Mesenchymal stromal cells and their small extracellular vesicles in allergic diseases: From immunomodulation to therapy.

Mesenchymal stromal cells (MSCs) have long been considered a potential tool for treatment of allergic inflammatory diseases, owing to their immunomodulatory characteristics. In recent decades, the medical utility of MSCs has been evaluated both in vitro and in vivo, providing a foundation for therapeutic applications. However, the existing limitations of MSC therapy indicate the necessity for novel therapies. Notably, small extracellular vesicles (sEV) derived from MSCs have emerged rapidly as candidates instead of their parental cells. The acquisition of abundant and scalable MSC-sEV is an obstacle for clinical applications. The potential application of MSC-sEV in allergic diseases has attracted increasing attention from researchers. By carrying biological microRNAs or active proteins, MSC-sEV can modulate the function of various innate and adaptive immune cells. In this review, we summarise the recent advances in the immunomodulatory properties of MSCs in allergic diseases, the cellular sources of MSC-sEV, and the methods for obtaining high-quality human MSC-sEV. In addition, we discuss the immunoregulatory capacity of MSCs and MSC-sEV for the treatment of asthma, atopic dermatitis, and allergic rhinitis, with a special emphasis on their immunoregulatory effects and the underlying mechanisms of immune cell modulation.

Intranasal delivery of small extracellular vesicles reduces the progress of amyotrophic lateral sclerosis and the overactivation of complement-coagulation cascade and NF-ĸB signaling in SOD1G93A mice.

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive motoneuron degeneration, and effective clinical treatments are lacking. In this study, we evaluated whether intranasal delivery of mesenchymal stem cell-derived small extracellular vesicles (sEVs) is a strategy for ALS therapy using SOD1G93A mice. In vivo tracing showed that intranasally-delivered sEVs entered the central nervous system and were extensively taken up by spinal neurons and some microglia. SOD1G93A mice that intranasally received sEV administration showed significant improvements in motor performances and survival time. After sEV administration, pathological changes, including spinal motoneuron death and synaptic denervation, axon demyelination, neuromuscular junction degeneration and electrophysiological defects, and mitochondrial vacuolization were remarkably alleviated. sEV administration attenuated the elevation of proinflammatory cytokines and glial responses. Proteomics and transcriptomics analysis revealed upregulation of the complement and coagulation cascade and NF-ĸB signaling pathway in SOD1G93A mouse spinal cords, which was significantly inhibited by sEV administration. The changes were further confirmed by detecting C1q and NF-ĸB expression using Western blots. In conclusion, intranasal administration of sEVs effectively delays the progression of ALS by inhibiting neuroinflammation and overactivation of the complement and coagulation cascades and NF-ĸB signaling pathway and is a potential option for ALS therapy.

Mesenchymal stromal cells-derived small extracellular vesicles modulate DC function to suppress Th2 responses via IL-10 in patients with allergic rhinitis.

Mesenchymal stromal cells (MSCs) are well known for their immunoregulatory roles on allergic inflammation particularly by acting on T cells, B cells, and dendritic cells (DCs). MSC-derived small extracellular vesicles (MSC-sEV) are increasingly considered as one of the main factors for the effects of MSCs on immune responses. However, the effects of MSC-sEV on DCs in allergic diseases remain unclear. MSC-sEV were prepared from the induced pluripotent stem cells (iPSC)-MSCs by anion-exchange chromatography, and were characterized with the size, morphology, and specific markers. Human monocyte-derived DCs were generated and cultured in the presence of MSC-sEV to differentiate the so-called sEV-immature DCs (sEV-iDCs) and sEV-mature DCs (sEV-mDCs), respectively. The phenotypes and the phagocytic ability of sEV-iDCs were analyzed by flow cytometry. sEV-mDCs were co-cultured with isolated CD4+ T cells or peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis. The levels of Th1 and Th2 cytokines produced by T cells were examined by ELISA and intracellular flow staining. And the following mechanisms were further investigated. We demonstrated that MSC-sEV inhibited the differentiation of human monocytes to iDCs with downregulation of the expression of CD40, CD80, CD86, and HLA-DR, but had no effects on mDCs with these markers. However, MSC-sEV treatment enhanced the phagocytic ability of mDCs. More importantly, using anti-IL-10 monoclonal antibody or IL-10Rα blocking antibody, we identified that sEV-mDCs suppressed the Th2 immune response by reducing the production of IL-4, IL-9, and IL-13 via IL-10. Furthermore, sEV-mDCs increased the level of Treg cells. Our study identified that mDCs treated with MSC-sEV inhibited the Th2 responses, providing novel evidence of the potential cell-free therapy acting on DCs in allergic airway diseases.

MicroRNA-19b-3p dysfunction of mesenchymal stem cell-derived exosomes from patients with abdominal aortic aneurysm impairs therapeutic efficacy.

Senescence of vascular smooth muscle cells (VSMCs) contributes to the formation of abdominal aortic aneurysm (AAA). Although mesenchymal stem cell exosomes (MSC-EXO) have been confirmed to restrict the development of AAA, their biological activity depends largely on the physiological state of the MSCs. This study aimed to compare the effects of adipose-derived MSC-EXO from healthy donors (HMEXO) and AAA patients (AMEXO) on senescence of VSMCs in AAA and explore the underlying mechanisms. An ApoE-/- mouse model of AAA was used to investigate the therapeutic effects of HMEXO, AMEXO or miR-19b-3p-AMEXO on AAA development. This in vitro model of AAA was established by treating VSMCs with Ang II (Angiotensin II). The senescence of VSMCs was determined by senescence-associated ß-galactosidase (SA-ß-gal) staining. The morphology of mitochondria in VSMCs was examined by MitoTracker staining. HMEXO exhibited superior capacity compared with AMEXO to inhibit VSMC senescence and attenuate AAA formation in Ang II-treated ApoE-/- mice. In vitro, both AMEXO and HMEXO inhibited Ang II-induced VSMC senescence via downregulation of mitochondrial fission. Notably, compared with HMEXO, the ability of AMEXO to inhibit VSMC senescence was significantly decreased. miRNA sequencing and the expression of miR-19b-3p was significantly decreased in AMEXO compared with HMEXO. Luciferase assay suggested that MST4 (Mammalian sterile-20-like kinase 4) is a potential target of miR-19b-3p. Mechanistically, miR-19b-3p in HMEXO ameliorated VSMC senescence by inhibiting mitochondrial fission via regulation of the MST4/ERK/Drp1 signaling pathway. Overexpression of miR-19b-3p in AMEXO improved their beneficial effect on AAA formation. Our study reveals that MSC-exosomal miR-19b-3p exerts protective effects against Ang II-induced AAA and VSMC senescence via regulation of the MST4/ERK/Drp1 pathway. The pathological state of AAA patients alters the miRNA components of AMEXO and impairs their therapeutic benefits.

Effect of phosphorus fertilizer on phytoextraction using Ricinus communis L. in Cu and Cd co-contaminated soil.

Mining activities have led to Cu and Cd contaminated of surrounding agricultural soil. To decrease the Cu and Cd accumulation in crops, the Ricinus communis L. (castor) has been used for phytoremediation. A pot experiment was served to investigate the effect of phosphate fertilizer (Ca(H2PO4)2) on the growth and Cu/Cd uptake of castor in contaminated soil. The results showed that the application of P fertilizer improved the leaf cell morphology, decreased the malonaldehyde (MDA) content of castor leaves, and increased the plant biomass (28.2-34.2%). Besides, phosphate fertilizer still facilitated accumulation Cu and Cd by castor. The addition of phosphate fertilizer increased the contents of Cu in the root of castor, improved the bioconcentration factor (BCF) of Cu, and observably enhanced the accumulation of Cu (up to 201 µg/plant) in castor. Applying phosphorus increased the percentage of residual Cd, diminished the percentage of acid extractable Cd in soil, and the accumulation of Cd in castor was not significantly increased. These results suggest that phosphorus alleviated the stress of heavy metals on castor leaves and enhanced the accumulation of Cu and Cd in castor by promoting the growth of castor.

Applying phosphate fertilizer effectively alleviated the stress of heavy metals on castor and significantly increased the biomass of castor.The reason of applying phosphorus enhanced the castor uptake Cu and Cd was that phosphorus promoted the growth of castor.Applying phosphorus markedly increased the percentage of residual Cd but diminished the percentage of acid extractable Cd in soil.

Mesenchymal stem cells regulate type 2 innate lymphoid cells via regulatory T cells through ICOS-ICOSL interaction.

Group 2 innate lymphoid cells (ILC2s) are recognized as key controllers and effectors of type 2 inflammation. Mesenchymal stem cells (MSCs) have been shown to alleviate type 2 inflammation by modulating T lymphocyte subsets and decreasing TH 2 cytokine levels. However, the effects of MSCs on ILC2s have not been investigated. In this study, we investigated the potential immunomodulatory effects of MSCs on ILC2s in peripheral blood mononuclear cells (PBMCs) from allergic rhinitis patients and healthy subjects. We further investigated the mechanisms involved in the MSC modulation using isolated lineage negative (Lin- ) cells. PBMCs and Lin- cells were cocultured with induced pluripotent stem cell-derived MSCs (iPSC-MSCs) under the stimulation of epithelial cytokines IL-25 and IL-33. And the ILC2 levels and functions were examined and the possible mechanisms were investigated based on regulatory T (Treg) cells and ICOS-ICOSL pathway. iPSC-MSCs successfully decreased the high levels of IL-13, IL-9, and IL-5 in PBMCs in response to IL-25, IL-33, and the high percentages of IL-13+ ILC2s and IL-9+ ILC2s in response to epithelial cytokines were significantly reversed after the treatment of iPSC-MSCs. However, iPSC-MSCs were found directly to enhance ILC2 levels and functions via ICOS-ICOSL interaction in Lin- cells and pure ILC2s. iPSC-MSCs exerted their inhibitory effects on ILC2s via activating Treg cells through ICOS-ICOSL interaction. The MSC-induced Treg cells then suppressed ILC2s by secreting IL-10 in the coculture system. This study revealed that human MSCs suppressed ILC2s via Treg cells through ICOS-ICOSL interaction, which provides further insight to regulate ILC2s in inflammatory disorders.

Influence mechanisms of iron, aluminum and manganese oxides on the mineralization of organic matter in paddy soil.

The mineralization of soil organic matter (SOM) is closely related to the emission of greenhouse gas into atmosphere and the stability of organic carbon in soil. The influence of minerals on SOM mineralization in the specific soil received very few attentions. The influence characteristics and potential mechanisms of oxides on the mineralization of SOM in the paddy soil were observed in this study by incubating soil with the addition (dosage: 10 g kg-1) of prepared gibbsite, goethite, ferrihydrite or birnessite for 60 days. A sequence control treatment (753 mg CO2-C kg-1) > goethite treatment (656 mg CO2-C kg-1) ≈ gibbsite treatment (649 mg CO2-C kg-1) > birnessite treatment (529 mg CO2-C kg-1) > ferrihydrite treatment (441 mg CO2-C kg -1) was found in the cumulative amount of released CO2 in 60 days of incubation. Oxides especially ferrihydrite significantly decreased the content of dissolved organic matter (DOM) but tended to increase the content of microbial biomass carbon (MBC). The molecular structure of DOM in the paddy soil was simplified by gibbsite, ferrihydrite and birnessite after the incubation. Oxides especially birnessite and ferrihydrite reduced soil pH and the content of soil available N but increased soil redox potential (Eh). All examined oxides especially Fe oxides enhanced soil bacterial abundance but only birnessite significantly affected bacterial composition at phyla level. The stimulation on the immobilization and/or microbial assimilation of labile organic carbon, the modulation on soil basic properties (available N, pH, Eh), and the decrease of the relative abundance of some decomposing bacteria phyla such as Actinobacteria were the potential pathways of oxides in decreasing SOM mineralization.

Hemin enhances the cardioprotective effects of mesenchymal stem cell-derived exosomes against infarction via amelioration of cardiomyocyte senescence.

BACKGROUND: Application of mesenchymal stem cell-derived exosomes (MSC-EXO) has emerged as a novel therapeutic strategy for myocardial infarction (MI). Our previous study showed that pretreatment with hemin, a potent heme oxygenase-1 (HO-1) inducer, enhanced the cardioprotective effects of MSCs in a mouse model of MI. This study aimed to investigate the therapeutic effects of EXO derived from hemin-pretreated MSCs (Hemin-MSC-EXO) in MI and explore the potential mechanisms. METHODS: MSC-EXO and Hemin-MSC-EXO were collected and characterized. MSC-EXO and Hemin-MSC-EXO were intramuscularly injected into the peri-infarct region in a mouse model of MI. Heart function of mice was assessed by echocardiography. The mitochondrial morphology of neonatal mice cardiomyocytes (NMCMs) under serum deprivation and hypoxic (SD/H) conditions was examined by Mitotracker staining. The cellular senescence of NMCMs was determined by senescence-associated-ß-galactosidase assay. A loss-of-function approach was adopted to determine the role of Hemin-MSC-exosomal-miR-183-5p in the regulation of cardiomyocyte senescence RESULTS: EXO were successfully isolated from the supernatant of MSCs and Hemin-pretreated MSCs. Compared with MSC-EXO, injection of Hemin-MSC-EXO significantly improved cardiac function and reduced fibrosis. Both MSC-EXO and Hemin-MSC-EXO ameliorated cardiomyocyte senescence and mitochondrial fission in vitro and in vivo, and the latter exhibited better protective effects. MicroRNA sequencing revealed a higher level of miR-183-5p in Hemin-MSC-EXO than in MSC-EXO. MiR-183-5p knockdown partially abrogated the protective effects of Hemin-MSC-EXO in attenuating mitochondrial fission and cellular senescence of cardiomyocytes induced by SD/H. High mobility group box-1 (HMGB1) abundance was lower in Hemin-MSC-EXO-treated than MSC-EXO-treated mouse hearts, and HMGB1 was identified as one of the potential target genes of miR-183-5p. Mechanistically, Hemin-MSC-EXO inhibited SD/H-induced cardiomyocyte senescence partially by delivering miR-183-5p into recipient cardiomyocytes via regulation of the HMGB1/ERK pathway. Furthermore, knockdown of miR-183-5p reduced the Hemin-MSC-EXO-mediated cardioprotective effects in a mouse model of MI. CONCLUSION: Our results reveal that Hemin-MSC-EXO are superior to MSC-EXO in treating MI. Exosomal miR-183-5p mediates, at least partially, the cardioprotective effects of Hemin-MSC-EXO by inhibiting cardiomyocyte senescence via regulation of the HMGB1/ERK pathway. This study highlights that MSC-EXO have high translational value in repairing cardiac dysfunction following infarction.

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy.

Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell-cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies.

Effects of myeloid and plasmacytoid dendritic cells on ILC2s in patients with allergic rhinitis.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) were reported to serve a critical role in allergic diseases. Myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) play significant roles in allergic immune response. However, effects of DCs on ILC2s in allergic diseases, especially for patients with allergic rhinitis (AR), remain unclear. OBJECTIVE: We sought to address the roles of mDCs and pDCs in regulating ILC2 function in AR. METHODS: mDCs and pDCs were cocultured with human PBMCs isolated from patients with AR or ILC2s to measure soluble or intracellular TH2 cytokines, transcription factors, signaling pathways in ILC2s, and the following mechanisms were further investigated. The levels of peripheral IL-33+mDCs, pDCs, and ILC2s were studied in patients under an inhaled allergen challenge. RESULTS: We confirmed the presence of ILC2s, mDCs, and pDCs in the nasal mucosa of patients with AR. Both allogenic and autologous mDCs were found to activate ILC2s from patients with AR to produce TH2 cytokines, and increase the levels of GATA-3 and signal transducer and activator of transcription signaling pathways, in which IL-33-producing mDCs exerted the major role by binding on ST2 on ILC2s. We further identified high levels of IL-33+mDCs and ILC2s in patients with AR under antigen challenge. Activated pDCs inhibited the cytokine production of ILC2s isolated from patients with AR by secretion of IL-6. CONCLUSIONS: mDCs promote ILC2 function by the IL-33/ST2 pathway, and activation of pDCs suppresses ILC2 function through IL-6 in patients with AR. Our findings provide new understanding of the interplay between DCs and ILC2s in allergic diseases.

Human gingiva-derived mesenchymal stem cells are therapeutic in lupus nephritis through targeting of CD39-CD73 signaling pathway.

Cell specific and cytokine targeted therapeutics have underperformed in systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) have emerged as a novel therapy to address the dysregulation in autoimmune diseases but also have limitations. Human gingiva derived MSCs (GMSCs) are superior in regulating immune responses. Here, we demonstrate that the adoptive transfer of GMSCs homes to and maintains in the kidney and has a robust therapeutic effect in a spontaneous lupus nephritis model. Specifically, GMSCs limits the development of autoantibodies as well as proteinuria, decreases the frequency of plasma cells and lupus nephritis histopathological scores by directly suppressing B cells activation, proliferation and differentiation. The blockage of CD39-CD73 pathway dramatically abrogates the suppressive capacities of GMSCs in vitro and in vivo and highlights the significance of this signaling pathway in SLE. Collectively, manipulation of GMSCs provides a promising strategy for the treatment of patients with SLE and other autoimmune diseases.

Ras homolog family member A/Rho-associated protein kinase 1 signaling modulates lineage commitment of mesenchymal stem cells in asthmatic patients through lymphoid enhancer-binding factor 1.

BACKGROUND: Numbers of mesenchymal stem cells (MSCs) are increased in the airways after allergen challenge. Ras homolog family member A (RhoA)/Rho-associated protein kinase 1 (ROCK) signaling is critical in determining the lineage fate of MSCs in tissue repair/remodeling. OBJECTIVES: We sought to investigate the role of RhoA/ROCK signaling in lineage commitment of MSCs during allergen-induced airway remodeling and delineate the underlying mechanisms. METHODS: Active RhoA expression in lung tissues of asthmatic patients and its role in cockroach allergen-induced airway inflammation and remodeling were investigated. RhoA/ROCK signaling-mediated MSC lineage commitment was assessed in an asthma mouse model by using MSC lineage tracing mice (nestin-Cre; ROSA26-EYFP). The role of RhoA/ROCK in MSC lineage commitment was also examined by using MSCs expressing constitutively active RhoA (RhoA-L63) or dominant negative RhoA (RhoA-N19). Downstream RhoA-regulated genes were identified by using the Stem Cell Signaling Array. RESULTS: Lung tissues from asthmatic mice showed increased expression of active RhoA when compared with those from control mice. Inhibition of RhoA/ROCK signaling with fasudil, a RhoA/ROCK inhibitor, reversed established cockroach allergen-induced airway inflammation and remodeling, as assessed based on greater collagen deposition/fibrosis. Furthermore, fasudil inhibited MSC differentiation into fibroblasts/myofibroblasts but promoted MSC differentiation into epithelial cells in asthmatic nestin-Cre; ROSA26-EYFP mice. Consistently, expression of RhoA-L63 facilitated differentiation of MSCs into fibroblasts/myofibroblasts, whereas expression of RhoA-19 switched the differentiation toward epithelial cells. The gene array identified the Wnt signaling effector lymphoid enhancer-binding factor 1 (Lef1) as the most upregulated gene in RhoA-L63-transfected MSCs. Knockdown of Lef1 induced MSC differentiation away from fibroblasts/myofibroblasts but toward epithelial cells. CONCLUSIONS: These findings uncover a previously unrecognized role of RhoA/ROCK signaling in MSC-involved airway repair/remodeling in the setting of asthma.

Effect of rice straw, biochar and calcite on maize plant and Ni bio-availability in acidic Ni contaminated soil.

Metals that contaminate soil is one of the major problems seriously affecting sustainable agriculture worldwide. Nickel (Ni) toxicity to agricultural crops is a global problem. Mobility of heavy metals present in contaminated soil can be reduced by the amendment of soil passivators, which will ultimately reduce the risk of them entering the food chain. A greenhouse pot experiment was conducted to investigate the effects of rice straw (RS), biochar derived from rice straw (BI) and calcium carbonate (calcite) on Ni mobility and its up take by maize (Zea maize L.) plant. Maize crop was grown in Ni spiked (100 mg kg-1) soil with three application rates of passivators (equivalent to 0, 1and 2% of each RS, BI and calcite) applied separately to the soil. Results revealed that the post-harvest soil properties (pH, DOC and MBC), plant phenology (plant height, root length, total dry weight) and physiological characteristics were significantly enhanced with passivator application. Additionally, incorporating passivator into the soil reduced Ni mobility (DTPA) by 68%, 88.9% and 79.3%, and leachability (TCLP) by 72.4%, 76.7% and 66.7% for RS, BI and calcite, respectively at 2% application rate. The Ni concentration in the maize shoots reduced by 30%, 95.2% and 95% and in the roots by 56%, 66% and 63.8% with RS, BI and calcite at 2% application rate, respectively. These findings suggest that the application of 2% biochar (BI) is very promising in reducing Ni uptake, and can reduce toxicity to plants, decrease mobility and leachability in the soil.

Water management of alternate wetting and drying reduces the accumulation of arsenic in brown rice - as dynamic study from rhizosphere soil to rice.

There have been no controlled systematic studies on the dynamic variation of As in soil - soil porewater - root surface (Fe plaques) - rice plant system under alternate wetting and drying (AWD) irrigation. Therefore, effects of continuous flooding (CF) and AWD treatments (2F2D: 2-day flooding followed by 2-day drying; 7F2D: 7-day flooding followed by 2-day drying) on the migration of As from soil to brown rice were studied. Results indicated that As contents in brown rice of AWD treatments (0.03-0.17 mg/kg) were 43.3%-85.0% lower than CF (0.20-0.30 mg/kg). AWD irrigation promoted the transformation of Fe and associated As in rhizosphere soil from highly active forms (H2O and HCl-extracted Fe-bound As) to stable states (oxalate and DCB-extracted Fe-bound As), which decreased the release of As from rhizosphere soil. The dynamic variation of As contents in porewater was described by a dissolution factor (DF) which decreased significantly in AWD treatments and had a significant positive correlation (R2 = 0.83; P < 0.05) with As contents in brown rice. In addition, contents of Fe and associated As on the root surface were about 17.1% and 11.0% higher in AWD treatments than in CF treatment, respectively, and the transfer factor (TF) of As from root surface into root was 22.7% lower in AWD treatments than in CF. In summary, AWD irrigation reduced As contents in porewater through decreasing availability of As in rhizosphere soil; and AWD also reduced the transfer of As into rice roots through promoting As sequestration by Fe plaques on root surface.

Oxalic acid activated phosphate rock and bone meal to immobilize Cu and Pb in mine soils.

The contamination of soil by copper (Cu) and lead (Pb) is a serious concern because of its high health risk via the food chain. Oxalic acid-activated phosphate rock (APR) and bone meal (BM) were applied to Cu and Pb co-contaminated soil to investigate their efficacy in the immobilization of Cu and Pb. APR and BM were applied into the contaminated soil (158.8 mg/kg total Pb and 573.2 mg/kg Cu) at four levels of dosages (0.1%, 0.5%, 2%, and 4%) and incubated for one year. The results demonstrated that the acid exchangeable Pb fraction in the soil treated with APR and BM decreased compared to the control, while there was no noticeable change in the acid-exchangeable Cu fraction in the soil treated with either APR or BM. Meanwhile, the application of BM and APR increased the fraction of residual Cu and Pb in the polluted soils. Moreover, the addition of either APR or BM at the dose of 4% decreased the concentrations of CaCl2-extractable Cu and Pb in the amended soil, and the percentages of that reduction in the APR amended soils were 56% and 91% and in BM amended soils were 67% and 64%, respectively. The immobilization of Cu and Pb by APR and BM might be induced by the increased soil pH and soluble P contents in the amended soils. In general, BM is more effective than APR on the immobilization of Cu in polluted soil, while APR had greater efficiency than BM on the immobilization of Pb when the levels of amendments were above 2%.

Human iPSC-MSC-Derived Xenografts Modulate Immune Responses by Inhibiting the Cleavage of Caspases.

Mesenchymal stem cells (MSCs) negatively modulate immune properties. Induced pluripotent stem cells (iPSCs)-derived MSCs are alternative source of MSCs. However, the effects of iPSC-MSCs on T cells phenotypes in vivo remain unclear. We established an iPSC-MSC-transplanted host versus graft reaction mouse model using subcapsular kidney injection. Th1, Th2, regulatory T cells (Treg), and Th17 phenotypes and their cytokines were investigated in vivo and in vitro. The role of caspases and the soluble factors involved in the effects of MSCs were examined. We found that iPSC-MSC grafts led to more cell survival and less infiltration of inflammatory cells in mice. iPSC-MSC transplantation inhibited T cell proliferation, decreased Th1 and Th2 phenotypes and cytokines, upregulated Th17 and Treg subsets. Moreover, iPSC-MSCs inhibited the cleavage of caspases 3 and 8 and inhibition of caspases downregulated Th1, Th2 responses and upregulated Th17, Treg responses. Soluble factors were determined using protein array and TGF-ß1/2/3, IL-10, and MCP-1 were found to be highly expressed in iPSC-MSCs. The administration of the soluble factors decreased Th1/2 response, upregulated Treg response and inhibited the cleavage of caspases. Our results demonstrate that iPSC-MSCs regulate T cell responses as a result of a combined action of the above soluble factors secreted by iPSC-MSCs. These factors suppress T cell responses by inhibiting the cleavage of caspases. These data provide a novel immunomodulatory mechanism for the underlying iPSC-MSC-based immunomodulatory effects on T cell responses. Stem Cells 2017;35:1719-1732.

Increased Group 2 Innate Lymphoid Cells Are Correlated with Eosinophilic Granulocytes in Patients with Allergic Airway Inflammation.

The T helper 2 (Th2)-type response was considered the hypostasis of allergic airway diseases, including asthma and allergic rhinitis (AR). However, more recent studies have suggested that allergic airway inflammation also depends on innate immunity and is closely related to group 2 innate lymphoid cells (ILC2s). This study evaluated the ILC2 levels of asthma subjects, patients with asthma and AR, and healthy individuals, regarding how to investigate the relationship between clinical data and ILC2 levels. It was found that asthma patients and asthma with AR patients had higher ILC2 levels compared to healthy subjects. ILC2s were positively correlated with the percentage of eosinophils in patients with asthma and AR, but not with pulmonary function. ILC2 levels were higher in mild asthma subjects than in patients with severe asthma. This study provides a new interpretation of the pathogenesis of allergic airway inflammation and may provide a new direction for the diagnosis and assessment of allergic airway diseases.

Comparative efficiency of rice husk-derived biochar (RHB) and steel slag (SS) on cadmium (Cd) mobility and its uptake by Chinese cabbage in highly contaminated soil.

Cadmium (Cd) contamination in red soil has been considered as a severe threat due to its toxic effects on plants and food security. This study aims to evaluate the comparative efficiency of rice husk-derived biochar (RHB) and steel slag (SS) metal stabilizer on decreasing Cd mobility and bioavailability to Chinese cabbage grown on acidic contaminated red soil. Several extraction techniques: a sequential extraction procedure, the European Community Bureau of Reference, toxicity characteristics leaching procedure, ammonium nitrate, and simple bioaccessibility extraction test were used to measure Cd mobility after amelioration of the investigated soil. The results indicated that application of stabilizer significantly increased soil chemical properties including soil pH, cation exchange capacity, nutrients, and organic matter. The soluble portion of Cd in soil was significantly decreased by 17.6-31.2% and 7.8-11.7% for RHB and SS at 1.5% and 3% application rate, respectively. Moreover, Cd bioaccessibility was significantly declined by 37.08% with RHB and 11.3% with SS at 3% rate. Inlcorporation of RHB at 3% can effectively immobilize Cd and thereby, reduce its phytoavailability to cabbage in Cd-contaminated soil to mitigate food security risks.

Identifying the functional groups and the influence of synthetic chelators on Cd availability and microbial biomass carbon in Cd-contaminated soil.

Synthetic chelators play an important role in boosting the microbial biomass carbon (MBC), dissolved organic carbon (DOC), and heavy metal solubility in a contaminated soil toward a sustainability of environment for agricultural crops. Castor plant was grown under different levels of Cd contaminated soil (-Cd and +Cd) following adding three chelating agents, ethylenediaminetetraacetic acid (H4EDTA), nitriloacetic acid (H3 NTA), and NH4 citrate (ammonium citrate) to the soil at rates of 10, 15, and 25 mmol in 5 kg of soil per pot. The highest bioavailable Cd concentrations in soil and castor plant were obtained from NH4 citrate and H4EDTA treatments in the contaminated soil. Fourier transform infrared (FTIR) analysis showed that NH4 citrate was the most effective chelator in Cd-contaminated soil. MBC and DOC contents were significantly increased and reached at 81.98-80.37 and 1.96-1.90 mg kg-1 respectively, in the (H3 NTA) and NH4 citrate treatments in Cd-contaminated soil. Further research is needed to investigate the use of chelators in the phytoextraction of Cd-contaminated soils under field conditions and whether it may be beneficial in accelerating the phytoextraction of Cd through hyperaccumulating plants.