ArticleArteriosclerosis, thrombosis, and vascular biology2010
Embryonic stem cell-derived endothelial cells engraft into the ischemic hindlimb and restore perfusion.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 133 citations in OpenAlex.
- Direct in vivo reprogramming to relieve tissue ischemia via induced vasculogenesis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- SCIG: Machine learning uncovers cell identity genes in single cells by genetic sequence codes.Nucleic acids research · 2025Article
- Advances and challenges in regenerative therapies for abdominal aortic aneurysm.Frontiers in cardiovascular medicine · 2024Review
- Enhancing endothelial colony-forming cells for treating diabetic vascular complications: challenges and clinical prospects.Frontiers in endocrinology · 2024Review
- Clonal and Scalable Endothelial Progenitor Cell Lines from Human Pluripotent Stem Cells.Biomedicines · 2023Article
- Single-Cell RNA-seq Analysis of a Human Embryonic Stem Cell to Endothelial Cell System Based on Transcription Factor Overexpression.Stem cell reviews and reports · 2023Article
- Chronic nicotine impairs the angiogenic capacity of human induced pluripotent stem cell-derived endothelial cells in a murine model of peripheral arterial disease.JVS-vascular science · 2023Article
- Single-photon emission computed tomography as a fundamental tool in evaluation of myocardial reparation and regeneration therapies.Postepy w kardiologii interwencyjnej = Advances in interventional cardiology · 2022Review
- Therapeutic angiogenesis-based strategy for peripheral artery disease.Theranostics · 2022Review
- Human Induced Pluripotent Stem Cell-Derived Vascular Cells: Recent Progress and Future Directions.Journal of cardiovascular development and disease · 2021Review
- New Directions in Therapeutic Angiogenesis and Arteriogenesis in Peripheral Arterial Disease.Circulation research · 2021Review
- Cell Therapy for Critical Limb Ischemia: Advantages, Limitations, and New Perspectives for Treatment of Patients with Critical Diabetic Vasculopathy.Current diabetes reports · 2021Review
- Hypoxia as a Driving Force of Pluripotent Stem Cell Reprogramming and Differentiation to Endothelial Cells.Biomolecules · 2020Review
- Reservoir of Fibroblasts Promotes Recovery From Limb Ischemia.Circulation · 2020Article
- Vascular Regeneration in Peripheral Artery Disease.Arteriosclerosis, thrombosis, and vascular biology · 2020Review
- Organic NIR-II molecule with long blood half-life for in vivo dynamic vascular imaging.Nature communications · 2020Article
- Novel Cell-Based and Tissue Engineering Approaches for Induction of Angiogenesis as an Alternative Therapy for Diabetic Retinopathy.International journal of molecular sciences · 2020Review
- Delivery of Human Stromal Vascular Fraction Cells on Nanofibrillar Scaffolds for Treatment of Peripheral Arterial Disease.Frontiers in bioengineering and biotechnology · 2020Article
- Cell Therapy With Human ESC-Derived Cardiac Cells: Clinical Perspectives.Frontiers in bioengineering and biotechnology · 2020Review
- Treatment of volumetric muscle loss in mice using nanofibrillar scaffolds enhances vascular organization and integration.Communications biology · 2019Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
objectiveWe examined the effect of delivery modality on the survival, localization, and functional effects of exogenously administered embryonic stem cells (ESCs) or endothelial cells derived from them (ESC-ECs) in the ischemic hindlimb. METHODS AND
resultsMurine ESCs or ESC-ECs were stably transduced with a construct for bioluminescence imaging (BLI) and fluorescent detection. In a syngeneic murine model of limb ischemia, ESCs or ESC-ECs were delivered by intramuscular (IM), intrafemoral artery (IA), or intrafemoral vein injections (n=5 in each group). For 2 weeks, cell survival and localization were tracked by BLI and confirmed by immunohistochemistry, and functional improvement was assessed by laser Doppler perfusion. BLI showed that ESCs localized to the ischemic limb after IM or IA, but not after intrafemoral vein administration. Regardless of the route of administration, ESCs were detected outside the hindlimb circulation in the spleen or lungs. ESCs did not improve limb perfusion and generated teratomas. In contrast, ESC-ECs delivered by all 3 modalities localized to the ischemic limb, as assessed by BLI. Most surprisingly, ESC-EC injected intrafemoral vein eventually localized to the ischemic limb after initially lodging in the pulmonary circulation. Immunohistochemical studies confirmed the engraftment of ESC-ECs into the limb vasculature after 2 weeks. Notably, ESC-ECs were not detected in the spleen or lungs after 2 weeks, regardless of route of administration. Furthermore, ESC-ECs significantly improved limb perfusion and neovascularization compared with the parental ESCs or the vehicle control group.
conclusionIn contrast to parental ESCs, ESC-ECs preferentially localized in the ischemic hindlimb by IA, IM, and intrafemoral vein delivery. ESC-ECs engrafted into the ischemic microvasculature, enhanced neovascularization, and improved limb perfusion.
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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.