《自然》子刊：心包内注射是一种微创治疗心脏损伤的有效方法

编辑翻译：奇奇

译文校对：菁菁

本文献在2021年3月最新的国际顶级期刊《自然通讯》（Nature Communications）上首次刊发。文献中美国北卡罗来纳州的研究人员发现了一种侵入性更小、成本更低且更有效的治疗心脏损伤的方法。

根据北卡罗来纳州立大学和北卡罗来纳大学教堂山分校的最新研究，他们有可能发现了一种侵入性较小、成本较低且更有效的治疗心脏损伤的方法，即将含有干细胞或外泌体治疗剂的水凝胶直接注射到心包腔内。

干细胞疗法有望治疗心脏损伤，但将治疗药物直接作用于损伤部位并保持足够长的时间以使其有效是一项持续的挑战。尽管可以直接在受伤部位上方安置心脏补片，但这种疗法也有缺点，因为它们需要采用侵入性外科手术方法进行放置。

北卡罗来纳州分子生物医学科学系再生医学杰出教授、北卡罗来纳州和北卡罗来纳大学教堂山分校的生物医学工程联合系教授Ke Cheng和Randall B. Terry表示："我们需要一种侵入性较小的方法来治疗受伤部位。心室腔作为一个自然的"模具"，使我们可以用含有治疗药物的水凝胶在受伤部位搭建心脏补片。”

在一项概念验证研究中，来自北卡罗来纳州和北卡罗来纳州大学教堂山分校的Cheng及其同事研究了两种不同类型的水凝胶（一种是天然来源的水凝胶，另一种是合成水凝胶）以及两种不同的干细胞衍生疗法在小鼠和大鼠心脏病发作模型中的治疗应用。该治疗通过心包内注射（iPC）进行。

通过荧光成像，研究人员能够看到水凝胶散开在心包腔中形成心脏补片。他们还证实，动物实验中，与只采用水凝胶而不使用治疗药物的疗法相比，将干细胞或外泌体治疗药物释放到心肌的疗法，可以减少细胞死亡，改善心脏功能。

研究人员随后开始用猪的模型来测试这一方法的安全性和可靠性。他们使用了只需要两个小切口的微创手术进行了iPC注射，然后监测猪的不良反应。他们在术后三天未发现猪有呼吸并发症、心包炎或血液化学变化。

“我们希望这种将药物输送到心脏的方法可以使手术侵入性更小、成本更低但有更好的治疗效果，”Cheng说，“我们的早期研究结果有良好的应用前景——该方法是安全的，并且能比目前使用的方法有更高的治疗药物留存率。接下来，我们将对大型动物进行额外的临床前研究，以进一步测试该疗法的安全性和有效性，然后再开始临床试验。”

Joe Rossi博士说：“我预计在将来的临床环境中，iPC注射可以通过类似于套索程序的心包通路进行。就这种疗法而言，仅需要在患者局部麻醉下的胸壁上开一个小切口。” Joe Rossi博士是北卡罗来纳州大学教堂山分校心脏病学系的副教授，也是本论文的合著者。

英语原文

Pericardial Injection Effective, Lessinvasive Way to Get Regenerative Therapies to Heart

Injecting hydrogels containing stem cell orexosome therapeutics directly into the pericardial cavity could be a lessinvasive, less costly, and more effective means of treating cardiac injury,according to new research from North Carolina State University and theUniversity of North Carolina at Chapel Hill.

Stem cell therapy holds promise as a way totreat cardiac injury,but delivering the therapy directly to the site of the injury and keeping it inplace long enough to be effective are ongoing challenges. Even cardiac patches,which can be positioned directly over the site of the injury, have drawbacks inthat they require invasive surgical methods for placement.

"We wanted a less invasive way to gettherapeutics to the injury site," says Ke Cheng, Randall B. Terry, Jr.Distinguished Professor in Regenerative Medicine at NC State's Department ofMolecular Biomedical Sciences and professor in the NC State/UNC-Chapel HillJoint Department of Biomedical Engineering. "Using the pericardial cavityas a natural "mold" could allow us to create cardiac patches—at the site of injury—from hydrogelscontaining therapeutics."

In a proof-of-concept study, Cheng andcolleagues from NC State and UNC-Chapel Hill looked at two different types ofhydrogels—one naturally derived and one synthetic—and two different stem cell-derived therapeutics in mouse and ratmodels of heart attack. The therapeutics were delivered via intrapericardial(iPC) injection.

Via fluorescent imaging the researcherswere able to see that the hydrogel spread out to form a cardiac patch in thepericardial cavity. They also confirmed that the stem cell or exosometherapeutics can be released into the myocardium, leading to reduced cell deathand improved cardiac function compared to animals in the group who receivedonly the hydrogel without therapeutics.

The team then turned to a pig model to testthe procedure's safety and feasibility. They delivered the iPC injections usinga minimally invasive procedure that required only two small incisions, thenmonitored the pigs for adverse effects. They found no breathing complications,pericardial inflammation, or changes in blood chemistry up to three dayspost-procedure.

"Our hope is that this method of drugdelivery to the heart will result in less invasive, less costly procedures withhigher therapeutic efficacy," Cheng says. "Our early results arepromising—the method is safe and generates a higherretention rate of therapeutics than those currently in use. Next we willperform additional preclinical studies in large animals to further test thesafety and efficacy of this therapy, before we can start a clinicaltrial."

"I anticipate in a clinical setting inthe future, iPC injection could be performed with pericardial access similar tothe LARIAT procedure. In that regard, only one small incision under local anesthesia isneeded on the patient's chest wall," says Dr. Joe Rossi, associateprofessor in the division of cardiology at UNC-Chapel Hill and co-author of thepaper.

参考文献：

Dashuai Zhu et al, Minimally invasivedelivery of therapeutic agents by hydrogel injection into the pericardialcavity for cardiac repair, Nature Communications (2021). DOI: 10.1038/s41467-021-21682-7

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