CD140b and CD73 are markers for human induced pluripotent stem cell‐derived erythropoietin‐producing cells

Renal anemia in chronic kidney disease is treated with recombinant human erythropoietin (rhEPO). However, some patients with anemia do not respond well to rhEPO, emphasizing the need for a more biocompatible EPO. Differentiation protocols for hepatic lineages have been modified to enable production from human induced pluripotent stem cell (hiPSC)‐derived EPO‐producing cells (EPO cells). However, markers for hiPSC‐EPO cells are lacking, making it difficult to purify hiPSC‐EPO cells and therefore to optimize EPO production and cell counts for transplantation. To address these issues, we investigated whether CD140b and CD73 could be used as markers for hiPSC‐EPO cells. We measured the expression of EPO, CD140b, and CD73 in hiPSC‐EPO cells and the EPO concentration in the cell supernatant by immunohistochemistry and enzyme‐linked immunosorbent assays on culture day 13, revealing that expression levels of CD140b and CD73 are correlated with the level of EPO. In addition, rates of CD140b+ CD73+ cells were observed to be correlated with the concentration of EPO. Thus, our results suggest that CD140b and CD73 may be markers for hiPSC‐EPO cells

Lymphatic flow restoration after stripping surgery for varicose veins: A case report

It has been suggested that the dynamics of the venous and lymphatic systems interact as a mutually dependent dual outflow system and that derangement of lymph flow could be reversed by surgical treatment of venous incompetence. In this report, we describe a patient in whom lymphatic function was restored after stripping of the great saphenous vein for varicosity. The patient was a 79-year-old woman who had varicose veins along the medial side of an edematous left leg. Lymphatic function was investigated using indocyanine green imaging to evaluate for the presence of lymphedema. Based on the findings, we made a diagnosis of bilateral varicosity of the great saphenous vein with left-sided lymphedema. The great saphenous vein was stripped between the groin and ankle on both sides. At 3 months after the stripping procedure, lymphatic flow was observed immediately after injection of indocyanine green in both legs along the medial side from the foot to the groin. We therefore determined that lymphatic flow had been restored after the stripping surgery. The functions of the venous and lymphatic systems are thought to be closely related, and that, if the function of one declines, the other will also be affected. Treatment of venous system, including stripping, may help to break the vicious cycle of lymphatic stasis and venous insufficiency

Correlation between Lymphatic Surgery Outcome and Lymphatic Image-Staging or Clinical Severity in Patients with Lymphedema

Lymphoscintigraphy and indocyanine green (ICG) lymphography reveal the severity of extremity lymphedema. Lower extremity lymphedema (LEL) index and NECST classification are related to the clinical severity of lymphedema. We aimed to investigate the correlation between lymphatic surgery, lymphatic imaging, and clinical severity in patients with lymphedema. Thirty-five patients with lower-extremity lymphedema who underwent lymphatic venous anastomosis (LVA) were evaluated. Ten of the thirty-five patients underwent multi-surgery (additional vascularized lymphatic transfer and/or liposuction). We investigated the correlation between the LEL index, NECST classification, lymphoscintigraphy staging, ICG lymphography staging, and rate of improvement (RI: [preoperative LEL index − postoperative LEL index]/[preoperative LEL index] × 100). The LEL index in 35 patients after LVA and all procedures decreased significantly compared to that of preoperative (272.4 vs. 256.2 vs. 243.5, p < 0.05). RI after LVA and all procedures showed positive correlations with the preoperative LEL index; however, there was no correlation with any other lymphatic image or clinical severity. LVA can reduce lymphedema circumference at any stage. Additional surgery improved the circumference. Hence, LVA as the first line of treatment, and vascularized lymphatic transfer and liposuction as additional procedures, should be considered as the standard treatment for lymphedema

Fibroblast Growth Factor Family in the Progression of Prostate Cancer

Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) play an important role in the maintenance of tissue homeostasis and the development and differentiation of prostate tissue through epithelial-stromal interactions. Aberrations of this signaling are linked to the development and progression of prostate cancer (PCa). The FGF family includes two subfamilies, paracrine FGFs and endocrine FGFs. Paracrine FGFs directly bind the extracellular domain of FGFRs and act as a growth factor through the activation of tyrosine kinase signaling. Endocrine FGFs have a low affinity of heparin/heparan sulfate and are easy to circulate in serum. Their biological function is exerted as both a growth factor binding FGFRs with co-receptors and as an endocrine molecule. Many studies have demonstrated the significance of these FGFs and FGFRs in the development and progression of PCa. Herein, we discuss the current knowledge regarding the role of FGFs and FGFRs—including paracrine FGFs, endocrine FGFs, and FGFRs—in the development and progression of PCa, focusing on the representative molecules in each subfamily

Comparison of therapeutic effects of mesenchymal stem cells derived from superficial and deep subcutaneous adipose tissues

Abstract Background Fibrosis is a common histological feature in the process from chronic organ injury to organ failure. Chronic tissue injury causes inflammatory cell infiltration into the injured tissue. The persistence of this inflammatory cell infiltration leads to fibrosis and organ failure. Adipose-derived mesenchymal stem cells (ASCs) have received much attention as a regenerative therapeutic tool to prevent progression from organ injury to failure. Subcutaneous abdominal adipose tissue is divided into superficial and deep layers by a superficial fascia. Adipose tissue easily collected by liposuction is usually obtained from a deep layer, so ASCs derived from a deep layer are generally used for regenerative medicine. However, no research has been conducted to investigate differences in the therapeutic effects of ASCs from the superficial and deep layers (Sup-ASCs and Deep-ASCs, respectively). Therefore, we compared the therapeutic potencies of Sup-ASCs and Deep-ASCs. Methods ASCs were isolated from superficial and deep subcutaneous abdominal adipose tissues collected from patients who underwent breast reconstruction. We first compared cell characteristics, such as morphology, cell proliferation, cell surface markers, adipogenic and osteogenic differentiation, cell senescence markers, and expression of coagulation and anticoagulant factors between Sup-ASCs and Deep-ASCs. Furthermore, we compared their ability to promote polarization of M2 macrophages and to inhibit transforming growth factor (TGF)-β/Smad signaling using THP-1 cells and TGF-β1 stimulated HK-2 cells incubated with conditioned media from Sup-ASCs or Deep-ASCs. In in vivo experiments, after renal ischemia–reperfusion injury (IRI) procedure, Sup-ASCs or Deep-ASCs were injected through the abdominal aorta. At 21 days post-injection, the rats were sacrificed and their left kidneys were collected to evaluate fibrosis. Finally, we performed RNA-sequencing analysis of Sup-ASCs and Deep-ASCs. Results Sup-ASCs had greater proliferation and adipogenic differentiation compared with Deep-ASCs, whereas both ASC types had similar morphology, cell surface markers, senescence markers, and expression of coagulation and anticoagulant factors. Conditioned media from Sup-ASCs and Deep-ASCs equally promoted polarization of M2 macrophages and suppressed TGF-β/Smad signaling. Moreover, administration of Sup-ASCs and Deep-ASCs equally ameliorated renal fibrosis induced by IRI in rats. RNA-sequencing analysis revealed no significant difference in the expression of genes involved in anti-inflammatory and anti-fibrotic effects between Sup-ASCs and Deep-ASCs. Conclusions These results indicate that both Sup-ASCs and Deep-ASCs can be used effectively and safely as an intravascular ASC therapy for organ injury

Combined Environment Simulator for Low-Dose-Rate Radiation and Partial Gravity of Moon and Mars

Deep space exploration by humans has become more realistic, with planned returns to the Moon, travel to Mars, and beyond. Space radiation with a low dose rate would be a constant risk for space travelers. The combined effects of space radiation and partial gravity such as on the Moon and Mars are unknown. The difficulty for such research is that there are no good simulating systems on the ground to investigate these combined effects. To address this knowledge gap, we developed the Simulator of the environments on the Moon and Mars with Neutron irradiation and Gravity change (SwiNG) for in vitro experiments using disposable closed cell culture chambers. The device simulates partial gravity using a centrifuge in a three-dimensional clinostat. Six samples are exposed at once to neutrons at a low dose rate (1 mGy/day) using Californium-252 in the center of the centrifuge. The system is compact including two SwiNG devices in the incubator, one with and one without radiation source, with a cooling function. This simulator is highly convenient for ground-based biological experiments because of limited access to spaceflight experiments. SwiNG can contribute significantly to research on the combined effects of space radiation and partial gravity