Pim1 Kinase Overexpression Enhances ckit+ Cardiac Stem Cell Cardiac Repair Following Myocardial Infarction in Swine
| Autor: | Adam R. Williams, Luiza Bagno, Bo Wang, Ariel Wolf, Joshua M. Hare, Mark A. Sussman, Viky Y. Loescher, Shathiyah Kulandavelu, Wayne Balkan, Julia Fritsch, Samuel Golpanian, Vasileios Karantalis, Frederic McCall, Aaron Rosenfeld, Sadia Mohsin, Azorides R. Morales, Aaron Kupin, Konstantinos E. Hatzistergos, Justin Grenet |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Swine Cell Myocardial Infarction heart failure 030204 cardiovascular system & hematology Cardiorespiratory Medicine and Haematology Regenerative Medicine Cardiovascular 0302 clinical medicine Stem Cell Research - Nonembryonic - Human Myocardial infarction Kinase medicine.anatomical_structure Heart Disease Cardiology Public Health and Health Services Female Stem Cell Research - Nonembryonic - Non-Human Stem cell Mitogen-Activated Protein Kinases Cardiology and Cardiovascular Medicine Cardiac medicine.medical_specialty PIM1 Placebo Fungal Proteins 03 medical and health sciences Rare Diseases Internal medicine Precursor cell medicine Animals Humans Heart Disease - Coronary Heart Disease Myocytes human cardiac progenitor cells business.industry Animal medicine.disease pressure volume Stem Cell Research 030104 developmental biology Gene Expression Regulation injection Cardiovascular System & Hematology Heart failure Disease Models Cancer research business Stem Cell Transplantation |
| Zdroj: | Journal of the American College of Cardiology, vol 68, iss 22 |
| Popis: | 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 alsoproduced a 2-fold increase of viable mass compared to hCSCs at 8 weeks (113.7 ± 7.2% vs. 65.6 ± 6.8%; p |
| Databáze: | OpenAIRE |
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