Direct differentiation of human pluripotent stem cells into vascular network along with supporting mural cells
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 08, 2023
- Source ID
- 10.1063/5.0155207
Entities
People
- Alexander Grath
- Daylon James
- Guohao Dai
- Katherine Stevens
- Keith Lane
- Max A. Winkelman
- Sally Temple
- Shravani Kakarla
- Steven Lotz
- Taylor Bertucci
Organizations
- American Heart Association
- National Heart, Lung, and Blood Institute
- National Institute on Aging
- Neural Stem Cell Institute
- Northeastern University
- United States Department of Defense
- Weill Cornell Medicine