Abstract：
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.
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.
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.
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.
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.
摘要：
多能间充质基质细胞(MSC)是各种细胞类型的前体。通过可溶性因素，直接的细胞-细胞相互作用和其他细胞间通讯机制，如细胞外囊泡和隧道纳米管，MSC支持组织稳态。在骨髓微环境中，它们促进造血。MSC与癌细胞之间的相互作用增强了癌症和转移潜力。这里,我们已经证明，从人类骨髓中分离的塑料粘附的MSCs会产生迁移体，一种新发现的细胞器，在细胞间通讯中起作用。
迁移体形成网络，在迁移的MSC后面或在膜回缩后围绕它们的回缩纤维。MSC标记，CD44，CD73，CD90，CD105和CD166存在于迁移体网络上，后者特定于偏头痛。一些迁徙体带有晚期内体GTP酶Rab7和外泌体标记CD63，表明存在多囊泡体。在迁移体中检测到基质细胞衍生因子1（SDF-1），表明它们起着化学引诱作用。与KG-1a白血病细胞或原代CD34造血祖细胞的共培养表明，MSC相关的迁移体吸引了它们，通过添加特定的CXCR4受体抑制剂AMD3100来拦截的过程，或重组SDF-1。针对CD166的抗体减少了造血细胞和MSC相关的迁移体的关联。与初级CD34+祖细胞相反，白血病细胞可以吸收迁移体。
总的来说，我们描述了MSCs与造血源细胞通讯的新机制,需要进一步的研究来破译健康和转化的骨髓微环境中迁移体的所有生物学方面.视频摘要。
迁移体形成网络，在迁移的MSC后面或在膜回缩后围绕它们的回缩纤维。
总的来说，
