Bridging Stem Cell Technology with Tissue Vascularization in Regenerative Medicine

John P. Fisher Fischell Family Distinguished Professor, University of Maryland, College Park, MD

Versione stampabile

June 10, 2014
Room B102, Edificio Povo 2, Via Sommarive 9, Povo (TN)

11.00 a.m.

Blood vessels are an integral component of tissues as they provide a mechanism for the transport of oxygen, carbon dioxide, nutrients, and waste. A major challenge in regenerative medicine, however, is that engineered tissues cultured in the laboratory often lack a similar mechanism for cellular respiration following implantation into a tissue defect site. A lack of proper nutrition can result in hypoxia, non-uniform cell distribution, and altered stem cell differentiation resulting in decreased tissue function. Ultimately, In vitro and in vivo nutrient transfer limits must be overcome in order to increase the feasibility of stem cell based therapeutic strategies. In this presentation we will explore the interplay between stem cell based engineered tissues and tissue vascularization strategies. To enhance in vitro nutrient transport, we have recently develop a novel tubular perfusion system (TPS) that consists of a bioreactor for culture of human mesenchymal stem cells in three-dimensional scaffolds. This system utilizes an elegant design to create an effective cell culture environment without the drawbacks often associated with more complicated perfusion systems. The TPS design consists of hMSCs encapsulated in biomaterial scaffolds that are tightly packed in a tubular growth chamber.  Perfusing media through this growth chamber enhances nutrient transfer while exposing the cells to shear stress, thus imparting mechanical cues that are often thought to promote some MSC differentiation pathways. To consider in vivo vascularization, we are exploring concepts related to the templating of a prevascular network with an engineered tissue. For example, initial studies have demonstrated that the TPS bioreactor does support MSC-endothelial coculture. Finally, recent efforts in our laboratory have focused on the development of small diameter vascular grafts. We will present novel approaches for the development and characterization of these grafts, as well as discuss their ultimate integration into engineered tissues.  The presentation aims to integrate tissue vascularization in stem cell based engineered tissues so as to initiate new strategies in regenerative medicine.