Biology subjects

Hurwitz, S. N.

Publications and source records attributed to Hurwitz, S. N..

3 recordsLinked to original sources

bioRxiv2026

Modeling competitive transplantation using HLA-mismatched human hematopoietic stem cells

BackgroundCompetitive transplantation is essential for defining intrinsic repopulating capacity of murine hematopoietic stem and progenitor cells (HSPCs), yet comparable assays for human cells have been limited by the lack of a robust in vivo platform. MethodsHere, we describe a novel competitive transplantation method in humanized NOD.Cg-KitW-41J Tyr + Prkdcscid Il2rgtm1Wjl/ThomJ (NBSGW) mice that enables simultaneous engraftment and longitudinal tracking of distinct human grafts within a shared microenvironment. ResultsUsing human leukocyte antigen-mismatched donor CD34+ cells, this method facilitates standard flow cytometry panels to track multiple donor cell chimerism, lineage output, and HSPC composition. The experimental framework may be adapted to different mouse models, conditioning strategies, donor sources, and treatments. ConclusionsOverall, this humanized competitive repopulation assay fills a critical translational gap and offers a flexible foundation for advancing mechanistic discovery in human hematopoietic biology and improving clinical strategies for stem cell transplantation.

cell biology↗

bioRxiv2025

Advanced Deep Learning Enables Prediction of Allogeneic Stem Cell Mobilization Success

Hematopoietic stem and progenitor cell (HSPC) transplantation offers a potentially curative therapy for aggressive hematologic malignancies and bone marrow failure syndromes. Successful transplantation depends on effective mobilization of donor CD34+ cells, yet some healthy donors fail to achieve adequate CD34+ yields despite standard granulocyte colony-stimulating factor (G-CSF)-based regimens. Early identification of such donors enables timely intervention, improving transplantation outcomes and reducing healthcare costs. We analyzed demographic and pre- and post-G-CSF laboratory data from 1,160 healthy donors from across multiple institutions and developed two complementary machine-learning frameworks to predict mobilization outcome. A transformer-based probabilistic model (TabPFN) trained on baseline complete blood counts (CBCs) rigorously discriminates poor from good mobilizers. Applying the same architecture to donor data after mobilization attains near-perfect discrimination. To unify the predictions across time points, we introduce an attention-aware neural network that ingests either baseline or post-mobilization data via a "lab-type" context flag, enabling accurate prediction of poor mobilizers both before and after GCSF mobilization. We further validated the framework on data from over 19,000 healthy donors compiled by the Center for International Blood and Marrow Transplant Research. These interpretable models enable early triage and "just-in-time" rescue interventions, providing a data driven foundation for personalized donor mobilization strategies.

bioinformatics↗

bioRxiv2023

Inflammatory Recruitment of Healthy Hematopoietic Stem and Progenitor Cells in the Acute Myeloid Leukemia Niche

Inflammation in the bone marrow (BM) microenvironment is a constitutive component of leukemogenesis in acute myeloid leukemia (AML). Current evidence suggests that both leukemic blasts and stroma secrete proinflammatory factors that actively suppress the function of healthy hematopoietic stem and progenitor cells (HSPCs). HSPCs are also cellular components of the innate immune system, and we reasoned that they may actively propagate the inflammation in the leukemic niche. In two separate congenic models of AML we confirm by evaluation of the BM plasma secretome and HSPC-selective single-cell RNA sequencing (scRNA-Seq) that multipotent progenitors and long-lived stem cells adopt inflammatory gene expression programs, even at low BM leukemic burden. In particular, we observe interferon gamma (IFN-{gamma}) pathway activation, along with secretion of its chemokine target, CXCL10. We show that AML-derived nanometer-sized extracellular vesicles (EVAML) are sufficient to trigger this inflammatory HSPC response, both in vitro and in vivo. Altogether, our studies indicate that HSPCs are an unrecognized component of the inflammatory adaptation of the BM by leukemic cells. The pro-inflammatory conversion and long-lived presence of HSPC in the BM along with their regenerative re-expansion during remission may impact clonal selection and disease evolution.

cancer biology↗