Assistant Professor, Department of Surgery, Harvard Medical School
Associate Scientific Research, Cardiac Surgery, Boston Children's Hospital
DF/HCC Program AffiliationAngiogenesis, Invasion and Metastasis
Lab WebsiteMelero-Martin Lab
The goal of my laboratory is to develop cell-based technologies that will allow engineering vascularized tissues in vivo using postnatal progenitor cells obtained from patients by non-invasive means. In particular, our focus is on the combined use of bone marrow-derived mesenchymal progenitor cells (MPCs) and human blood-derived endothelial progenitor cells (EPCs) to regenerate adipose and skeletal muscle tissues in vivo lost after tumor resections (e.g., mastectomy and carcinoma removal). The research conducted in my laboratory is trying to address whether generating a vascular implants with highly purified and defined MPCs and EPCs will drive tissue development in vivo. We hypothesize that for this to happen, 1) both MPCs and EPCs need first to create a vascular network that will allow blood perfusion through the implants; and 2) this vascularization will promote resident cells to undergo appropriate tissue development by adopting the phenotype of the surrounding tissue at the site of implantation. We have previously characterized the phenotype of human MPCs and EPCs and demonstrated the ability of these cells to form vascular networks in vivo within 7 days after implantation. In addition, our preliminary data also show that the formation of vascular networks is accompanied by a progressive appearance of differentiated cells throughout the implants and that these differentiated cells are specific to the site of implantation (i.e., adipocytes in subcutaneous implants and myocytes in intramuscular implants). We propose that this two-cell, two-step system is a cell-based technology that can be applied to many different tissues/organs wherein functional blood vessels are needed. We are currently focused on formation of adipose tissue and skeletal muscle, but we envision that our strategy will be applicable to many aspects of regenerative medicine. What is unique about our approach, in comparison to most tissue engineering approaches, is that 1) the tissues are developed entirely in vivo (i.e., using the body’s regenerative capacity), and 2) we incorporate highly defined EPCs as one of the cellular building blocks. We give priority to the initial establishment of a functional vascular network within the implant, and propose that as a result of this neo-vascularization appropriate tissue formation and remodeling will be achieved.
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