Organoids are becoming widespread in drug-screening technologies but have been used sparingly for cell therapy as current approaches for producing selforganized cell clusters lack scalability or reproducibility in size and cellular organization. We introduce a method of using hydrogels as sacrificial scaffolds, which allow cells to form self-organized clusters followed by gentle release, resulting in highly reproducible multicellular structures on a large scale. We demonstrated this strategy for endothelial cells and mesenchymal stem cells to self-organize into blood-vessel units, which were injected into mice, and rapidly formed perfusing vasculature. Moreover, in a mouse model of peripheral artery disease, intramuscular injections of blood-vessel units resulted in rapid restoration of vascular perfusion within seven days. As cell therapy transforms into a new class of therapeutic modality, this simple method-by making use of the dynamic nature of hydrogels-could offer high yields of self-organized multicellular aggregates with reproducible sizes and cellular architectures.

No abstract

Molecularly, breast cancer represents a highly heterogenous family of neoplastic disorders, with substantial interpatient variations regarding genetic mutations, cell composition, transcriptional profiles, and treatment response. Consequently, there is an increasing demand for alternative diagnostic approaches aimed at the molecular annotation of the disease on a patient‐by‐patient basis and the design of more personalized treatments. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated (Cas) technology enables the development of such novel approaches. For instance, in diagnostics, the use of the RNA‐specific C2c2 system allows ultrasensitive nucleic acid detection and could be used to characterize the mutational repertoire and transcriptional breast cancer signatures. In disease modeling, CRISPR/Cas9 technology can be applied to selectively engineer oncogenes and tumor‐suppressor genes involved in disease pathogenesis. In treatment, CRISPR/Cas9 can be used to develop gene‐therapy, while its catalytically‐dead variant (dCas9) can be applied to reprogram the epigenetic landscape of malignant cells. As immunotherapy becomes increasingly prominent in cancer treatment, CRISPR/Cas9 can engineer the immune cells to redirect them against cancer cells and potentiate antitumor immune responses. In this review, CRISPR strategies for the advancement of breast cancer diagnostics, modeling, and treatment are highlighted, culminating in a perspective on developing a precision medicine‐based approach against breast cancer.

AbstractOrganoids, by promoting self-organization of cells into native-like structures, are becoming widespread in drug-screening technologies, but have so far been used sparingly for cell therapy as current approaches for producing self-organized cell clusters lack scalability or reproducibility in size and cellular organization. We introduce a method of using hydrogels as sacrificial scaffolds, which allow cells to form self-organized clusters followed by gentle release, resulting in highly reproducible multicellular structures on a large scale. We demonstrated this strategy for endothelial cells and mesenchymal stem cells to self-organize into blood-vessel units, which were injected into mice using hypodermic needles, and observed in real time to rapidly form perfusing vasculature. As cell therapy transforms into a new class of therapeutic modality, this simple method – by making use of the dynamic nature of hydrogels – could offer high yields of self-organized multicellular aggregates with reproducible sizes and cellular architectures.

The American Academy of Pediatrics recommends the use of donor human milk in infants when mother’s own milk is not available. Our objective was to analyze whether the use of donor human milk in preterm, very-low-birth-weight (VLBW, <1500 g) infants affected the rates of necrotizing enterocolitis, duration of parenteral nutrition (PN), growth, culture-positive sepsis, length of hospital stay, and mortality in an urban NICU population with low exclusive breast-feeding rates. A retrospective cohort study was conducted comparing two 2-year epochs of VLBW neonates before and after the introduction of donor breast milk in our neonatal intensive care unit (NICU). With the introduction of donor human milk, there was a significant reduction in the rate of necrotizing enterocolitis (NEC) (5% vs. 13%; p = 0.04) and less severe NEC as defined by Stage III based on the Modified Bell Staging Criteria (10% to 3%; p = 0.04). In the donor milk era, there was earlier initiation of enteral feeding (2.69 days vs. 3.84; p = 0.006) and a more rapid return to birthweight (9.5 days. 10.9 days; p = 0.006). In this study, a change in practice to the use of donor breast milk in a population with low rates of human milk provision was associated with earlier initiation of enteral feeding, faster return to birth weight, and a reduced incidence of NEC.