ArticleFrontiers in cardiovascular medicine2025
Neonatally-derived multipotent Islet-1+ Mesp1+FOXA2+ stem cell clones restore cardiac function in sheep.
Article in Frontiers in cardiovascular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Stem cell therapeutics is an area of active investigation for the treatment of cardiovascular disease. Unlike adults, neonatal hearts possess unique regenerative capacity immediately after birth, suggesting that neonatal cardiovascular tissue may be a promising and untapped resource of stem cells. In the current study, we present the unique transcriptome and differentiation capability of neonatal Methods: The transcriptome of early-stage, human neonatal ISL1+ stem cell clones was identified by RNAseq analysis. Differentiation capability was validated by flow cytometry, RT-qPCR and electrophysiology. Matched ISL1+ neonatal sheep stem cell clones were isolated for the purpose of developing an allogeneic, preclinical large animal model of ISL1+ stem cell-based repair in sheep. A myocardial infarction was induced by ligation of left anterior descending coronary artery followed by ISL1+ stem cell transplantation three-four weeks later by direct intracardiac injection in the absence of immunosuppression. The Results: Neonatally-derived ISL1+ clones restored cardiac function to normal levels as shown by echocardiography. Stem cell retention was identified by histology in the cardiovascular repair zone and transcriptomic analysis identified the contribution of several signaling pathways leading to activation of paracrine and cardiogenic effects in the stem-cell treated regions of the heart. We further define the contribution of immunosuppressive mediators that contribute to stem cell retention and factors that stimulate endothelial cell recruitment in this allogeneic model of stem cell-based therapy. Conclusion:
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