Juan M Melero-Martin, PhD

Bioengineering and engraftment of microvascular networks

Our laboratory is interested in understanding how vascular networks are formed and the mechanisms by which vascular networks engraftment occurs upon transplantation. Every year, millions of grafting procedures are performed in the United States to replace damaged and/or diseased tissues, including pancreatic islets, skin, bones, nerves, blood vessels, and fat. The success of these procedures closely depends on achieving adequate revascularization of the grafts. However, inadequate revascularization remains a common outcome, leading to various degrees of graft resorption and failure. As a result, patients often require additional grafting, which imposes added donor site morbidity, operating room time, and cost. Moreover, repetitive grafting is limited by donor tissue availability. Thus, the search for new approaches to improve graft revascularization continues to be a pressing clinical need.

We specialize in the biology of human Endothelial Colony-Forming Cells (ECFCs). These ECFCs are progenitors of endothelial cells that circulate in cord blood and adult peripheral blood and have enormous potential in Regenerative Medicine because they can generate large amounts of autologous endothelial cells for vascular therapies. We also specialize in methods to bioengineer functional microvascular networks in vivo. Our approach combines human endothelial cells with human mesenchymal stem cells (MSCs) into a biocompatible hydrogel to form organized vascular networks that when implanted into immunodeficient mice join with the host vasculature. This model is ideally suited for studies on the cellular and molecular mechanisms of human vascular network formation and for developing strategies to improve microvascular engraftment in surgical grafting. In addition, our model allows us to study the mechanisms by which the endothelium modulates the activity of co-transplanted stem cells and to elucidate how tissue-specific endothelial cells influence the cross-talk that occurs between these stem cells and the vasculature

Human endothelial colony-forming cells serve as trophic mediators for mesenchymal stem cell engraftment via paracrine signaling. Lin RZ, Moreno-Luna R, Li D, Jaminet SCS, Greene AK, Melero-Martin JM. Proc Natl Acad Sci USA 2014; 111(28):10137-10142

Transdermal regulation of vascular network bioengineering using a photopolymerizable methacrylated gelatin hydrogel. Lin RZ, Chen YC, Moreno-Luna R, Khademhosseini A, Melero-Martin JM. Biomaterials 2013; 34(28):6785-96

Functional human vascular network generated in photocrosslinkable gelatin methacrylate hydrogels. Chen YC*, Lin RZ*, Qi H, Yang Y, Bae H, Melero-Martin JM, Khademhosseini A. Adv Funct Mater 2012; 22(10):2027-39

Induction of erythropoiesis using human vascular networks genetically-engineered for controlled erythropoietin release. Lin RZ, Dreyzin A, Aamodt K, Li D, Jaminet SC, Dudley AC, Melero-Martin JM. Blood 2011; 118(20):5420-8