title: Stimulatory effect of HGF-overexpressing adipose tissue-derived mesenchymal stem cells on thymus regeneration in a rat thymus involution model.
abstract: 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.
authors.affiliation: Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea.
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Jung
authors.forename: Sei-Myoung
authors.initials: SM
authors.lastname: Han
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Kim
authors.forename: Mi-Eun
authors.initials: ME
authors.lastname: Kim
authors.forename: Jun-Sik
authors.initials: JS
authors.lastname: Lee
authors.forename: Kyoung-Won
authors.initials: KW
authors.lastname: Seo
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Youn
authors.forename: Hee-Woo
authors.initials: HW
authors.lastname: Lee
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017077:Culture Media, Conditioned; D020381:Interleukin-17; D017228:Hepatocyte Growth Factor
keywords: adipose tissue-derived mesenchymal stem cells; gene therapy; hepatocyte growth factor; regeneration; thymocytes; thymus