High endogenous CCL2 expression promotes the aggressive phenotype of human inflammatory breast cancer.

Inflammatory Breast Cancer (IBC) is a highly aggressive malignancy with distinct clinical and histopathological features whose molecular basis is unresolved. Here we describe a human IBC cell line, A3250, that recapitulates key IBC features in a mouse xenograft model, including skin erythema, diffuse tumor growth, dermal lymphatic invasion, and extensive metastases. A3250 cells express very high levels of the CCL2 chemokine and induce tumors enriched in macrophages.

Introducing dorsoventral patterning in adult regenerating lizard tails with gene-edited embryonic neural stem cells.

Lizards regenerate amputated tails but fail to recapitulate the dorsoventral patterning achieved during embryonic development. Regenerated lizard tails form ependymal tubes (ETs) that, like embryonic tail neural tubes (NTs), induce cartilage differentiation in surrounding cells via sonic hedgehog (Shh) signaling. However, adult ETs lack characteristically roof plate-associated structures and express Shh throughout their circumferences, resulting in the formation of unpatterned cartilage tubes.

Acceleration of chondrogenic differentiation of human mesenchymal stem cells by sustained growth factor release in 3D graphene oxide incorporated hydrogels.

Damaged articular cartilage has limited self-healing capabilities, leading to degeneration that affects millions of people. Although cartilage tissue engineering is considered a promising approach for treatment, robust and long-term chondrogenesis within a 3-dimensional (3D) scaffold remains a major challenge for complete regeneration. Most current approaches involve incorporation of transforming growth factor-β (TGF-β) into the scaffold, but have limited utility owing to the short functional half-life and/or rapid clearance of TGF-β.

Conduits harnessing spatially controlled cell-secreted neurotrophic factors improve peripheral nerve regeneration.

An essential structure in nerve regeneration within engineered conduits is the "nerve bridge" initiated by centrally migrating Schwann cells in response to chemokine gradients. Introducing exogenous cells secreting neurotrophic factors aims to augment this repair process, but conventional cell-seeding methods fail to produce a directional chemokine gradient. We report a versatile method to encapsulate cells within conduit walls, allowing for reproducible control of spatial distribution along the conduit.

Enhancing chondrogenesis and mechanical strength retention in physiologically relevant hydrogels with incorporation of hyaluronic acid and direct loading of TGF-β.

Cell-loaded hydrogels are frequently applied in cartilage tissue engineering for their biocompatibility, ease of application, and ability to conform to various defect sites. As a bioactive adjunct to the biomaterial, transforming growth factor beta (TGF-β) has been shown to be essential for cell differentiation into a chondrocyte phenotype and maintenance thereof, but the low amounts of endogenous TGF-β in the in vivo joint microenvironment necessitate a mechanism for controlled delivery and release of this growth factor. In this study, TGF-β3 was directly loaded with human bone marrow-derived mesenchymal stem cells (MSCs) into poly-d,l-lactic acid/polyethylene glycol/poly-d,l-lactic acid (PDLLA-PEG) hydrogel, or PDLLA-PEG with the addition of hyaluronic acid (PDLLA/HA), and cultured in vitro.

Differences in neural stem cell identity and differentiation capacity drive divergent regenerative outcomes in lizards and salamanders.

While lizards and salamanders both exhibit the ability to regenerate amputated tails, the outcomes achieved by each are markedly different. Salamanders, such as , regenerate nearly identical copies of original tails. Regenerated lizard tails, however, exhibit important morphological differences compared with originals.

TISSUE REPAIR AND EPIMORPHIC REGENERATION: AN OVERVIEW.

Purpose Of The Review: This manuscript discusses wound healing as a component of epimorphic regeneration and the role of the immune system in this process.

Recent Findings: Epimorphic regeneration involves formation of a blastema, a mass of undifferentiated cells capable of giving rise to the regenerated tissues. The apical epithelial cap plays an important role in blastemal formation.

Chondroinductive factor-free chondrogenic differentiation of human mesenchymal stem cells in graphene oxide-incorporated hydrogels.

Graphene-based nanomaterials have been applied as biomaterials to enhance stem cell adhesion, growth and differentiation by serving as nanocarriers for growth factors or other small molecules. However, the direct effect of graphene oxide (GO) itself on stem cells, in the absence of exogenous differentiation inductive factors, has not been tested. In this study, we loaded GO nanosheets and human bone marrow-derived mesenchymal stem cells (hBMSC) into a photopolymerizable poly-d,l-lactic acid/polyethylene glycol (PDLLA) hydrogel, a robust chondrosupportive scaffold recently developed in our laboratory, and assessed hBMSC differentiation along the chondrogenic lineage without supplemental chondroinductive factors.

Neurotrophically Induced Mesenchymal Progenitor Cells Derived from Induced Pluripotent Stem Cells Enhance Neuritogenesis via Neurotrophin and Cytokine Production.

Adult tissue-derived mesenchymal stem cells (MSCs) are known to produce a number of bioactive factors, including neurotrophic growth factors, capable of supporting and improving nerve regeneration. However, with a finite culture expansion capacity, MSCs are inherently limited in their lifespan and use. We examined here the potential utility of an alternative, mesenchymal-like cell source, derived from induced pluripotent stem cells, termed induced mesenchymal progenitor cells (MiMPCs).

Selective Formation of Functionalized α-Quaternary Malononitriles toward 5,5-Disubstituted Pyrrolopyrimidinones.

A modular, selective approach to complex α-tertiary substituted malononitriles is reported. The method takes advantage of β-ester-substituted α,α-dinitrile alkenes as highly reactive, chemoselective electrophiles for 1,4-additions with organometallic nucleophiles to produce functionally and sterically dense all-carbon quaternary centers. In the presence of a chiral ester auxiliary bearing an aromatic ring, the 1,4-addition occurs with good to excellent selectivity due to favorable cation-π interactions.

Chondrogenesis of human bone marrow mesenchymal stem cells in 3-dimensional, photocrosslinked hydrogel constructs: Effect of cell seeding density and material stiffness.

Unlabelled: Three-dimensional hydrogel constructs incorporated with live stem cells that support chondrogenic differentiation and maintenance offer a promising regenerative route towards addressing the limited self-repair capabilities of articular cartilage. In particular, hydrogel scaffolds that augment chondrogenesis and recapitulate the native physical properties of cartilage, such as compressive strength, can potentially be applied in point-of-care procedures. We report here the synthesis of two new materials, [poly-l-lactic acid/polyethylene glycol/poly-l-lactic acid] (PLLA-PEG 1000) and [poly-d,l-lactic acid/polyethylene glycol/poly-d,l-lactic acid] (PDLLA-PEG 1000), that are biodegradable, biocompatible (>80% viability post fabrication), and possess high, physiologically relevant mechanical strength (∼1500 to 1800kPa).

Projection Stereolithographic Fabrication of Human Adipose Stem Cell-Incorporated Biodegradable Scaffolds for Cartilage Tissue Engineering.

The poor self-healing ability of cartilage necessitates the development of methods for cartilage regeneration. Scaffold construction with live stem cell incorporation and subsequent differentiation presents a promising route. Projection stereolithography (PSL) offers high resolution and processing speed as well as the ability to fabricate scaffolds that precisely fit the anatomy of cartilage defects using medical imaging as the design template.

Incorporating conditional random fields and active learning to improve sentiment identification.

Many machine learning, statistical, and computational linguistic methods have been developed to identify sentiment of sentences in documents, yielding promising results. However, most of state-of-the-art methods focus on individual sentences and ignore the impact of context on the meaning of a sentence. In this paper, we propose a method based on conditional random fields to incorporate sentence structure and context information in addition to syntactic information for improving sentiment identification.

Redox-neutral copper(II) carboxylate catalyzed α-alkynylation of amines.

A new strategy for iminium ion isomerization was applied to the direct, redox-neutral α-alkynylation of amines. Cu(II) 2-ethylhexanoate was identified as the optimal catalyst for this three-component coupling reaction of secondary amines, aldehydes and alkynes.