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Neonatally-derived multipotent Islet-1+ Mesp1+FOXA2+ stem cell clones restore cardiac function in sheep
Lorelei Hughes1, Jonathan Baio1, Nahidh Hasaniya2
1Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA, United States.
Frontiers in Cardiovascular Medicine
|January 21, 2026
Summary
Neonatal cardiovascular stem cells (ISL1+ MESP1+ FOXA2+) show promise for heart repair. These cells restored cardiac function in a sheep model of myocardial infarction without immunosuppression, highlighting a novel therapeutic resource.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Stem Cell Biology
Background:
- Neonatal hearts have unique regenerative potential absent in adults.
- Neonatal cardiovascular tissue is an untapped source for stem cells.
- ISL1+ MESP1+ FOXA2+ stem cell clones possess distinct characteristics.
Purpose of the Study:
- To characterize human neonatal ISL1+ MESP1+ FOXA2+ stem cell clones.
- To evaluate the therapeutic potential of these stem cells in a large animal model.
- To establish an allogeneic stem cell-based repair model without immunosuppression.
Main Methods:
- RNA sequencing to determine transcriptome of human neonatal stem cell clones.
- Flow cytometry, RT-qPCR, and electrophysiology to assess differentiation.
- Induction of myocardial infarction in sheep followed by allogeneic stem cell transplantation.
- Echocardiography, histology, and molecular analyses to evaluate in vivo outcomes.
Main Results:
- Neonatal ISL1+ stem cell clones restored cardiac function to normal levels.
- Histology confirmed stem cell retention in the repair zone.
- Transcriptomic analysis revealed paracrine and cardiogenic signaling pathways.
Conclusions:
- ISL1+ MESP1+ FOXA2+ stem cell clones from neonatal cardiovascular tissue are a novel cell source.
- These cells can restore cardiac function after myocardial infarction in a preclinical model.
- The study defines mechanisms of stem cell retention and immune modulation in allogeneic therapy.
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