title: Thermo-responsive polymeric nanoparticles for enhancing neuronal differentiation of human induced pluripotent stem cells.
abstract: We report thermo-responsive retinoic acid (RA)-loaded poly(N-isopropylacrylamide)-co-acrylamide (PNIPAM-co-Am) nanoparticles for directing human induced pluripotent stem cell (hiPSC) fate. Fourier transform infrared spectroscopy and (1)H nuclear magnetic resonance analysis confirmed that RA was efficiently incorporated into PNIAPM-co-Am nanoparticles (PCANs). The size of PCANs dropped with increasing temperatures (300-400 nm at room temperature, 80-90 nm at 37°C) due to its phase transition from hydrophilic to hydrophobic. Due to particle shrinkage caused by this thermo-responsive property of PCANs, RA could be released from nanoparticles in the cells upon cellular uptake. Immunocytochemistry and quantitative real-time polymerase chain reaction analysis demonstrated that neuronal differentiation of hiPSC-derived neuronal precursors was enhanced after treatment with 1-2 μg/ml RA-loaded PCANs. Therefore, we propose that this PCAN could be a potentially powerful carrier for effective RA delivery to direct hiPSC fate to neuronal lineage.
  
  
  BACKGROUND
  The use of induced pluripotent stem cells (iPSCs) has been at the forefront of research in the field of regenerative medicine, as these cells have the potential to differentiate into various terminal cell types. In this article, the authors utilized a thermo-responsive polymer, Poly(N-isopropylacrylamide) (PNIPAM), as a delivery platform for retinoic acid. It was shown that neuronal differentiation could be enhanced in hiPSC-derived neuronal precursor cells. This method may pave a way for future treatment of neuronal diseases.
authors.affiliation: Department of Mechanical Engineering, Sogang University, Seoul, Republic of Korea.
authors.forename: Hye In
authors.initials: HI
authors.lastname: Seo
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Ann-Na
authors.initials: AN
authors.lastname: Cho
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jiho
authors.initials: J
authors.lastname: Jang
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul, Republic of Korea; Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: seungwoocho@yonsei.ac.kr.
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Mechanical Engineering, Sogang University, Seoul, Republic of Korea. Electronic address: bchung@sogang.ac.kr.
authors.forename: Bong Geun
authors.initials: BG
authors.lastname: Chung
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects*; D004337:Drug Carriers; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009474:Neurons / Q000187:drug effects*; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D013696:Temperature; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D011108:Polymers; C052970:poly-N-isopropylacrylamide; D014212:Tretinoin
keywords: Human induced pluripotent stem cells; Neuronal differentiation; Poly(N-isopropylacrylamide)-co-acrylamide; Retinoic acid; Thermo-responsive nanoparticle