title: Inducible HGF-secreting Human Umbilical Cord Blood-derived MSCs Produced via TALEN-mediated Genome Editing Promoted Angiogenesis.
abstract: Mesenchymal stem cells (MSCs) promote therapeutic angiogenesis to cure serious vascular disorders. However, their survival period and cytokine-secretory capacity are limited. Although hepatocyte growth factor (HGF) can accelerate the rate of angiogenesis, recombinant HGF is limited because of its very short half-life (<3-5 minutes). Thus, continuous treatment with HGF is required to obtain an effective therapeutic response. To overcome these limitations, we produced genome-edited MSCs that secreted HGF upon drug-specific induction. The inducible HGF expression cassette was integrated into a safe harbor site in an MSC chromosome using the TALEN system, resulting in the production of TetOn-HGF/human umbilical cord blood-derived (hUCB)-MSCs. Functional assessment of the TetOn-HGF/hUCB-MSCs showed that they had enhanced mobility upon the induction of HGF expression. Moreover, long-term exposure by doxycycline (Dox)-treated TetOn-HGF/hUCB-MSCs enhanced the anti-apoptotic responses of genome-edited MSCs subjected to oxidative stress and improved the tube-formation ability. Furthermore, TetOn-HGF/hUCB-MSCs encapsulated by arginine-glycine-aspartic acid (RGD)-alginate microgel induced to express HGF improved in vivo angiogenesis in a mouse hindlimb ischemia model. This study showed that the inducible HGF-expressing hUCB-MSCs are competent to continuously express and secrete HGF in a controlled manner. Thus, the MSCs that express HGF in an inducible manner are a useful therapeutic modality for the treatment of vascular diseases requiring angiogenesis.
authors.affiliation: Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Chang
authors.affiliation: Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.|Current address: Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon, South Korea.
authors.forename: Pyung-Hwan
authors.initials: PH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Hyun-Min
authors.initials: HM
authors.lastname: Cho
authors.affiliation: Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Soo-Young
authors.initials: SY
authors.lastname: Yum
authors.affiliation: Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: YeonSung
authors.initials: Y
authors.lastname: Son
authors.affiliation: Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: DaBin
authors.initials: D
authors.lastname: Lee
authors.affiliation: Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: InSung
authors.initials: I
authors.lastname: Kang
authors.affiliation: Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
authors.affiliation: Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Goo
authors.initials: G
authors.lastname: Jang
authors.affiliation: Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Je-Yoel
authors.initials: JY
authors.lastname: Cho