A role for bone marrow-derived cells in diabetic nephropathy.

Diabetes mellitus causes systemic disorders. We previously demonstrated that diabetic condition forced bone marrow-derived cells (BMDCs) to express TNF-α, leading to the development of diabetic neuropathy in mice. Here, we hypothesized that these abnormal BMDCs are also involved in diabetic nephropathy. To test our hypothesis, mice were irradiated to receive total bone marrow (BM) from the transgenic mice expressing green fluorescent protein before diabetes was induced by streptozotocin. Confocal microscopy showed that the diabetic glomerulus had more BMDCs compared with the nondiabetic glomerulus. Most of these cells exhibited endothelial phenotypes, being negative for several markers, including podocin (a maker of podocyte), α8 integrin (mesangial cell), CD68, and F4/80 (macrophage). Next, the total BM of diabetic mice was transplanted into nondiabetic mice to examine if diabetic BM per se could cause glomerular injury. The recipient mice exhibiting normal glycemia developed albuminuria and mesangial expansion with an increase in capillary area. The number of BMDCs increased in the glomerulus of the recipient mice. These cells were found to exhibit the endothelial phenotype and to express TNF-α. These data suggest that diabetic BMDCs per se could initiate glomerular disease. Finally, eNOS knockout mice were used to examine if residential endothelial injury could attract BMDCs into the glomerulus. However, endothelial dysfunction due to eNOS deficiency failed to attract BMDCs into the glomerulus. In summary, BMDCs may be involved in the development of diabetic nephropathy.-Nobuta, H., Katagi, M., Kume, S., Terashima, T., Araki, S., Maegawa, H., Kojima, H., Nakagawa, T. A role for bone marrow-derived cells in diabetic nephropathy.

Characteristics of Patients and Their Ascites Who Underwent Repeated Cell-Free and Concentrated Ascites Reinfusion Therapy.

Novel cell-free and concentrated ascites reinfusion therapy (KM-CART) is easy to use, safe and applicable for refractory ascites. We can get the full amount of ascites, filtrate, and concentrate in a short time. KM-CART can be applied as palliative care for dying patients including patients with massive malignant ascites. Some patients who underwent repeated KM-CART survived longer than those who did not repeat the therapy. The aim of this study was to identify the type of patients with ascites for whom KM-CART would be effective and candidates for repeated KM-CART. In this retrospective cohort observational study, we examined 123 CART processes performed on 58 patients with refractory ascites. Data were collected before and after processing of the ascites. We compared two groups; patients who underwent KM-CART ≥ 5 times and those who underwent this process ≤ 4 times. Age, disease, benign or malignant status of the disease, the amount of ascites, concentrations of total protein (TP) and albumin (Alb) and their amounts in the original ascites and the filtered and concentrated ascitic fluid and the recovery ratio of TP and Alb were determined. No significant difference was observed between the two groups in age, disease, amount of ascites, and the recovery ratio of TP and Alb. Significant differences were observed in the amounts of TP and Alb in the original ascites and the filtered and concentrated ascitic fluid. Patients who underwent KM-CART ≥ 5 times had higher Alb levels in the original ascites than those who underwent this therapy ≤ 4 times. Patients with higher Alb concentrations in the original ascites could be candidates for repeated KM-CART.