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Objectives: Mesangial damage represents a crucial event in the pathogenesis and progression of many renal diseases. Using mesenchymal stem cells (MSCs) to repair the damaged mesangium has been shown to be a very promising therapeutic approach. However, the precise roles MSCs play in the repair process are still unclear. In the present study, we investigated the phagocytotic function of MSCs using fluorescent latex beads during the mesangium repair process. Methods: Mesangial cells (MCs) were cultured as a single layer in 48 glass-bottom well plates. Confluent MCs were made quiescent for 48 hours. Then they were incubated with glomerulopathic light chains (GLCs; 10 ug/mL), which were purified from the urine of patients with renal biopsy-proven light chain-related amyloidosis (n = 3) and light chain deposition disease (n = 3) for four days to establish an in vitro mesangial injury model. Subsequently, green fluorescent protein-labeled MSCs together with the florescent-labeled latex beads were added to assess the phagocytotic activity of MSCs. The entire process was monitored by fluorescence microscopy, and sequential photos were taken with the 6D Life Cell Imaging System (Carl Zeiss Microscopy, Thornwood, NY). Samples were collected 10 days after the introduction of the MSCs (day 14), and processed for light and transmission electron microscopy (TEM). Results: Within 24 hours, MSCs migrated to the damaged mesangial areas and transformed into a macrophage phenotype (CD68+, CD29−). During the repair process, florescent-labeled latex beads were engulfed by the transformed MSCs observed by fluorescence microscopy and further confirmed by TEM, indicating active phagocytotic function of MSCs. Conclusion: MSCs undergo both morphological and functional transformations as they proceed to repair the damaged mesangium. In contrast to previously believed paracrine fashion as the primary mode of MSCs repair, we provided strong evidence that phagocytotic activity of MSCs is an important mechanism involved in mesangial repairing. [ABSTRACT FROM AUTHOR]

Background: Hemophagocytic lymphohistiocytosis is a rare rapidly progressive condition of immune dysregulation characterized by a hyperinflammatory response and uncontrolled T-cell and macrophage activation. Concomitant involvement of acute myeloid leukemia (AML) and hemophagocytic lymphohistiocytosis (HLH) is even more rare and presents a challenge for clinical management. Clinical Course: We present a 76-year-old man with fatigue, shortness of breath, thrombocytopenia and leukocytosis. CT revealed splenomegaly, enlarged mediastinal lymph nodes, and PET study showed bone marrow hypermetabolic activity. Hematology work up established diagnosis of AML, concomitant HLH and tumor lysis syndrome. Considering the primary problem is AML, CHEMOTHERAPY with Cytarabine was initiated. Due to continuous increasing bilirubin, liver biopsy was performed. Later the patient developed septicemia and expired. Pathology Findings: Microscopically, it revealed extensive cholestasis, bile ductule proliferation, and ballooning degeneration. The iron stain demonstrated 4+ iron and hemosiderin depositions. Within hepatic sinusoids, there were increased immature monocytic cells in single cells or in clusters, with slightly open chromatin, irregular nuclear contours, and relatively abundant cytoplasm, which were positive for CD14, CD68, and negative for CD34, CD56, and MPO. CD3 highlighted T-cells in portal tracts and occasionally in sinusoids. In hepatic sinusoids, hemophagocytic lymphohistiocytosis was seen, with macrophages or monocytes engulfing red cells. The findings are consistent with acute myeloid leukemia with monocytic differentiation, involving hepatic sinusoids, with concurrent hemophagocytic lymphohistiocytosis. Molecular studies including JAK2V617F mutation analysis, fluorescence in situ hybridization for BCR/ABL1, and cytogenetic analysis were unremarkable. Discussion: Hemophagocytic lymphohistiocytosis can be found in up to 10% of AML patients going through chemotherapy and frequently leads to rapid mortality. Since clinical treatment for leukemia and HLH is drastically different, recognizing the morphologic changes and the immunophenotypic features of the infiltrates are critical for a rapid diagnosis and a prompt institution of treatment. [ABSTRACT FROM AUTHOR]