Transplantation of stem cells from umbilical cord blood as therapy for type I diabetes.

In recent years, human umbilical cord blood has emerged as a rich source of stem, stromal and immune cells for cell-based therapy. Among the stem cells from umbilical cord blood, CD45+ multipotent stem cells and CD90+ mesenchymal stem cells have the potential to treat type I diabetes mellitus (T1DM), to correct autoimmune dysfunction and replenish ß-cell numbers and function. In this review, we compare the general characteristics of umbilical cord blood-derived multipotent stem cells (UCB-SCs) and umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) and introduce their applications in T1DM. Although there are some differences in surface marker expression between UCB-SCs and UCB-MSCs, the two cell types display similar functions such as suppressing function of stimulated lymphocytes and imparting differentiation potential to insulin-producing cells (IPCs) in the setting of low immunogenicity, thereby providing a promising and safe approach for T1DM therapy.

Ultrahigh oxygen evolution reaction activity in Au doped co-based nanosheets.

Oxygen evolution reaction (OER) has attracted enormous interest as a key process for water electrolysis over the past years. The advance of this process relies on an effective catalyst. Herein, we employed single-atom Au doped Co-based nanosheets (NSs) to theoretically and experimentally evaluate the OER activity and also the interaction between Co and Au. We reveal that Au-Co(OH)2 NSs achieved a low overpotential of 0.26 V at 10 mA cm-2. This extraordinary phenomenon presents an overall superior performance greater than state-of-the-art Co-based catalysts in a sequence of α-Co(OH)2 < Co3O4 < CoOOH < Au-Co(OH)2. With ab initio calculations and analysis in the specific Au-Co(OH)2 configuration, we reveal that OER on highly active Au-Co(OH)2 originates from lattice oxygen, which is different from the conventional adsorbate evolution scheme. Explicitly, the configuration of Au-Co(OH)2 gives rise to oxygen non-bonding (ONB) states and oxygen holes, allowing direct O-O bond formation by a couple of oxidized oxygen with oxygen holes, offering a high OER activity. This study provides new insights for elucidating the origins of activity and synthesizing efficient OER electrocatalysts.

Intrapulmonary delivery of human umbilical cord mesenchymal stem cells attenuates acute lung injury by expanding CD4+CD25+ Forkhead Boxp3 (FOXP3)+ regulatory T cells and balancing anti- and pro-inflammatory factors.

BACKGROUND: Systemic and local inflammatory processes play key, mainly detrimental roles in the pathophysiology of acute lung injury (ALI). The present study was designed to determine whether human umbilical cord mesenchymal stem cells (UCMSC) are able to act on CD4(+)CD25(+) Foxp3(+)Treg cells and lead to an improvement in ALI. METHODS: Mice were administered intratracheally endotoxin (lipopolysaccharide [LPS]) and received intrapulmonary 1×10(6) UCMSC 4 hours after challenge. The CD4(+)CD25(+) Foxp3(+)Treg, survival time, body weight, histology and lung injury scores were assessed after transplantation of UCMSC. In addition, anti-inflammatory factor IL10 and pro-inflammatory mediators production including tumor necrosis factor-a (TNF-α), macrophage inflammatory protein-2(MIP-2) and interferon-γ (IFN-γ) were detected. RESULTS: Transplantation of UCMSC resulted in significant increase in the level of CD4(+)CD25(+) Foxp3(+)Treg in ALI. Increased level of anti-inflammatory factor IL-10 and reduced levels of TNF-α, MIP-2 and IFN-γ were simultaneously observed in ALI in comparison with control mice. CONCLUSION: Our data demonstrate for the first time that transplantation of UCMSC ameliorates ALI by enhancing the diminished levels of alveolar CD4(+)CD25(+) Foxp3(+)Treg and balancing anti- and pro-inflammatory factors in ALI mice.

Highly Conductive PDMS Composite Mechanically Enhanced with 3D-Graphene Network for High-Performance EMI Shielding Application.

A highly conductive three-dimensional (3D) graphene network (GN) was fabricated by chemical vapor deposition on a 3D nickel fiber network and subsequent etching process. Then a lightweight and flexible polydimethylsiloxane (PDMS)/GN composite was prepared by a vacuum infiltration method by using the graphene network as a template. The composite showed the superior electrical conductivity of 6100 S/m even at a very low loading level of graphene (1.2 wt %). As a result, an outstanding electromagnetic interference (EMI) shielding effectiveness (SE) of around 40 and 90 dB can be achieved in the X-band at thicknesses of 0.25 and 0.75 mm, respectively, which are much higher than most of the conductive polymers filled with carbon. The 3D graphene network can also act as a mechanical enhancer for PDMS. With a loading level of 1.2 wt %, the composite shows a significant increase by 256% in tensile strength.

Preclinical Evaluation of a Single Intravenous Infusion of hUC-MSC (BX-U001) in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an inflammatory disease of the joints, which causes severe pain and excessive systemic circulation of harmful inflammatory cytokines. Current treatments are limited, with some patients not responding well, and some experiencing severe and detrimental side effects. Mesenchymal stem cells (MSC) are cell-based therapeutics being evaluated as potent immunomodulators in RA and may provide relief to patients not responding well to drug-based treatments. We evaluated the safety and efficacy of BX-U001 human umbilical cord tissue-derived mesenchymal stem cells (hUC-MSC) to treat RA, in support of a successful investigational new drug application. A collagen-induced arthritis (CIA) mouse model of RA was established in DBA/1 J mice. Mice from the treatment assessment group were given a tail vein infusion of hUC-MSC 24 days after primary RA induction, while control assessment (CA) group mice were given cell-free carrier solution. All animals were evaluated daily for RA symptoms via clinical scoring, blood was taken periodically for cytokine analysis, and mice were dissected at end point for histological analysis. A linear mixed model was used to compare the rate of change among groups. The clinical scores of TA group were significantly reduced compared with CA group (P < 0.01), indicating therapeutic effects. The histological scores of the joints in TA group were significantly lower than those in the CA group (P < 0.05), but had no significant difference compared with Healthy groups (P > 0.05). The concentration of (interleukin) IL-6 in TA group was significantly reduced by 80.0% (P < 0.0001) 2 days after treatment and by 93.4% at the experimental endpoint compared with levels prior to hUC-MSC injection. A single intravenous infusion of hUC-MSC (2 × 106 cells/mouse), to CIA-induced DBA/1 J mice, resulted in significant alleviation of RA symptoms and may provide significant therapeutic benefits in humans.

Therapeutic benefit of human umbilical cord derived mesenchymal stromal cells in intracerebral hemorrhage rat: implications of anti-inflammation and angiogenesis.

Cell-based therapy represents a promising strategy in the treatment of neurological disorders. Human umbilical cord tissue has recently been recognized as an ideal source of mesenchymal stromal cells due to accessibility, vast abundance and safety. Here, an intracerebral hemorrhage (ICH) rat model was established by injection of bacterial collagenase VII and CM-DiI labeled human umbilical cord tissue derived mesenchymal stromal cells (UC-MSC) were intracerebrally transplanted into rat brain 24 h after ICH. The results demonstrated that UC-MSC treatment significantly improved neurological function deficits and decreased injury volume of ICH rats. Leukocytes infiltration, microglial activation, ROS level and matrix metalloproteinases (MMPs) production were substantially reduced in peri-ICH area in cell-treated group as compared with PBS control at day 3 post-transplantation. In addition, UC-MSC treatment significantly increased vascular density in peri-ICH area and transplanted UC-MSC were found to be able to incorporate into cerebral vasculature in ipsilateral hemisphere at 14 days after transplantation. In summary, intracerebral administration of UC-MSC could accelerate neurological function recovery of ICH rat, the underlying mechanism may ascribe to their ability to inhibit inflammation and promote angiogenesis. Thus UC-MSC may provide a potential cell candidate for cell-based therapy in neurological disorders.

NH3-Sensing Mechanism Using Surface Acoustic Wave Sensor with AlO(OH) Film.

In this study, AlO(OH) (boehmite) film was deposited onto a surface acoustic wave (SAW) resonator using a combined sol-gel and spin-coating technology, and prepared and used as a sensitive layer for a high-performance ammonia sensor. The prepared AlO(OH) film has a mesoporous structure and a good affinity to NH3 (ammonia gas) molecules, and thus can selectively adsorb and react with NH3. When exposed to ammonia gases, the SAW sensor shows an initial positive response of the frequency shift, and then a slight decrease of the frequency responses. The sensing mechanism of the NH3 sensor is based on the competition between mass-loading and elastic-loading effects. The sensor operated at room temperature shows a positive response of 1540 Hz to 10 ppm NH3, with excellent sensitivity, selectivity and stability.

AZGP1 suppresses epithelial-to-mesenchymal transition and hepatic carcinogenesis by blocking TGFß1-ERK2 pathways.

Zinc-α2-glycoprotein 1 (AZGP1) has been found to play important roles in TGF-ß1 induced epithelial-to-mesenchymal transition (EMT). However, the mechanisms of AZGP1 inhibiting EMT and its therapeutic potential remain unknown in hepatocellular carcinoma (HCC). AZGP1, TGF-ß1 or ERK2 expressions were examined in liver tissues of HCC patients and rat model. The effect of AZGP1 on EMT and crosstalking of TGFß1-ERK2 signaling in human hepatic cancer cell was tested in vitro and in vivo. Hepatic expression of AZGP1 was nearly deficient in HCC patients and rats. It was proved that AZGP1 has the ability of down-regulating mesenchymal markers, up-regulating epithelial marker, inhibiting cell invasion and suppressing EMT in human HCC cells. The results clarified that AZGP1 has the effect on blocking TGF-ß1 mediated ERK2 phosphorylation leading to depressing EMT and invasive potential in vitro. Local injection of AZGP1 mimic in vivo could significantly withhold lung metastasis in HCC. In conclusion, loss of AZGP1 could trigger EMT induced by TGFß1-ERK2 signaling, confuse in energy metabolism, reduce cell proliferation and apoptosis, activate survival signals and promote invasion. Up-regulation of AZGP1 should be proposed to reverse EMT and might be a new promising therapy for HCC.

FOXP1 and SPINK1 reflect the risk of cirrhosis progression to HCC with HBV infection.

BACKGROUND: Hepatocellular carcinoma (HCC) deriving from cirrhosis with HBV infection harbors higher morbidity and poor prognosis. The diagnosis of HCC at its early stage is essential for improving the effect of treatment and survival rate of patients. METHOD: Affymetrix GeneChip was practiced to establish gene expression profile and significance analysis of microarray (SAM) as well as prediction analysis of microarray (PAM) was utilized to screen candidate marker genes in tissue of carcinoma and para-cancerous with cirrhosis from 15 hepatitis B virus (HBV) related HCC patients. RESULT: Total 497 differential genes were selected by microarray (fold change >2; P value<0.01). Then 162 significant genes were determined by SAM (fold change -1.46 to 1.28). A number of 8-genes showing "poor risk signature" was validated with threshold of 6.2, which was associated with cirrhosis progressing to HCC. Only 3 down-regulated and 2 up-regulated predictor genes had statistical difference in HCC and cirrhosis groups by RT-PCR (P value<0.01). Forkhead box protein 1 (FOXP1) and serine protease inhibitor Kazal-type 1 (SPINK1) proteins were found significantly increased in carcinoma tissues than para-cancerous cirrhotic tissues by IH and WB. CONCLUSION: Over-expression of FOXP1 and SPINK1 may participate in the carcinogenesis of HBV related cirrhosis. They could use as potential biomarkers for diagnosing early HCC.

Direct Conversion of Cord Blood CD34+ Cells Into Neural Stem Cells by OCT4.

UNLABELLED: : Cellular reprogramming or conversion is a promising strategy to generate desired stem cell types from somatic cells. Neural stem cells (NSCs) have the potential to regenerate central nervous system tissue and repair damage in response to injury. However, NSCs are difficult to isolate from human tissues and expand in sufficient quantities for therapy. Here, we report a method to generate neural stem cells from cord blood CD34-positive cells by ectopic expression of OCT4 in a feeder-free system. The induced cells (iNSCs) show a characteristic NSC-like morphology and can be expanded in vitro for more than 20 passages. In addition, the iNSCs are positive for neural stem cell-specific markers such as Nestin and Musashi-1 and are similar in gene expression patterns to a human neural stem cell line. The iNSCs express distinct transcriptional factors for forebrain, hindbrain, and spinal cord regions. Upon differentiation, the iNSCs are able to commit into multilineage mature neural cells. Following in vivo introduction into NOD/SCID mice, iNSCs can survive and differentiate in the mouse brain 3 months post-transplantation. Alternatively, we were also able to derive iNSCs with an episomal vector expressing OCT4. Our results suggest a novel, efficient approach to generate neural precursor cells that can be potentially used in drug discovery or regenerative medicine for neurological disease and injury. SIGNIFICANCE: This study describes a novel method to generate expandable induced neural stem cells from human cord blood cells in a feeder-free system by a single factor, OCT4. The data are promising for future applications that require the generation of large amounts of autologous neural stem cells in disease modeling and regenerative medicine.

Evidence for high translational potential of mesenchymal stromal cell therapy to improve recovery from ischemic stroke.

Although ischemic stroke is a major cause of morbidity and mortality, current therapies benefit only a small proportion of patients. Transplantation of mesenchymal stromal cells (MSC, also known as mesenchymal stem cells or multipotent stromal cells) has attracted attention as a regenerative therapy for numerous diseases, including stroke. Mesenchymal stromal cells may aid in reducing the long-term impact of stroke via multiple mechanisms that include induction of angiogenesis, promotion of neurogenesis, prevention of apoptosis, and immunomodulation. In this review, we discuss the clinical rationale of MSC for stroke therapy in the context of their emerging utility in other diseases, and their recent clinical approval for treatment of graft-versus-host disease. An analysis of preclinical studies examining the effects of MSC therapy after ischemic stroke indicates near-universal agreement that MSC have significant favorable effect on stroke recovery, across a range of doses and treatment time windows. These results are interpreted in the context of completed and ongoing human clinical trials, which provide support for MSC as a safe and potentially efficacious therapy for stroke recovery in humans. Finally, we consider principles of brain repair and manufacturing considerations that will be useful for effective translation of MSC from the bench to the bedside for stroke recovery.

[Umbilical cord mesenchymal stem cell transplantation for treatment of experimental autoimmune myasthenia gravis in rats].

Umbilical cord mesenchymal stem cell (UCMSC) transplantation has been widely used in the treatment of a variety of diseases due to their advantages such as abundant resources, low immunogenicity and large ex vivo expansion capacity. This study was aimed to investigate the effects of UCMSC on experimental autoimmune myasthenia gravis (EAMG) rats. The distribution of human-derived cells was observed by immunofluorescence method, the effect of MSC on B-cell in situ-secreted antibodies was assayed by ELISPOT, the secreted IFN-γ level was detected by using Transwell test. The results showed that UCMSC were able to migrate to inflammation region and lymph nudes, moreover human-derived cells could be detected in medulla zone of lymph nudes. In vitro in situ detection of AchR specific antibody secretion revealed that the full contact of MSC with lymphnode-derived lymphocytes could effectively inhibit production of AchR antibody. Transwell test indicated that the direct contact of UCMSC with CD4 T cells could effectively decrease production of IFN-γ, which modulated the unbalance between Th1/Th2 to a certain extent. It is concluded that UCMSC can regulate the immune system by direct cell-cell contact or/and release of cytokines, which bring a new insight into knowledge about MSC-based therapy for EAMG.