Gelatin methacrylate hydrogels culture model for glioblastoma cells enriches for mesenchymal-like state and models interactions with immune cells.

Glioblastoma is the most lethal primary malignant brain tumor in adults. Simplified two-dimensional (2D) cell culture and neurospheres in vitro models fail to recapitulate the complexity of the tumor microenvironment, limiting its ability to predict therapeutic response. Three-dimensional (3D) scaffold-based models have emerged as a promising alternative for addressing these concerns.

Analysis of solid tumor mutation profiles in liquid biopsy.

Liquid biopsy is increasingly gaining traction as an alternative to invasive solid tumor biopsies for prognosis, treatment decisions, and disease monitoring. Matched tumor-plasma samples were collected from 180 patients across different cancers with >90% of the samples below Stage IIIB. Tumors were profiled using next-generation sequencing (NGS) or quantitative PCR (qPCR), and the mutation status was queried in the matched plasma using digital platforms such as droplet digital PCR (ddCPR) or NGS for concordance.

Gold nanoparticle-based rapid detection and isolation of cells using ligand-receptor chemistry.

Identification and isolation of low-frequency cells of interest from a heterogeneous cell mixture is an important aspect of many diagnostic applications (including enumeration of circulating tumor cells) and is integral to various assays in (cancer) biology. Current techniques typically require expensive instrumentation and are not amenable to high throughput. Here, we demonstrate a simple and effective platform for cell detection and isolation using gold nanoparticles (Au NPs) conjugated with hyaluronic acid (HA) i.

Gelatin Methacrylate Hydrogels as Biomimetic Three-Dimensional Matrixes for Modeling Breast Cancer Invasion and Chemoresponse in Vitro.

Recent studies have shown that three-dimensional (3D) culture environments allow the study of cellular responses in a setting that more closely resembles the in vivo milieu. In this context, hydrogels have become popular scaffold options for the 3D cell culture. Because the mechanical and biochemical properties of culture matrixes influence crucial cell behavior, selecting a suitable matrix for replicating in vivo cellular phenotype in vitro is essential for understanding disease progression.

Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity.

Acute myelogenous leukemia (AML) subtypes that result from oncogenic activation of homeobox (HOX) transcription factors are associated with poor prognosis. The HOXA9 transcription activator and growth factor independent 1 (GFI1) transcriptional repressor compete for occupancy at DNA-binding sites for the regulation of common target genes. We exploited this HOXA9 versus GFI1 antagonism to identify the genes encoding microRNA-21 and microRNA-196b as transcriptional targets of HOX-based leukemia oncoproteins.

Structural and biomechanical responses of osseous healing: a novel murine nonunion model.

Background: Understanding the biological mechanisms of why certain fractures are at risk for delayed healing or nonunion requires translational animal models that take advantage of transgenic and other genetic manipulation technologies. Reliable murine nonunion models can be an important tool to understand the biology of nonunion. In this study, we report the results of a recently established model for creating critical defects that lead to atrophic nonunions based on a unique fracture fixation technique.

Characterization of the differentiation and leptin secretion profile of adult stem cells on patterned polylactide films.

Several issues need to be better understood before breast tissue engineering becomes a clinically viable option. One of the most important aspects is the interaction between cells and the microtopography of the implant surface. The aim of this study was to evaluate the efficacy of D1 cells, multipotent mouse bone marrow stromal precursors, in differentiating to adipocytes and to characterize their metabolic activity (lactic acid released and glucose consumed), leptin secretion and lipid production when cultured on patterned poly(L-lactide) (PLLA) films.

Gfi1 integrates progenitor versus granulocytic transcriptional programming.

In patients with severe congenital neutropenia (SCN) and mice with growth factor independent-1 (Gfi1) loss of function, arrested myeloid progenitors accumulate, whereas terminal granulopoiesis is blocked. One might assume that Gfi-null progenitors accumulate because they lack the ability to differentiate. Instead, our data indicate that Gfi1 loss of function deregulates 2 separable transcriptional programs, one of which controls the accumulation and lineage specification of myeloid progenitors, but not terminal granulopoiesis.

Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization.

Chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene produce chimeric proteins that cause abnormal expression of a subset of HOX genes and leukemia development. Here, we show that MLL normally regulates expression of mir-196b, a hematopoietic microRNA located within the HoxA cluster, in a pattern similar to that of the surrounding 5' Hox genes, Hoxa9 and Hoxa10, during embryonic stem (ES) cell differentiation. Within the hematopoietic lineage, mir-196b is most abundant in short-term hematopoietic stem cells and is down-regulated in more differentiated hematopoietic cells.

Surface patterning: tool to modulate stem cell differentiation in an adipose system.

There are several issues that need to be better understood before breast tissue-engineering becomes viable clinically. One of the key issues is the interaction between cells and the microtopography of the implant surface. The aim of this study was to evaluate the efficacy of D1 cells, multipotent mouse bone marrow stromal precursors, in differentiating to fat and to characterize their metabolic activity (lactic acid released and glucose consumed) and lipid production when cultured on patterned poly-L-lactide (PLLA) films.