Modeling mesenchymal stromal cell support to hematopoiesis within a novel 3D artificial marrow organoid system

• Published in: Scientific reports Vol. 15; no. 1; pp. 23603 - 13
• Main Authors: Schell, Bérénice, Zhao, Lin-Pierre, M’Sibih, Inés, Kalogeraki, Maria, Kergaravat, Camille, Lereclus, Emilie, Fenaux, Pierre, Adès, Lionel, Toubert, Antoine, Espéli, Marion, Balabanian, Karl, Clave, Emmanuel, Dulphy, Nicolas, Bisio, Valeria
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.07.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/232/2058; 631/250/232/2059; 631/532/1542; Bone marrow; Bone Marrow - metabolism; Bone Marrow Cells - cytology; CD34 antigen; CD57 antigen; Cell Differentiation; Cells; Cytokines; Experiments; Flow cytometry; Granulocytes; Hematopoiesis; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Hemopoiesis; Humanities and Social Sciences; Humans; Killer Cells, Natural - cytology; Killer Cells, Natural - metabolism; Leukemia; Leukocytes (neutrophilic); Leukocytes (polymorphonuclear); Localization; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Microenvironments; Microscopy; Models, Biological; Monocytes; multidisciplinary; Natural killer cells; NKG2 antigen; Organoids; Organoids - cytology; Organoids - metabolism; Potassium channels (inwardly-rectifying); Progenitor cells; Reproducibility; Science; Science (multidisciplinary); Stromal cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-07717-9

The human bone marrow (BM) microenvironment involves hematopoietic and non-hematopoietic cell subsets organized in a complex architecture. Tremendous efforts have been made to model it in order to analyze normal or pathological hematopoiesis and its stromal counterpart. Herein, we report an original, fully-human in vitro 3D model of the BM microenvironment dedicated to study interactions taking place between mesenchymal stromal cells (MSC) and hematopoietic stem and progenitor cells (HSPC) during the hematopoietic differentiation. This fully-human Artificial Marrow Organoid (AMO) model is highly efficient to recapitulate MSC support to myeloid differentiation and NK cell development from the immature CD34 + HSPCs to the most terminally differentiated CD15 + polymorphonuclear neutrophils, CD64 + monocytes or NKG2A-KIR2D + CD57 + NK subset. Lastly, our model is suitable for evaluating anti-leukemic NK cell function in presence of therapeutic agents. Overall, the AMO is a versatile, low cost and simple model able to recapitulate normal hematopoiesis and allowing more physiological drug testing by taking into account both immune and non-immune BM microenvironment interactions.