Direct differentiation of human pluripotent stem cells into vascular network along with supporting mural cells

Author:

Bertucci Taylor1ORCID,Kakarla Shravani2ORCID,Winkelman Max A.2ORCID,Lane Keith1,Stevens Katherine1ORCID,Lotz Steven1,Grath Alexander2ORCID,James Daylon3,Temple Sally1ORCID,Dai Guohao2ORCID

Affiliation:

1. Neural Stem Cell Institute 1 , Rensselaer, New York 12144, USA

2. Northeastern University, Department of Bioengineering 2 , Boston, Massachusetts 02115, USA

3. Weill Cornell Medicine 3 , New York, New York 10065, USA

Abstract

During embryonic development, endothelial cells (ECs) undergo vasculogenesis to form a primitive plexus and assemble into networks comprised of mural cell-stabilized vessels with molecularly distinct artery and vein signatures. This organized vasculature is established prior to the initiation of blood flow and depends on a sequence of complex signaling events elucidated primarily in animal models, but less studied and understood in humans. Here, we have developed a simple vascular differentiation protocol for human pluripotent stem cells that generates ECs, pericytes, and smooth muscle cells simultaneously. When this protocol is applied in a 3D hydrogel, we demonstrate that it recapitulates the dynamic processes of early human vessel formation, including acquisition of distinct arterial and venous fates, resulting in a vasculogenesis angiogenesis model plexus (VAMP). The VAMP captures the major stages of vasculogenesis, angiogenesis, and vascular network formation and is a simple, rapid, scalable model system for studying early human vascular development in vitro.

Funder

National Heart, Lung, and Blood Institute

U.S. Department of Defense

National Institute on Aging

American Heart Association

Publisher

AIP Publishing

Subject

Biomedical Engineering,Biomaterials,Biophysics,Bioengineering

Reference78 articles.

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