Investigating the Transient Regenerative Potential of Cardiac Muscle Using a Neonatal Pig Partial Apical Resection Model.
Investigating the Transient Regenerative Potential of Cardiac Muscle Using a Neonatal Pig Partial Apical Resection Model.
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DOI：
10.3390/bioengineering9080401
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发表时间：
2022-08-18
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研究人员已经证明，成年斑马鱼有潜力在心尖切除后两个月内再生20%的心室肌，新生小鼠有能力在心尖切除后再生心脏，直到出生后第7天。本研究的目的是确定大型哺乳动物（猪心模型）是否有能力在新生儿阶段完全再生左心室心尖的切除部分，如果有，再生潜力持续多久。将总共36头仔猪分为以下组：0天对照组和手术组以及7天对照组和手术组。对于心尖切除组，对每只仔猪进行部分壁厚切除（约30%的心室壁厚度）。通过经胸超声心动图评估心肌功能; 7天手术组的射血分数和短轴缩短率降低。大体尸检时，对于术后4周处死的仔猪，所有0日龄心脏均未显示瘢痕形成迹象或任何诱导损伤迹象。组织学分析证实，0天手术组中的仔猪表现出不同程度的再生，其中一半仔猪显示完全再生，另一半显示部分再生。然而，7天手术组中的每头仔猪均表现出心外膜纤维化沿着中度至重度夹层间质纤维化，并伴有大量胶原性细胞外基质，这是切除部位瘢痕形成的结果。一只0天心尖切除术仔猪（手术后3天短暂躺下并被母猪意外杀死）的组织学显示，致密的增殖性间充质细胞与纤维蛋白和出血区接壤，并向未成熟的心肌细胞分化。我们在术后5天（5D PO）和术后1周（1 W PO）进一步检查了心脏外植体，以评估修复进展。对于在5D PO和1 W PO处以安乐死的0天手术仔猪，一半具有丰富的增殖间充质细胞，表明主动再生，而另一半显示细胞外胶原增加。在术后5天和术后1周处死的7天手术仔猪显示细胞外胶原蛋白大大增加的证据，而一些仔猪具有增殖的间充质细胞，表明再生努力正在进行，而瘢痕形成似乎占主导地位。总之，我们的定性研究结果表明，仔猪出生后7天失去了完全的心肌再生潜力，但在产后1天内极大地保留了再生潜力。
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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影响因子：
14
作者：
Martino, Mikael M.;Mochizuki, Mayumi;Rothenfluh, Dominique A.;Rempel, Sandra A.;Hubbell, Jeffrey A.;Barker, Thomas H.
通讯作者：
Barker, Thomas H.
影响因子：
56.9
作者：
Poss, KD;Wilson, LG;Keating, MT
通讯作者：
Keating, MT
影响因子：
37.8
作者：
Go, Alan S.;Mozaffarian, Dariush;Turner, Melanie B.
通讯作者：
Turner, Melanie B.
影响因子：
14
作者：
Guan, Jianjun;Wang, Feng;Li, Zhenqing;Chen, Joseph;Guo, Xiaolei;Liao, Jun;Moldovan, Nicanor I.
通讯作者：
Moldovan, Nicanor I.
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW