title: The influence of BDNF on human umbilical cord blood stem/progenitor cells: implications for stem cell-based therapy of neurodegenerative disorders.
abstract: Umbilical cord blood (UCB)-derived stem/progenitor cells (SPCs) have demonstrated the potential to improve neurologic function in different experimental models. SPCs can survive after transplantation in the neural microenvironment and indu ce neuroprotection, endogenous neurogenesis by secreting a broad repertoire of trophic and immunomodulatory cytokines. In this study, the influence of brain-derived neurotrophic factor (BDNF) pre-treatment was comprehensively evaluated in a UCB-derived lineage-negative (Lin-) SPC population. UCB-derived Lin- cells were evaluated with respect to the expression of (i) neuronal markers using immunofluorescence staining and (ii) specific (TrkB) receptors for BDNF using flow cytometry. Next, after BDNF pre-treatment, Lin- cells were extensively assessed with respect to apoptosis using Western blotting and proliferation via BrdU incorporation. Furthermore, NT-3 expression levels in Lin- cells using RQ PCR and antioxidative enzyme activities were assessed. We demonstrated neuronal markers as well as TrkB expression in Lin- cells and the activation of the TrkB receptor by BDNF. BDNF pre-treatment diminished apoptosis in Lin- cells and influenced the proliferation of these cells. We observed significant changes in antioxidants as well as in the increased expression of NT-3 in Lin- cells following BDNF exposure. Complex global miRNA and mRNA profiling analyses using microarray technology and GSEA revealed the differential regulation of genes involved in the proliferation, gene expression, biosynthetic processes, translation, and protein targeting. Our results support the hypothesis that pre-treatment of stem/progenitor cells could be beneficial and may be used as an auxiliary strategy for improving the properties of SPCs.
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Paczkowska
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Łuczkowska
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Piecyk
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Rogińska
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Pius-Sadowska
authors.affiliation: Department of Feto-Maternal Medicine and Gynecology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Przemysław
authors.initials: P
authors.lastname: Ustianowski
authors.affiliation: Department of Laboratory Diagnostics and Molecular Medicine, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Cecerska
authors.affiliation: Department of Laboratory Diagnostics and Molecular Medicine, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Dołęgowska
authors.affiliation: Department of Feto-Maternal Medicine and Gynecology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Celewicz
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland; Email: machalin@pum.edu.pl.
authors.forename: Bogusław
authors.initials: B
authors.lastname: Machaliński
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000628:therapy; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; D020813:Receptor, trkB