Brain-Derived Neurotrophic Factor Loaded PS80 PBCA Nanocarrier for In Vitro Neural Differentiation of Mouse Induced Pluripotent Stem Cells.
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-1α 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.
Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan. yen5103106@gmail.com.
Chiu-Yen
CY
Chung
Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan. martin.lin@uclmail.net.
Martin Hsiu-Chu
MH
Lin
Department of Medical Research, Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan. geneasylum@yahoo.com.tw.
I-Neng
IN
Lee
College of Medicine, Chang Gung University, Tao-Yuan 33302, Taiwan. thlee@adm.cgmh.org.tw.|Stroke Center and Department of Neurology, Chang Gung Memorial Hospital, Linkou 33305, Taiwan. thlee@adm.cgmh.org.tw.
Tsong-Hai
TH
Lee
Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan. ming2072@cgmh.org.tw.
Ming-Hsueh
MH
Lee
Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan. jents716@ms32.hinet.net.|College of Medicine, Chang Gung University, Tao-Yuan 33302, Taiwan. jents716@ms32.hinet.net.
Jen-Tsung
JT
Yang
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002460:Cell Line; D004659:Enbucrilate / Q000009:adverse effects / Q000737:chemistry*; D005822:Genetic Vectors / Q000008:administration & dosage; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011136:Polysorbates / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012313:RNA / Q000008:administration & dosage; D020218:Response Elements
D019208:Brain-Derived Neurotrophic Factor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011136:Polysorbates; C039919:RNA, recombinant; D012313:RNA; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D004659:Enbucrilate
brain-derived neurotrophic factor; hypoxia-responsive element; induced pluripotent stem cell; polybutylcyanoacrylate nanocarrier