Multi-functional nanotracers for image-guided stem cell gene therapy.
Stem cell therapy based on human mesenchymal stem cells (hMSCs) has shown great promise for various disease treatments. However, traditional stem cell-mediated therapy is limited due to their multipotent differentiation ability (uncontrolled spontaneous differentiation) and the difficulty in monitoring cells after implantation in vivo. Here, we report a new multi-functional stem cell nanotracer (M-NT) for directing controlled differentiation through gene delivery, as well as tracking stem cells with dual-modal imaging (optical and CT imaging). The M-NT was prepared through a facile surface modification process of ∼100 nm-sized gold nanoparticles with catechol-functionalized branched polyethylenimine (C-bPEI). The C-bPEI-functionalized M-NT exhibited greatly enhanced long-term colloidal stability in aqueous solution and a capability to complex with plasmid DNA (pDNA; i.e., pEGFP) through electrostatic interaction for gene delivery and transfection to control differentiation. M-NT/pEGFP complexes showed an enhanced transfection efficiency into hMSCs with low cytotoxicity compared with branched polyethylenimine/pDNA complexes. Accordingly, successful in vitro chondrogenic differentiation was achieved in hMSCs treated with M-NT/pSOX9 complexes. Finally, hMSCs transfected with M-NT/pEGFP complexes were transplanted into Balb/c nude mice and successfully visualized through dual-modal optical fluorescence and computed tomography (CT) imaging. We believe that this approach could represent a promising platform for genetic material-mediated direction of differentiation and cell tracking in stem cell therapy.
Department of Biomedical Science, College of Life Science, CHA University, 6F, CHA Biocomplex, Sampyeong-Dong, Bundang-gu, Seongnam-si, 13488, Republic of Korea. pkh0410@cha.ac.kr.
Ji Sun
JS
Park
Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Wooram
http://orcid.org/0000-0002-4614-0530
W
Park
Department of Biomedical Science, College of Life Science, CHA University, 6F, CHA Biocomplex, Sampyeong-Dong, Bundang-gu, Seongnam-si, 13488, Republic of Korea. pkh0410@cha.ac.kr.
A Young
AY
Kang
Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA and Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA and Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA and Department of Electrical Engineering and Computer Science, Evanston, IL 60208, USA and International Institute of Nanotechnology (IIN), Northwestern University, Evanston, IL 60208, USA.
Andrew C
AC
Larson
Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA and Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA.
Dong-Hyun
http://orcid.org/0000-0001-6815-3319
DH
Kim
Department of Biomedical Science, College of Life Science, CHA University, 6F, CHA Biocomplex, Sampyeong-Dong, Bundang-gu, Seongnam-si, 13488, Republic of Korea. pkh0410@cha.ac.kr.
Keun-Hong
http://orcid.org/0000-0002-3489-2890
KH
Park
D000818:Animals; D002396:Catechols; D002478:Cells, Cultured; D015316:Genetic Therapy; D006046:Gold; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D053768:Metal Nanoparticles; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010957:Plasmids; D011094:Polyethyleneimine; D014162:Transfection
D002396:Catechols; D006046:Gold; D011094:Polyethyleneimine; C034221:catechol