Human ISL1+ Ventricular Progenitors Self-Assemble into an In Vivo Functional Heart Patch and Preserve Cardiac Function Post Infarction

Foo, Kylie S.; Lehtinen, Markku; Leung, Chuen Yan; Lian, Xiaojun; Xu, Jiejia; Keung, Wendy; Geng, Lin; Kolstad, Terje R Selnes; Thams, Sebastian; Wong, Andy On Tik; Wong, Nicodemus; Bylund, Kristine; Zhou, Chikai; He, Xianli; Jin, Shao Bo; Clarke, Jonathan; Lendahl, Urban; Tse, Gary; Louch, William E.; Chien, Kenneth R.

doi:10.1016/j.ymthe.2020.11.015

Cited by 8 publications

(10 citation statements)

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“…1B ). These features are necessary for improving cardiac function and regeneration 20 , 21 . The changes in miRNA expression that were identified within the cardiovascular repair zone following islet-1+ neonatal CPC transplantation are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA Expression in the Infarcted Heart Following Neonatal Cardiovascular Progenitor Cell Transplantation in a Sheep Model of Stem Cell–Based Repair

et al. 2022

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Myocardial infarctions affect approximately 735,000 people annually in the United States and have a substantial impact on quality of life. Neonates have an enhanced capability of repairing cardiovascular damage, while adults do not. The mechanistic basis for this age-dependent difference in regenerative capacity remains unknown. Recent studies have shown that microRNAs (miRNAs) play a significant role in regulating the regenerative ability of cardiovascular cells. This report defines the alterations in miRNA expression within the cardiovascular repair zone of infarcted sheep hearts following intracardiac injection of neonatal islet-1+ cardiovascular progenitor cells. Sheep were infarcted via left anterior descending coronary artery ligation. After 3 to 4 weeks of infarction, sheep neonatal islet-1+ cardiovascular progenitor cells were injected into the infarcted area for repair. Cell-treated sheep were euthanized 2 months following cell injection, and their hearts were harvested for the analysis of miRNA and gene expression within the cardiovascular repair zone. Ten miRNAs were differentially regulated in vivo, including miR-99, miR-100, miR-302a, miR-208a, miR-665, miR-1, miR-499a, miR-34a, miR-133a, and miR-199a. These miRNAs promote stemness, cell division, and survival. Several signaling pathways are regulated by these miRNAs, including Hippo, Wnt, and Erythroblastic Leukemia Viral Oncogene B (ERBB). Transcripts encoding Wnt, ERBB, and Neuregulin 1 (NRG1) were elevated in vivo in the infarct repair zone. Wnt5a signaling and ERBB/NRG1 transcripts contribute to activation of Yes-Associated Protein 1. MiRNAs that impact proliferation, cell survival, and signaling pathways that promote regeneration were induced during cardiovascular repair in the sheep model. This information can be used to design new approaches for the optimization of miRNA-based treatments for the heart.

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Section: Resultsmentioning

confidence: 99%

MicroRNA Expression in the Infarcted Heart Following Neonatal Cardiovascular Progenitor Cell Transplantation in a Sheep Model of Stem Cell–Based Repair

et al. 2022

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“…A promising therapeutic approach under development is the endovascular delivery of human ventricular progenitor (HVP) cells to the infarcted region of the heart with the goal of generating new cardiac myocytes that can be assembled into a three-dimensional functional ventricular heart tissue (Poch et al, 2022). Such an approach has the potential of providing a safe and efficacious therapy leading to full cardiac functional recovery for patients suffering from heart failure with reduced ejection fraction (Foo et al, 2021).…”

Section: Case 2: Heart Regeneration Following Myocardial Infarctionmentioning

confidence: 99%

Quantitative systems modeling approaches towards model-informed drug development: Perspective through case studies

et al. 2023

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Quantitative systems pharmacology (QSP) modeling has become an increasingly popular approach impacting our understanding of disease mechanisms and helping predict patients’ treatment responses to facilitate study design or development go/no-go decisions. In this paper, we highlight the notable contributions and opportunities that QSP approaches are to offer during the drug development process by sharing three examples that have facilitated internal decisions. The barriers to successful applications and the factors that facilitate the success of the modeling approach is discussed.

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“…A promising therapeutic approach under development is the endovascular delivery of human ventricular progenitor (HVP) cells to the infarcted region of the heart with the goal of generating new cardiac myocytes that can be assembled into a three-dimensional functional ventricular heart tissue. Such an approach has the potential of providing a safe and e cacious therapy leading to full cardiac functional recovery for patients suffering from heart failure with reduced ejection fraction [30].…”

Section: Computational Modeling Approachmentioning

confidence: 99%

Quantitative Systems Modeling Approaches Towards Model-Informed Drug Development: Perspective Through Case Studies

Verma

Gall

Biasetti

et al. 2022

Preprint

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Quantitative systems pharmacology modeling has become an increasingly popular approach impacting our understanding of disease mechanisms and helping predict patients’ treatment responses to facilitate study design or development go/no-go decisions. In this paper, we present examples of QSP modeling applications to highlight the notable contributions and opportunities that these approaches are to offer during the drug development process. We also consider the barriers to successful applications; outline the factors required to support the success of these modeling approaches; and provide insights for a strategy to enhance acceptance by the regulatory agencies.

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Human ISL1+ Ventricular Progenitors Self-Assemble into an In Vivo Functional Heart Patch and Preserve Cardiac Function Post Infarction

Cited by 8 publications

References 0 publications

MicroRNA Expression in the Infarcted Heart Following Neonatal Cardiovascular Progenitor Cell Transplantation in a Sheep Model of Stem Cell–Based Repair

MicroRNA Expression in the Infarcted Heart Following Neonatal Cardiovascular Progenitor Cell Transplantation in a Sheep Model of Stem Cell–Based Repair

Quantitative systems modeling approaches towards model-informed drug development: Perspective through case studies

Quantitative Systems Modeling Approaches Towards Model-Informed Drug Development: Perspective Through Case Studies

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