In humans, the lacrimal gland (LG) is the primary contributor to the aqueous layer of the tear film. Production of tears in insufficient quantity or of inadequate quality may lead to aqueous‐deficiency dry eye (ADDE). Currently there is no cure for ADDE. The development of strategies to reliably isolate LG stem/progenitor cells from the LG tissue brings great promise for the design of cell replacement therapies for patients with ADDE. We analyzed the therapeutic potential of epithelial progenitor cells (EPCPs) isolated from adult wild‐type mouse LGs by transplanting them into the LGs of TSP ‐1−/− mice, which represent a novel mouse model for ADDE. TSP‐1−/− mice are normal at birth but progressively develop a chronic form of ocular surface disease, characterized by deterioration, inflammation, and secretory dysfunction of the lacrimal gland. Our study shows that, among c‐kit‐positive epithelial cell adhesion molecule (EpCAM+) populations sorted from mouse LGs, the c‐kit+dim/EpCAM+/Sca1−/CD34−/CD45− cells have the hallmarks of an epithelial cell progenitor population. Isolated EPCPs express pluripotency factors and markers of the epithelial cell lineage Runx1 and EpCAM, and they form acini and ducts when grown in reaggregated three‐dimensional cultures. Moreover, when transplanted into injured or “diseased” LGs, they engraft into acinar and ductal compartments. EPCP‐injected TSP‐1−/− LGs showed reduction of cell infiltration, differentiation of the donor EPCPs within secretory acini, and substantial improvement in LG structural integrity and function. This study provides the first evidence for the effective use of adult EPCP cell transplantation to rescue LG dysfunction in a model system. Stem Cells Translational Medicine 2017;6:88–98

Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders.

Focal adhesion kinase (FAK) is an important mediator of extracellular matrix–integrin mechano-signal transduction that regulates cell motility, survival, and proliferation. As such, FAK is being investigated as a potential therapeutic target for malignant and fibrotic diseases, and numerous clinical trials of FAK inhibitors are underway. The function of FAK in nonmalignant, nonmotile epithelial cells is not well understood. We previously showed that hepatocytes demonstrated activated FAK near stiff collagen tracts in fibrotic livers. In this study, we examined the role of liver epithelial FAK by inducing fibrotic liver disease in mice with liver epithelial FAK deficiency. We found that mice that lacked FAK in liver epithelial cells developed more severe liver injury and worse fibrosis as compared with controls. Increased fibrosis in liver epithelial FAK-deficient mice was linked to the activation of several profibrotic pathways, including the hedgehog/smoothened pathway. FAK-deficient hepatocytes produced increased Indian hedgehog in a manner dependent on matrix stiffness. Furthermore, expression of the hedgehog receptor, smoothened, was increased in macrophages and biliary cells of hepatocyte-specific FAK-deficient fibrotic livers. These results indicate that liver epithelial FAK has important regulatory roles in the response to liver injury and progression of fibrosis.

A 30-year-old man walked into the emergency department after a suicide attempt by firing a nail from a pneumatic nail gun directed at his left temple. He was haemodynamically stable and neurologically intact, able to recall all events and moving all extremities with a Glascow Coma Scale of 15. CT of the brain showed a 6.3 cm nail in the right frontal region without major intracerebral vessel disruption. He was taken to the operating room for left temporal wound washout, debridement of gross contamination and closure with titanium cranial fixation plate. The foreign body was not accessible on initial surgical intervention and was left in place to define anatomy and plan for subsequent removal. Thin slice CT images were used to create 3D reconstructions to facilitate stereotactic navigation and foreign body removal via right craniotomy the following day. The patient tolerated the procedures well and recovered with full neurological function.

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Myeloid sarcoma (MS) is a rare extra-medullary solid tumor of immature myeloid cells. While it can be an isolated diagnosis, MS is frequently associated with acute myeloid leukemia, chronic myeloid leukemia and myelodysplastic disorders. Although there have been few cases documented that demonstrate the presence of MS in multiple organs at presentation, concomitant involvement of ileum and appendix has never been described. We treated a patient who presented with a small bowel obstruction at the ileum secondary to MS with involvement of the appendix. The patient subsequently underwent a bone marrow biopsy which was negative for evidence of leukemia. He began treatment with induction chemotherapy.

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