Hassoun, Shaimaa

Stem cell-derived β (SC-β) cells are a promising therapy for type 1 diabetes (T1D), but their long-term efficacy is limited by immune-mediated graft rejection. Platelet-derived exosome product (PEP) has emerged as a novel immunomodulatory agent, although its effect on SC-β cell xenograft rejection remains unclear. Here, we evaluated PEP in stimulated human peripheral blood mononuclear cells (PBMCs) and in an immunocompetent mouse model of SC-β cell transplantation under the kidney capsule. Immune-related gene expression was assessed by quantitative PCR, immune cell infiltration by immunofluorescence, and graft function by circulating human insulin. In vitro, PEP reduced NK-cell-associated gene expression, including NK1.1, EOMES, and KLRK1, and increased IL-10 expression. In vivo, untreated SC-β cell xenografts showed progressive immune infiltration and loss of detectable human insulin by day 14, whereas PEP-treated grafts retained detectable insulin through day 14 across co-transplantation, pretreatment, and systemic administration strategies. PEP co-transplantation delayed, but did not prevent, xenograft rejection, with graft loss observed by day 21. This delay was associated with reduced NK1.1+ cell infiltration and lower expression of selected inflammatory and rejection-associated markers, including NK1.1, Nos2, and Nlrp3. These findings suggest that PEP modulates graft-associated immune responses and may serve as an adjunct immunomodulatory strategy for stem cell-based therapies for type 1 diabetes. Further studies are needed to evaluate sustained graft durability, safety, and translational efficacy.

Abstract Background: Chronic dry eye disease (CDED) is a condition of the ocular surface that causes discomfort, visual disturbance, conjunctival injection, and photophobia. A debilitating form of CDED in patients undergoing allogeneic bone marrow transplant results from ocular graft versus host disease (oGVHD). Autologous serum eye drops (ASED) have beneficial effects on the ocular surface. The aim of this study is to compare improvements in symptoms and function in a cohort of CDED patients with ocular GVHD treated with ASED and a cohort of CDED without GVHD (non-GVHD). We additionally report on some of the biologic characteristics of one specific ASED formulation. Materials and Methods: A total of 71 patients seen in a multi-specialty ophthalmology practice in a university hospital setting receiving ASEDs underwent ocular surface disease index (OSDI) and visual function questionnaire measurements at baseline, 3 months, and 6 months. Twenty-four ASED samples were studied for biomarkers. Results: Compared to baseline, OSDI scores significantly decreased after 3 and 6 months of ASED treatment in both oGVHD and non-GVHD CDED groups. Additionally, visual function questionnaire-25 (VFQ-25) subscales (ocular pain, distance activity, driving, role difficulties, dependency, and mental health) were significantly improved at 3 months and 6 months, and social functioning was improved at 6 months. The majority of patients in both groups had severe disease. Improvements in patient-reported outcomes were greater in the oGHD CDED group than in the non-GVHD CDED group There were no reported complications. Conclusion: ASED is safe and effective in patients with CDED due to oGVHD and non-GVHD. Those with oGVHD had greater improvements. These findings potentiate the wider adoption of this therapy in CDED patients and warrant additional studies into the biochemical makeup of ASED.