Human pluripotent stem cell-derived mesothelium functions in regenerative medicine as a multipotent vascular progenitor
Colunga, Thomas Anthony
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The human body contains two major coelomic cavities, thoracic and abdominal, that are lined with an epithelial cell called mesothelium. Mesothelium also forms the outer layer of internal organs within these cavities and an additional protective pouch surrounding the heart called the pericardium. Mesothelium contributes to the development of the coelomic organs including the vasculature by acting as a multipotent vascular progenitor. During development and upon reactivation after injury, the mesothelium of the outer layer of organs loses its polarity and migrates to the underlying tissue in a process called epithelial-to-mesenchymal transition (EMT). After undergoing EMT, mesothelium can differentiate to vascular lineages required for the growth of new blood vessels that play an important role in organ repair and regeneration processes. For these reasons, mesothelium constitutes a resident vascular progenitor cell type found in all coelomic organs including the heart, lung, liver and gut and may have utility in regenerative medicine. Utilizing human pluripotent stem cells (hPSCs), we have developed an in vitro-derived mesothelial cell (MesoT) that can give rise to all the required vascular lineages. When using MesoT as a cellular therapeutic for a mechanically injured neonatal mouse model we uncovered its ability to incorporate into newly formed blood vessels. MesoT cells were also used to reseed the vascular network of a decellularized biological scaffold. Subsequent in vivo implantation of the newly vascularized graft displayed patency, did not thrombose and was able to perfuse blood down to the capillary bed which confirmed its utility in tissue engineering and possible corrective surgery. This work constitutes one of the first reports of a true vascular progenitor that can give rise to all required cell types of the vasculature and highlights the utility of MesoT cells in regenerative medicine.