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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
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Summary
This summary is machine-generated.

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.

Keywords:
FOXA2Islet-1Mesp-1allogeneiccardiac repairlarge animalstem cell transplantationtranscriptomics

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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.