ArticleCirculation research2010
Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice.
Article in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 354 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
354 citing papers in PubMed, 1 synthesis or guideline pooled it, 654 citations in OpenAlex.
- Cell Therapy Strategies on Duchenne Muscular Dystrophy: A Systematic Review of Clinical Applications.Stem cell reviews and reports · 2024Pooled it
- Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial.Open heart · 2021Trial
- Differentiation of arterioles and capillaries in human blood vessel organoids with decellularized splenic matrix.Bioactive materials · 2026Article
- Progress on cell therapy for skeletal muscle disorders.Advanced drug delivery reviews · 2026Review
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- Cytochrome P450-derived metabolites of docosahexaenoic acid or arachidonic acid enhance contractility of cultured rat cardiomyocytes: a pilot study.Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs · 2026Article
- Small extracellular vesicles reflect senescence progression in human bone marrow-derived mesenchymal stem cells during hollow fiber bioreactor culture.Nanotheranostics · 2026Article
- Decreased Corneal Endothelial Cell Apoptosis Due to U/S Power Injury With Limbal Mesenchymal Stem Cell Secretome Therapy.Stem cells international · 2026Article
- Targeting Strategies of Stem Cell-Derived Extracellular Vesicles in the Treatment of Cardiovascular Diseases.Stem cell reviews and reports · 2026Review
- Comparative regenerative mechanisms of adipose-derived mesenchymal stem cell- and conditioned medium-loaded three-dimensional bioprinted hydrogels in chronic diabetic wounds.Regenerative biomaterials · 2026Article
- The 3D World of Spheroids: Searching for an Optimal Method of Fabricating Pro-Reparative Cardiospheres.International journal of molecular sciences · 2025Article
- The Promise of Exosomes in Cardiac Repair: When 'Best Things Come in Small Packages'.Journal of cellular and molecular medicine · 2025Review
- A Novel In Vitro Potency Assay Demonstrating the Anti-Fibrotic Mechanism of Action of CDCs in Deramiocel.Biomedicines · 2025Article
- Review
- Review
- Heart-derived endogenous stem cells.Molecular biology reports · 2025Review
- Stem Cell Therapy in Ischemic Heart Failure.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2025Review
- Cardioprotective effects of ghrelin and Wharton's jelly-derived mesenchymal stem cells, alone and in combination, in doxorubicin-induced myocardial injury in rats.Journal of molecular histology · 2025Article
- Unraveling the aging-reversal potency of stem cell-derived extracellular vesicles in a rat model of premature cardiac senescence.iScience · 2025Article
- Stem Cell Therapy Approaches for Ischemia: Assessing Current Innovations and Future Directions.International journal of molecular sciences · 2025Review
294 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleMultiple biological mechanisms contribute to the efficacy of cardiac cell therapy. Most prominent among these are direct heart muscle and blood vessel regeneration from transplanted cells, as opposed to paracrine enhancement of tissue preservation and/or recruitment of endogenous repair.
objectiveHuman cardiac progenitor cells, cultured as cardiospheres (CSps) or as CSp-derived cells (CDCs), have been shown to be capable of direct cardiac regeneration in vivo. Here we characterized paracrine effects in CDC transplantation and investigated their relative importance versus direct differentiation of surviving transplanted cells. METHODS AND
resultsIn vitro, many growth factors were found in media conditioned by human adult CSps and CDCs; CDC-conditioned media exerted antiapoptotic effects on neonatal rat ventricular myocytes, and proangiogenic effects on human umbilical vein endothelial cells. In vivo, human CDCs secreted vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor 1 when transplanted into the same SCID mouse model of acute myocardial infarction where they were previously shown to improve function and to produce tissue regeneration. Injection of CDCs in the peri-infarct zone increased the expression of Akt, decreased apoptotic rate and caspase 3 level, and increased capillary density, indicating overall higher tissue resilience. Based on the number of human-specific cells relative to overall increases in capillary density and myocardial viability, direct differentiation quantitatively accounted for 20% to 50% of the observed effects.
conclusionsTogether with their spontaneous commitment to cardiac and angiogenic differentiation, transplanted CDCs serve as "role models," recruiting endogenous regeneration and improving tissue resistance to ischemic stress. The contribution of the role model effect rivals or exceeds that of direct regeneration.
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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.