Rationale: Cortical bone stem cells (CBSCs) have been shown to reduce ventricular remodeling and improve cardiac function in a murine myocardial infarction (MI) model. These effects were superior to other stem cell types that have been used in recent early stage clinical trials. However, CBSC efficacy has not been tested in a preclinical large animal model using approaches that could be applied to patients. Objective: To determine if post-MI transendocardial injection of allogeneic CBSCs reduces pathological structural and functional remodeling and prevents the development of heart failure in a swine MI model. Methods and Results: Female Göttingen swine underwent left anterior descending coronary artery occlusion, followed by reperfusion (ischemia-reperfusion MI). Animals received, in a randomized, blinded manner, 1:1 ratio, CBSCs (n = 9) (2x10(7) cells total) or placebo (vehicle; VEH, n = 9) through NOGA® guided transendocardial injections. 5-ethynyl-2'deoxyuridine (EdU), a thymidine analog, containing minipumps were inserted at the time of MI induction. At 72hrs (n=8) initial injury and cell retention were assessed. At 3 Months post-MI, cardiac structure and function was evaluated by serial echocardiography, and terminal invasive hemodynamics. CBSCs were present in the MI border zone and proliferating at 72hrs post-MI but had no effect on initial cardiac injury or structure. At 3 months, CBSC-treated hearts had significantly reduced scar size, smaller myocytes and increased myocyte nuclear density. Noninvasive echocardiographic measurements showed that left ventricular (LV) volumes and ejection fraction were significantly more preserved in CBSC-treated hearts and invasive hemodynamic measurements documented improved cardiac structure and functional reserve. The number of EdU(+) cardiac myocytes was increased in CBSC- vs. VEH- treated animals. Conclusions: CBSC administration into the MI border zone reduces pathological cardiac structural and functional remodeling and improves LV functional reserve. These effects reduce those processes that can lead to heart failure with reduced ejection fraction (HFrEF). es that can lead to heart failure with reduced ejection fraction (HFrEF).
Pharmacology, Toxicology and Pharmaceutical Science
1
2%
Other
3
6%
Unknown
17
35%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 November 2017.
All research outputs
#6,931,729
of 25,382,440 outputs
Outputs from Circulation Research
#2,845
of 7,667 outputs
Outputs of similar age
#100,279
of 323,438 outputs
Outputs of similar age from Circulation Research
#47
of 102 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 7,667 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.6. This one has gotten more attention than average, scoring higher than 62% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 323,438 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.
We're also able to compare this research output to 102 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
