RESUMEN
Chronic ocular graft-versus-host disease (oGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and can lead to vision loss if not diagnosed and treated promptly. Currently, no approved drugs exist for oGVHD treatment. However, umbilical cord-derived mesenchymal stem cells (UCMSCs) have known immunoregulatory properties and have been employed in clinical trials for immune-mediated diseases. To address oGVHD, the application of UCMSCs to the ocular surface is a logical approach. Intravenous administration of UCMSCs poses risks, necessitating topical and local delivery. Retaining UCMSCs on the ocular surface remains a challenge. To overcome this, we invented mesenchymal stem cell-coating high oxygen-permeable hydrogel lenses combining UCMSCs and machinery to enable the long-term retention of UCMSCs on the ocular surface. Animal model experiments demonstrated that these lenses effectively retained UCMSCs, providing therapeutic benefits by decreasing corneal inflammation and damage, and inhibiting immune rejection and response, all crucial aspects in oGVHD treatment.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Células Madre Mesenquimatosas , Animales , Ojo , Enfermedad Injerto contra Huésped/terapia , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Modelos AnimalesRESUMEN
Cancer remains the primary cause of death worldwide. To develop less toxic anti-cancer drugs to relieve the suffering and improve the survival of cancer patients is the major focus in the anti-cancer field. To this end, marine creatures are being extensively studied for their anti-cancer effects, since extracts from at least 10% of the marine organisms have been shown to possess anti-tumor activities. As a classic Chinese traditional medicine, sea cucumbers and compounds extracted from the sea cucumbers, such as polysaccharides and saponins, have recently been shown to exhibit anti-cancer, anti-inflammatory, and anti-oxidant effects. Holothuria leucospilota (H. leucospilota) is a tropical edible sea cucumber species that has been successfully cultivated and farmed in large scales, providing a readily available source of raw materials to support the development of novel marine anti-cancer drugs. However, very few studies have so far been performed on the biological activities of H. leucospilota. In this study, we first investigated the anti-cancer effect of H. leucospilota protein on three cancer cell lines (i.e., HepG2, A549, Panc02) and three normal cell lines (NIH-3T3, HaCaT, 16HBE). Our data showed that H. leucospilota protein decreased the cell viabilities of HepG2, A549, HaCaT, 16HBE in a concentration-dependent manner, while Panc02 and NIH-3T3 in a time- and concentration-dependent manner. We also found that the inhibitory effect of H. leucospilota protein (≥10 µg/mL) on cell viability is near or even superior to EPI, a clinical chemotherapeutic agent. In addition, our data also demonstrated that H. leucospilota protein significantly affected the cell cycle and induced apoptosis in the three cancer cell lines investigated; in comparison, it showed no effects on the normal cell lines (i.e., NIH-3T3, HaCaT and 16HBE). Finally, our results also showed that H. leucospilota protein exhibited the excellent performance in inhibiting cell immigrations. In conclusion, H. leucospilota protein targeted the cancer cell cycles and induced cancer cell apoptosis; its superiority to inhibit cancer cell migration compared with EPI, shows the potential as a promising anti-cancer drug.