{"doi":"10.3390/bioengineering9080401","title":"Investigating the Transient Regenerative Potential of Cardiac Muscle Using a Neonatal Pig Partial Apical Resection Model","abstract":"Researchers have shown that adult zebrafish have the potential to regenerate 20% of the ventricular muscle within two months of apex resection, and neonatal mice have the capacity to regenerate their heart after apex resection up until day 7 after birth. The goal of this study was to determine if large mammals (porcine heart model) have the capability to fully regenerate a resected portion of the left ventricular apex during the neonatal stage, and if so, how long the regenerative potential persists. A total of 36 piglets were divided into the following groups: 0-day control and surgical groups and seven-day control and surgical groups. For the apex removal groups, each piglet was subjected to a partial wall thickness resection (~30% of the ventricular wall thickness). Heart muscle function was assessed via transthoracic echocardiograms; the seven-day surgery group experienced a decrease in ejection fraction and fractional shortening. Upon gross necropsy, for piglets euthanized four weeks post-surgery, all 0-day-old hearts showed no signs of scarring or any indication of the induced injury. Histological analysis confirmed that piglets in the 0-day surgery group exhibited various degrees of regeneration, with half of the piglets showing full regeneration and the other half showing partial regeneration. However, each piglet in the seven-day surgery group demonstrated epicardial fibrosis along with moderate to severe dissecting interstitial fibrosis, which was accompanied by an abundant collagenous extracellular matrix as the result of a scar formation in the resection site. Histology of one 0-day apex resection piglet (briefly lain on and accidentally killed by the mother sow three days post-surgery) revealed dense, proliferative mesenchymal cells bordering the fibrin and hemorrhage zone and differentiating toward immature cardiomyocytes. We further examined the heart explants at 5-days post-surgery (5D PO) and 1-week post-surgery (1W PO) to assess the repair progression. For the 0-day surgery piglets euthanized at 5D PO and 1W PO, half had abundant proliferating mesenchymal cells, suggesting active regeneration, while the other half showed increased extracellular collagen. The seven-day surgery piglets euthanized at 5D PO, and 1W PO showed evidence of greatly increased extracellular collagen, while some piglets had proliferating mesenchymal cells, suggesting a regenerative effort is ongoing while scar formation seems to predominate. In short, our qualitative findings suggest that the piglets lose the full myocardial regenerative potential by 7 days after birth, but greatly preserve the regenerative potential within 1 day post-partum.","journal":"Bioengineering","year":2022,"id":291322,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":316563,"name":"Bryn Brazile","orcid":"0000-0003-4496-8542","position":1,"is_corresponding":false},{"id":723206,"name":"J. 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Nguyen","orcid":"0000-0003-3233-3021","position":10,"is_corresponding":false},{"id":270972,"name":"Yi Hong","orcid":"0000-0002-5846-2596","position":11,"is_corresponding":false},{"id":972725,"name":"Sharan Ramaswamy","orcid":"0000-0003-4108-7141","position":12,"is_corresponding":false},{"id":250305,"name":"Zhiping Liu","orcid":"0000-0001-7272-6917","position":13,"is_corresponding":false},{"id":664303,"name":"Pietro Bajona","orcid":null,"position":14,"is_corresponding":false},{"id":517428,"name":"Matthias Peltz","orcid":"0000-0002-7384-252X","position":15,"is_corresponding":false},{"id":296179,"name":"Jun Liao","orcid":"0000-0003-1049-5783","position":16,"is_corresponding":false},{"id":297076,"name":"Katherine M. 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