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American Heart Association

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Final ID: MDP1275

Engineering Human-Induced Pluripotent Stem Cells Overexpressing Ferritin for In Vivo Graft Tracking via Magnetic Resonance Imaging

Abstract Body (Do not enter title and authors here): Heart disease continues to be the leading cause of death globally, even with the development and implementation of numerous pharmacological and surgical treatments. Transplanting cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) shows potential for repairing heart damage. However, tracking and quantifying these cells after transplantation in large animals remains challenging. This study aimed to develop a hiPSC line that overexpresses ferritin heavy chain (FHC) to enable tracking of transplanted hiPSC-CMs via magnetic resonance imaging (MRI). Using the CRISPR/dCas9 activation system, we increased FHC expression in hiPSCs and hiPSC-CMs. Both mRNA and protein levels of FHC were significantly elevated following transfection. Cell viability was unaffected by iron chloride concentrations between 0 μM and 2000 μM. hiPSCs and hiPSC-CMs overexpressing FHC (hiPSC-FHCOE and hiPSC-CM-FHCOE) showed enhanced iron chloride uptake without changes in their electrophysiological properties compared to control hiPSC-CMs. Additionally, hiPSC-CM-FHCOE cells provided strong contrast and lower T2* values, indicating their effectiveness for cardiac MRI. When hiPSC-CM-FHCOE cells were injected into mouse hearts and imaged three days later, MRI revealed distinct signals from these cells with lower T2* values and rapid signal decay. Overall, endogenous FHC labeling in hiPSC-CMs could significantly improve the precision of cardiac MRI, marking a crucial advancement in assessing the success of hiPSC-CM transplantation in large animal models and enhancing cardiac regenerative therapies.
  • Son, Yura  ( Mayo Clinic Arizona , Scottsdale , Arizona , United States )
  • Li, Pengsheng  ( Mayo Clinic Arizona , Scottsdale , Arizona , United States )
  • Ortega, Dakota  ( Arizona State University , Tempe , Arizona , United States )
  • Qiu, Huiliang  ( Mayo Clinic Arizona , Scottsdale , Arizona , United States )
  • Prachyl, Hannah  ( Mayo Clinic Arizona , Scottsdale , Arizona , United States )
  • Yang, Ming  ( Mayo Clinic Arizona , Scottsdale , Arizona , United States )
  • Zhu, Wuqiang  ( Mayo Clinic Arizona , Scottsdale , Arizona , United States )
  • Author Disclosures:
    Yura Son: DO NOT have relevant financial relationships | Pengsheng Li: No Answer | Dakota Ortega: DO NOT have relevant financial relationships | Huiliang Qiu: DO NOT have relevant financial relationships | Hannah Prachyl: DO NOT have relevant financial relationships | Ming Yang: DO NOT have relevant financial relationships | Wuqiang Zhu: DO NOT have relevant financial relationships
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Novel Approaches and New Models for Cardiovascular Research

Monday, 11/18/2024 , 11:10AM - 12:40PM

Moderated Digital Poster Session

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