PMID- 28335495 OWN - NLM STAT- MEDLINE DCOM- 20170428 LR - 20200306 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 18 IP - 3 DP - 2017 Mar 19 TI - Brain-Derived Neurotrophic Factor Loaded PS80 PBCA Nanocarrier for In Vitro Neural Differentiation of Mouse Induced Pluripotent Stem Cells. LID - 10.3390/ijms18030663 [doi] LID - 663 AB - Brain derived neurotrophic factor (BDNF) can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC) was constructed to deliver plasmid DNAs (pDNAs) containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF). The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs) to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting. The HRE-cmvBDNF appeared to adsorb onto the surface of PS80 PBCA NC, with a resultant mean diameter of 92.6 +/- 1.0 nm and zeta potential of -14.1 +/- 1.1 mV. HIF-1alpha level in iPSCs was significantly higher in hypoxia, which resulted in a 51% greater BDNF expression when transfected with PS80 PBCA NC/HRE-cmvBDNF than those without hypoxia. TrkB and phospho-Akt were also elevated which correlated with neural differentiation. The findings suggest that PS80 PBCA NC too can be endocytosed to serve as an efficient vector for genes coupled to the HRE in hypoxia-sensitive cells, and activation of the PI3/Akt pathway in iPSCs by BDNF is capable of neural lineage specification. FAU - Chung, Chiu-Yen AU - Chung CY AD - Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan. yen5103106@gmail.com. FAU - Lin, Martin Hsiu-Chu AU - Lin MH AD - Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan. martin.lin@uclmail.net. FAU - Lee, I-Neng AU - Lee IN AD - Department of Medical Research, Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan. geneasylum@yahoo.com.tw. FAU - Lee, Tsong-Hai AU - Lee TH AD - College of Medicine, Chang Gung University, Tao-Yuan 33302, Taiwan. thlee@adm.cgmh.org.tw. AD - Stroke Center and Department of Neurology, Chang Gung Memorial Hospital, Linkou 33305, Taiwan. thlee@adm.cgmh.org.tw. FAU - Lee, Ming-Hsueh AU - Lee MH AD - Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan. ming2072@cgmh.org.tw. FAU - Yang, Jen-Tsung AU - Yang JT AD - Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan. jents716@ms32.hinet.net. AD - College of Medicine, Chang Gung University, Tao-Yuan 33302, Taiwan. jents716@ms32.hinet.net. LA - eng PT - Journal Article DEP - 20170319 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Polysorbates) RN - 0 (RNA, recombinant) RN - 63231-63-0 (RNA) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - F8CEP82QNP (Enbucrilate) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - *Cell Differentiation MH - Cell Hypoxia MH - Cell Line MH - Enbucrilate/adverse effects/*chemistry MH - Genetic Vectors/administration & dosage MH - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism MH - Induced Pluripotent Stem Cells/*cytology/metabolism MH - Mice MH - Nanoparticles/*chemistry MH - Neurons/*cytology/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Polysorbates/chemistry MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA/administration & dosage MH - Response Elements PMC - PMC5372675 OTO - NOTNLM OT - brain-derived neurotrophic factor OT - hypoxia-responsive element OT - induced pluripotent stem cell OT - polybutylcyanoacrylate nanocarrier COIS- The authors declared no conflicts of interest. EDAT- 2017/03/25 06:00 MHDA- 2017/04/30 06:00 PMCR- 2017/03/01 CRDT- 2017/03/25 06:00 PHST- 2017/01/30 00:00 [received] PHST- 2017/03/14 00:00 [revised] PHST- 2017/03/15 00:00 [accepted] PHST- 2017/03/25 06:00 [entrez] PHST- 2017/03/25 06:00 [pubmed] PHST- 2017/04/30 06:00 [medline] PHST- 2017/03/01 00:00 [pmc-release] AID - ijms18030663 [pii] AID - ijms-18-00663 [pii] AID - 10.3390/ijms18030663 [doi] PST - epublish SO - Int J Mol Sci. 2017 Mar 19;18(3):663. doi: 10.3390/ijms18030663.