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Crohn's disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as 'LND') with high expression of LCN2, NOS2, and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn's ileitis and colitis., (© 2024. The Author(s).)

The etiology of anemia in liver cirrhosis is multifactorial; one less recognized cause is hemolytic anemia due to spur cells, known as spur cell anemia. We present the case of a 57-year-old woman with alcoholic cirrhosis who presented with symptomatic macrocytic anemia with a hemoglobin level of 7.4 g/dL and signs of decompensated liver disease. Notably, she had no signs of overt bleeding. Further workup was consistent with hemolysis, with peripheral smear demonstrating spur cells. The patient was treated with both steroids and IVIG, although she eventually expired. The characteristic morphology of spur cells is due to alteration of the lipid composition of the erythrocyte membrane, changing its shape and leading to splenic sequestration and destruction. Characteristic of this disorder is an increased ratio of cholesterol to phospholipid on the membrane, as well as low levels of apolipoproteins and low- and high-density lipoproteins. The presence of spur cells is an indicator of poor prognosis and high risk of mortality. Currently, the only definitive cure is liver transplantation. There is a paucity of literature on the prevalence of this phenomenon and even less about treatment. This case highlights the importance of recognition of spur cell anemia as a cause of anemia in cirrhosis as well as the importance of the peripheral smear in the diagnostic workup. Early recognition can lead to avoidance of unnecessary procedures. Further research is needed to elucidate the true prevalence of spur cell anemia and examine further treatment options., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Gabriella A. Raffa et al.)

Purpose: Human corneal endothelial cell (HCEC) density decreases with age, surgical complications, or disease, leading to vision impairment. Such endothelial dysfunction is an indication for corneal transplantation, although there is a worldwide shortage of transplant-grade tissue. To overcome the current poor donor availability, here we isolate, expand, and characterize HCECs in vitro as a step toward cell therapy., Methods: Human corneal endothelial cells were isolated from cadaveric corneas and expanded in vitro. Cell identity was evaluated based on morphology and immunocytochemistry, and gene expression analysis and flow cytometry were used to identify novel HCEC-specific markers. The functional ability of HCEC to form barriers was assessed by transendothelial electrical resistance (TEER) assays., Results: Cultured HCECs demonstrated canonical morphology for up to four passages and later underwent endothelial-to-mesenchymal transition (EnMT). Quality of donor tissue influenced cell measures in culture including proliferation rate. Cultured HCECs expressed identity markers, and microarray analysis revealed novel endothelial-specific markers that were validated by flow cytometry. Finally, canonical HCECs expressed higher levels of CD56, which correlated with higher TEER than fibroblastic HCECs., Conclusions: In vitro expansion of HCECs from cadaveric donor corneas yields functional cells identifiable by morphology and a panel of novel markers. Markers described correlated with function in culture, suggesting a basis for cell therapy for corneal endothelial dysfunction.

To improve the delivery and integration of cell therapy using magnetic cell guidance for replacement of corneal endothelium, here we assess magnetic nanoparticles' (MNPs') effects on human corneal endothelial cells (HCECs) in vitro. Biocompatible, 50 nm superparamagnetic nanoparticles endocytosed by cultured HCECs induced no short- or long-term change in viability or identity. Assessment of guidance of the magnetic HCECs in the presence of different magnet shapes and field strengths showed a 2.4-fold increase in delivered cell density compared to gravity alone. After cell delivery, HCECs formed a functional monolayer, with no difference in tight junction formation between MNP-loaded and control HCECs. These data suggest that nanoparticle-mediated magnetic cell delivery may increase the efficiency of cell delivery without compromising HCEC survival, identity or function. Future studies may assess the safety and efficacy of this therapeutic modality in vivo. From the clinical editor: The authors show in this article that magnetic force facilitates the delivery of human corneal endothelial cells loaded by superparamagnetic nanoparticles to cornea, without changing their morphology, identity or functional properties. This novel idea can potentially have vast impact in the treatment of corneal endothelial dystrophies by providing self-endothelial cells after ex-vivo expansion., (Copyright © 2015 Elsevier Inc. All rights reserved.)