{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kulandavelu S"],"funding":["NHLBI NIH HHS"],"pagination":["2454-2464"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5223744"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["68(22)"],"pubmed_abstract":["<h4>Background</h4>Pim1 kinase plays an important role in cell division, survival, and commitment of precursor cells towards a myocardial lineage, and overexpression of Pim1 in ckit<sup>+</sup> cardiac stem cells (CSCs) enhances their cardioreparative properties.<h4>Objectives</h4>The authors sought to validate the effect of Pim1-modified CSCs in a translationally relevant large animal preclinical model of myocardial infarction (MI).<h4>Methods</h4>Human cardiac stem cells (hCSCs, n = 10), hckit<sup>+</sup> CSCs overexpressing Pim1 (Pim1<sup>+</sup>; 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.<h4>Results</h4>Whereas both hCSCs reduced MI size compared to placebo, Pim1<sup>+</sup> 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<sup>+</sup> 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 <0.003), and a greater increase in regional contractility in both infarct and border zones (both p < 0.05). Both CSC types significantly increased ejection fraction at 4 weeks but this was only sustained in the Pim1<sup>+</sup> group at 8 weeks compared to placebo. Both hCSC and Pim1<sup>+</sup> hCSC treatment reduced afterload (p = 0.02 and p = 0.004, respectively). Mechanoenergetic recoupling was significantly greater in the Pim1<sup>+</sup> hCSC group (p = 0.005).<h4>Conclusions</h4>Pim1 overexpression enhanced the effect of intramyocardial delivery of CSCs to infarcted porcine hearts. These findings provide a rationale for genetic modification of stem cells and consequent translation to clinical trials."],"journal":["Journal of the American College of Cardiology"],"pubmed_title":["Pim1 Kinase Overexpression Enhances ckit<sup>+</sup> Cardiac Stem Cell Cardiac Repair Following Myocardial Infarction in Swine."],"pmcid":["PMC5223744"],"funding_grant_id":["R01 HL122525","R01 HL117163","R01 HL110737","R37 HL091102","R01 HL137355","R01 HL107110","R01 HL105759","R01 HL113647","R01 HL084275","P01 HL085577","R01 HL067245","UM1 HL113460"],"pubmed_authors":["Hatzistergos KE","Balkan W","Karantalis V","Wang B","Loescher VY","Mohsin S","Williams A","Hare JM","Kulandavelu S","Sussman MA","Morales A","Fritsch J","Bagno L","Wolf A","Kupin A","McCall F","Grenet J","Rosenfeld A","Golpanian S"],"additional_accession":[]},"is_claimable":false,"name":"Pim1 Kinase Overexpression Enhances ckit<sup>+</sup> Cardiac Stem Cell Cardiac Repair Following Myocardial Infarction in Swine.","description":"<h4>Background</h4>Pim1 kinase plays an important role in cell division, survival, and commitment of precursor cells towards a myocardial lineage, and overexpression of Pim1 in ckit<sup>+</sup> cardiac stem cells (CSCs) enhances their cardioreparative properties.<h4>Objectives</h4>The authors sought to validate the effect of Pim1-modified CSCs in a translationally relevant large animal preclinical model of myocardial infarction (MI).<h4>Methods</h4>Human cardiac stem cells (hCSCs, n = 10), hckit<sup>+</sup> CSCs overexpressing Pim1 (Pim1<sup>+</sup>; 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.<h4>Results</h4>Whereas both hCSCs reduced MI size compared to placebo, Pim1<sup>+</sup> 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<sup>+</sup> 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 <0.003), and a greater increase in regional contractility in both infarct and border zones (both p < 0.05). Both CSC types significantly increased ejection fraction at 4 weeks but this was only sustained in the Pim1<sup>+</sup> group at 8 weeks compared to placebo. Both hCSC and Pim1<sup>+</sup> hCSC treatment reduced afterload (p = 0.02 and p = 0.004, respectively). Mechanoenergetic recoupling was significantly greater in the Pim1<sup>+</sup> hCSC group (p = 0.005).<h4>Conclusions</h4>Pim1 overexpression enhanced the effect of intramyocardial delivery of CSCs to infarcted porcine hearts. These findings provide a rationale for genetic modification of stem cells and consequent translation to clinical trials.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Dec","modification":"2026-05-05T14:59:01.222Z","creation":"2019-03-27T02:33:46Z"},"accession":"S-EPMC5223744","cross_references":{"pubmed":["27908351"],"doi":["10.1016/j.jacc.2016.09.925"]}}