title: Effects of Salvia miltiorrhiza on neural differentiation of induced pluripotent stem cells.
abstract: BACKGROUND
  Salvia miltiorrhiza, a well-known traditional Chinese medicine, is commonly used to treat some neurological diseases because of its anti-oxidative, anti-inflammatory and anti-apoptotic properties. We investigate whether Salvia miltiorrhiza can improve the differentiation of induced pluripotent stem cells (iPSCs) into neurons in vitro, and promote iPSCs-derived neural stem cells survival, integrate, and differentiation after their transplantation to the ischemic brain tissues.
  
  
  METHODS
  Induced pluripotent stem cells were used to differentiate into neural stem cells, and further into neurons in induction medium with various concentrations of Salvia miltiorrhiza. The effects were assessed by immunofluorescence staining, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. iPSC-derived neural stem cells were transplanted into the brains of rats with middle cerebral artery occlusion, immunofluorescence staining was used to evaluate survival, integrate, and differentiation of grafted cells, the functional recovery of the animals was tested by the Longa scores and spontaneous motor activity.
  
  
  RESULTS
  Salvia miltiorrhiza (5μg/ml) significantly increased the gene and protein expression of Nestin compared with that in other groups. Microtubule-associated protein 2 (MAP2) expression in induction medium with 5μg/ml Salvia miltiorrhiza was significantly higher than that in the control group. After cells transplantation into the ischemic brain, more grafted MAP2(+) cells were found in Salvia miltiorrhiza-treated rats than others at 7 days. Salvia miltiorrhiza-treated rats showed the most remarkable functional recovery at 7 and 14 days.
  
  
  CONCLUSIONS
  Salvia miltiorrhiza induces differentiation of induced pluripotent stem cells to differentiate into neurons efficiently. The plant provides neuroprotection to implanted cells and improves functional recovery after their transplantation to the ischemic brain tissues.
authors.affiliation: Department of Spine Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shu
authors.affiliation: Department of Spine Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Pang
authors.affiliation: Department of Spine Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Rong
authors.affiliation: Department of Spine Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Gynecology, Baiyun Women׳s and Children׳s Hospital, Guangzhou, Guangdong 510000, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Spine Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects*; D020244:Infarction, Middle Cerebral Artery; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D013997:Time Factors
chemical_list: D008869:Microtubule-Associated Proteins; D010936:Plant Extracts
keywords: Induced pluripotent stem cells; Middle cerebral artery occlusion; Neural stem cells; Neuronal differentiation; Salvia miltiorrhiza