期刊
ACS APPLIED MATERIALS & INTERFACES
卷 10, 期 39, 页码 33088-33096出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b13571
关键词
microvessels; hydrodynamic focusing; cardiac stem cells; cardiomyocyte proliferation; angiogenesis; myocardial infarction
资金
- National Institutes of Health [R01 HL123920, HL137093]
- North Carolina State University Chancellor's Innovation Fund
- UNC General Assembly Research Opportunities Initiative award
- State of North Carolina
- National Science Foundation [ECCS-1542015]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL137093, R01HL123920, T32HL069768] Funding Source: NIH RePORTER
Cardiac stem cell (CSC) therapy has shown preclinical and clinical evidence for ischemic heart repair but is limited by low cellular engraftment and survival after transplantation. Previous versions of the cardiac patch strategy improve stem cell engraftment and encourage repair of cardiac tissue. However, cardiac patches that can enhance cardiomyo-genesis and angiogenesis at the injured site remain elusive. Therapies that target cardiomyocyte proliferation and new blood vessel formation hold great potential for the protection against acute myocardial infarction (MI). Here, we report a new strategy for creating a vascularized cardiac patch in a facile and modular fashion by leveraging microfluidic hydrodynamic focusing to construct the biomimetic micro vessels (BMVs) that include human umbilical vein endothelial cells (HUVECs) lining encapsulating the BMVs in a fibrin gel spiked with human CSCs. We show that the endothelialized BMVs mimicked the natural architecture and function of capillaries and that the resultant vascularized cardiac patch (BMV-CSC patch) exhibited equivalent release of paracrine factors compared to those of coculture of genuine human CSCs and HUVECs after 7 days of in vitro culture. In a rat model of acute MI, the BMV-CSC patch therapy induced profound mitotic activities of cardiomyocytes in the peri-infarct region 4 weeks post-treatment. A significant increase in myocardial capillary density was noted in the infarcted hearts that received BMV-CSC patch treatment compared to the infarcted hearts treated with conventional CSC patches. The striking therapeutic benefits and the fast and facile fabrication of the BMV-CSC patch make it promising for practical applications. Our findings suggest that the BMV-CSC patch strategy may open up new possibilities for the treatment of ischemic heart injury.
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