The single pass transmembrane protein CD33 is enriched in phagocytic and hematopoietic cell types, such as monocytes. CD33 is thought to be associated with immune cell function, susceptibility to Alzheimer's disease, and rare leukemias. Antagonism or genetic ablation of CD33 has been proposed to treat Alzheimer's disease, hematological cancers, and as a selection mechanism for enriching genetically altered blood cells. To understand the impact of chronic CD33 loss or ablation, we describe individuals who we confirmed to be missing CD33 due to germline loss of function variants. Through PheWAS-based approaches using existing whole exome biobanks and bespoke phenotyping using recall-by-genotype (RBG) studies, we show that CD33 loss of function alters circulating white blood cell counts and distributions, albeit mildly and with no overt clinical pathology. These findings indicate that chronic CD33 antagonism/ablation is likely to be safe in humans.
Copyright: © 2025 Dominy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bone marrow aspirate concentrate (BMAC) and adipose-derived stromal vascular fraction (ADSVF) are the most marketed stem cell therapies to treat a variety of conditions in the general population and elite athletes. Both tissues have been used interchangeably clinically even though their detailed composition, heterogeneity, and mechanisms of action have neither been rigorously inventoried nor compared. This lack of information has prevented investigations into ideal dosages and has facilitated anecdata and misinformation. Here, we analyzed single-cell transcriptomes, proteomes, and flow cytometry profiles from paired clinical-grade BMAC and ADSVF. This comparative transcriptional atlas challenges the prevalent notion that there is one therapeutic cell type present in both tissues. We also provide data of surface markers that may enable isolation and investigation of cell (sub)populations. Furthermore, the proteome atlas highlights intertissue and interpatient heterogeneity of injected proteins with potentially regenerative or immunomodulatory capacities. An interactive webtool is available online.

Glioblastoma (GBM) is one of the most common types of brain tumor in adults. Despite the availability of treatments for this disease, GBM remains one of the most lethal and difficult types of tumors to treat, and thus, a majority of patients die within 2 years of diagnosis. Infection with Zika virus (ZIKV) inhibits cell proliferation and induces apoptosis, particularly in developing neuronal cells, and thus could potentially be considered an alternative for GBM treatment. In the present study, two GBM cell lines (U-138 and U-251) were infected with ZIKV at different multiplicities of infection (0.1, 0.01 and 0.001), and cell viability, migration, adhesion, induction of apoptosis, interleukin levels and CD14/CD73 cell surface marker expression were analyzed. The present study demonstrated that ZIKV infection promoted loss of cell viability and increased apoptosis in U-138 cells, as measured by MTT and triplex assay, respectively. Changes in cell migration, as determined by wound healing assay, were not observed; however, the GBM cell lines exhibited an increase in cell adhesion when compared with non-tumoral cells (Vero). The Luminex immunoassay showed a significant increase in the expression levels of IL-4 specifically in U-251 cells (MOI 0.001) following exposure to ZIKV. There was no significant change in the expression levels of IFN-γ upon ZIKV infection in the cell lines tested. Furthermore, a marked increase in the percentage of cells expressing the CD14 surface marker was observed in both GBM cell lines compared with in Vero cells; and significantly increased CD73 expression was observed particularly in U-251 cells, when compared with uninfected cells. These findings indicate that ZIKV infection could lead to reduced cell viability, elevated CD73 expression, improved cellular adherence, and higher rates of apoptosis in glioblastoma cells. Further studies are required to explore the potential use of ZIKV in the treatment of GBM.
Copyright: © 2024 Marinowic et al.

Glioblastoma (GBM) is an aggressive brain tumor giving a poor prognosis with the current treatment options. The advent of chimeric antigen receptor (CAR) T-cell therapy revolutionized the field of immunotherapy and has provided a new set of therapeutic options for refractory blood cancers. In an effort to apply this therapeutic approach to solid tumors, various immune cell types and CAR constructs are being studied. Notably, macrophages have recently emerged as potential candidates for targeting solid tumors, attributed to their inherent tumor-infiltrating capacity and abundant presence in the tumor microenvironment.
In this study, we developed a chemically defined differentiation protocol to generate macrophages from human pluripotent stem cells (hPSCs). A GBM-specific CAR was genetically incorporated into hPSCs to generate CAR hPSC-derived macrophages.
The CAR hPSC-derived macrophages exhibited potent anticancer activity against GBM cells in vitro.
Our findings demonstrate the feasibility of generating functional CAR-macrophages from hPSCs for adoptive immunotherapy, thereby opening new avenues for the treatment of solid tumors, particularly GBM.
© 2023 The Author(s).

Alzheimer's disease (AD), the most common neurodegenerative disease and the first cause of dementia worldwide, has no effective treatment, and its pathological mechanisms are not yet fully understood. We conducted this study to explore the proteomic differences associated with Familial Alzheimer's Disease (FAD) in olfactory ecto-mesenchymal stem cells (MSCs) derived from PSEN1 (A431E) mutation carriers compared with healthy donors paired by age and gender through two label-free liquid chromatography-mass spectrometry approaches. The first analysis compared carrier 1 (patient with symptoms, P1) and its control (healthy donor, C1), and the second compared carrier 2 (patient with pre-symptoms, P2) with its respective control cells (C2) to evaluate whether the protein alterations presented in the symptomatic carrier were also present in the pre-symptom stages. Finally, we analyzed the differentially expressed proteins (DEPs) for biological and functional enrichment. These proteins showed impaired expression in a stage-dependent manner and are involved in energy metabolism, vesicle transport, actin cytoskeleton, cell proliferation, and proteostasis pathways, in line with previous AD reports. Our study is the first to conduct a proteomic analysis of MSCs from the Jalisco FAD patients in two stages of the disease (symptomatic and presymptomatic), showing these cells as a new and excellent in vitro model for future AD studies.