ArticleJCI insight2020
Plasminogen regulates mesenchymal stem cell-mediated tissue repair after ischemia through Cyr61 activation.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Systematic review and meta-analysis of the effect of bone marrow-derived cell therapies on hind limb perfusion.Disease models & mechanisms · 2024Pooled it
- CYR61 delivery promotes angiogenesis during bone fracture repair.NPJ Regenerative medicine · 2025Article
- Comparative computational analysis to distinguish mesenchymal stem cells from fibroblasts.Frontiers in immunology · 2023Article
- Substance P modulates BMSCs migration for tissue repair through NK-1R/CXCR4/p-Akt signal activation.Molecular biology reports · 2022Article
- The Plasminogen-Activator Plasmin System in Physiological and Pathophysiological Angiogenesis.International journal of molecular sciences · 2021Review
- Serum CYR61 Is Associated With Airway Inflammation and Is a Potential Biomarker for Severity in Chronic Obstructive Pulmonary Disease.Frontiers in medicine · 2021Article
- Association of serum Cyr61 levels with peripheral arterial disease in subjects with type 2 diabetes.Cardiovascular diabetology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stem cell transplantation has emerged as a promising strategy in regenerative medicine. However, the poor survival and persistence of the transplanted cells, including mesenchymal stem cells (MSCs), in the hostile ischemic microenvironments represents a major therapeutic barrier. Here we report that plasminogen (Plg) stimulated MSC functions and promoted MSC survival during tissue repair after ischemia. Genetic Plg ablation abolished MSC survival, migration, and proliferation in mouse ischemic limbs, and abrogated MSC-mediated blood reperfusion, neovascularization, and tissue repair after ischemia, suggesting a critical role for Plg in MSC-mediated tissue repair. Furthermore, multiplex cytokine array analysis identified that Plg cleaved and activated cysteine-rich protein 61 (Cyr61), an ECM-associated growth factor, to stimulate MSC survival and migration. Overexpression with truncated Cyr61 in MSCs rescued blood reperfusion after hind limb ischemia in Plg-deficient mice. Finally, Plg-mediated Cyr61 cleavage promoted endothelial cell migration and neovascularization in vitro and in vivo. Our study reveals that Plg promotes MSC survival, persistence, and paracrine effects and improves postischemic neovascularization and tissue repair through Cyr61 cleavage and activation. Thus, targeting Plg/Cyr61 may offer exciting therapeutic opportunities for strengthening MSC therapy in ischemic diseases.
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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.