Document Detail

Mesenchymal stem cells induce granulocytic differentiation of acute promyelocytic leukemic cells via IL-6 and MEK/ERK pathways.
MedLine Citation:
PMID:  23391335     Owner:  NLM     Status:  MEDLINE    
All-trans retinoic acid (ATRA) induces clinical remission in most acute promyelocytic leukemia (APL) patients by inducing terminal differentiation of APL cells toward mature granulocytes. Here we report that human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are capable of inducing granulocytic differentiation of the APL-derived NB4 cell line as well as primary APL cells and also cooperate with ATRA in an additive manner. Transwell coculture experiments revealed that UC-MSCs' differentiation-inducing effect was mediated through some soluble factors. Differentiation attenuation by IL-6Ra neutralization and induction by addition of exogenous IL-6 confirmed that IL-6 secreted by UC-MSCs was at least partially responsible for this differentiation induction process. Moreover, we found that UC-MSCs activated the MEK/ERK signaling pathway in promyelocytic cells and pharmacological inhibition of the MEK/ERK pathway reversed UC-MSC-induced differentiation, indicating that UC-MSCs exerted effect through activation of the MEK/ERK signaling pathway. These results demonstrate for the first time a stimulatory effect of MSCs on the differentiation of APL cells and bring a new insight into the interaction between MSCs and leukemic cells. Our data suggest that UC-MSCs/ATRA combination could be used as a novel therapeutic strategy for APL patients.
Fang Chen; Kang Zhou; Lei Zhang; Fengxia Ma; Dandan Chen; Junjie Cui; Xiaoming Feng; Shaoguang Yang; Ying Chi; Zhibo Han; Feng Xue; Lijuan Rong; Meili Ge; Li Wan; Shuxia Xu; Wenjing Du; Shihong Lu; Hongying Ren; Zhongchao Han
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-15
Journal Detail:
Title:  Stem cells and development     Volume:  22     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-17     Completed Date:  2014-02-13     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1955-67     Citation Subset:  IM    
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MeSH Terms
Cell Differentiation / drug effects,  genetics
Cell Line, Tumor
Cell- and Tissue-Based Therapy
Granulocytes / cytology,  metabolism
Interleukin-6 / biosynthesis*,  genetics
Leukemia, Promyelocytic, Acute / pathology,  therapy*
MAP Kinase Signaling System / genetics*
Mesenchymal Stromal Cells / cytology*,  drug effects
Tretinoin / pharmacology*
Umbilical Cord / cytology,  drug effects
Reg. No./Substance:
0/Interleukin-6; 5688UTC01R/Tretinoin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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