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Background Besides long-term trans-differentiation into neural cells, benefits of stem cell therapy (SCT) in ischemic stroke may include secretion of protective factors, which partly reflects extracellular vesicle (EVs) released by stem cell. However, the mechanism(s) by which stem cells/EVs limit stroke injury have yet to be fully defined. Methods We evaluated the protection effect of human placenta mesenchymal stem cells (hPMSC) as a potential form of SCT in experimental ischemic stroke ‘transient middle cerebral artery occusion (MCAO)/reperfusion’ mice model. Findings We found for the first time that intraperitoneal administration of hPMSCs or intravenous hPMSC-derived EVs, given at the time of reperfusion, significantly protected the ipsilateral hemisphere from ischemic injury. This protection was associated with significant restoration of normal blood flow to the post-MCAO brain. More importantly, EVs derived from hPMSC promote paracrine-based protection of SCT in the MCAO model in a cholesterol/lipid-dependent manner. Interpretation Together, our results demonstrated beneficial effects of hPMSC/EVs in experimental stroke models which could permit the rapid “translation” of these cells into clinical trials in the near-term.

BackgroundSelected medical implants and other 3D printed constructs could potentially benefit from the ability to incorporate contrast agents into their structure. The purpose of the present study is to create 3D printed surgical meshes impregnated with iodinated, gadolinium, and barium contrast agents and characterize their computed tomography (CT) imaging characteristics. Commercial fused deposition layering 3D printing was used to construct surgical meshes impregnated with imaging contrast agents in an in vitro model. Polycaprolactone (PCL) meshes were printed containing iodinated, gadolinium, or barium contrast; control PCL meshes without contrast were also fabricated. The three different contrast agents were mixed with PCL powder and directly loaded into the 3D printer. CT images of the three contrast-containing meshes and the control meshes were acquired and analyzed using small elliptical regions of interest to record the Hounsfield units (HU) of each mesh. Subsequently, to test their solubility and sustainability, the contrast-containing meshes were placed in a 37 °C agar solution for 7 days and imaged by CT at days 1, 3 and 7.ResultsAll 3D printed meshes were visible on CT. Iodinated contrast meshes had the highest attenuation (2528 mean HU), significantly higher than both and gadolinium (1178 mean HU) and barium (592 mean HU) containing meshes. Only barium meshes sustained their visibility in the agar solution; the iodine and gadolinium meshes were poorly perceptible and had significantly lower mean HU compared to their pre-agar solution imaging, with iodine and gadolinium present in the adjacent agar at day 7 CT.Conclusion3D prints embedded with contrast materials through this method displayed excellent visibility on CT; however, only barium mesh maintained visibility after 7 days incubation on agar at human body temperature. This method of 3D printing with barium may have potential applications in a variety of highly personalized and CT visible medical devices.

Three-dimensional (3D) printing is an additive manufacturing method that holds great potential in a variety of future patient-specific medical technologies. This project validated a novel crosslinked polyvinyl alcohol (XL-PVA) 3D printed stent infused with collagen, human placental mesenchymal stem cells (PMSCs), and cholangiocytes. The biofabrication method in the present study examined 3D printing and collagen injection molding for rapid prototyping of customized living biliary stents with clinical applications in the setting of malignant and benign bile duct obstructions. XL-PVA stents showed hydrophilic swelling and addition of radiocontrast to the stent matrix improved radiographic opacity. Collagen loaded with PMSCs contracted tightly around hydrophilic stents and dense choloangiocyte coatings were verified through histology and fluorescence microscopy. It is anticipated that design elements used in these stents may enable appropriate stent placement, provide protection of the stent-stem cell matrix against bile constituents, and potentially limit biofilm development. Overall, this approach may allow physicians to create personalized bio-integrating stents for use in biliary procedures and lays a foundation for new patient-specific stent fabrication techniques.

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