期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 6, 期 11, 页码 6309-6320出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.0c00942
关键词
microfluidics; cardiac patch; cardiac stromal cells; myocardial infarction; porcine model
资金
- National Institutes of Health [R01 HL123920, HL137093, HL144002, HL149940, HL147357, HL146153]
- American Heart Association [18TPA34230092, 19EIA34660286, 18TPA34230031]
- National Science Foundation through the Nanosystems Engineering Research Center for Advanced Self-Powered Systems of Integrated Sensors and Technologies (ASSIST) [EEC-1160483]
- North Carolina State University Chancellor's Innovation Fund
- UNC General Assembly Research Opportunities Initiative award
- State of North Carolina
- National Science Foundation [ECCS1542015]
The vascularized cardiac patch strategy is promising for ischemic heart repair after myocardial infarction (MI), but current fabrication processes are quite complicated. Vascularized cardiac patches that can promote concurrent restoration of both the myocardium and vasculature at the injured site in a large animal model remain elusive. The safety and therapeutic benefits of a cardiac stromal cell patch integrated with engineered biomimetic microvessels (BMVs) were determined for treating MI. By leveraging a microfluidic method employing hydrodynamic focusing, we constructed the endothelialized microvessels and then encapsulated them together with therapeutic cardiospherederived stromal cells (CSCs) in a fibrin gel to generate a prevascularized cardiac stromal cell patch (BMV-CSC patch). We showed that BMV-CSC patch transplantation significantly promoted cardiac function, reduced scar size, increased viable myocardial tissue, promoted neovascularization, and suppressed inflammation in rat and porcine MI models, demonstrating enhanced therapeutic efficacy compared to conventional cardiac stromal cell patches. BMV-CSC patches did not increase renal and hepatic toxicity or exhibit immunogenicity. We noted a significant increase in endogenous progenitor cell recruitment to the peri-infarct region of the porcine hearts treated with BMV-CSC patch as compared to those that received control treatments. These findings establish the BMV-CSC patch as a novel engineered-tissue therapeutic for ischemic tissue repair.
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