title: miR-21 modulates tumor outgrowth induced by human adipose tissue-derived mesenchymal stem cells in vivo.
abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in clinical situations, due principally to their potential use in regenerative medicine and tissue engineering applications. However, the therapeutic application of MSCs remains limited, unless the favorable effects of MSCs on tumor growth in vivo, and the long-term safety of the clinical applications of MSCs, can be more thoroughly understood. In this study, we determined whether microRNAs can modulate MSC-induced tumor outgrowth in BALB/c nude mice. Overexpression of miR-21 in human adipose-derived stem cells (hADSCs) inhibited hADSC-induced tumor growth, and inhibition of miR-21 increased it. Downregulation of transforming growth factor beta receptor II (TGFBR2), but not of signal transducer and activator of transcription 3, in hADSCs showed effects similar to those of miR-21 overexpression. Downregulation of TGFBR2 and overexpression of miR21 decreased tumor vascularity. Inhibition of miR-21 and the addition of TGF-β increased the levels of vascular endothelial growth factor and interleukin-6 in hADSCs. Transplantation of miR-21 inhibitor-transfected hADSCs increased blood flow recovery in a hind limb ischemia model of nude mice, compared with transplantation of control oligo-transfected cells. These findings indicate that MSCs might favor tumor growth in vivo. Thus, it is necessary to study the long-term safety of this technique before MSCs can be used as therapeutic tools in regenerative medicine and tissue engineering.
authors.affiliation: Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea.
authors.forename: Keun Koo
authors.initials: KK
authors.lastname: Shin
authors.forename: Ae Lim
authors.initials: AL
authors.lastname: Lee
authors.forename: Jee Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Yong Chan
authors.initials: YC
authors.lastname: Bae
authors.forename: Jin Sup
authors.initials: JS
authors.lastname: Jung
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000098:blood supply / Q000601:surgery*; D009389:Neovascularization, Pathologic / Q000601:surgery; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015850:Interleukin-6; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II