Downregulated CXCL12 expression in mesenchymal stem cells associated with severe aplastic anemia in children

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• 作者：Yu-Hua Chao (1) (2) (3)
  Kang-Hsi Wu (4) (5)
  Shiow-Her Chiou (6)
  Shu-Fen Chiang (6)
  Chih-Yang Huang (6)
  Hsiu-Ching Yang (7)
  Chin-Kan Chan (8)
  Ching-Tien Peng (4) (5) (9)
  Han-Ping Wu (10)
  Kuan-Chih Chow (7)
  Maw-Sheng Lee (1) (11)
  
  1. Institute of Medicine ; Chung Shan Medical University ; No. 110 ; Sec. 1 ; Chien-Kuo N. Road ; Taichung ; 402 ; Taiwan
  2. Department of Pediatrics ; Chung Shan Medical University Hospital ; Taichung ; Taiwan
  3. School of Medicine ; Chung Shan Medical University ; Taichung ; Taiwan
  4. Department of Hemato-oncology ; Children鈥檚 Hospital ; China Medical University Hospital ; China Medical University ; Taichung ; Taiwan
  5. School of Chinese Medicine ; China Medical University ; Taichung ; Taiwan
  6. Graduate Institute of Microbiology and Public Health ; National Chung Hsing University ; Taichung ; Taiwan
  7. Graduate Institute of Biomedical Sciences ; National Chung Hsing University ; No. 250 ; Kuo-Kuang Road ; Taichung ; 40227 ; Taiwan
  8. Department of Pediatrics ; Taoyuan General Hospital ; Taoyuan ; Taiwan
  9. Department of Biotechnology and Bioinformatics ; Asia University ; Taichung ; Taiwan
  10. Department of Pediatrics ; Buddhist Tzu-Chi General Hospital ; Taichung Branch ; Taichung ; Taiwan
  11. Department of Obstetrics and Gynecology ; Chung Shan Medical University Hospital ; Taichung ; Taiwan
  
• 关键词：Aplastic anemia ; Bone marrow failure ; CXCL12 ; Gene expression ; Mesenchymal stem cells
• 刊名：Annals of Hematology
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：94
• 期：1
• 页码：13-22
• 全文大小：4,649 KB
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• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Hematology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0584

文摘

The mechanisms of idiopathic severe aplastic anemia (SAA) in children are not completely understood. Insufficiency of the bone marrow microenvironment, in which mesenchymal stem cells (MSCs) are an important element, can be a potential factor associated with hematopoietic impairment. In the current study, we studied whether aberrant gene expression could be found in MSCs from children with SAA. Using microarray analysis, two different patterns of global gene expression were detected in the SAA MSCs. Fourteen genes (POLE2, HGF, KIF20A, TK1, IL18R1, KITLG, FGF18, RRM2, TTK, CXCL12, DLG7, TOP2A, NUF2, and TYMS), which are related to DNA synthesis, cytokines, or growth factors, were significantly downregulated. Further, knockdown of gene expression was performed using the small hairpin RNA (shRNA)-containing lentivirus method. We found that knockdown of CXCL12, HGF, IL-18R1, FGF18, or RRM2 expression compelled MSCs from the controls to behave like those from the SAA children, with decreased survival and differentiation potential. Among them, inhibition of CXCL12 gene expression had the most profound effects on the behavior of MSCs. Further experiments regarding re-introduction of the CXCL12 gene could largely recover the survival and differentiation potential in MSCs with inhibition of CXCL12 expression. Our findings suggest that MSCs from children with SAA exhibit aberrant gene expression profiles and downregulation of CXCL12 gene may be associated with alterations in the bone marrow microenvironment.