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The human corneal endothelium has limited regeneration capacity. Several methods have been developed in an attempt to repair it. Descemet stripping automated endothelial keratoplasty (DSAEK) is commonly performed on patients with endothelial dysfunction. However, donor demand far exceeds donor supply. Here, we prepared fish-scale collagen membrane (FSCM) and seeded it with CECs in preparation for corneal endothelial transplantation. The fish scales were decellularized, decalcified, and curved. The FSCM was inspected by fluorescence microscopy, SEM, and TGA to validate decellularization, microstructure, and decalcification, respectively. The cytotoxicity of FSCM and the viability of the cells in contact with it were evaluated by LDH and WST-1, respectively. CEC tight junctions and ZO-1 structure were observed by SEM and confocal microscopy. FSCM seeded with CECs were implanted to rabbit anterior chambers to evaluate host tissue reactions to it. FSCM biocompatibility and durability were also assessed. The results showed that FSCM has excellent transparency, adequate water content, and good biocompatibility. The cultivated CECs mounted on the FSCM were similar to normal CECs in vivo. The FSCM plus CECs developed here have high potential efficacy for endothelial keratoplasty transplantation.

Traditional photodynamic therapy (PDT) is limited by the penetration depth of visible light. Although the light source has been changed to near infrared, infrared light is unable to overcome the penetration barrier and it is only effective at the surface of the tumors. In this study, we used X-ray as a light source for deep-seated tumor treatment. A particle with a narrow band gap when exposed to soft X-rays would produce reactive oxygen species (ROS) to kill tumor cell, with less damage to the normal tissues. Anatase TiO2 has been studied as a photosensitizer in PDT. In the experiment, C was doped into the anatase lattice at an optimum atomic ratio to make the band gap narrower, which would be activated by X-ray to produce more ROS and kill tumor cells under stress. The results showed that the synthesized TiO2:C particles were identified as crystal structures of anatase. The synthesized particles could be activated effectively by soft X-rays to produce ROS, to degrade methylene blue by up to 30.4%. Once TiO2:C was activated by X-ray irradiation, the death rate of A549 cells in in vitro testing was as high as 16.57%, on day 2. In the animal study, the tumor size gradually decreased after treatment with TiO2:C and exposure to X-rays on day 0 and day 8. On day 14, the tumor declined to nearly half of its initial volume, while the tumor in the control group was twice its initial volume. After the animal was sacrificed, blood, and major organs were harvested for further analysis and examination, with data fully supporting the safety of the treatment. Based on the results of the study, we believe that TiO2:C when exposed to X-rays could overcome the limitation of penetration depth and could improve PDT effects by inhibiting tumor growth effectively and safely, in vivo.

BackgroundAcute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization.ObjectivesThis phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention.MethodsConsenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period.ResultsEight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline.ConclusionThis pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients.