1. Pim1 Kinase Overexpression Enhances ckit+ Cardiac Stem Cell Cardiac Repair Following Myocardial Infarction in Swine
- Author
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Kulandavelu, Shathiyah, Karantalis, Vasileios, Fritsch, Julia, Hatzistergos, Konstantinos E, Loescher, Viky Y, McCall, Frederic, Wang, Bo, Bagno, Luiza, Golpanian, Samuel, Wolf, Ariel, Grenet, Justin, Williams, Adam, Kupin, Aaron, Rosenfeld, Aaron, Mohsin, Sadia, Sussman, Mark A, Morales, Azorides, Balkan, Wayne, and Hare, Joshua M
- Subjects
Medical Biotechnology ,Biomedical and Clinical Sciences ,Rare Diseases ,Stem Cell Research - Nonembryonic - Human ,Heart Disease ,Heart Disease - Coronary Heart Disease ,Stem Cell Research - Nonembryonic - Non-Human ,Cardiovascular ,Stem Cell Research ,Regenerative Medicine ,Animals ,Disease Models ,Animal ,Female ,Fungal Proteins ,Gene Expression Regulation ,Humans ,Mitogen-Activated Protein Kinases ,Myocardial Infarction ,Myocytes ,Cardiac ,Stem Cell Transplantation ,Swine ,heart failure ,human cardiac progenitor cells ,injection ,pressure volume ,Cardiorespiratory Medicine and Haematology ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundPim1 kinase plays an important role in cell division, survival, and commitment of precursor cells towards a myocardial lineage, and overexpression of Pim1 in ckit+ cardiac stem cells (CSCs) enhances their cardioreparative properties.ObjectivesThe authors sought to validate the effect of Pim1-modified CSCs in a translationally relevant large animal preclinical model of myocardial infarction (MI).MethodsHuman cardiac stem cells (hCSCs, n = 10), hckit+ CSCs overexpressing Pim1 (Pim1+; n = 9), or placebo (n = 10) were delivered by intramyocardial injection to immunosuppressed Yorkshire swine (n = 29) 2 weeks after MI. Cardiac magnetic resonance and pressure volume loops were obtained before and after cell administration.ResultsWhereas both hCSCs reduced MI size compared to placebo, Pim1+ cells produced a ∼3-fold greater decrease in scar mass at 8 weeks post-injection compared to hCSCs (-29.2 ± 2.7% vs. -8.4 ± 0.7%; p < 0.003). Pim1+ hCSCs also produced a 2-fold increase of viable mass compared to hCSCs at 8 weeks (113.7 ± 7.2% vs. 65.6 ± 6.8%; p
- Published
- 2016