2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field

Human amniotic membrane patch and platelet-rich plasma to promote retinal hole repair in a recurrent retinal detachment

Purpose: To present a modified surgical technique, based on a combination of human amniotic membrane (hAM) patch and autologous Platelet-rich plasma (PRP) in a case of recurrent retinal detachment (RRD) due to a perivascular retinal hole over an area of staphyloma in an eye with pathologic myopia. Methods: Presenting the surgical technique with the disposal of surgical video. After performing 23-gauge pars plana vitrectomy (PPV) the hAM patch was inserted under the neuroretina through the perivascular hole and PRP was injected on top to speed up the closure of the hole. To complete the surgical procedure High Viscosity Silicon oil (5000cst) was used as tamponade. The patient was prescribed to maintain a face-down position for the first 3 days after the operation. Follow-up was evaluated through Optical coherence tomography (OCT) scans. Results: The 3 days postoperative OCT showed a flat retina with the filling of the myopic staphyloma. The hAM patch was well positioned and the retinal hole could not be identified. At 6 weeks from intervention, the site of the retinal hole at OCT scan was covered by new tissue. Silicone oil was removed 3 months later with no recurrence. Conclusion: hAM transplantation is a novel technique in case of retinal detachment recurrences to seal retinal holes over high myopic chorioretinal atrophy. The adjunctive use of PRP and high viscosity silicon oil allows to reducing the standard face-down positioning timing, representing a valid solution for elderly patients who have difficulties maintaining the position for long periods

Treatment of refractory conjunctivitis associated to dupilumab with topical pimecrolimus applied to the eyelid skin

Patients with atopic dermatitis commonly experience ophthalmic complications, and a higher incidence of conjunctivitis has been observed during treatment with dupilumab. We present the case of a 49-year-old woman with persistent severe atopic dermatitis who complained of refractory conjunctivitis associated with dupilumab. Ocular examination showed features of atopic conjunctivitis for which an external topical application to the eyelids of pimecrolimus 10 mg/g cream was prescribed. The patient showed substantial clinical remission after only 12 days. This case was remarkable as the medication applied externally to the eyelid skin was effective in treating the conjunctival involvement possibly due to penetration of pimecrolimus through the eyelid layers. Further studies are needed to support the use of this drug for dupilumab-related conjunctivitis

Treatment of capecitabine corneal side effects with autologous blood-derived serum eye drops

Background/Aim: To describe the clinical progress and management of ocular side effects in a 35-yearold patient with metastatic breast cancer who underwent oral chemotherapy with capecitabine and lapatinib. Materials and Methods: Slit lamp evaluation revealed bilateral perikeratic hyperemia, perilimbal conjunctival edema associated with corneal marginal infiltrates and epithelial and anterior stromal defects in both eyes. Slit lamp examination, in vivo confocal microscopy and anteriorsegment optical coherence tomography were highly suggestive for limbal stem cell deficiency. The decision to administer autologous blood- derived serum eye drops was made. Results: Following administration of autologous blood-derived serum eye drops, corneal marginal infiltrates, epithelial and stromal defects significantly regressed in both eyes after only 10 days. Chemotherapy was resumed and serum eye drops were prescribed simultaneously. Conclusion: Autologous blood-derived serum eye drops may be an adequate therapeutic choice for bilateral corneal lesions detected as ocular side effects of capecitabine

Multiple myeloma plasma cells show different chemokine receptor profiles at sites of disease activity

Chemokines and their receptors play a pivotal role in the regulation of B-lymphocyte trafficking. This study was aimed at investigating the pattern of chemokine receptor expression, including CCR1 to CCR3, CCR5 to CCR7, CXCR1 to CXCR5, and the migration ability of multiple myeloma (MM) plasma cells (PC). PC were recovered from the bone marrow (BM) of 29 MM patients, extramedullary sites of 10 patients and the BM of five controls. Flow cytometry analysis showed that the receptors mainly expressed on malignant BM PC were represented by CXCR4 (70% of patients), CCR1 (25%), CCR2 (25%), CCR5 (17%) and CXCR3 (20%), while other receptors were commonly lacking. The analysis performed on extramedullary (peripheral blood and pleural effusion) malignant PC demonstrated that the most represented receptors were CXCR4 (100%), CCR2 (66%) and CXCR1 (60%). The migratory capability of malignant PC at resting conditions identified three groups of patients with different migration (low, intermediate and high). As CXCR4 was the relevant chemokine receptor expressed by MM PC, its ligand CXCL12 induced their migration. These data suggest that malignant PC from MM display different chemokine receptor profiles and that CXCR4 is fully functional and might play a role in the spreading of the disease

High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse.

Cancer is a major cause of death in children worldwide, with B-lineage cell acute lymphoblastic leukemia (B-ALL) being the most frequent childhood malignancy. Relapse, treatment failure and organ infiltration worsen the prognosis, warranting a better understanding of the implicated mechanisms. Cortactin is an actin-binding protein involved in cell adhesion and migration that is overexpressed in many solid tumors and in adult B-cell chronic lymphocytic leukemia. Here, we investigated cortactin expression and potential impact on infiltration and disease prognosis in childhood B-ALL. B-ALL cell lines and precursor cells from bone marrow (BM) and cerebrospinal fluid (CSF) of B-ALL patients indeed overexpressed cortactin. In CXCL12-induced transendothelial migration assays, transmigrated B-ALL cells had highest cortactin expression. In xenotransplantation models, only cortacti