Multi-Niche Human Bone Marrow On-A-Chip for Studying the Interactions of Adoptive CAR-T Cell Therapies with Multiple Myeloma.

Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment. Yet, it is unclear which BM niches give rise to MM pathophysiology. Here, we present a 3D microvascularized culture system, which models the endosteal and perivascular bone marrow niches, allowing us to study MM-stroma interactions in the BM niche and model responses to therapeutic CAR-T cells. We demonstrated the prolonged survival of cell line-based and patient-derived multiple myeloma cells within our in vitro system and successfully flowed in donor-matched CAR-T cells. We then measured T cell survival, differentiation, and cytotoxicity against MM cells using a variety of analysis techniques. Our MM-on-a-chip system could elucidate the role of the BM microenvironment in MM survival and therapeutic evasion and inform the rational design of next-generation therapeutics. TEASER: A multiple myeloma model can study why the disease is still challenging to treat despite options that work well in other cancers.

Generation of LexA enhancer-trap lines in Drosophila by an international scholastic network.

Conditional gene regulation in Drosophila through binary expression systems like the LexA-LexAop system provides a superb tool for investigating gene and tissue function. To increase the availability of defined LexA enhancer trap insertions, we present molecular, genetic, and tissue expression studies of 301 novel Stan-X LexA enhancer traps derived from mobilization of the index SX4 line. This includes insertions into distinct loci on the X, II, and III chromosomes that were not previously associated with enhancer traps or targeted LexA constructs, an insertion into ptc, and seventeen insertions into natural transposons. A subset of enhancer traps was expressed in CNS neurons known to produce and secrete insulin, an essential regulator of growth, development, and metabolism. Fly lines described here were generated and characterized through studies by students and teachers in an international network of genetics classes at public, independent high schools, and universities serving a diversity of students, including those underrepresented in science. Thus, a unique partnership between secondary schools and university-based programs has produced and characterized novel resources in Drosophila, establishing instructional paradigms devoted to unscripted experimental science.

Carboxylated nanocellulose foams as superabsorbents.

HYPOTHESIS: Carboxylated nanocellulose fibres formed into foam structures can demonstrate superabsorption capacity. Their performance can be engineered by changing process variables. EXPERIMENTS: TEMPO-oxidised cellulose nanofibres of varying concentration and surface charge are produced from hardwood kraft pulp. Foams were prepared through a 2-step freezing and lyophilisation process. The absorption capacity of water and saline solution (0.9 wt%) were measured as a function of time and related to the foam structure. FINDINGS: The absorption capacity of nanocellulose foams can be manipulated from initial gel properties and processing conditions. Pore structure and distribution of nanocellulose foams are dictated by fibre content and charge density and freezing rate. The best performing foams are at 0.3-0.5 wt%, with a carboxylate concentration of 1.2 mmol/g and frozen at -86 °C before freeze-drying, which can absorb 120 g H2O/g fibre. Fibre surface charge influences the absorption capacity of the foams by dictating the amount of participating carboxylate groups. Absorption capacity in saline (60 g/g) is lower than in deionised water (120 g/g); but is only slightly lower than that of a commercial polyacrylic acid (PAA) SAPs (80 g/g). Nanocellulose foams are attractive renewable alternatives for superabsorbent applications, contributing to a reduction of plastic microspheres.