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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.

Sec. Clinical and Translational Cardiovascular Medicine

This article is part of the Research TopicBridging Translational Gaps in Cardiovascular Disease Through Large Animal ResearchView all 4 articles

Neonatally-Derived Multipotent Islet-1+Mesp-1+FOXA2+ Stem Cell Clones Restore Cardiac Function in Sheep

Provisionally accepted
Lorelei HughesLorelei Hughes1Jonathan BaioJonathan Baio1Nahidh HasaniyaNahidh Hasaniya1Leonard BaileyLeonard Bailey1Julia KimJulia Kim1Danielle YanezDanielle Yanez2Edward AustinEdward Austin2Richard VegaRichard Vega1Paola Rivera MoralesPaola Rivera Morales1Victor CamberosVictor Camberos1Christopher G WilsonChristopher G Wilson1Alicia L VelizAlicia L Veliz1Mary Kearns-JonkerMary Kearns-Jonker3*
  • 1Loma Linda University School of Medicine, Loma Linda, United States
  • 2Loma Linda University Medical Center, Loma Linda, United States
  • 3School of Medicine, Loma Linda University, Loma Linda, United States

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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 ISL1+ MESP1+ FOXA2+ stem cell clones isolated from humans. Comparable ISL1+ MESP1+ FOXA2+ stem cell clones were then isolated from sheep for functional analysis in a sheep model of myocardial infarction and allogeneic stem cell-based repair without immunosuppression. Neonatally-derived ISL1+ clones restored cardiac function shown by echocardiography and demonstrated both paracrine and cardiogenic effects in the repair zone. Stem cell retention was identified by histology and transcriptomics was used to identify signaling pathways contributing to regeneration. This novel resource of cells has the capacity to restore cardiac function in a preclinical large animal model.

Keywords: Islet 1, Foxa2, MESP1, Allogeneic, Cardiac repair, Stem Cell Transplantation, Transcriptomics, Large animal

Received: 23 Jul 2025; Accepted: 02 Dec 2025.

Copyright: © 2025 Hughes, Baio, Hasaniya, Bailey, Kim, Yanez, Austin, Vega, Rivera Morales, Camberos, Wilson, Veliz and Kearns-Jonker. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mary Kearns-Jonker

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material