ArticleStem cells (Dayton, Ohio)2021
Human placenta mesenchymal stem cell protection in ischemic stroke is angiotensin converting enzyme-2 and masR receptor-dependent.
Article in Stem cells (Dayton, Ohio), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- The efficacy and safety of stem cell therapy for ischemic stroke: a systematic review and network meta-analysis study.BMC neurology · 2025Pooled it
- Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Effects of stem cell therapy on preclinical stroke.Open veterinary journal · 2025Review
- ACE2 Rescues Sepsis-Associated Encephalopathy by Reducing Inflammation, Oxidative Stress, and Neuronal Apoptosis via the Nrf2/Sestrin2 Signaling Pathway.Molecular neurobiology · 2024Article
- Brain repair mechanisms after cell therapy for stroke.Brain : a journal of neurology · 2024Review
- Priming and Combined Strategies for the Application of Mesenchymal Stem Cells in Ischemic Stroke: A Promising Approach.Molecular neurobiology · 2024Review
- Exploring SSEA3 as an emerging biomarker for assessing the regenerative potential of dental pulp-derived stem cells.Regenerative therapy · 2024Article
- Research progress and challenges of stem cell therapy for ischemic stroke.Frontiers in cell and developmental biology · 2024Review
- Pathophysiology, Management, and Therapeutics in Subarachnoid Hemorrhage and Delayed Cerebral Ischemia: An Overview.Pathophysiology : the official journal of the International Society for Pathophysiology · 2023Review
- Current state of stem cell research in non-human primates: an overview.Medical review (2021) · 2023Review
- State of the Art and Future of Stem Cell Therapy in Ischemic Stroke: Why Don't We Focus on Their Administration?Bioengineering (Basel, Switzerland) · 2023Review
- Human PMSCs-derived small extracellular vesicles alleviate neuropathic pain through miR-26a-5p/Wnt5a in SNI mice model.Journal of neuroinflammation · 2022Article
- Review
- Stem Cell Transplantation Therapy and Neurological Disorders: Current Status and Future Perspectives.Biology · 2022Review
- Differential Lung Protective Capacity of Exosomes Derived from Human Adipose Tissue, Bone Marrow, and Umbilical Cord Mesenchymal Stem Cells in Sepsis-Induced Acute Lung Injury.Oxidative medicine and cellular longevity · 2022Article
- The Role of the ACE2/MasR Axis in Ischemic Stroke: New Insights for Therapy.Biomedicines · 2021Review
- Human placenta mesenchymal stem cell protection in ischemic stroke is angiotensin converting enzyme-2 and masR receptor-dependent.Stem cells (Dayton, Ohio) · 2021Article
- Stem cells part of the innate and adaptive immune systems as a therapeutic for Covid-19.Communicative & integrative biology · 2021Review
- Integrated Analysis of the Cecal Microbiome and Plasma Metabolomics to Explore NaoMaiTong and Its Potential Role in Changing the Intestinal Flora and Their Metabolites in Ischemic Stroke.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Thromboembolic stroke remains a major cause of neurological disability and death. Current stroke treatments (aspirin, tissue plasminogen activator) are significantly limited by timing and risks for hemorrhage which have driven researchers to explore other approaches. Stem cell-based therapy appears to be an effective option for ischemic stroke. Besides trans-differentiation into neural cells, stem cells also provide acute protection via paracrine signaling pathways through which releasing neuroprotective factors. We previously reported that intraperitoneal administration of human placenta mesenchymal stem cell (hPMSC) therapy upon reperfusion significantly protected the brain against middle cerebral artery occlusion (MCAO)-induced injury. In the present study, we specifically investigated the role of hPMSC-derived angiotensin converting enzyme-2 (ACE-2) in protection of MCAO-induced brain injury by measurement of brain tissue viability, cerebral blood flow, and neurological score. Here, we report for the first time that hPMSC expressing substantial amount of ACE-2, which mediates hPMSC protection in the MCAO model. Strikingly, we found that the protective effects of hPMSC in MCAO-induced brain injury could be attenuated by pretreatment of hPMSCs with MLN-4760, a specific inhibitor of ACE-2 activity, or by transfection of hPMSCs with ACE-2-shRNA-lentivirus. The hPMSC-derived ACE-2 specific protective mechanism was further demonstrated by administration of PD123319, an Angiotensin type-2 receptor antagonist, or A779, a MasR antagonist. Importantly, our study demonstrated that the protective effects of hPMSC in experimental stroke are ACE-2/MasR dependent and this signaling pathway represents an innovative and highly promising approach for targeted stroke therapy.
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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.