The Melero-Martin Lab
Our lab uses a two-cell approach to bioengineer human vascular networks in vivo. In this model, human bone marrow-derived mesenchymal stem cells (MSC) and human blood-derived endothelial colony-forming cells (ECFC; also known as EPC) are combined in a biocompatible hydrogel and injected subcutaneously into immunodeficient mice where they form an organized vascular network that joins with the mouse vasculature. This model is perfectly suited for studies on the cellular and molecular mechanisms of human vascular network formation and for the development of strategies to vascularize engineered tissues.
Expanding from this model, our lab is pursuing the following topics:
Engineering vascularized tissues
We are developing sequential cell-based strategies to engineer tissues. This sequence involves 1) generation of a vascular network and 2) induction of specific tissue development around the newly-formed vasculature. One goal is to engineer tissues entirely in vivo from their cellular building blocks. A second goal is to engineer vascularized tissues in vitro that can serve as surrogate tissues for pharmacological and physiological studies.
We know that depletion of host myeloid cells from peripheral blood prior to implantation of our progenitor cells impairs the formation of bioengineered human blood vessels in vivo. This indicates that the presence of myeloid cells is necessary during the early stages of this process. Our lab aims to elucidate the cellular and molecular mechanisms by which host myeloid cells interact with donor vascular progenitor cells to drive the formation of functional vascular beds.
The ability to engineer vasculature creates the possibility to introduce additional instructions into tissues by genetically modifying the cells that will actually build these blood vessels. We are developing technologies that combine cell and gene therapy-based approaches that can be applied to diseases wherein routine or protracted administration of therapeutic proteins is needed.