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K562 cell-derived exosomes suppress the adhesive function of bone marrow mesenchymal stem cells via delivery of miR-711
Institution:1. Department of Cytogenetics, National Institute of Immunohaematology, 13th Floor, New Multistoried Building, KEM Hospital Campus, Parel, Mumbai 400012, India;2. Department of Haematology, 10th Floor, New Multistoried Building, KEM Hospital, Parel, Mumbai 400012, India
Abstract:A failure of bone marrow mesenchymal stem cells (BM-MSCs) to adhere to hematopoietic cells is an essential cause of the progression of chronic myelogenous leukemia and is also a cause of failure of bone marrow (BM) transplantation, but the exact mechanisms of this have not been fully elucidated. Recent studies have indicated that microRNAs (miRNAs) are contained in leukemia-derived exosomes and are involved in modulating the BM microenvironment. In this study, we found that K562 cell-derived exosomes transfer miR-711 to BM-MSCs and suppress the adhesive function of BM-MSCs. Using qRT-PCR, we also confirmed a significantly higher level of miR-711 in exosomes derived from K562 cells than in exosomes derived from parental cells. The BM-MSCs co-cultured with exosomes derived from K562 cells showed a lower adhesion rate than did controls. We further demonstrated that exosomal transfer of miR-711 induced decreased adhesive abilities by inhibiting expression of adhesion molecule CD44 in BM-MSCs. In conclusion, our study reveals that K562 cell-derived exosomal miR-711 can be transferred to BM-MSCs and weaken adhesive abilities by silencing the expression of the adhesion molecule CD44.
Keywords:K562 cells  Exosomes  miR-711  Bone marrow mesenchymal stem cells  BM-MSCs"}  {"#name":"keyword"  "$":{"id":"kwrd0035"}  "$$":[{"#name":"text"  "_":"Bone marrow mesenchymal stem cells  CML"}  {"#name":"keyword"  "$":{"id":"kwrd0045"}  "$$":[{"#name":"text"  "_":"Chronic myelogenous leukemia  TKIs"}  {"#name":"keyword"  "$":{"id":"kwrd0055"}  "$$":[{"#name":"text"  "_":"Tyrosine kinase inhibitors  HSCT"}  {"#name":"keyword"  "$":{"id":"kwrd0065"}  "$$":[{"#name":"text"  "_":"Hematopoietic stem cell transplantation  BM"}  {"#name":"keyword"  "$":{"id":"kwrd0075"}  "$$":[{"#name":"text"  "_":"Bone marrow  MSCs"}  {"#name":"keyword"  "$":{"id":"kwrd0085"}  "$$":[{"#name":"text"  "_":"Mesenchymal stem cells  DMEM"}  {"#name":"keyword"  "$":{"id":"kwrd0095"}  "$$":[{"#name":"text"  "_":"Dulbecco’s Modified Eagle Medium  IMDM"}  {"#name":"keyword"  "$":{"id":"kwrd0105"}  "$$":[{"#name":"text"  "_":"Iscove’s Modified Dubecco’s Medium  FBS"}  {"#name":"keyword"  "$":{"id":"kwrd0115"}  "$$":[{"#name":"text"  "_":"Fetal bovine serum  HUCBMNCs"}  {"#name":"keyword"  "$":{"id":"kwrd0125"}  "$$":[{"#name":"text"  "_":"Human umbilical cord blood mononuclear cells  PBS"}  {"#name":"keyword"  "$":{"id":"kwrd0135"}  "$$":[{"#name":"text"  "_":"Phosphate-buffered saline  TEM"}  {"#name":"keyword"  "$":{"id":"kwrd0145"}  "$$":[{"#name":"text"  "_":"Transmission Electron Microscopy  PVDF"}  {"#name":"keyword"  "$":{"id":"kwrd0155"}  "$$":[{"#name":"text"  "_":"Polyvinylidene difluoride  HSCs"}  {"#name":"keyword"  "$":{"id":"kwrd0165"}  "$$":[{"#name":"text"  "_":"Hematopoietic stem cells
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