Generation of human ILC3 from allogeneic and autologous CD34 hematopoietic progenitors toward adoptive transfer.

Type 3 innate lymphoid cells (ILC3) are important in tissue homeostasis. In the gut, ILC3 repair damaged epithelium and suppress inflammation. In allogeneic hematopoietic cell transplantation (HCT), ILC3 protect against graft-versus-host disease (GvHD), most likely by restoring tissue damage and preventing inflammation.

Optimized Guide RNA Selection Improves Cas9 Gene Editing of Human Hematopoietic Stem and Progenitor Cells.

Ribonucleoproteins (RNPs) are frequently applied for therapeutic gene editing as well as fundamental research because the method is fast, viral free, and shows fewest off target effects. We evaluated various parameters to genetically engineer human hematopoietic stem and progenitor cells (HSPCs) using Cas9 (Cas9) RNPs, and achieve gene editing efficiencies up to 80%. We find that guide RNA (gRNA) design is critical to achieve high gene editing efficiencies.

Impact of cholesterol on proinflammatory monocyte production by the bone marrow.

Aim: Preclinical work indicates that low-density lipoprotein cholesterol (LDL-C) not only drives atherosclerosis by directing the innate immune response at plaque level but also augments proinflammatory monocyte production in the bone marrow (BM) compartment. In this study, we aim to unravel the impact of LDL-C on monocyte production in the BM compartment in human subjects.

Methods And Results: A multivariable linear regression analysis in 12 304 individuals of the EPIC-Norfolk prospective population study showed that LDL-C is associated with monocyte percentage (β = 0.

The Role of Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals.

The identification of molecular drivers of disease and the compelling rise of biotherapeutics have impacted clinical care but have also come with challenges. Such therapeutics include peptides, monoclonal antibodies, antibody fragments and nontraditional binding scaffolds, activatable antibodies, bispecific antibodies, immunocytokines, antibody-drug conjugates, enzymes, polynucleotides, and therapeutic cells, as well as alternative drug carriers such as nanoparticles. Drug development is expensive, attrition rates are high, and efficacy rates are lower than desired.

The Metastatic Bone Marrow Niche in Neuroblastoma: Altered Phenotype and Function of Mesenchymal Stromal Cells.

: The bone marrow (BM) is the main site of metastases and relapse in patients with neuroblastoma (NB). BM-residing mesenchymal stromal cells (MSCs) were shown to promote tumor cell survival and chemoresistance. Here we characterize the MSC compartment of the metastatic NB BM niche.