title: Humoral activity of cord blood-derived stem/progenitor cells: implications for stem cell-based adjuvant therapy of neurodegenerative disorders.
abstract: BACKGROUND
  Stem/progenitor cells (SPCs) demonstrate neuro-regenerative potential that is dependent upon their humoral activity by producing various trophic factors regulating cell migration, growth, and differentiation. Herein, we compared the expression of neurotrophins (NTs) and their receptors in specific umbilical cord blood (UCB) SPC populations, including lineage-negative, CD34(+), and CD133(+) cells, with that in unsorted, nucleated cells (NCs).
  
  
  RESULTS
  The expression of NTs and their receptors was detected by QRT-PCR, western blotting, and immunofluorescent staining in UCB-derived SPC populations (i.e., NCs vs. lineage-negative, CD34(+), and CD133(+) cells). To better characterize, global gene expression profiles of SPCs were determined using genome-wide RNA microarray technology. Furthermore, the intracellular production of crucial neuro-regenerative NTs (i.e., BDNF and NT-3) was assessed in NCs and lineage-negative cells after incubation for 24, 48, and 72 h in both serum and serum-free conditions. We discovered significantly higher expression of NTs and NT receptors at both the mRNA and protein level in lineage-negative, CD34(+), and CD133(+) cells than in NCs. Global gene expression analysis revealed considerably higher expression of genes associated with the production and secretion of proteins, migration, proliferation, and differentiation in lineage-negative cells than in CD34(+) or CD133(+) cell populations. Notably, after short-term incubation under serum-free conditions, lineage-negative cells and NCs produced significantly higher amounts of BDNF and NT-3 than under steady-state conditions. Finally, conditioned medium (CM) from lineage-negative SPCs exerted a beneficial impact on neural cell survival and proliferation.
  
  
  CONCLUSIONS
  Collectively, our findings demonstrate that UCB-derived SPCs highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and that CM from SPCs favorable influence neural cell proliferation and survival. Understanding the mechanisms governing the characterization and humoral activity of subsets of SPCs may yield new therapeutic strategies that might be more effective in treating neurodegenerative disorders.
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: Katarzyna
authors.initials: K
authors.lastname: Kaczyńska
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 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: Miłosz
authors.initials: M
authors.lastname: Kawa
authors.affiliation: Department of Obstetrics and Gynecology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Przemysław
authors.initials: P
authors.lastname: Ustianowski
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Safranow
authors.affiliation: Department of Obstetrics 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.
authors.forename: Bogusław
authors.initials: B
authors.lastname: Machaliński
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D009414:Nerve Growth Factors / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor