Microvesicles (MVs) released by cells are involved in a multitude of physiological events as important mediators of intercellular communication. MVs derived from mesenchymal stem cells (MSCs) contain various paracrine factors from the cells that primarily contribute to their therapeutic efficacy observed in numerous clinical trials. As nano-sized and bi-lipid layered vesicles retaining therapeutic potency equivalent to that of MSCs, MSC-derived MVs have been in focus as ideal medicinal candidates for regenerative medicine, and are preferred over MSC infusion therapy with their improved safety profiles. However, technical challenges in obtaining sufficient amounts of MVs have limited further progress in studies and clinical application. Of the multiple efforts to reinforce the therapeutic capacity of MSCs, few studies have reportedly examined the scale-up of MSC-derived MV production. In this study, we successfully amplified MV secretion from MSCs compared to the conventional culture method using a simple and efficient 3D-bioprocessing method. The MSC-derived MVs produced in our dynamic 3D-culture contained numerous therapeutic factors such as cytokines and micro-RNAs, and showed their therapeutic potency in in vitro efficacy evaluation. Our results may facilitate diverse applications of MSC-derived MVs from the bench to the bedside, which requires the large-scale production of MVs.
A heparin-conjugated biodegradable polymer (PLA-heparin) by the direct coupling of heparin to polylactide (PLA) was synthesized and characterized. The surface exposed heparin content associated PLA-heparin was measured to be 0.067 microg/cm2. PLA-heparin coated surface has shown higher hydrophilicity rather than control PLA surface. The clotting time of PLA-heparin conjugate measured by activated partial thromboplastin time (APTT) was significantly prolonged as compared to PLA. The bioactivity of bound heparin measured by APTT corresponds to 17.4% of free heparin. It has been also demonstrated that the conjugation of heparin suppresses the protein adsorption as well as the platelet adhesion. These results indicate that the unique property of bound heparin has an inhibiting influence on the coagulation, plasma protein adsorption, and subsequent platelet adhesion systems. This novel PLA-heparin conjugate could be applied as blood/tissue compatible biodegradable materials for implantable medical devices and tissue engineering.
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