Mesenchymal stromal cell-associated migrasomes: a new source of chemoattractant for cells of hematopoietic origin

Cell Communication and Signaling

Research

Jana Karbanová¹  Ilker A. Deniz¹  Denis Corbeil²  Martin Bornhäuser³  Manja Wobus³  Jan Dominik Kuhlmann⁴  Pauline Wimberger⁴ 

[1] Biotechnology Center (BIOTEC) and Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, 01307, Dresden, Germany;Biotechnology Center (BIOTEC) and Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, 01307, Dresden, Germany;Tissue Engineering Laboratories, Biotechnology Center, Technische Universität Dresden, Tatzberg 47-49, 01307, Dresden, Germany;Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany;Center for Regenerative Therapies Dresden, Technische Universität Dresden, 01307, Dresden, Germany;National Center for Tumor Diseases (NCT) & German Cancer Research Center (DKFZ) & Faculty of Medicine, University Hospital Carl Gustav Carus & Technische Universität Dresden & Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden and Heidelberg, Germany;National Center for Tumor Diseases (NCT) & German Cancer Research Center (DKFZ) & Faculty of Medicine, University Hospital Carl Gustav Carus & Technische Universität Dresden & Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden and Heidelberg, Germany;Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany;German Cancer Consortium (DKTK), Partner Site Dresden and German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany;

关键词: Cellular adhesion;    Extracellular vesicle;    Hematopoietic stem cell;    Intercellular signaling;    Mesenchymal stromal cell;    Migrasome;    Motility;   

DOI  :  10.1186/s12964-022-01028-6

 received in 2022-09-27, accepted in 2022-12-24,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundMultipotent mesenchymal stromal cells (MSCs) are precursors of various cell types. Through soluble factors, direct cell–cell interactions and other intercellular communication mechanisms such as extracellular vesicles and tunneling nanotubes, MSCs support tissue homeostasis. In the bone marrow microenvironment, they promote hematopoiesis. The interaction between MSCs and cancer cells enhances the cancer and metastatic potential. Here, we have demonstrated that plastic-adherent MSCs isolated from human bone marrow generate migrasomes, a newly discovered organelle playing a role in intercellular communication.ResultsMigrasomes are forming a network with retraction fibers behind the migrating MSCs or surrounding them after membrane retraction. The MSC markers, CD44, CD73, CD90, CD105 and CD166 are present on the migrasome network, the latter being specific to migrasomes. Some migrasomes harbor the late endosomal GTPase Rab7 and exosomal marker CD63 indicating the presence of multivesicular bodies. Stromal cell-derived factor 1 (SDF-1) was detected in migrasomes, suggesting that they play a chemoattractant role. Co-cultures with KG-1a leukemic cells or primary CD34+ hematopoietic progenitors revealed that MSC-associated migrasomes attracted them, a process intercepted by the addition of AMD3100, a specific CXCR4 receptor inhibitor, or recombinant SDF-1. An antibody directed against CD166 reduced the association of hematopoietic cells and MSC-associated migrasomes. In contrast to primary CD34+ progenitors, leukemic cells can take up migrasomes.ConclusionOverall, we described a novel mechanism used by MSCs to communicate with cells of hematopoietic origin and further studies are needed to decipher all biological aspects of migrasomes in the healthy and transformed bone marrow microenvironment.1ydn92XG6FRTxRi1UCUyVwVideo Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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