title: Neural differentiation of human umbilical cord mesenchymal stem cells by cerebrospinal fluid.
abstract: OBJECTIVE
  Wharton's jelly (WJ) is the gelatinous connective tissue from the umbilical cord. It is composed of mesenchymal stem cells, collagen fibers, and proteoglycans. The stem cells in WJ have properties that are interesting for research. For example, they are simple to harvest by noninvasive methods, provide large numbers of cells without risk to the donor, the stem cell population may be expanded in vitro, cryogenically stored, thawed, genetically manipulated, and differentiated in vitro. In our study, we investigated the effect of human cerebrospinal fluid (CSF) on neural differentiation of human WJ stem cells.
  
  
  METHODS
  The cells in passage 2 were induced into neural differentiation with different concentrations of human cerebrospinal fluid. Differentiation along with neural lineage was documented by expression of three neural markers: Nestin, Microtubule-Associated Protein 2 (MAP2), and Glial Fibrillary Astrocytic Protein (GFAP) for 21 days. The expression of the identified genes was confirmed by Reverse Transcriptase PCR (RT-PCR).
  
  
  RESULTS
  Treatment with 100 and 200μg/ml CSF resulted in the expression of GFAP and glial cells marker on days 14 and 21. The expression of neural-specific genes following CSF treatment was dose-dependent and time-dependent. Treatment of the cells with a twofold concentration of CSF, led to the expression of MAP2 on day 14 of induction. No expression of GFAP was detected before day 14 or MAP2 before day 21, which shows the importance of the treatment period. In the present study, expression analysis for the known neural markers: Nestin, GFAP, and MAP2 using RT-PCR were performed. The data demonstrated that CSF could play a role as a strong inducer.
  
  
  CONCLUSIONS
  RT-PCR showed that cerebrospinal fluid promotes the expression of Nestin, MAP2, and GFAP mRNA in a dose-dependent manner, especially at a concentration of 200 μl/ml. In summary, CSF induces neurogenesis of WJ stem cells that encourages tissue engineering applications with these cells for treatments of neurodegenerative defects and traumatic brain injury.
authors.affiliation: Department of Genetics, Faculty of Biological Sciences, Shahid Beheshti University, Tehran, Iran ; Laser and Plasma Research Institute, Shahid Beheshti University, Tehran, Iran.
authors.forename: Shirin
authors.initials: S
authors.lastname: Farivar
authors.affiliation: Department of Genetics, Faculty of Biological Sciences, Shahid Beheshti University, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Mohamadzade
authors.affiliation: Department of Pediatrics, Shahid Beheshti University of Medical Sciences, Tehran, Iran ; Mofid Children's Hospital, Pediatrics Infectious Research Center (PIRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Shiari
authors.affiliation: Mofid Children's Hospital, Pediatrics Infectious Research Center (PIRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Fahimzad
keywords: Cerebrospinal fluid; Glial fibrillary astrocytic protein; Mesenchymal stem cells; Microtubule-associated protein 2; Nestin; Neurogenesis