title: Characterization of Regenerative Phenotype of Unrestricted Somatic Stem Cells (USSC) from Human Umbilical Cord Blood (hUCB) by Functional Secretome Analysis.
abstract: Stem cell transplantation is a promising therapeutic strategy to enhance axonal regeneration after spinal cord injury. Unrestricted somatic stem cells (USSC) isolated from human umbilical cord blood is an attractive stem cell population available at GMP grade without any ethical concerns. It has been shown that USSC transplantation into acute injured rat spinal cords leads to axonal regrowth and significant locomotor recovery, yet lacking cell replacement. Instead, USSC secrete trophic factors enhancing neurite growth of primary cortical neurons in vitro. Here, we applied a functional secretome approach characterizing proteins secreted by USSC for the first time and validated candidate neurite growth promoting factors using primary cortical neurons in vitro. By mass spectrometric analysis and exhaustive bioinformatic interrogation we identified 1156 proteins representing the secretome of USSC. Using Gene Ontology we revealed that USSC secretome contains proteins involved in a number of relevant biological processes of nerve regeneration such as cell adhesion, cell motion, blood vessel formation, cytoskeleton organization and extracellular matrix organization. We found for instance that 31 well-known neurite growth promoting factors like, e.g. neuronal growth regulator 1, NDNF, SPARC, and PEDF span the whole abundance range of USSC secretome. By the means of primary cortical neurons in vitro assays we verified SPARC and PEDF as significantly involved in USSC mediated neurite growth and therewith underline their role in improved locomotor recovery after transplantation. From our data we are convinced that USSC are a valuable tool in regenerative medicine as USSC's secretome contains a comprehensive network of trophic factors supporting nerve regeneration not only by a single process but also maintained its regenerative phenotype by a multitude of relevant biological processes.
authors.affiliation: From the ‡Molecular Proteomics Laboratory (MPL), Institute for Molecular Medicine, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany; §Molecular Neurobiology Laboratory, Department of Neurology, Heinrich Heine University Medical Centre Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany;
authors.forename: Jessica
authors.initials: J
authors.lastname: Schira
authors.affiliation: From the ‡Molecular Proteomics Laboratory (MPL), Institute for Molecular Medicine, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany;
authors.forename: Heiner
authors.initials: H
authors.lastname: Falkenberg
authors.affiliation: §Molecular Neurobiology Laboratory, Department of Neurology, Heinrich Heine University Medical Centre Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany;
authors.forename: Marion
authors.initials: M
authors.lastname: Hendricks
authors.affiliation: From the ‡Molecular Proteomics Laboratory (MPL), Institute for Molecular Medicine, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany;
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Waldera-Lupa
authors.affiliation: ¶Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Medical Center, Düsseldorf, Germany.;
authors.forename: Gesine
authors.initials: G
authors.lastname: Kögler
authors.affiliation: ‖Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Bunsen-Kirchhoff-Str. 11, Dortmund, Germany;
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.affiliation: §Molecular Neurobiology Laboratory, Department of Neurology, Heinrich Heine University Medical Centre Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany; **Biologisch-Medizinisches Forschungszentrum (BMFZ), Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors.forename: Hans Werner
authors.initials: HW
authors.lastname: Müller
authors.affiliation: From the ‡Molecular Proteomics Laboratory (MPL), Institute for Molecular Medicine, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany; **Biologisch-Medizinisches Forschungszentrum (BMFZ), Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany Kai.Stuehler@uni-duesseldorf.de.
authors.forename: Kai
authors.initials: K
authors.lastname: Stühler
mesh_terms: D001369:Axons / Q000502:physiology; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D012038:Regeneration; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D009414:Nerve Growth Factors