Affiliations: Department of Neuroregeneration, Netherlands Institute for Neurosciences, Amsterdam, The Netherlands | Department of Neurosurgery, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands | Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands | Department of Physical Medicine & Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, USA | Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands | Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, USA | Department of Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, USA
Note: [] Corresponding author: Dr. Martin Oudega, University of Pittsburgh School of Medicine, W1452 BST, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Tel.:/Fax: +1 412 383 6575; E-mail: [email protected]
Abstract: Purpose: The assessment of the capacity of bone marrow stromal cells (BMSC) to repair the nervous system using gene expression profiling. The evaluation of effects of long-term culturing on the gene expression profile of BMSC. Methods: Fourty four k whole genome rat microarrays were used to study gene expression of cultured BMSC at passage (P)3 and to compare expression profiles between P3 and P14 BMSC. Quantitative PCR was employed to validate the microarray results. Results: P3 BMSC expressed genes involved in neural developmental events such as glial differentiation, neuron proliferation, and neurite formation. They also express genes encoding for growth factors and for proteins involved in growth factor signaling. A total of 6687 genes were co-expressed in P3 and P14 BMSC. Of these co-expressed genes, 3% (202 genes) was differentially expressed with 159 genes higher in P3 BMSC and 43 genes higher in P14 BMSC. The gene expression patterns were independently validated using quantitative PCR. Functional data mining by Gene Ontology (GO)-analysis revealed that 85/159 and 22/43 genes were annotated in the GO database. In P3 BMSC, 53 GO-classes were overrepresented with several involved in organ development, cell proliferation, and neural repair. In P14 BMSC, three GO-classes were overrepresented with one involved in organ development. Conclusions: Our gene profiling results suggested a decreased plasticity and repair aptitude of long-term cultured BMSC. Our data indicated the use of early passage BMSC for neural repair approaches.
