychiatric diseases: from plasticity to pharmacological targeting.Acta pharmacologica Sinica · 2026Review
- Human stem cell-derived neurons establish functional inhibitory-excitatory cortical circuits in a chimeric transplantation model.Scientific reports · 2026Article
- The Reparative Mechanisms Underlying Preclinical Neural Stem/Progenitor Cell Therapy for Ischemic Stroke: A Systematic Review.Neurology research international · 2026Review
- Transplantation of Human iPS Cell-derived Cerebral Cortical Neurons Promotes Fine Motor Recovery in a Female Mouse Model of Ischemic Stroke.Stem cell reviews and reports · 2026Article
- Stem cell-mediated recovery in stroke: partnering with the immune system.Nature reviews. Neuroscience · 2026Review
- "Time Is Brain" - for Cell Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Cost-effectiveness of stem cell therapy versus standard of care for acute and subacute ischemic stroke.PloS one · 2026Article
- Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury.Neural regeneration research · 2025Article
- Human cortical neurons rapidly generated by embryonic stem cell programming integrate into the stroke-injured rat cortex.Stem cells (Dayton, Ohio) · 2025Article
- Neural xenografts contribute to long-term recovery in stroke via molecular graft-host crosstalk.Nature communications · 2025Article
- BDNF Overexpression Enhances Neuronal Activity and Axonal Growth in Human iPSC-Derived Neural Cultures.International journal of molecular sciences · 2025Article
- Brain organoid maturation and implantation integration based on electrical signals input.Journal of advanced research · 2025Article
- How neural stem cell therapy promotes brain repair after stroke.Stem cell reports · 2025Review
- Functional recovery through the plastic adaptation of organoid grafts in cortical tissue.Cellular and molecular life sciences : CMLS · 2025Review
- Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke.Nature communications · 2025Article
- Compact transcription factor cassettes generate functional, engraftable motor neurons by direct conversion.Cell systems · 2025Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stem cell transplantation can improve behavioral recovery after stroke in animal models but whether stem cell-derived neurons become functionally integrated into stroke-injured brain circuitry is poorly understood. Here we show that intracortically grafted human induced pluripotent stem (iPS) cell-derived cortical neurons send widespread axonal projections to both hemispheres of rats with ischemic lesions in the cerebral cortex. Using rabies virus-based transsynaptic tracing, we find that at 6 mo after transplantation, host neurons in the contralateral somatosensory cortex receive monosynaptic inputs from grafted neurons. Immunoelectron microscopy demonstrates myelination of the graft-derived axons in the corpus callosum and that their terminals form excitatory, glutamatergic synapses on host cortical neurons. We show that the stroke-induced asymmetry in a sensorimotor (cylinder) test is reversed by transplantation. Light-induced inhibition of halorhodopsin-expressing, grafted neurons does not recreate the impairment, indicating that its reversal is not due to neuronal activity in the graft. However, we find bilateral decrease of motor performance in the cylinder test after light-induced inhibition of either grafted or endogenous halorhodopsin-expressing cortical neurons, located in the same area, and after inhibition of endogenous halorhodopsin-expressing cortical neurons by exposure of their axons to light on the contralateral side. Our data indicate that activity in the grafted neurons, probably mediated through transcallosal connections to the contralateral hemisphere, is involved in maintaining normal motor function. This is an example of functional integration of efferent projections from grafted neurons into the stroke-affected brain's neural circuitry, which raises the possibility that such repair might be achievable also in humans affected by stroke.
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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.