title: Iron oxide nanoparticle-mediated development of cellular gap junction crosstalk to improve mesenchymal stem cells' therapeutic efficacy for myocardial infarction.
abstract: Electrophysiological phenotype development and paracrine action of mesenchymal stem cells (MSCs) are the critical factors that determine the therapeutic efficacy of MSCs for myocardial infarction (MI). In such respect, coculture of MSCs with cardiac cells has windowed a platform for cardiac priming of MSCs. Particularly, active gap junctional crosstalk of MSCs with cardiac cells in coculture has been known to play a major role in the MSC modification through coculture. Here, we report that iron oxide nanoparticles (IONPs) significantly augment the expression of connexin 43 (Cx43), a gap junction protein, of cardiomyoblasts (H9C2), which would be critical for gap junctional communication with MSCs in coculture for the generation of therapeutic potential-improved MSCs. MSCs cocultured with IONP-harboring H9C2 (cocultured MSCs: cMSCs) showed active cellular crosstalk with H9C2 and displayed significantly higher levels of electrophysiological cardiac biomarkers and a cardiac repair-favorable paracrine profile, both of which are responsible for MI repair. Accordingly, significantly improved animal survival and heart function were observed upon cMSC injection into rat MI models compared with the injection of unmodified MSCs. The present study highlights an application of IONPs in developing gap junctional crosstalk among the cells and generating cMSCs that exceeds the reparative potentials of conventional MSCs. On the basis of our finding, the potential application of IONPs can be extended in cell biology and stem cell-based therapies.
authors: †School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
authors: Jin
authors: J
authors: Han
authors: Bokyoung
authors: B
authors: Kim
authors: †School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
authors: Jung-Youn
authors: JY
authors: Shin
authors: §Interdisciplinary Program of Bioengineering, Seoul National University, Seoul 151-744, Republic of Korea.
authors: Seungmi
authors: S
authors: Ryu
authors: †School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
authors: Myungkyung
authors: M
authors: Noh
authors: Jongsu
authors: J
authors: Woo
authors: Jin-Sil
authors: JS
authors: Park
authors: †School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea.|∥Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 151-744, Republic of Korea.
authors: Youjin
authors: Y
authors: Lee
authors: ⊥School of Advanced Materials Engineering, Kookmin University, Seoul 136-702, Republic of Korea.
authors: Nohyun
authors: N
authors: Lee
authors: †School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea.|∥Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 151-744, Republic of Korea.
authors: Taeghwan
authors: T
authors: Hyeon
authors: Donghoon
authors: D
authors: Choi
authors: †School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea.|§Interdisciplinary Program of Bioengineering, Seoul National University, Seoul 151-744, Republic of Korea.
authors: Byung-Soo
authors: BS
authors: Kim
mesh_terms: D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002469:Cell Separation; D018920:Coculture Techniques; D018031:Connexin 43 / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles; D019899:Paracrine Communication; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D020257:Ventricular Remodeling
chemical_list: D018031:Connexin 43; D005290:Ferric Compounds; C000499:ferric oxide
keywords: ion delivery; iron oxide nanoparticle; mesenchymal stem cells; myocardial infarction; tissue engineering