Beating human heart tissue engineered on decellularized mouse hearts

Image: PD

1. Human multipotent stem cells inserted into decellularized mouse hearts differentiated into cardiomyocytes, endothelial cells, and smooth muscle cells, recapitulating the original tissue architecture.

2. After 20 days, the engineered tissue contracted at 40-50 beats per minute and responded to cardiac medications.

Evidence Rating Level:  N/A

Study Rundown:  Engineering functional 3D tissues from stem cells requires proper cell differentiation as well as a structural scaffold on which to build the tissue.  Biocompatibility problems have limited the use of artificial matrix scaffolds prompting investigation of natural matrixes.  Decellularized mouse tissue is a promising scaffold option as it permits stem cells to populate a natural structure and subsequently differentiate into organized cardiac and vascular tissues.  In this experiment, human pluripotent stem cells were first chemically induced into cardiac lineage. These multipotent cardiac cells were then injected into decellularized mouse hearts where they developed into heart tissue. The resultant tissue showed coordinated contractions and responsiveness to cardiac medications, demonstrating marked progress towards the ultimate goal of personalized heart tissue replacements for failing human hearts.

Click to read the study in Nature

Relevant Reading: Cardiogenesis and the complex challenges of regenerative cardiovascular medicine

In-Depth [basic science study]: Human induced pluripotent stem cells were treated with growth factors that led to differentiation into multipotent cardiac cells. These multipotent cardiac cells were then implanted into coronary vessels of mouse cadaveric hearts treated with trypsin and detergents. After incubation in these decellularized scaffolds, the multipotent stem cells differentiated into endothelial cells, smooth muscle cells, and cardiomyocytes. They demonstrated organizational patterns of small blood vessels and myofibril muscle bundles. There was no fibroblast lineage found in the samples, a cell type that exists in natural heart tissue. After 20 days the bioengineered cardiac tissue beat at 40-50 beats per minute and increased to 80-100 with isoproterenol treatment (p<0.01). Notably, the tissue contractions were not coordinated enough to pump blood and there was not an electrical conduction system.

By Gina Siddiqui and Chaz Carrier

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