Overview

Vascularization is a primary concern when developing implantable cardiac tissues, as it is critical for superior engraftment and integration.  We have developed a method for engineering a vascular supply for engineered human myocardium to ensure tissue survival and engraftment upon implantation and improve therapeutic efficacy.

Market Opportunity

Myocardial infarction (MI) interrupts vascular blood flow to downstream muscle, resulting in ischemia and necrosis of cardiac tissue. Restoration of cardiac contractility after MI is important to prevent heart failure. Research on heart regeneration after MI using human stem cell-derived cardiomyocytes (CMs) is advancing rapidly, with approaches currently in large-animal and human clinical trials. At the same time, vascularization methods to adequately support the engraftment, survival, and development of implanted CMs in the harsh ischemic environment of the infarcted heart remain a key challenge. There is a need for methods to engineer a vascular supply for engineered human myocardium, to improve therapeutic efficacy.

Innovation and Meaningful Advantages

We have developed a dual remuscularization-revascularization therapy comprising vEHMs. Our engineered cardiac tissues are comprised of differentiated human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) alone or in mixtures with fibroblasts and/or vascular cells to create a solid 3D myocardial tissue. Sacrificially patterned biomaterials are embedded in myocardial tissues and coated with vascular endothelial cells.  Removal of the sacrificial material washes away the core biomaterial of the vessel pattern to leave hollow channels lined by endothelial cells in the tissue.

This system allows for robust engraftment of vEHMs onto infarcted myocardium, with increased hiPSC-CM engraftment density and hierarchical vascularization of vEHMs.  Efficacy was improved with prior in vitro perfusion (P VEHM), compared with non-perfused (NP vEHM) or non-vascularized (EHM) controls. Our work advances progress toward the goal of biomanufacturing vascularized hiPSC-CM patches for clinical use. It is easily adaptable for bench-side, preclinical, and translational applications in cardiac tissue engineering.

Collaboration Opportunity

We are interested in exploring 1) startup opportunities with investors; 2) collaborations with leading medical research companies; and 3) licensing opportunities with companies.

Principal Investigator

Kareen L. K. Coulombe, PhD

Associate Professor of Engineering

Brown University

kareen_coulombe@brown.edu

https://vivo.brown.edu/display/kcoulomb

IP Information

US Utility Application 18/358,808 Filed July 25, 2023

Publications

Kant RJ, Dwyer KD, Lee J-H, Polucha C, Kobayashi M, Pyon S, Soepriatna AH, Lee J, Coulombe KLK. Patterned Arteriole-Scale Vessels Enhance Engraftment, Perfusion, and Vessel Branching Hierarchy of Engineered Human Myocardium for Heart Regeneration. Cells 2023 July;12(13):1698. PMC: 10340601.

Contact

Melissa Simon, PhD

Director of Business Development

melissa_j_simon@brown.edu

Brown Tech ID 3256