Las vesículas extracelulares placentarias estimulan el recrecimiento intestinal después de una resección masiva del...

Extracellular vesicles (EVs) are released by most cells, including stem cells, into the extracellular environment and regulate cell function and tissue regeneration through cell-cell communication. The EVs derived from human placenta have a crucial role in regulating the maternal immune response for a successful pregnancy outcome. The purpose of the current study was to evaluate the effects of human villous trophoblasts (HVT)-derived EVs on structural intestinal adaptation, cell proliferation and apoptosis in a rat model of short bowel syndrome (SBS). HVT-EVs were isolated from cell media after 24 and 48 h of starvation (medium without serum) by subsequent centrifugation and ultracentrifugation (UC). HVT-EV protein content were screened by protein array. Male Sprague-Dawley rats were divided into four experimental groups: sham rats underwent bowel transection and re-anastomosis, sham-EV rats underwent bowel transection and re-anastomosis and were treated with HVT-EVs given intraperitoneally (IP) at a dose of 200ug/200ul once daily from postoperative day 3 through 14, SBS rats underwent a 75% small bowel resection and anastomosis, and SBS-EV rats underwent similar bowel resection and were likewise treated with HVT-EVs. Parameters of intestinal adaptation, enterocyte proliferation and enterocyte apoptosis were determined on postoperative day 15. Apoptosis/inflammatory-related protein levels were determined by ELISA (TNF-α) and immunohistochemistry (caspase-3). SBS rats demonstrated a significant increase in jejunal and ileal bowel (400%) and mucosal (250%) weight, jejunal (18%) and ileal (13%) villus height, ileal crypt depth (17%), cell proliferation rates in jejunum (45%) and ileum (54%) and concomitant increase in cell apoptosis in jejunum (400%) and ileum (500%) compared to sham animals. Treatment of SBS rats with HVT-EVs which contain proangiogenic proteins such as angiogenin and angiopoietin-1 resulted in additional increase in jejunal bowel weight (39%), ileal mucosal weight (25%), ileal villus height (23%) and jejunal crypt depth (14%) compared to SBS-nontreated animals. Enhanced adaptation in SBS-EVs rats was achieved by a mild increase in cell proliferation and a significant decrease in cell apoptosis rates (four-fold decrease in jejunum and ten-fold decrease in ileum) vs SBS-nontreated animals. Inhibited cell apoptosis in this group was accompanied by decrease in TNF-α and caspase-3 expression. In conclusion, in a rat model of SBS, parenteral HVT-EVs stimulate structural intestinal adaptation. Increased cell proliferation and decreased cell death via apoptosis (probably by the intrinsic pathway) appears to be responsible for the increased cell mass.