Stimulatory effect of HGF-overexpressing adipose tissue-derived mesenchymal stem cells on thymus regeneration in a rat thymus involution model

被引:16
作者
Jung, Woo-Sung [1 ]
Han, Sei-Myoung [1 ]
Kim, Sung-Min [2 ]
Kim, Mi-Eun [3 ]
Lee, Jun-Sik [3 ]
Seo, Kyoung-Won [4 ]
Youn, Hwa-Young [1 ,5 ]
Lee, Hee-Woo [5 ]
机构
[1] Seoul Natl Univ, Dept Vet Internal Med, Coll Vet Med, Seoul 151742, South Korea
[2] Korea Basic Sci Inst, Div Magnet Resonance Res, Ochang, Chungbuk, South Korea
[3] Chosun Univ, Dept Biol, Coll Nat Sci, Kwangju, South Korea
[4] Chungnam Natl Univ, Coll Vet Med, Dept Vet Internal Med, Taejon 305764, South Korea
[5] Seoul Natl Univ, Res Inst Vet Sci, Coll Vet Med, Seoul 151742, South Korea
基金
新加坡国家研究基金会;
关键词
adipose tissue-derived mesenchymal stem cells; gene therapy; hepatocyte growth factor; regeneration; thymocytes; thymus; HEPATOCYTE GROWTH-FACTOR; BONE-MARROW TRANSPLANTATION; CORTICAL EPITHELIAL-CELLS; T-CELL; IN-VITRO; THYMOCYTE PROLIFERATION; RECEPTOR EXPRESSION; MOLECULAR-CLONING; HIV-INFECTION; UP-REGULATION;
D O I
10.1002/cbin.10306
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The thymus is the central lymphoid organ providing a unique and essential microenvironment for T-cell precursor development into mature functionally competent T-lymphocytes. Thus, it is important to develop the strategies for enhancing thymic regeneration from involution induced by a variety of clinical treatments and conditions. Hepatocyte growth factor (HGF) promotes proliferation in a variety of cell types. We have used stem cell-based HGF gene therapy to enhance regeneration from acute thymic involution. HGF-overexpressing human adipose tissue-derived mesenchymal stem cells (HGF-hATMSCs) were generated by liposomal transfection with the pMEX expression vector, constructed by inserting the HGF gene. Significantly increased HGF expression in these cells was confirmed by reverse transcription-polymerase chain reaction and an enzyme-linked immunosorbent assay. HGF produced by HGF-hATMSCs enhanced the proliferation of a mouse thymic epithelial cell line and the expression of interleukin-7 in vitro. We also examined the effect of HGF-hATMSCs on thymic regeneration in rats with acute thymic involution. Significant increases in thymus size and weight, as well as the number of thymocytes (especially, early thymocyte progenitors), were seen in the HGF-hATMSCs-treated rats compared to saline-treated control animals. A stimulatory effect of HGF-hATMSCs on thymic regeneration has therefore been shown, highlighting the clinical value of HGF-hATMSCs for treating thymic involution.
引用
收藏
页码:1106 / 1117
页数:12
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