[ 89 Zr]Zr-DBN labeled cardiopoietic stem cells proficient for heart failure.

Introduction: Radiolabeling of stem cells with a positron emitting radioisotope represents a major advancement in regenerative biotherapy enabling non-invasive imaging. To assess the value of such an approach in a clinically relevant scenario, the tolerability and therapeutic aptitude of [ ⁸⁹ Zr]zirconium-p-isothiocyanatobenzyl-desferrioxamine ([ ⁸⁹ Zr]Zr-DBN) labeled human cardiopoietic stem cells (CPs) were evaluated in a model of ischemic heart failure.
Methods and Results: [ ⁸⁹ Zr]Zr-DBN based radiolabeling of human CPs yielded [ ⁸⁹ Zr]Zr-DBN-CPs with radioactivity yield of 0.70 ± 0.20 MBq/10 ⁶ cells and excellent label stability. Compared to unlabeled cell counterparts, [ ⁸⁹ Zr]Zr-DBN-CPs maintained morphology, viability, and proliferation capacity with characteristic expression of mesodermal and pro-cardiogenic transcription factors defining the cardiopoietic phenotype. Administered in chronically infarcted murine hearts, [ ⁸⁹ Zr]Zr-DBN-CPs salvaged cardiac pump failure, documented by improved left ventricular ejection fraction not inferior to unlabeled CPs and notably superior to infarcted hearts without cell treatment.
Conclusion: The present study establishes that [ ⁸⁹ Zr]Zr-DBN labeling does not compromise stem cell identity or efficacy in the setting of heart failure, offering a non-invasive molecular imaging platform to monitor regenerative biotherapeutics post-transplantation.
Competing Interests: Declaration of competing interest S.Y., A. Behfar, and A.T. are co-inventors on regenerative sciences related intellectual property disclosed to Mayo Clinic. A. Bansal., M.P., and T.D. are co-inventors on (89)Zr related intellectual property disclosed to Mayo Clinic. Previously, Mayo Clinic has administered research grants from Celyad. Mayo Clinic, A. Behfar, and A.T. have interests in Rion LLC.
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