Silicate ions as soluble form of bioactive ceramics alleviate aortic aneurysm and dissection

Aortic aneurysm and dissection(AAD)are leading causes of death in the elderly.Recent studies have demonstrated that silicate ions can manipulate multiple cells,especially vascular-related cells.We demonstrated in this study that silicate ions as soluble form of bioactive ceramics effectively alleviated aortic aneurysm and dissection in both Ang II andβ-BAPN induced AAD models.Different from the single targeting therapeutic drug approaches,the bioactive ceramic derived approach attributes to the effect of bioactive silicate ions on the inhibition of the AAD progression through regulating the local vascular microenvironment of aorta systematically in a multi-functional way.The in vitro experiments revealed that silicate ions did not only alleviate senescence and inflammation of the mouse aortic endothelial cells,enhance M2 polarization of mouse bone marrow-derived macrophages,and reduce apoptosis of mouse aortic smooth muscle cells,but also regulate their interactions.The in vivo studies further confirm that silicate ions could effectively alleviate senescence,inflammation,and cell apoptosis of aortas,accomplished with reduced aortic dilation,collagen deposition,and elastin laminae degradation.This bioactive ceramic derived therapy provides a potential new treatment strategy in attenuating AAD progression.

Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization

Currently,stem cell transplantations in cardiac repair are limited owing to disadvantages,such as immunological rejection and poor cell viability.Although direct injection of exosomes can have a curative effect similar to that of stem cell transplantation,high clearance hinders its application in clinical practice.Previous reports suggested that induction of coronary collateralization can be a desired method of adjunctive therapy for someone who had missed the optimal operation time to attenuate myocardial ischemia.In this study,to mimic the paracrine and biological activity of stem cells,we developed artificial stem cells that can continuously release Tβ4-exosomes(Tβ4-ASCs)by encapsulating specific exosomes within microspheres using microfluidics technology.The results show that Tβ4-ASCs can greatly promote coronary collateralization in the periphery of the myocardial infarcted area,and its therapeutic effect is superior to that of directly injecting the exosomes.In addition,to better understand how it works,we demonstrated that the Tβ4-ASC-derived exosomes can enhance the angiogenic capacity of coronary endothelial cells(CAECs)via the miR-17-5p/PHD3/Hif-1αpathway.In brief,as artificial stem cells,Tβ4-ASCs can constantly release functional exosomes and stimulate the formation of collateral circulation after myocardial infarction,providing a feasible and alternative method for clinical revascularization.