Endothelium-mediated contributions to fibrosis.

Fibrosis, characterized by abnormal and excessive deposition of extracellular matrix, results in compromised tissue and organ structure. This can lead to reduced organ function and eventual failure. Although activated fibroblasts, called myofibroblasts, are considered the central players in fibrosis, the contribution of endothelial cells to the inception and progression of fibrosis has become increasingly recognized. Endothelial cells can contribute to fibrosis by acting as a source of myofibroblasts via endothelial-mesenchymal transition (EndoMT), or by becoming senescent, by secretion of profibrotic mediators and pro-inflammatory cytokines, chemokines and exosomes, promoting the recruitment of immune cells, and by participating in vascular rarefaction and decreased angiogenesis. In this review, we provide an overview of the different aspects of fibrosis in which endothelial cells have been implicated.

Cell-based therapies for vascular regeneration: Past, present and future.

Tissue vascularization remains one of the outstanding challenges in regenerative medicine. Beyond its role in circulating oxygen and nutrients, the vasculature is critical for organ development, function and homeostasis. Importantly, effective vascular regeneration is key in generating large 3D tissues for regenerative medicine applications to enable the survival of cells post-transplantation, organ growth, and integration into the host system. Therefore, the absence of clinically applicable means of (re)generating vessels is one of the main obstacles in cell replacement therapy. In this review, we highlight cell-based vascularization strategies which demonstrate clinical potential, discuss their strengths and limitations and highlight the main obstacles hindering cell-based therapeutic vascularization.

GP2-enriched pancreatic progenitors give rise to functional beta cells in vivo and eliminate the risk of teratoma formation.

Human pluripotent stem cell (hPSC)-derived pancreatic progenitors (PPs) can be differentiated into beta-like cells in vitro and in vivo and therefore have therapeutic potential for type 1 diabetes (T1D) treatment. However, the purity of PPs varies across different hPSC lines, differentiation protocols, and laboratories. The uncommitted cells may give rise to non-pancreatic endodermal, mesodermal, or ectodermal derivatives in vivo, hampering the safety of hPSC-derived PPs for clinical applications and their differentiation efficiency in research settings. Recently, proteomics and transcriptomics analyses identified glycoprotein 2 (GP2) as a PP-specific cell surface marker. The GP2-enriched PPs generate higher percentages of beta-like cells in vitro, but their potential in vivo remains to be elucidated. Here, we demonstrate that the GP2-enriched-PPs give rise to all pancreatic cells in vivo, including functional beta-like cells. Remarkably, GP2 enrichment eliminates the risk of teratomas, which establishes GP2 sorting as an effective method for PP purification and safe pancreatic differentiation.