在新型三维人工骨髓类器官系统中模拟间充质基质细胞对造血作用的支持。

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

作者信息

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

机构信息

Université Paris Cité, Institut de Recherche Saint Louis, INSERM UMR1342, 75010, Paris, France.

Leukemia Institute Paris Saint-Louis, 75010, Paris, France.

出版信息

Sci Rep. 2025 Jul 2;15(1):23603. doi: 10.1038/s41598-025-07717-9.

DOI:10.1038/s41598-025-07717-9

PMID:40604201

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12222448/

Abstract

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.

摘要

人类骨髓（BM）微环境由以复杂结构组织的造血和非造血细胞亚群组成。为了分析正常或病理性造血及其基质对应物，人们付出了巨大努力来对其进行建模。在此，我们报告了一种原始的、完全人源的体外三维BM微环境模型，该模型致力于研究间充质基质细胞（MSC）与造血干细胞和祖细胞（HSPC）在造血分化过程中发生的相互作用。这种完全人源的人工骨髓类器官（AMO）模型在重现MSC对髓系分化的支持以及从未成熟的CD34 + HSPC到最终末分化的CD15 + 多形核中性粒细胞、CD64 + 单核细胞或NKG2A - KIR2D + CD57 + NK亚群的NK细胞发育方面非常高效。最后，我们的模型适用于评估治疗药物存在时抗白血病NK细胞的功能。总体而言，AMO是一种通用、低成本且简单的模型，能够重现正常造血过程，并通过考虑免疫和非免疫BM微环境相互作用来进行更具生理性的药物测试。