BackgroundThe suppressive effect of mesenchymal stromal/stem cells (MSCs) on diverse immune cells is well known, but it is unclear whether MSCs additionally possess immunostimulatory properties. We investigated the impact of human MSCs on the responsiveness of primary natural killer (NK) cells in terms of cytokine secretion.MethodsHuman MSCs were generated from bone marrow and nasal mucosa. NK cells were isolated from peripheral blood of healthy volunteers or of immunocompromised patients after severe injury. NK cells were cultured with MSCs or with MSC-derived conditioned media in the absence or presence of IL-12 and IL-18. C-C chemokine receptor (CCR) 2, C-C chemokine ligand (CCL) 2, and the interferon (IFN)-γ receptor was blocked by specific inhibitors or antibodies. The synthesis of IFN-γ and CCL2 was determined.ResultsIn the absence of exogenous cytokines, trace amounts of NK cell-derived IFN-γ licensed MSCs for enhanced synthesis of CCL2. In turn, MSCs primed NK cells for increased release of IFN-γ in response to IL-12 and IL-18. Priming of NK cells by MSCs occurred in a cell–cell contact-independent manner and was impaired by inhibition of the CCR2, the receptor of CCL2, on NK cells. CD56bright NK cells expressed higher levels of CCR2 and were more sensitive to CCL2-mediated priming by MSCs and by recombinant CCR2 ligands than cytotoxic CD56dim NK cells. NK cells from severely injured patients were impaired in cytokine-induced IFN-γ synthesis. Co-culture with MSCs or with conditioned media from MSCs and MSC/NK cell co-cultures from healthy donors improved the IFN-γ production of the patients’ NK cells in a CCR2-dependent manner.ConclusionsA positive feedback loop driven by NK cell-derived IFN-γ and MSC-derived CCL2 increases the inflammatory response of cytokine-stimulated NK cells not only from healthy donors but also from immunocompromised patients. Therapeutic application of MSCs or their soluble factors might thus improve the NK function after severe injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0353-9) contains supplementary material, which is available to authorized users.

ObjectiveThe aim of our study was to investigate the relationship among age, sex, body mass index (BMI), serum lipid profiles, blood glucose (BG), and bone mineral density (BMD), making an assessment of the risk of osteoporosis.Materials and methodsA total of 1,035 male and 3,953 female healthy volunteers (aged 41–95 years) were recruited by an open invitation. The basic information, including age, sex, height, weight, waistline, hipline, menstrual cycle, and medical history, were collected by a questionnaire survey and physical examination. Serum lipid profiles, BG, postprandial blood glucose, and glycosylated hemoglobin were obtained after 12 hours fasting. BMD in lumbar spine was measured by dual-energy X-ray absorptiometry scanning.ResultsThe age-adjusted BMD in females was significantly lower than in males. With aging, greater differences of BMD distribution exist in elderly females than in males (P<0.001), and the fastigium of bone mass loss was in the age range from 51 to 55 in females and from 61 to 65 years in males. After adjustment for sex, there were significant differences in BMD among BMI-stratified groups in both males and females. The subjects with a BMI of <18.5 had a higher incidence of osteoporosis than BMI ≥18.5 in both sexes. BMD in type 2 diabetes mellitus with a BG of >7.0 mmol/L was lower than in people with BG of ≤7.0 mmol/L (P<0.001). People with serum high-density lipoprotein cholesterol levels of ≥1.56 mmol/L had a greater prevalence of osteoporosis compared with high-density lipoprotein cholesterol ≤1.55 mmol/L. Logistic regression with odds ratios showed that no association was found among total cholesterol, triglyceride, low-density lipoprotein cholesterol, glycosylated hemoglobin, postprandial blood glucose and BMD.ConclusionThe present study further confirmed that factors such as age, sex, weight, BMI, high-density lipoprotein cholesterol, and diabetes are significant predictors of osteoporosis in the Chinese people.

Introduction The therapies of using exosomes derived from mesenchymal stem cells (MSC-Exo) for wound healing and scar attenuation and micro RNAs (miRNAs) for regulation of genes by translational inhibition and mRNA destabilization obtained great achievements. Silent information regulator 1 (SIRT1) is the silent information, which has an intricate role in many biological processes. However, the effects of SIRT1 and miR-138-5p loaded in MSC-Exo on pathological scars remain unclear. Methods MSC-Exo was isolated and identified by ultracentrifugation, transmission electron microscopy, nanoparticle size measuring instrument and Western blot assays. The relationship between SIRT1 and miR-138-5p was verified by a double-luciferase reporter assay. Cell Counting Kit-8, Τranswell, scratch, and Western blot assays were used to evaluate the proliferation and migration of human skin fibroblasts (HSFs), and the protein expression of SIRT1, NF-κB, α-SMA and TGF-β1 in HSFs, respectively. Flow cytometry was used to assess the apoptosis and cell cycle of HSFs affected by SIRT1. Results Our study demonstrated that miR-138-5p loaded in MSC-Exo could attenuate proliferation, migration and protein expression of HSFs-derived NF-κB, α-SMA, and TGF-β1 by targeting to SIRT1 gene, which confirmed the potential effects of MSC-Exo in alleviating pathological scars by performing as a miRNA’s delivery vehicle. Conclusion Exosomes derived from MSCs acting as a delivery vehicle to deliver miR-138-5p can downregulate SIRT1 to inhibit the growth and protein expression of HSFs and attenuate pathological scars.

ObjectivePeople with type 2 diabetes are at an increased risk of hypertension, arteriosclerosis, heart disease, and stroke. Glucose intolerance (insulin resistance) is the main feature of type 2 diabetes. Obesity leads to insulin resistance, dyslipidemia, etc. The aim of this study was to assess the biochemical parameters and measures of obesity in type 2 diabetes mellitus (T2DM).MethodsA total of 2,273 males and 6,547 females previously healthy volunteers (aged 41–95 years old) were recruited by open invitation. The basic information, including age, sex, height, weight, body mass index (BMI), waistline, hipline, menstrual cycle, and medical history, was collected by questionnaire survey and physical examination. Serum lipid profile, liver transaminase, blood glucose, postprandial blood glucose, and hemoglobin A1c were obtained after 12 hours of fasting.ResultsAccording to our results, diabetic patients presented serum lipid abnormality. Elevated triglyceride (TG) levels (≥1.7 mmol/L) were noted in 19.69% of males and 20.40% of females, and reduced high-density lipoprotein cholesterol (HDL-C) levels (≤1.15 mmol/L) were noted in 21.96% of males and 15.74% of females. The combination of elevated TG and reduced HDL-C was the most prevalent of the combined lipid abnormalities. In contrast, no differences were observed in the levels of low-density lipoprotein cholesterol and total cholesterol. Moreover, there were statistically significant differences in the levels of BMI and waistline between T2DM and non-T2DM participants. After adjustment for BMI, logistic regression analysis revealed that the subjects with BMI ≤20 kg/m2 and >30 kg/m2 had a significantly elevated hazard ratio of T2DM compared with participants having a BMI range of 20–30 kg/m2 in both males and females. However, there was a significant difference between T2DM patients and non-T2DM patients in waistline (χ2=8.57, P<0.001) than in BMI parameter (χ2=6.29, P<0.001).ConclusionThe present study shows for the first time that low levels of HDL-C, high levels of TG, and abnormal levels in BMI and waistline increase the risk of type 2 T2DM in Chinese people.

Pathological scars are the result of over-repair and excessive tissue proliferation of the skin injury. It may cause serious dysfunction, resulting in psychological and physiological burdens on the patients. Currently, mesenchymal stem cells-derived exosomes (MSC-Exo) displayed a promising therapeutic effect on wound repair and scar attenuation. But the regulatory mechanisms are opinions vary. In view of inflammation has long been proven as the initial factor of wound healing and scarring, and the unique immunomodulation mechanism of MSC-Exo, the utilization of MSC-Exo may be promising therapeutic for pathological scars. However, different immune cells function differently during wound repair and scar formation. The immunoregulatory mechanism of MSC-Exo would differ among different immune cells and molecules. Herein, this review gave a comprehensive summary of MSC-Exo immunomodulating different immune cells in wound healing and scar formation to provide basic theoretical references and therapeutic exploration of inflammatory wound healing and pathological scars.