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

Research output: Contribution to journalResearch articleContributedpeer-review

Abstract

BACKGROUND: Multipotent 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.

RESULTS: Migrasomes 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.

CONCLUSION: Overall, 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. Video Abstract.

Details

Original languageEnglish
Number of pages17
JournalCell Communication and Signaling
Volume21
Issue number1
Publication statusPublished - 14 Feb 2023
Peer-reviewedYes

External IDs

unpaywall 10.1186/s12964-022-01028-6
Mendeley b61732a4-4f1c-357a-acfa-ba512bd8e3ac
Scopus 85148052779
ORCID /0000-0003-1181-3659/work/142252262
ORCID /0000-0001-7687-0983/work/142253734

Keywords

Research priority areas of TU Dresden

Subject groups, research areas, subject areas according to Destatis

Sustainable Development Goals

Keywords

  • Cellular adhesion, Extracellular vesicle, Hematopoietic stem cell, Intercellular signaling, Mesenchymal stromal cell, Migrasome, Motility, Stromal Cells/metabolism, Humans, Cells, Cultured, Chemotactic Factors/metabolism, Mesenchymal Stem Cells/metabolism, Bone Marrow Cells, Antigens, CD34/metabolism, Cell Differentiation, Hematopoietic Stem Cells