Mesenchymal stromal/stem cells (MSCs) and their secreted factors have been shown to have immunomodulatory and regenerative effects. In this study, we investigated human bone-marrow-derived MSC secretome (MSC-S) for the treatment of corneal epithelial wounds. Specifically, we evaluated the role of MSC extracellular vesicles (EV)/exosomes in mediating the wound-healing effects of the MSC-S. In vitro studies using human corneal epithelial cells showed that MSC-CM increased cell proliferation in HCEC and HCLE cells, while EV-depleted MSC-CM showed lower cell proliferation in both cell lines compared to the MSC-CM group. In vitro and in vivo experiments revealed that 1X MSC-S consistently promoted wound healing more effectively than 0.5X MSC-S, and MSC-CM promoted wound healing in a dose-dependent manner, while exosome deprivation delayed wound healing. We further evaluated the incubation period of MSC-CM on corneal wound healing and showed that MSC-S collected for 72 h is more effective than MSC-S collected for 48 h. Finally, we evaluated the stability of MSC-S under different storage conditions and found that after one cycle of freeze–thawing, MSC-S is stable at 4 °C for up to 4 weeks. Collectively, we identified the following: (i) MSC-EV/Exo as the active ingredient in MSC-S that mediates the wound-healing effects in the corneal epithelium, providing a measure to optimize its dosing for a potential clinical product; (ii) Treatment with EV/Exo-containing MSC-S resulted in an improved corneal barrier and decreased corneal haze/edema relative to EV/Exo-depleted MSC-S; (iii) The stability of MSC-CM for up to 4 weeks showed that the regular storage condition did not significantly impact its stability and therapeutic functions.

Drug delivery to the ocular system is affected by anatomical factors like the corneal epithelium, blinking reflex, aqueous blood barrier, and retinal blood barrier, which lead to quick removal from the site and inefficient drug delivery. Developing a drug delivery mechanism that targets specific eye tissue is a major hurdle for researchers. Our study examines the challenges of drug absorption in these pathways. Hydrogels have been researched as a suitable delivery method to overcome some obstacles. These are developed alone or in conjunction with other technologies, such as nanoparticles. Many polymer hydrogel nanoparticle systems utilizing both natural and synthetic polymers have been created and investigated; each has pros and cons. The complex release mechanism of encapsulated agents from hydrogel nanoparticles depends on three key factors: hydrogel matrix swelling, drug-matrix chemical interactions, and drug diffusion. This mechanism exists regardless of the type of polymer. This study provides an overview of the classification of hydrogels, release mechanisms, and the role of controlled release systems in pharmaceutical applications. Additionally, it highlights the integration of nanotechnology in ocular disease therapy, focusing on different types of nanoparticles, including nanosuspensions, nanoemulsions, and pharmaceutical nanoparticles. Finally, the review discusses current commercial formulations for ocular drug delivery and recent advancements in non-invasive techniques. The objective is to present a comprehensive overview of the possibilities for enhancing ocular medication delivery through hydrogel nanoparticle systems.

Ocular surface exposure to nitrogen mustard (NM) leads to severe ocular toxicity which includes the separation of epithelial and stromal layers, loss of endothelial cells, cell death, and severe loss of tissue function. No definitive treatment for mustard gas-induced ocular surface disorders is currently available. The research was conducted to investigate the therapeutic potential of mesenchymal stem cell-conditioned media (MSC-CM) in NM-induced corneal wounds. NM was added to different types of corneal cells, the ocular surface of porcine, and the ocular surface of mice, followed by MSC-CM treatment. NM significantly induced apoptotic cell death, cellular ROS (Reactive oxygen species), and reduced cell viability, metabolic gene expression, and mitochondrial function, and, in turn, delayed wound healing. The application of MSC-CM post NM exposure partially restored mitochondrial function and decreased intracellular ROS generation which promoted cell survival. MSC-CM therapy enhanced wound healing process. MSC-CM inhibited NM-induced apoptotic cell death in murine and porcine corneal tissue. The application of MSC-CM following a chemical insult led to significant improvements in the preservation of corneal structure and wound healing. In vitro, ex vivo, and in vivo results suggest that MSC-CM can potentially provide targeted therapy for the treatment of chemical eye injuries, including mustard gas keratopathy (MGK) which presents with significant loss of vision alongside numerous corneal pathologies.

Chlorine (Cl₂) exposure poses a significant risk to ocular health, with the cornea being particularly susceptible to its corrosive effects. Antioxidants, known for their ability to neutralize reactive oxygen species (ROS) and alleviate oxidative stress, were explored as potential therapeutic agents to counteract chlorine-induced damage. In vitro experiments using human corneal epithelial cells showed decreased cell viability by chlorine-induced ROS production, which was reversed by antioxidant incubation. The mitochondrial membrane potential decreased due to both low and high doses of Cl₂ exposure; however, it was recovered through antioxidants. The wound scratch assay showed that antioxidants mitigated impaired wound healing after Cl₂ exposure. In vivo and ex vivo, after Cl₂ exposure, increased corneal fluorescein staining indicates damaged corneal epithelial and stromal layers of mice cornea. Likewise, Cl₂ exposure in human ex vivo corneas led to corneal injury characterized by epithelial fluorescein staining and epithelial erosion. However, antioxidants protected Cl₂-induced damage. These results highlight the effects of Cl₂ on corneal cells using in vitro, ex vivo, and in vivo models while also underscoring the potential of antioxidants, such as vitamin A, vitamin C, resveratrol, and melatonin, as protective agents against acute chlorine toxicity-induced corneal injury. Further investigation is needed to confirm the antioxidants’ capacity to alleviate oxidative stress and enhance the corneal healing process.

This retrospective study investigated the impact of dosing CD34+ cells on the basis of body weight, body surface area (BSA) and body mass index (BMI) on neutrophil and platelet engraftment after autologous stem cell transplantation (SCT) in patients with multiple myeloma (MM). We performed a retrospective chart review of 114 patients including 97 patients (48 male and 49 female) diagnosed with MM and 17 patients diagnosed with Non-Hodgkin lymphoma. The study categorized subjects on the basis of BMI (<25 and ≥25) and BSA (<1.9 m² and ≥1.9 m²). The findings revealed no significant difference in time to neutrophil engraftment after SCT for different BMI groups, which was on average 11.1 days. However, BSA played a significant role as patients with a BSA ≥1.9 m² exhibited delayed platelet engraftment in contrast to the low BSA group (18.55 days versus 16.42 days, P < 0.05). Furthermore, although CD34+ cell doses were comparable across groups when adjusted for body weight, a BSA-based analysis indicated a greater absolute number of CD34+ cells were administered to patients with BSA ≥1.9 m² (6.07 versus 4.78 cells × 10⁸/m², P < 0.05). By using a multivariate analysis, we showed that for neutrophil engraftment, the best predictive model included age, fat-free mass (FFM) and CD34+ cells (P < 0.1) along with BSA (P = 0.12). For platelet engraftment, the best predictive model included sex and FFM (P < 0.1), with BSA as a significant predictor (P = 0.02). Patients with greater BSA (≥1.9 m²) had a nonsignificantly shorter adjusted time to neutrophil engraftment (LS mean = 10.96) compared with those with lower BSA (<1.9) (LS mean = 11.23). However, greater BSA (≥1.9 m²) was significantly associated with a longer adjusted time to platelet engraftment (LS mean = 18.94) versus lower BSA (<1.9) (LS mean = 16.21). Our results highlight that male patients with a high BSA experienced a 4-day delay in platelet engraftment after autologous SCT. This delay emphasizes the need for optimized dosing strategies to enhance post-transplant recovery, particularly in patients with elevated BSA. Shortening the time to hematopoietic engraftment after SCT may significantly reduce hospital stays and lower the risk of infections, bleeding, and transfusion-related complications.