Phase I Study of Mesenchymal Stromal Cell Secretome for Promoting Corneal Regeneration

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Abstract Non-healing corneal wounds are a challenging condition with limited treatment options that can lead to significant loss of vision. They can occur in many settings such as: (1) chronic loss of nerves such as diabetes (2) following infectious/immune ulcers, and (3) corneas with insufficient stem cells (e.g. after severe injuries, or auto-immune diseases). The currently available therapies are limited by the inability to significantly promote tissue repair and prevent pathologic responses including ulcerations/melts and scarring/fibrosis. As a result, not only is there significant delay in epithelial wound closure but also there is significant scarring, and risk of perforation. The significant regenerative, immunomodulatory and anti-scarring effects of mesenchymal stromal cells (MSCs) have been shown in many studies, some of which were conducted by our team. Numerous studies have shown that the therapeutic effects of MSCs are mainly mediated through their secreted factors. We have optimized a treatment strategy based on MSC derived factors (secretome) to accelerate corneal wound healing and limit unnecessary inflammation and secondary scarring in pre-clinical models. This proposed clinical trial will address the gap between these extensive laboratory studies with promising results and the clinical application of MSC secreted factors. We propose a new treatment utilizing MSC secretome to use as an eye drop to accelerate corneal wound healing in patients with non-healing corneal wounds. Clinical grade MSC will be grown in the University of Illinois Stem Cell Laboratory using established protocols in line with the FDA requirements. Secretome will be collected and frozen in vials which will be later thawed individually dispensed to the patients by the pharmacy on a weekly basis. MSC Secretome will be applied as one drop four times per day in the affected eye in addition to the standard of care supportive therapy, as instructed by the investigator. The phase I safety study will involve 12 patients that will be treated with 2, 4, or 8 weeks of secretome to assess the safety and tolerated dose with weekly follow up visits. Following this, an additional group of 12 patients (different subsets of patients) will be enrolled and receive the maximum tolerable duration of treatment to further assess the safety and efficacy of the treatment with weekly follow up visits to serve as preliminary data for a possible future study. At the conclusion of these studies, we will gain valuable information regarding the safety of this treatment approach, as well as preliminary data about the efficacy in terms of wound healing. These will facilitate the development of novel stem cell based therapies for the management of visually disabling wound healing disorders of the cornea and potentially other tissues.