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J Tissue Eng Regen Med. 2018 Feb;12(2):e962-e972. doi: 10.1002/term.2418. Epub 2017 May 31.

Adipose-derived perivascular mesenchymal stromal/stem cells promote functional vascular tissue engineering for cardiac regenerative purposes.

Author information

1
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3
Department of Material Sciences & Engineering, Johns Hopkins University, School of Engineering, Baltimore, MD, USA.
4
Institute for Nanobiotechnology (INBT), Johns Hopkins University School of Engineering, Baltimore, MD, USA.

Abstract

Cardiac tissue engineering approaches have the potential to regenerate functional myocardium with intrinsic vascular networks. This study compared the relative effects of human adipose-derived stem/stromal cells (hASCs) and human dermal fibroblasts (hDFs) in cocultures with neonatal rat ventricular cardiomyocytes (NRVCMs) and human umbilical vein endothelial cells (HUVECs). At the same ratios of NRVCM:hASC and NRVCM:hDF, the hASC cocultures displayed shorter action potentials and maintained capture at faster pacing rates. Similarly, in coculture with HUVECs, hASC:HUVEC exhibited superior ability to support vascular capillary network formation relative to hDF:HUVEC. Based on these studies, a range of suitable cell ratios were determined to develop a triculture system. Six seeding ratios of NRVCM:hASC:HUVEC were tested and it was found that a ratio of 500:50:25 cells (i.e. 250,000:25,000:12,500 cells/cm2 ) resulted in the formation of robust vascular networks while retaining action potential durations and propagation similar to pure NRVCM cultures. Tricultures in this ratio exhibited an average conduction velocity of 20 ± 2 cm/s, action potential durations at 80% repolarization (APD80 ) and APD30 of 122 ± 5 ms and 59 ± 4 ms, respectively, and maximum capture rate of 7.4 ± 0.6 Hz. The NRVCM control groups had APD80 and APD30 of 120 ± 9 ms and 51 ± 5 ms, with a maximum capture rate of 7.3 ± 0.2 Hz. In summary, the combination of hASCs in the appropriate ratios with NRVCMs and HUVECs can facilitate the formation of densely vascularized cardiac tissues that appear not to impact the electrophysiological function of cardiomyocytes negatively.

KEYWORDS:

Adipose-derived stem cells; Cardiac tissue engineering; Neonatal rat ventricular cardiomyocytes; dermal fibroblasts; electrophysiology; vascularized grafts

PMID:
28103423
DOI:
10.1002/term.2418

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