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Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction.

Publication ,  Journal Article
Su, T; Huang, K; Daniele, MA; Hensley, MT; Young, AT; Tang, J; Allen, TA; Vandergriff, AC; Erb, PD; Ligler, FS; Cheng, K
Published in: ACS Appl Mater Interfaces
October 3, 2018

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 cardiomyogenesis 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 microvessels (BMVs) that include human umbilical vein endothelial cells (HUVECs) lining the luminal surface and then 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.

Duke Scholars

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Published In

ACS Appl Mater Interfaces

DOI

EISSN

1944-8252

Publication Date

October 3, 2018

Volume

10

Issue

39

Start / End Page

33088 / 33096

Location

United States

Related Subject Headings

  • Stem Cells
  • Rats, Nude
  • Rats
  • Neovascularization, Physiologic
  • Nanoscience & Nanotechnology
  • Myocytes, Cardiac
  • Myocardium
  • Myocardial Infarction
  • Microfluidic Analytical Techniques
  • Humans
 

Citation

APA
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MLA
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Su, T., Huang, K., Daniele, M. A., Hensley, M. T., Young, A. T., Tang, J., … Cheng, K. (2018). Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction. ACS Appl Mater Interfaces, 10(39), 33088–33096. https://doi.org/10.1021/acsami.8b13571
Su, Teng, Ke Huang, Michael A. Daniele, Michael Taylor Hensley, Ashlyn T. Young, Junnan Tang, Tyler A. Allen, et al. “Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction.ACS Appl Mater Interfaces 10, no. 39 (October 3, 2018): 33088–96. https://doi.org/10.1021/acsami.8b13571.
Su T, Huang K, Daniele MA, Hensley MT, Young AT, Tang J, et al. Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction. ACS Appl Mater Interfaces. 2018 Oct 3;10(39):33088–96.
Su, Teng, et al. “Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction.ACS Appl Mater Interfaces, vol. 10, no. 39, Oct. 2018, pp. 33088–96. Pubmed, doi:10.1021/acsami.8b13571.
Su T, Huang K, Daniele MA, Hensley MT, Young AT, Tang J, Allen TA, Vandergriff AC, Erb PD, Ligler FS, Cheng K. Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction. ACS Appl Mater Interfaces. 2018 Oct 3;10(39):33088–33096.
Journal cover image

Published In

ACS Appl Mater Interfaces

DOI

EISSN

1944-8252

Publication Date

October 3, 2018

Volume

10

Issue

39

Start / End Page

33088 / 33096

Location

United States

Related Subject Headings

  • Stem Cells
  • Rats, Nude
  • Rats
  • Neovascularization, Physiologic
  • Nanoscience & Nanotechnology
  • Myocytes, Cardiac
  • Myocardium
  • Myocardial Infarction
  • Microfluidic Analytical Techniques
  • Humans