Tissue Engineering Blood Vessels: Macrovasculature, Microvasculature and Molecular Mechanisms

Abstract

Organ donor shortage is a global problem, and patients die every day waiting for a transplant. In the field of tissue engineering, a major aim is to grow functional organs and tissues in the lab. Often using the patient’s own cells, this would not only mitigate the limited availability of donor organs, but also prevent organ rejection. In her doctoral work, Mia Hauge Rambøl has looked at various aspects regarding tissue engineering of blood vessels. This includes tissue engineering of larger blood vessels and microvascular networks, and studies of molecular mechanisms involved in blood vessel development. In her first paper, Rambøl critically evaluated a published method for generating blood vessels in the lab. It was claimed that only a small volume of the patient’s own blood would be sufficient to fully recellularize a decellularized donor blood vessel, ready for transplant. Through a number of imaging methods, Rambøl found that the method failed, and found a likely explanation for the misinterpreted results. In the second part of this work, mesenchymal stem cells (MSCs) and endothelial cells (ECs) were used to generate functional and perfusable microvascular networks in a microfluidic chip device. Combining the chip with pancreatic islets, it was possible to study the interactions between the microvasculature and the isles in real time. This platform would also be useful for studies on microvascular interaction with other organoids, or development of microvasculature within tissue engineered organs. The last part of this work investigates the molecular mechanisms involved in blood vessel development in vitro. When MSCs are cultured with ECs, the ECs change their morphology and transforms into vessel like structures. Using RNA sequencing to investigate the gene expression profiles of the different cell types, one can learn more about how stem cells affect blood vessel development. This may have implications for development of cell based therapies.