Severely damaged kidneys possess multipotent renoprotective stem cells

Background aimsTissue-specific stem cells are a promising target for kidney regeneration, because it has been shown that they play a primary role in kidney repair. Several methods have been developed for the isolation of stem/progenitor cells from healthy kidneys but the existence of these cells in chronically damaged kidneys has not been noticed so far.MethodsA mouse model of chronic kidney failure was developed by ligation of the left ureter for 5 months, and then isolation of stem cells from this tissue as well as normal kidneys was attempted.ResultsWe found that multipotent stem cells could be isolated from both types of tissue. In addition, the cells isolated from damaged kidneys showed potential for homing to the site of injury and a renoprotective effect in an animal model of cisplatin-induced nephropathy.ConclusionsThese results show that multipotent renoprotective stem cells exist in severely damaged kidneys, which could be a target for designing new therapies.     

Stem cell-conditioned medium does not protect against kidney failure

Paracrine secretion of mediators may be the main route by which stem cells protect against injuries. Stem cells commonly secrete different bioactive molecules. In this study, we examined the hypothesis that administration of conditioned media of stem cells can diminish the burden of kidney injury. A mouse model of cisplatin-induced nephropathy was developed to test the putative renoprotective effects of conditioned media of human umbilical cord blood USSCs (unrestricted somatic stem cells) as well as mouse bone marrow MSCs (mesenchymal stem cells). None of these two types of conditioned medium could protect against kidney failure in terms of serum urea and creatinine, histopathologic examinations and physical activity score. Neither MSC- nor USSC-conditioned media were effective in protecting against kidney injury in our study. Possible explanations for our observations are offered, and related literature is reviewed.     

Uncoupling between Inflammatory and Fibrotic Responses to Silica: Evidence from MyD88 Knockout Mice

The exact implication of innate immunity in granuloma formation and irreversible lung fibrosis remains to be determined. In this study, we examined the lung inflammatory and fibrotic responses to silica in MyD88-knockout (KO) mice. In comparison to wild-type (WT) mice, we found that MyD88-KO animals developed attenuated lung inflammation, neutrophil accumulation and IL-1β release in response to silica. Granuloma formation was also less pronounced in MyD88-KO mice after silica. This limited inflammatory response was not accompanied by a concomitant attenuation of lung collagen accumulation after silica. Histological analyses revealed that while pulmonary fibrosis was localized in granulomas in WT animals, it was diffusely distributed throughout the parenchyma in MyD88-KO mice. Robust collagen accumulation was also observed in mice KO for several other components of innate immunity (IL-1R, IL-1, ASC, NALP3, IL-18R, IL-33R, TRIF, and TLR2-3-4,). We additionally show that pulmonary fibrosis in MyD88-KO mice was associated with the accumulation of pro-fibrotic regulatory T lymphocytes (T regs) and pro-fibrotic cytokine expression (TGF-β, IL-10 and PDGF-B), not with T helper (Th) 17 cell influx. Our findings indicate that the activation of MyD88-related innate immunity is central in the establishment of particle-induced lung inflammatory and granuloma responses. The development of lung fibrosis appears uncoupled from inflammation and may be orchestrated by a T reg-associated pathway.     

Microstructural densification and alignment by aspiration-ejection influence cancer cell interactions with three-dimensional collagen networks

Extracellular matrix microstructure and mechanics are crucial to breast cancer progression and invasion into surrounding tissues. The peritumor collagen network is often dense and aligned, features which in vitro models lack. Aspiration of collagen hydrogels led to densification and alignment of microstructure surrounding embedded cancer cells. Two metastasis-derived breast cancer cell lines, MDA-MB-231 and MCF-7, were cultured in initially 4 mg/ml collagen gels for 3 days after aspiration, as well as in unaspirated control hydrogels. Videomicroscopy during aspiration, and at 0, 1, and 3 days after aspiration, epifluorescence microscopy of phalloidin-stained F-actin cytoskeleton, histological sections, and soluble metabolic byproducts from constructs were collected to characterize effects on the embedded cell morphology, the collagen network microstructure, and proliferation. Breast cancer cells remained viable after aspiration-ejection, proliferating slightly less than in unaspirated gels. Furthermore, MDA-MB-231 cells appear to partially relax the collagen network and lose alignment 3 days after aspiration. Aspiration-ejection generated aligned, compact collagen network microstructure with immediate cell co-orientation and higher cell number density apparently through purely physical means, though cell-collagen contact guidance and network remodeling influence cell organization and collagen network microstructure during subsequent culture. This study establishes a platform to determine the effects of collagen density and alignment on cancer cell behavior, with translational potential for anticancer drug screening in a biomimetic three-dimensional matrix microenvironment, or implantation in preclinical models.     

Monophasic synovial sarcoma presenting as a primary ileal mass: a case report and review of the literature

Introduction

Iliocaval fistulas can complicate an iliac artery aneurysm. The clinical presentation is classically a triad of hypotension, a pulsatile mass and heart failure. In this instance, following presentation with multiorgan failure, management included the immediate use of an endovascular stent graft on discovery of the fistula.

Case presentation

A 62-year-old Caucasian man presented to our tertiary hospital for management of iatrogenic trauma due to the insertion of a central venous line into his right common carotid artery, causing transient ischemic attack. Our patient presented to a peripheral hospital with fever, nausea, vomiting, acute renal failure, acute hepatic dysfunction and congestive heart failure. A provisional diagnosis of sepsis of unknown origin was made. There was a 6.5 cm×6.5 cm right iliac artery aneurysm present on a non-contrast computed tomography scan. An unexpected intra-operative diagnosis of an iliocaval fistula was made following the successful angiographic removal of the central line to his right common carotid artery. Closure of the iliocaval fistula and repair of the iliac aneurysm using a three-piece endovascular aortic stent graft was then undertaken as part of the same procedure. This was an unexpected presentation of an iliocaval fistula.

Conclusion

Our case demonstrates that endovascular repair of a large iliac artery aneurysm associated with a caval fistula is safe and effective and can be performed at the time of the diagnostic angiography. The presentation of an iliocaval fistula in this case was unusual which made the diagnosis difficult and unexpected at the time of surgery. The benefit of immediate repair, despite hemodynamic instability during anesthesia, is clear. Our patient had two coronary angiograms through his right femoral artery decades ago. Unusual iatrogenic causes of iliocaval fistulas secondary to previous coronary angiograms with wire and/or catheter manipulation should be considered in patients such as ours.     

The aggregate nature of human mesenchymal stromal cells in native bone marrow

Background aims. The clinical application of mesenchymal stromal cells (MSC) faces several obstacles, such as the lack of a standard method for direct isolation as well as a low frequency and concern about the safety of their in vitro expansion. Although the density-gradient separation technique is used as the first step in most methods of MSC isolation to enrich mononuclear cells, the efficiency of this method has not so far been examined. This study was designed to address this issue. Methods. Human bone marrow (BM) samples were laid over Ficoll-Paque, and after centrifugation the upper and lower fractions were cultured separately. Surface markers, differentiation potential and the number of emerged cells were determined. Results. The isolated cells from both the upper and lower fractions were characteristic of MSC. Although it is commonly believed that MSC are single suspending mononuclear cells and so are enriched in the upper fraction of Ficoll-Paque after density-gradient separation, our data showed that considerable numbers of these cells were accumulated in the lower fraction. Further data indicated that MSC were actually present as cell aggregates in BM and they could be enriched effectively by a simple filtration method. Conclusions. The aggregate nature of MSC in BM is in agreement with the concept that they are one of the main elements of the hematopoietic stem cell niche. In addition, the simple filtration method proposed here to isolate cell aggregates may provide opportunities for instant stem cell therapy without the need for extensive in vitro expansion.     

Biotransformation of glabratephrin, a rare type of isoprenylated flavonoids, by Aspergillus niger

Microbial transformation of glabratephrin, the major isolated compound from Tephrosia purpurea, afforded pseudosemiglabrin. The formation of the transformed compound seems to be performed via ring opening-closure of a five-membered ring causing transformation from a spiro into a fused system. The structure of the transformed compound was determined by comprehensive NMR studies, including DEPT, COSY, HMQC, NOE and MS.     

Once Weekly Low-dose Iron Supplementation Effectively Improved Iron Status in Adolescent Girls

Iron supplementation has been suggested as a strategy for prevention and treatment of iron deficiency (ID) and iron deficiency anemia (IDA) in many countries, but non-compliance of daily regimens and common dosage remain as major challenges. The aim of this study was to investigate the effects of low dose once weekly iron supplementation in adolescent girls. The study was designed as a community-based, randomized, supplementation trial. The initial sample consisted of 200 female high school students, aged 14–16 years old, of whom 193 students concluded the study. They were randomly selected and assigned into either iron-supplemented group (ISG) or iron-unsupplemented group (IUG). The ISG received 150 mg ferrous sulfate once weekly for 16 weeks, whereas the IUG received nothing. Weight, height, and hematological parameters were measured and compared between the two groups before and after the intervention. There was no significant difference between the initial measures of the two groups before the intervention. After 16 weeks of intervention, mean of hemoglobin and serum ferritin improved significantly in ISG compared to IUG. At the beginning of the study, percent of anemia, IDA, and ID in ISG were 12.5%, 8.3%, and 30.2%, whereas these figures for IUG in this period of study were 14.4, 10.3, and 38.2, respectively, which were not significantly different between the two groups. However, percentages of the above items at the end of study in ISG were 2.1%, 0%, and 21.9%, respectively. In contrast to IUG, all cases of IDA were abolished in the ISG. Our study showed that once weekly supplementation of 150 mg ferrous sulfate for 16 weeks significantly improved iron status in female adolescents and effectively treated IDA. There is no need for higher dosage of iron for supplementation that may cause adverse effects and bear higher costs.