Extracellular micro/nanovesicles rescue kidney from ischemia-reperfusion injury

Acute renal failure (ARF) is a clinical challenge that is highly resistant to treatment, and its high rate of mortality is alarming. Ischemia–reperfusion injury (IRI) is the most common cause of ARF. Especially IRI is implicated in kidney transplantation and can determine graft survival. Although the exact pathophysiology of renal IRI is unknown, the role of inflammatory responses has been elucidated. Because mesenchymal stromal cells (MSCs) have strong immunomodulatory properties, they are under extensive investigation as a therapeutic modality for renal IRI. Extracellular vesicles (EVs) play an integral role in cell-to-cell communication. Because the regenerative potential of the MSCs can be recapitulated by their EVs, the therapeutic appeal of MSC-derived EVs has dramatically increased in the past decade. Higher safety profile and ease of preservation without losing function are other advantages of EVs compared with their producing cells. In the current review, the preliminary results and potential of MSC-derived EVs to alleviate kidney IRI are summarized. We might be heading toward a cell-free approach to treat renal IRI.     

Differentiation of mesenchymal stem cells to insulin-producing cells and their impact on type 1 diabetic rats

Cell therapy is thought to be a possible approach for treatment of diabetes. Cells with the ability to differentiate into insulin-producing cells (IPCs) would provide an unlimited source of islet cells for transplantation. In this study, the differentiation capacity of rat bone-marrow-derived mesenchymal stem cells (MSCs) to IPCs and the feasibility of using them for reversal of hyperglycemia were investigated. In vitro studies indicated that treatment of cells with high glucose concentration, nicotinamide and β-mercaptoethanol resulted to differentiated cells, which had characteristics of IPCs including spherical, grape-like morphology, secretion of insulin, and being positive for dithizone. To test the in vivo function of differentiated MSCs, they were injected into the spleen of diabetic rats. It was shown that diabetic rats who received IPCs, significantly reduced the glucose level, in response to intraperitoneal glucose tolerance (IPGT) test. These results indicate that MSCs are capable of in vitro differentiation into functional IPCs, which can reverse hyperglycemia in rat model of diabetes.     

Living arrangement and life satisfaction in older malaysians: the mediating role of social support function

Background

This cross-sectional and correlational survey examines the association between different types of living arrangements and life satisfaction in older Malaysians, while taking into account the mediating effects of social support function.

Methodology and Findings

A total of 1880 of older adults were selected by multistage stratified sampling. Life satisfaction and social support were measured with the Philadelphia Geriatric Center Morale Scale and Medical Outcomes Study Social Support Survey. The result shows living with children as the commonest type of living arrangement for older adults in peninsular Malaysia. Compared to living alone, living only with a spouse especially and then co-residency with children were both associated with better life satisfaction (p<.01) and social support function (p<.01). The mediating effect of social support function enhanced the relation between living arrangements and life satisfaction.

Conclusion

This study revealed that types of living arrangement directly, and indirectly through social support function, play an important role in predicting life satisfaction for older adults in Malaysia. This study makes remarkable contributions to the Convoy model in older Malaysians.     

Development of a Lentivirus Vector-Based Assay for Non-Destructive Monitoring of Cell Fusion Activity

Cell-to-cell fusion can be quantified by endowing acceptor and donor cells with latent reporter genes/proteins and activators of these genes/proteins, respectively. One way to accomplish this goal is by using a bipartite lentivirus vector (LV)-based cell fusion assay system in which the cellular fusion partners are transduced with a flippase-activatable Photinus pyralis luciferase (PpLuc) expression unit (acceptor cells) or with a recombinant gene encoding FLPe^NLS+, a nuclear-targeted and molecularly evolved version of flippase (donor cells). Fusion of both cell populations will lead to the FLPe-dependent generation of a functional PpLuc gene. PpLuc activity is typically measured in cell lysates, precluding consecutive analysis of one cell culture. Therefore, in this study the PpLuc-coding sequence was replaced by that of Gaussia princeps luciferase (GpLuc), a secretory protein allowing repeated analysis of the same cell culture. In myotubes the spread of FLPe^NLS+ may be limited due to its nuclear localization signal (NLS) causing low signal outputs. To test this hypothesis, myoblasts were transduced with LVs encoding either FLPe^NLS+ or an NLS-less version of FLPe (FLPe^NLS−) and subsequently co-cultured in different ratios with myoblasts containing the FLPe-activatable GpLuc expression cassette. At different times after induction of cell-to-cell fusion the GpLuc activity in the culture medium was determined. FLPe^NLS+ and FLPe^NLS− both activated the latent GpLuc gene but when the percentage of FLPe-expressing myoblasts was limiting, FLPe^NLS+ generally yielded slightly higher signals than FLPe^NLS− while at low acceptor-to-donor cell ratios FLPe^NLS− was usually superior. The ability of FLPe^NLS+ to spread through myofibers and to induce reporter gene expression is thus not limited by its NLS. However, at high FLPe concentrations the presence of the NLS negatively affected reporter gene expression. In summary, a rapid and simple chemiluminescence assay for quantifying cell-to-cell fusion progression based on GpLuc has been developed.     

Vegetation Patterns of the Irano-Turanian Steppe along a 3,000 m Altitudinal Gradient in the Alborz Mountains of Northern Iran

The Irano-Turanian floristic region is a major center of endemism in the Holarctic of Eurasia. The Alborz Mountains of northern Iran are a complex and heterogeneous environmental system with rich water resources and great habitat diversity. We have investigated steppe plant communities along an altitudinal gradient ranging from approximately 1,000 m a.s.l. in the semi-desert steppes near Tehran to a height of 3,966 m a.s.l. at the summit of Mount Tochal. Our two-way indicator species analysis of 1,069 vegetation samples resulted in classification of five major vegetation zones: (1) a semi-desert Artemisia steppe near Tehran, (2) a Stipa grassland in the alluvial undulating hills north and west of Tehran, (3) a submontane and steppe zone, (4) a subalpine cushion formation zone and (5) an alpine meadow and subnival zone of Mount Tochal. Annuals and ephemerals in the semi-desert vegetation decline as altitude increases and almost disappear in the alpine zone. Past human impacts of ancient Persian civilization and a traditional pastoral economy have affected the physiognomy of plant communities; thorny dwarf shrubs now dominate the treeless vegetation of the region. Lower competition for space, different phenology and the presence of edaphic and hydrological layers associated with anthropogenic impacts are major reasons for entanglement of different plant communities in the arid- and semi-arid steppe. The phytogeography of the region changes from omni-Irano-Turanian and Saharo-Sindian transgressive species at lower altitudes to a more limited range of western Irano-Turanian species and local endemics at higher altitudes.     

Evaluating the biodegradability of Gelatin/Siloxane/Hydroxyapatite (GS-Hyd) complex in vivo and its ability for adhesion and proliferation of rat bone marrow mesenchymal stem cells

Recent studies have shown that the use of biomaterials and new biodegradable scaffolds for repair or regeneration of damaged tissues is of vital importance. Scaffolds used in tissue engineering should be biodegradable materials with three-dimensional structures which guide the growth and differentiation of the cells. They also tune physical, chemical and biological properties for efficient supplying of the cells to the selected tissues and have proper porosity along with minimal toxic effects. In this manner, the study of these characteristics is a giant stride towards scaffold design. In this study, Gelatin/Siloxane/Hydroxyapatite (GS-Hyd) scaffold was synthesized and its morphology, in vivo biodegradability, cytotoxic effects and ability for cell adhesion were investigated using mesenchymal stem cells (MSCs). The cells were treated with different volumes of the scaffold suspension for evaluation of its cytotoxic effects. The MSCs were also seeded on scaffolds and cultured for 2 weeks to evaluate the ability of the scaffold in promoting of cell adhesion and growth. To check the biodegradability of the scaffold in vivo, scaffolds were placed in the rat body for 21 days in three different positions of thigh muscle, testicle, and liver and they were analyzed by scanning electron microscopy (SEM) and weight changes. According to the results of the viability of this study, no cytotoxic effects of GS-Hyd scaffold was found on the cells and MSCs could adhere on the scaffold with expanding their elongations and forming colonies. The rate of degradation as assessed by weight loss was significant within each group along with significant differences between different tissues at the same time point. SEM micrographs also indicated the obvious morphological changes on the surface of the particles and diameter of the pores through different stages of implantation. The greatest amount of degradation happened to the scaffold particles implanted into the muscle, followed by testicle and liver, respectively.     

Intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells in rheumatoid arthritis patients with knee involvement: Results of a randomized,triple-blind,placebo-controlled phase 1/2 clinical trial

Background

In this study, we intend to assess the safety and tolerability of intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells (MSCs) in patients with rheumatoid arthritis (RA) and to determine the preliminary clinical efficacy data in this population. The trial registration numbers are as follows: Royan Institute Ethics Committee: AC/91/1133; NCT01873625.