Juan Melero-Martin, PhD

Institution: Children's Hospital
Research: Bioengineering and engraftment of microvascular networks
Grants & Publications: Harvard Catalyst
Categories: Children's

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.

In addition, an important part of our research relies on having high quality human pancreatic islets to study different strategies for vascularization and engraftment. For human islets, we worked with the Pancreatic Islet Isolation Core at the Massachusetts General Hospital. The service is provided through the Boston Area Diabetes Endocrinology Research Center (BADERC); this service has been exceptional and critical for our research progress. The islets we obtain through BADERC are of exceptional high quality as they are similar to those intended for transplantation and are isolated by standard clinical methods.

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