Erratum: Functional imaging of neuron–astrocyte interactions in a compartmentalized microfluidic device

[This corrects the article DOI: 10.1038/micronano.2015.45.]

Artificial extracellular matrix for embryonic stem cell cultures: a new frontier of nanobiomaterials

Nanobiomaterials can play a central role in regenerative medicine and tissue engineering by facilitating cellular behavior and function, such as those where extracellular matrices (ECMs) direct embryonic stem (ES) cell morphogenesis, proliferation, differentiation and apoptosis. However, controlling ES cell proliferation and differentiation using matrices from natural sources is still challenging due to complex and heterogeneous culture conditions. Moreover, the systemic investigation of the regulation of self-renewal and differentiation to lineage specific cells depends on the use of defined and stress-free culture conditions. Both goals can be achieved by the development of biomaterial design targeting ECM or growth factors for ES cell culture. This targeted application will benefit from expansion of ES cells for transplantation, as well as the production of a specific differentiated cell type either by controlling the differentiation in a very specific pathway or by elimination of undesirable cell types

Coupling tumor necrosis factor‐related apoptosis‐inducing ligand to iron oxide nanoparticles increases its apoptotic activity on HCT116 and HepG2 malignant cells: effect of magnetic core size

International audienceTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been considered as a potential anticancer agent owing to its selectivity for malignant cells. However, its clinical use remains limited because of its poor efficacy. Attempts to increase its antitumor activity include, among others, its functionalization by nanoparticles (NPs). In the present study, TRAIL was grafted onto magnetic spinel iron oxide NPs of defined core size, 10 and 100 nm on average, to see whether the size of the resulting nanovectors, NV10 and NV100, respectively, might affect TRAIL efficacy and selectivity. Apoptosis induced by NV10 and NV100 was higher than by TRAIL alone in both HCT116 and HepG2 cells. At equimolar concentrations, neither the nanovectors nor the corresponding NPs displayed cytotoxicity towards normal primary hepatocytes or TRAIL receptor-deficient HCT116 cells. NV100 exhibited superior proapoptotic activity than NV10, as evidenced by methylene blue and annexin V staining. Consistently, both caspase activation and TRAIL death-induced signaling complex formation, as assessed by immunoblot analysis, were found to be increased in cells treated with NV100 as compared with NV10 or TRAIL alone. These results suggest that the size of NPs is important when TRAIL is vectorized for cancer therapy

Detecting Transforming Growth Factor‑β Release from Liver Cells Using an Aptasensor Integrated with Microfluidics

We developed a cell-culture/biosensor platform consisting of aptamer-modified Au electrodes integrated with reconfigurable microfluidics for monitoring of transforming growth factor-beta 1 (TGF-β1), an important inflammatory and pro-fibrotic cytokine. Aptamers were thiolated, labeled with redox reporters, and self-assembled on gold surfaces. The biosensor was determined to be specific for TGF-β1 with an experimental detection limit of 1 ng/mL and linear range extending to 250 ng/mL. Upon determining figures of merit, aptasensor was miniaturized and integrated with human hepatic stellate cells inside microfluidic devices. Reconfigurable microfluidics were developed to ensure that seeding of “sticky” stromal cells did not foul the electrode and compromise sensor performance. This microsystem with integrated aptasensors was used to monitor TGF-β1 release from activated stellate cells over the course of 20 h. The electrochemical response went down upon infusing anti-TGF-β1 antibodies into the microfluidic devices containing activated stellate cells. To further validate aptasensor responses, stellate cells were stained for markers of activation (e.g., alpha smooth muscle actin) and were also tested for presence of TGF-β1 using enzyme linked immunosorbent assay (ELISA). Given the importance of TGF-β1 as a fibrogenic signal, a microsystem with integrated biosensors for local and continuous detection of TGF-β1 may prove to be an important tool to study fibrosis of the liver and other organs

Michigan Jewish history : official publication of the Jewish Historical Society of Michigan

In continuing search for effective treatments of cancer, the emerging model aims at efficient intracellular delivery of therapeutics into tumor cells in order to increase the drug concentration. However, the implementation of this strategy suffers from inefficient cellular uptake and drug resistance. Therefore, pH-sensitive nanosystems have recently been developed to target slightly acidic extracellular pH environment of solid tumors. The pH targeting approach is regarded as a more general strategy than conventional specific tumor cell surface targeting approaches, because the acidic tumor microclimate is most common in solid tumors. When nanosystems are combined with triggered release mechanisms in endosomal or lysosomal acidic pH along with endosomolytic capability, the nanocarriers demonstrated to overcome multidrug resistance of various tumors. Here, novel pH sensitive carbonate apatite has been fabricated to efficiently deliver anticancer drug Doxorubicin (DOX) to cancer cells, by virtue of its pH sensitivity being quite unstable under an acidic condition in endosomes and the desirable size of the resulting apatite-DOX for efficient cellular uptake as revealed by scanning electron microscopy. Florescence microscopy and flow cytometry analyses demonstrated significant uptake of drug (92%) when complexed with apatite nanoparticles. In vitro chemosensitivity assay revealed that apatite-DOX nanoparticles executed high cytotoxicity in several human cancer cell lines compared to free drugs and consequently apatite-DOX-facilitated enhanced tumor inhibitory effect was observed in colorectal tumor model within BALB/cA nude mice, thereby shedding light on their potential applications in cancer therapy

Construction of a Defined Biomimetic Matrix for Long-Term Maintenance of Mouse Induced Pluripotent Stem Cells

The existing in vitro culture systems often use undefined and animal-derived components for the culture of pluripotent stem cells. Artificial bioengineered peptides have the potential to become alternatives to these components of extracellular matrix (ECM). Integrins and cadherins are two cell adhesion proteins important for stem cell self-renewal, differentiation, and phenotype stability. In the present study, we sought to mimic the physico-biochemical properties of natural ECMs that allow self-renewal of mouse induced pluripotent stem cells (iPSCs). We develop a genetically engineered ECM protein (ERE-CBP) that contains (i) an integrin binding peptide sequence (RGD/R), (ii) an E-/N-cadherin binding peptide sequence (SWELYYPLRANL/CBP), and (iii) 12 repeats of APGVGV elastin-like polypeptides (ELPs/E).While ELPs allow efficient coating by binding to nontreated hydrophobic tissue culture plates, RGD/R and CBP support integrin- and cadherin-dependent cell attachment, respectively. Mouse iPSCs on this composite matrix exhibit a more compact phenotype compared to cells on control gelatin substrate. We also demonstrated that the ERE-CBP supports proliferation and long-term self-renewal of mouse iPSCs for up to 17 passages without GSK3β (CHIR99021) and Erk (PD0325901) inhibitors. Overall, our engineered ECM protein, which is cost-effective to produce in prokaryotic origin and flexible to modify with other cell adhesion peptides or growth factors, provides a novel approach for expansion of mouse iPSCs in vitro