{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:44:26Z","timestamp":1790844266576,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,10,14]],"date-time":"2018-10-14T00:00:00Z","timestamp":1539475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008257","name":"Tarbiat Modares University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008257","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Leukemic cells can impact the bone marrow niche to create a tumor\u2010favorable microenvironment using their secreted factors. Little knowledge is available about immunosuppressive and tumor\u2010promoting properties of chronic myeloid leukemia derived exosomes in bone marrow stromal components. We report here that K562\u2010derived exosomes can affect the gene expression, cytokine secretion, nitric oxide (NO) production, and redox potential of bone marrow mesenchymal stem cells (BM\u2010MSCs) and macrophages. Human BM\u2010MSCs and mouse macrophages were treated with K562\u2010derived exosomes. Our results demonstrated that the expression of the genes involved in hematopoietic developmental pathways and immune responses, including C\u2010X\u2010C motif chemokine 12 (Cxcl12), Dickkopf\u2010related protein 1 (DKK1), wnt5a, interleukin 6 (IL\u20106), transforming growth factor\u2010beta, and tumor necrosis factor\u2010alpha (TNF\u2010alpha), changed with respect to time and exosome concentration in BM\u2010MSCs. The TNF\u2010alpha level was higher in exosome\u2010treated BM\u2010MSCs compared with the control. Exosome treatment of BM\u2010MSCs led to an increased production of\u00a0NO and a decreased production of reactive oxygen species (ROS) in a time\u2010 and concentration\u2010dependent manner. We have shown that K562\u2010derived exosomes induce overexpression of IL\u201010 and TNF\u2010alpha and downregulation of iNOS transcript levels in macrophages. The enzyme\u2010linked immunosorbent assay results showed that TNF\u2010alpha and IL\u201010 secretions increased in macrophages. Treatment of macrophages with purified exosomes led to reduced NO and ROS levels. These results suggest that K562\u2010derived exosomes may alter the local bone marrow niche toward a leukemia\u2010reinforcing microenvironment. They can modulate the inflammatory molecules (TNF\u2010alpha and NO) and the redox potential of BM\u2010MSCs and macrophages and direct the polarization of macrophages toward tumor\u2010associated macrophages.<\/jats:p>","DOI":"10.1002\/jcp.27142","type":"journal-article","created":{"date-parts":[[2018,10,14]],"date-time":"2018-10-14T08:04:36Z","timestamp":1539504276000},"page":"3697-3710","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Alteration of cellular and immune\u2010related properties of bone marrow mesenchymal stem cells and macrophages by K562 chronic myeloid leukemia cell derived exosomes"],"prefix":"10.1002","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-0710","authenticated-orcid":false,"given":"Nazli","family":"Jafarzadeh","sequence":"first","affiliation":[{"name":"Department of Genetics Faculty of Biological Sciences, Tarbiat Modares University Tehran 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