ArticleNature medicine2016
3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
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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.
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Who cites it
72 citing papers in PubMed, 109 citations in OpenAlex.
- Trial
- Harnessing Lessons from Gel-Based and Advanced Biomaterial Therapeutics to Enable Direct Cellular Reprogramming.Gels (Basel, Switzerland) · 2026Review
- Allele-specific CRISPR perturbation of the imprinted Dlk1-Dio3 domain reveals regulation of BMP-NOTCH-VEGF signaling in embryonic organogenesis.Cell death and differentiation · 2026Article
- Epigenetic and O-glycosylation regulation of p66Shc mitigates mitochondrial oxidative stress in aortic dissection.Theranostics · 2026Article
- "Time Is Brain" - for Cell Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Stem cell-mediated recovery in stroke: partnering with the immune system.Nature reviews. Neuroscience · 2026Review
- Protease-activated receptor 1 in diabetes and its chronic complications: signaling mechanisms and emerging therapeutic advances.Frontiers in pharmacology · 2026Review
- Dl-3-n-Butylphthalide Promotes Cortical Angiogenesis via Akt/GSK-3β Signaling in Ischemic Stroke Mice.CNS neuroscience & therapeutics · 2025Article
- Neural xenografts contribute to long-term recovery in stroke via molecular graft-host crosstalk.Nature communications · 2025Article
- Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke.Nature communications · 2025Article
- Bone Marrow-Derived Inducible Microglia-like Cells Promote Recovery of Chronic Ischemic Stroke Through Modulating Neuroinflammation in Mice.Biomedicines · 2025Article
- Low-Intensity Pulsed Ultrasound Promotes Oligodendrocyte Maturation and Remyelination by Down-regulating the Interleukin-17A/Notch1 Signaling Pathway in Mice with Ischemic Stroke.Research (Washington, D.C.) · 2025Article
- Brain repair mechanisms after cell therapy for stroke.Brain : a journal of neurology · 2024Review
- Platelets at the intersection of inflammation and coagulation in the APC-mediated response to myocardial ischemia/reperfusion injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- An orthosteric/allosteric bivalent peptide agonist comprising covalently linked protease-activated receptor-derived peptides mimics in vitro and in vivo activities of activated protein C.Journal of thrombosis and haemostasis : JTH · 2024Article
- Stem Cell Therapy for Repair of the Injured Brain: Five Principles.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Article
- Revolutionizing Stroke Recovery: Unveiling the Promise of Stem Cell Therapy.Drug design, development and therapy · 2024Review
- Enabling Survival of Transplanted Neural Precursor Cells in the Ischemic Brain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Transplantation of hESCs-Derived Neural Progenitor Cells Alleviates Secondary Damage of Thalamus After Focal Cerebral Infarction in Rats.Stem cells translational medicine · 2023Article
- Ischemic stroke-related gene expression profiles across species: a meta-analysis.Journal of inflammation (London, England) · 2023Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Activated protein C (APC) is a blood protease with anticoagulant activity and cell-signaling activities mediated by the activation of protease-activated receptor 1 (F2R, also known as PAR1) and F2RL1 (also known as PAR3) via noncanonical cleavage. Recombinant variants of APC, such as the 3K3A-APC (Lys191-193Ala) mutant in which three Lys residues (KKK191-193) were replaced with alanine, and/or its other mutants with reduced (>90%) anticoagulant activity, engineered to reduce APC-associated bleeding risk while retaining normal cell-signaling activity, have shown benefits in preclinical models of ischemic stroke, brain trauma, multiple sclerosis, amyotrophic lateral sclerosis, sepsis, ischemic and reperfusion injury of heart, kidney and liver, pulmonary, kidney and gastrointestinal inflammation, diabetes and lethal body radiation. On the basis of proof-of-concept studies and an excellent safety profile in humans, 3K3A-APC has advanced to clinical trials as a neuroprotectant in ischemic stroke. Recently, 3K3A-APC has been shown to stimulate neuronal production by human neural stem and progenitor cells (NSCs) in vitro via a PAR1-PAR3-sphingosine-1-phosphate-receptor 1-Akt pathway, which suggests the potential for APC-based treatment as a strategy for structural repair in the human central nervous (CNS) system. Here we report that late postischemic treatment of mice with 3K3A-APC stimulates neuronal production by transplanted human NSCs, promotes circuit restoration and improves functional recovery. Thus, 3K3A-APC-potentiated neuronal recruitment from engrafted NSCs might offer a new approach to the treatment of stroke and related neurological disorders.
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What OpenQuestion holds
Registered trials
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.