Vascularized hiPSC-derived 3D cardiac microtissue on chip

Author(s):
Arslan, U.; Brescia, M.; Meraviglia, V.; Nahon, D.M.; Helden, R.W.J. van; Stein, J.M.; Hil, F.E. van den; Meer, B.J. van; Cuenca, M.V.; Mummery, C.L. (0000-0002-4549-6535); Orlova, V.V.
Published
2023
Publication type
Article / Letter to editor

Abstract

Functional vasculature is essential for delivering nutrients, oxygen, and cells to the heart and removing waste products. Here, we devel-oped an in vitro vascularized human cardiac microtissue (MT) model based on human induced pluripotent stem cells (hiPSCs) in a micro -fluidic organ-on-chip by coculturing hiPSC-derived, pre-vascularized, cardiac MTs with vascular cells within a fibrin hydrogel. We showed that vascular networks spontaneously formed in and around these MTs and were lumenized and interconnected through anastomosis. Anastomosis was fluid flow dependent: continuous perfusion increased vessel density and thus enhanced the formation of the hybrid vessels. Vascularization further improved endothelial cell (EC)-cardiomyocyte communication via EC-derived paracrine factors, such as nitric oxide, and resulted in an enhanced inflammatory response. The platform sets the stage for studies on how organ-specific EC barriers respond to drugs or inflammatory stimuli.

Date issued
2023-07-11
Language
English
Publisher
CELL PRESS
Is part of
Stem Cell Reports (2023), Vol. 18, no. 7, p. 1394-1404
hdl
1887/3721063
doi
10.1016/j.stemcr.2023.06.001
URL
https://www.sciencedirect.com/science/article/pii/S221367112300228X?via%3Dihub