Posts Tagged: regenerative medicine

Extracellular Vesicles in Angiogenesis

Extracellular Vesicles in Angiogenesis

Dilyana Todorova, Stéphanie Simoncini, Romaric Lacroix, Florence Sabatier, Françoise Dignat-George

Mechanisms involved in the modulation of Angiogenesis by endothelial cell (EC)–derived extracellular vesicles (EVs). EC release EVs rich in micro-RNA such as miR-214 and miR-126, that are transferred to recipient EC and induce proangiogenic signaling. EVs contain functional matrix metalloproteinases that facilitate angiogenesis through the degradation of components of the extracellular matrix. Dll4 is transferred to EC by the EVs and induces Notch receptor internalization and tip cell formation. EVs bear, at their surface, a tissue factor that interacts with β1 integrin and induces Rac1-ERK1/2-ETS1 signaling, leading to the increased secretion of CCL2. EVs transport the complex uPA/uPAR, which stimulates angiogenesis through plasmin generation. The phosphatidylserine present on the surface of the EVs interacts with CD36 and induces Fyn kinase signaling, which leads to increased oxidative stress and the inhibition of angiogenesis. ATM indicates ataxia telangiectasia mutated; CCl2, chemokine c-c motif ligand 2; Dll4, Delta-like 4; ECM, extracellular matrix; ERK1/2, extracellular signal-related kinase 1 and 2; ETS1, avian erythroblastosis virus E26 homolog-1; IL-3R, interleukin-3 receptor; MMPs, matrix metalloproteinases; NotchR, Notch receptor; PS, phosphatidylserine; Rac1, Ras-related C3 botulinum toxin substrate 1; ROS, reactive oxygen species; TF, tissue factor; TIMPS, tissue inhibitor of metalloproteinases; uPA, urokinase plasminogen activator; and uPAR, urokinase plasminogen activator receptor. [Powerpoint File]

Extracellular Vesicles in Angiogenesis

Extracellular Vesicles in Angiogenesis

Dilyana Todorova, Stéphanie Simoncini, Romaric Lacroix, Florence Sabatier, Françoise Dignat-George

Mechanisms involved in the modulation of Angiogenesis by platelet-derived extracellular vesicles (EVs). Platelet-derived EVs contain various growth factors and chemokines that induce proangiogenic signaling in endothelial cell (EC). Spingosine-1-phosphate (S1P1), present on the EV surface, induces PI3K activation and, together with VEGF and bFGF, promotes angiogenesis. The EVs released by platelets stimulate the proangiogenic potential of circulating angiogenic cells by increasing their expression of both membrane molecules and soluble factors. Platelet-derived EVs can inhibit angiogenesis by transferring the p22phox and gp91 subunits of NADPH oxidase and increasing the oxidative stress in EC. ? indicates that the exact content of the EVs is not reported; bFGF, basic fibroblast growth factor; EGF, epidermal growth factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; HGF, hepatocyte growth factor; NADPH, nicotinamide adenine dinucleotide phosphate; PI3K, phosphoinositide 3-kinase; RANTES, regulated on activation, normal T-cell–expressed and secreted; ROS, reactive oxygen species; VEGF, vascular endothelial growth factor; and VEGFR, vascular endothelial growth factor receptor. [Powerpoint FIle]

Induced Pluripotent Stem Cells for Post–Myocardial Infarction Repair: Remarkable Opportunities and Challenges

Induced Pluripotent Stem Cells for Post–Myocardial Infarction Repair: Remarkable Opportunities and Challenges

Pratik A. Lalit, Derek J. Hei, Amish N. Raval, Timothy J. Kamp

Cardiac cell therapy strategies using induced pluripotent stem cells (iPSCs) and derivatives. Patient-specific primary cells are isolated and cultured in vitro from a suitable cell source, such as blood or skin. These cells are reprogrammed to iPSCs using nonintegrating strategies under Current Good Manufacturing Practice conditions. The resulting iPSCs are rigorously tested for pluripotency, genetic/epigenetic abnormalities, and safety (Tables 3 and 4). The iPSC clones that pass test criteria are banked for later use. Alternatively, allogeneic iPSCs can be used from a haplotype-matched iPSC bank. The iPSCs are then differentiated into the desired cardiac lineage cells: cardiac progenitors, cardiomyocytes (CMs), smooth muscle (SM) cells, or endothelial cells (ECs). The desired cell lineage or combination of cell lineages is transplanted into damaged heart via intracoronary/intramuscular injection or epicardially by tissue engineered cardiac patches. Ongoing studies will define the optimal cell preparations and associated delivery strategies for repair of the post–myocardial infarction heart. [Powerpoint File]