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THE STEM CELL NICHE

Gene-Expression Profiling of CD34⁺ Hematopoietic Cells Expanded in a Collagen I Matrix

Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus, Leibniz Institute of Polymer Research Dresden & Max Bergmann Center of Biomaterials, Dresden, Germany

Key Words. Cord blood • Hematopoietic stem/progenitor cells • Collagen I • Matrix gene expression

Correspondence: Martin Bornhäuser, M.D., Med. Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany. Telephone: 49-351-458-4704; Fax: 49-351-458-5389; e-mail: martin.bornhaeuser{at}uniklinikum-dresden.de

Received June 17, 2005; accepted for publication September 9, 2005.
CD34⁺ hematopoietic stem/progenitor cells (HSCs) reside in the bone marrow in close proximity to the endosteal bone surface, surrounded by osteoblasts, stromal cells, and various extracellular matrix molecules. We used a bioartificial matrix of fibrillar collagen I, the major matrix component of bone, as a scaffold for ex vivo expansion of HSCs. CD34⁺ HSCs were isolated from umbilical cord blood and cultivated within reconstituted collagen I fibrils in the presence of fms-like tyrosine kinase-3 ligand, stem cell factor, and interleukin (IL)-3. After 7 days of culture, the cell number, number of colony-forming units (CFU-C), and gene-expression profile of the cultured cells were assessed. Although the total expansion factor of CD34⁺ cells was slightly lower when cells were cultivated in the collagen I gel, the frequency of CFU-C was greater than in control suspension cultures. Gene-expression analysis with microarray chip technology revealed the upregulation of more than 50 genes in the presence of collagen I. Among these, genes for several growth factors, cytokines, and chemokines (e.g., IL-8 and macrophage inhibitory protein 1) could be confirmed using quantitative polymerase chain reaction. Furthermore, greater expression levels of the negative cell-cycle regulator BTG2/TIS21 and an inhibitor of the mitogen-activated protein kinase pathway, DUSP2, underline the regulatory role of the extracellular matrix. Together, these data show that the expansion of CD34⁺ cord blood cells in a culture system containing a three-dimensional collagen I matrix induces a qualitative change in the gene-expression profile of cultivated HSCs.

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