BackgroundSmall and large preclinical animal models have shown that antagomir‐92a‐based therapy reduces early postischemic loss of function, but its effect on postinfarction remodeling is not known. In addition, the reported remote miR‐92a inhibition in noncardiac organs prevents the translation of nonvectorized miR‐targeted therapy to the clinical setting. We investigated whether a single intracoronary administration of antagomir‐92a encapsulated in microspheres could prevent deleterious remodeling of myocardium 1 month after acute myocardial infarction AUTHOR: Should “acute” be added before “myocardial infarction” (since abbreviation is AMI)? Also check at first mention in main text (AMI) without adverse effects.Methods and ResultsIn a percutaneous pig model of reperfused AMI, a single intracoronary administration of antagomir‐92a encapsulated in specific microspheres (9 μm poly‐d,‐lactide‐co‐glycolide [PLGA]) inhibited miR‐92a in a local, selective, and sustained manner (n=3 pigs euthanized 1, 3, and 10 days after treatment; 8×, 2×, and 5×‐fold inhibition at 1, 3, and 10 days). Downregulation of miR‐92a resulted in significant vessel growth (n=27 adult minipigs randomly allocated to blind receive encapsulated antagomir‐92a, encapsulated placebo, or saline [n=8, 9, 9]; P=0.001), reduced regional wall‐motion dysfunction (P=0.03), and prevented adverse remodeling in the infarct area 1 month after injury (P=0.03). Intracoronary injection of microspheres had no significant adverse effect in downstream myocardium in healthy pigs (n=2), and fluorescein isothiocyanate albumin‐PLGA microspheres were not found in myocardium outside the left anterior descending coronary artery territory (n=4) or in other organs (n=2).ConclusionsEarly single intracoronary administration of encapsulated antagomir‐92a in an adult pig model of reperfused AMI prevents left ventricular remodeling with no local or distant adverse effects, emerging as a promising therapeutic approach to translate to patients who suffer a large AMI.

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Current developments in tissue engineering strategies for articular cartilage regeneration focus on the design of supportive three-dimensional scaffolds and their use in combination with cells from different sources. The challenge of translating initial successes in small laboratory animals into the clinics involves pilot studies in large animal models, where safety and efficacy should be investigated during prolonged follow-up periods. Here we present, in a single study, the long-term (up to 1 year) effect of biocompatible porous scaffolds non-seeded and seeded with fresh ex vivo expanded autologous progenitor cells that were derived from three different cell sources [cartilage, fat and bone marrow (BM)] in order to evaluate their advantages as cartilage resurfacing agents. An ovine model of critical size osteochondral focal defect was used and the test items were implanted arthroscopically into the knees. Evidence of regeneration of hyaline quality tissue was observed at 6 and 12 months post-treatment with variable success depending on the cell source. Cartilage and BM-derived mesenchymal stromal cells (MSC), but not those derived from fat, resulted in the best quality of new cartilage, as judged qualitatively by magnetic resonance imaging and macroscopic assessment, and by histological quantitative scores. Given the limitations in sourcing cartilage tissue and the risk of donor site morbidity, BM emerges as a preferential source of MSC for novel cartilage resurfacing therapies of osteochondral defects using copolymeric poly-D,L-lactide-co-glycolide scaffolds.

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The SAFE patch and glue coverage of surgically created fetal MMC is feasible and effective in restoring gross neurologic function in the fetal lamb model.