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Journal article
Investigating the Transient Regenerative Potential of Cardiac Muscle Using a Neonatal Pig Partial Apical Resection Model
Bioengineering (Basel), v 9(8), 401
01 Aug 2022
PMID: 36004926
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Investigating the Transient Regenerative Potential of Cardiac Muscle Using a Neonatal Pig Partial Apical Resection Model
- Creators
- Katherine M Copeland - The University of Texas at ArlingtonBryn L Brazile - Department of Biological Engineering, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USAJ Ryan Butler - Mississippi State UniversityJim Cooley - Mississippi State UniversityErin Brinkman-Ferguson - Mississippi State UniversityAndrew Claude - Mississippi State UniversitySallie Lin - Mississippi State UniversitySammira Rais-Rohani - Mississippi State UniversityBradley Welch - Mississippi State UniversitySara R McMahan - The University of Texas at ArlingtonKytai T Nguyen - The University of Texas at ArlingtonYi Hong - The University of Texas at ArlingtonSharan Ramaswamy - Florida International UniversityZhi-Ping Liu - The University of Texas Southwestern Medical CenterPietro Bajona - Drexel UniversityMatthias Peltz - College Station Medical CenterJun Liao - The University of Texas at Arlington
- Publication Details
- Bioengineering (Basel), v 9(8), 401
- Publisher
- MDPI
- Grant note
- R01 HL157050 / NHLBI NIH HHS R15 HL140503 / NHLBI NIH HHS T32 HL134613 / NHLBI NIH HHS R01 EB022018 / NIBIB NIH HHS R01 CA215063 / NCI NIH HHS R01HL157050; R01EB022018; T32HL134613 / NIH HHS R15 HL159599 / NHLBI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:000847021800001
- Scopus ID
- 2-s2.0-85137327234
- Other Identifier
- 991021861210004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biotechnology & Applied Microbiology
- Engineering, Biomedical