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Acute graft-versus-host disease (GVHD) is a frequent and potentially life-threatening complication following allogeneic hematopoietic cell transplantation (HCT). Mesenchymal stromal cells (MSCs), rare precursors found in all body tissues, possess immunosuppressive properties and can inhibit alloreactivity both in vitro and in vivo. Two decades ago, we introduced bone marrow-derived (BM) MSCs as a novel therapy for acute GVHD. While some patients responded to BM-MSCs, the response was not universal. Commercially available BM-MSCs are now used for acute GVHD treatment in Canada, Japan, and New Zealand. The fetus is protected from the mother's immune system by the placenta, and our research found that placenta-derived decidua stromal cells (DSCs) offer a stronger immunosuppressive effect than other sources of stromal cells. Safety studies in rabbits, rats, mice, and humans have shown negligible or no side effects from BM-MSCs or DSCs. In a phase I/II trial for severe acute GVHD, we treated 21 patients (median age, 49 years; range 1.6-72 years) with severe biopsy-proven gastrointestinal acute GVHD. The median cell dose of DSCs was 1.2 × 106 (range 0.9-2.9) cells/kg body weight, with a median of 2 (range 1-6) infusions given 1 week apart. The cell viability of DSCs was 93% (range, 69%-100%), and the median cell passage number was 4 (range, 2-4). All patients responded, with a complete response of acute GVHD in 11 patients and partial response in 10 and 1-year survival of 81%. Randomized trials are needed to prove the superiority of DSCs compared to ruxolitinib and/or other novel immunosuppressive therapies. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the use of a chromatic pupillometry test for the early detection of functional impairment in intrinsically photosensitive retinal ganglion cells (ipRGCs) in an experimental glucocorticoid model of ocular hypertension (OH) treated with intravitreal injection of human Wharton's jelly derived mesenchymal stromal cells (hWJ-MSCs). For this purpose, fifteen New Zealand rabbits were randomly assigned to three groups: OH (G1), hWJ-MSCs (G2), and OH + hWJMSCs (G3). The chromatic pupillary light reflex (cPLR) was assessed after dark adaptation to high-illuminance red and blue light stimuli. Response to blue light was used as a marker of ipRGC activity. Amplitude and latency were evaluated using flashvisual evoked potentials (VEP). Intraocular pressure (IOP) (mmHg) was monitored over time. The results indicated a significant increase (P<0.001) in the IOP by third week. Pupil diameter (mm) for blue light significantly increased (P<0.05) in all groups compared to the control eyes. However, the pupillary diameter in G3 tended to remain constant. Red light elicited significant differences in the responses in G1 (P=0.025) and G2 (P=0.007). Moreover, we found no correlation between the parameters of blue light intensity and flash-VEP (P>0.05). A non-significant increase in the latency of G2 (P=0.437) and G3 (P=0.779), and a slight increase in the amplitude of G3 were observed (P=0.268). The changes generated by the OH can be recognized early through quantitative measurements of the pupillary function. We found that intravitreal injection of human hWJ-MSCs appears to influence ipRGC activity, detectable early through cPLR in eyes with OH. In summary, our study indicates that intravitreal injection of human hWJ-MSCs appears to influence ipRGC activity facilitating the early detection capabilities for ocular hypertension-related changes through cPLR in eyes with OH. [ABSTRACT FROM AUTHOR]

Introduction: Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells. Recent research suggests immunological changes such as cytokine imbalance may affect its pathophysiology. This implies that immunomodulation, like that of mesenchymal cells, could be a potential therapeutic avenue for this disease. However, the effects of intravitreal injections of human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) on intraocular immune response have not been assessed in ocular hypertension (OH) models. Methods: We explored this by measuring cytokine levels and expression of other markers, such as glial fibrillary acidic protein (GFAP) and T cells, in 15 randomly divided New Zealand rabbits: G1: OH, G2: hWJ-MSCs, and G3: OH+hWJ-MSCs. We analyzed the aqueous humor (IL-6, IL-8, and TNF-α) and vitreous humor (IFN-γ, IL-10, and TGF-β) using ELISA and flow cytometry (cell populations), as well as TCD3+, TCD3+/TCD4+, and TCD3+/TCD8+ lymphocytes, and GFAP in the retina and optic nerve through immunohistochemistry. Results: We found a decrease in TNF-α, IL-6, IFN-γ, IL-10, and IL-8 in G3 compared to G1 and an increase in TGF-β in both G2 and G3. TCD3+ retinal infiltration in all groups was primarily TCD8+ rather than TCD4+ cells, and strong GFAP expression was observed in both the retina and optic nerves in all groups. Conclusion: Our results suggest that cellular and humoral immune responses may play a role in glaucomatous optic neuropathy and that intravitreal hWJ-MSCs can induce an immunosuppressive environment by inhibiting proinflammatory cytokines and enhancing regulatory cytokines. [ABSTRACT FROM AUTHOR]