Seminar by Ninna S. Rossen

High throughput engineering of pre-vascularized micro-tissues for rapid host vascularization and stem cell delivery  

Vascularization is critical to ensure survival of engineered
tissues and to treat ischemic pathologies, but there are currently few
effective strategies for large-scale production of vascularized tissues.
Here, we demonstrate a method to produce prevascularized microtissues in
sufficient numbers (250 million cells demonstrated) to form a macrotissue in
vivo for therapeutic purposes.  This method is based on sacrificial release
of dissolvable microwell templates, a novel and scalable strategy which
enables gentle harvesting of microtissues with control over size and
composition.  We used the method to form microtissues containing endothelial
cells and mesenchymal stem cells, which were co-cultured under dynamic
conditions and self-organized into blood-vessel units.  We injected the
microtissues into mice, and observed in real time (via window chambers) the
formation and perfusion of implanted vasculature within seven days.
Moreover, in a mouse model of peripheral artery disease, intramuscular
injections of prevascularized microtissues into ischemic hindlimbs produced
new vasculature, host anastomosis, and vascular re-perfusion in seven days.
Overall, this method addresses a critical challenge in regenerative medicine
with a strategy of high-throughput production of microtissues suitable for
injectable cell therapy and rapid in vivo host vascularization.