Limitations in mitochondrial programming restrain the differentiation and maturation of human stem cell-derived β cells.

Pluripotent stem cell (SC)-derived islets offer hope as a renewable source for β cell replacement for type 1 diabetes (T1D), yet functional and metabolic immaturity may limit their long-term therapeutic potential. Here, we show that limitations in mitochondrial transcriptional programming impede the formation and maturation of SC-derived β (SC-β) cells. Utilizing transcriptomic profiling, assessments of chromatin accessibility, mitochondrial phenotyping, and lipidomics analyses, we observed that SC-β cells exhibit reduced oxidative and mitochondrial fatty acid metabolism compared to primary human islets that are related to limitations in key mitochondrial transcriptional networks.

Polymer scaffolds delineate healthy from diseased states at sites distal from the pancreas in two models of type 1 diabetes.

Type 1 diabetes (T1D) prevention is currently limited by the lack of diagnostic tools able to identify disease before autoimmune destruction of the pancreatic β cells. Autoantibody tests are used to predict risk and, in combination with glucose dysregulation indicative of β cell loss, to determine administration of immunotherapies. Our objective was to remotely identify immune changes associated with the disease, and we have employed a subcutaneously implanted microporous poly(e-caprolactone) (PCL) scaffold to function as an immunological niche (IN) in two models of T1D.

An engineered niche delineates metastatic potential of breast cancer.

Metastatic breast cancer is often not diagnosed until secondary tumors have become macroscopically visible and millions of tumor cells have invaded distant tissues. Yet, metastasis is initiated by a cascade of events leading to formation of the pre-metastatic niche, which can precede tumor formation by a matter of years. We aimed to distinguish the potential for metastatic disease from nonmetastatic disease at early times in triple-negative breast cancer using sister cell lines 4T1 (metastatic), 4T07 (invasive, nonmetastatic), and 67NR (nonmetastatic).

Extrahepatic transplantation of 3D cultured stem cell-derived islet organoids on microporous scaffolds.

Stem cell differentiation methods have been developed to produce cells capable of insulin secretion which are showing promise in clinical trials for treatment of type-1 diabetes. Nevertheless, opportunities remain to improve cell maturation and function. Three-dimensional (3D) culture has demonstrated improved differentiation and metabolic function in organoid systems, with biomaterial scaffolds employed to direct cell assembly and facilitate cell-cell contacts.

Fas Ligand-Modified Scaffolds Protect Stem Cell Derived β-Cells by Modulating Immune Cell Numbers and Polarization.

Stem cell derived β-cells have demonstrated the potential to control blood glucose levels and represent a promising treatment for Type 1 diabetes (T1D). Early engraftment post-transplantation and subsequent maturation of these β-cells are hypothesized to be limited by the initial inflammatory response, which impacts the ability to sustain normoglycemia for long periods. We investigated the survival and development of immature hPSC-derived β-cells transplanted on poly(lactide--glycolide) (PLG) microporous scaffolds into the peritoneal fat, a site being considered for clinical translation.

Membrane-coated nanoparticles for direct recognition by T cells.

The direct modulation of T cell responses is an emerging therapeutic strategy with the potential to modulate undesired immune responses including, autoimmune disease, and allogeneic cells transplantation. We have previously demonstrated that poly(lactide-co-glycolide) particles were able to modulate T cell responses indirectly through antigen-presenting cells (APCs). In this report, we investigated the design of nanoparticles that can directly interact and modulate T cells by coating the membranes from APCs onto nanoparticles to form membrane-coated nanoparticles (MCNPs).

Chemical Exposure-Induced Developmental Neurotoxicity in Head-Regenerating Schmidtea mediterranea.

The growing number of commercially used chemicals that are under-evaluated for developmental neurotoxicity (DNT) combined with the difficulty in describing the etiology of exposure-related neurodevelopmental toxicity has created a reticent threat to human health. Current means of screening chemicals for DNT are limited to expensive, time-consuming, and labor-intensive traditional laboratory animal models. In this study, we hypothesize that exposed head-regenerating planarian flatworms can effectively and efficiently categorize DNT in known developmental neurotoxins (ethanol and bisphenol A [BPA]).

Protein-Polysaccharide Composite Materials: Fabrication and Applications.

Protein-polysaccharide composites have been known to show a wide range of applications in biomedical and green chemical fields. These composites have been fabricated into a variety of forms, such as films, fibers, particles, and gels, dependent upon their specific applications. Post treatments of these composites, such as enhancing chemical and physical changes, have been shown to favorably alter their structure and properties, allowing for specificity of medical treatments.

Protein and Polysaccharide-Based Magnetic Composite Materials for Medical Applications.

The combination of protein and polysaccharides with magnetic materials has been implemented in biomedical applications for decades. Proteins such as silk, collagen, and elastin and polysaccharides such as chitosan, cellulose, and alginate have been heavily used in composite biomaterials. The wide diversity in the structure of the materials including their primary monomer/amino acid sequences allow for tunable properties.