title: Predicting the therapeutic efficacy of MSC in bone tissue engineering using the molecular marker CADM1.
abstract: Mesenchymal stromal cells (hMSCs) are advancing into the clinic but the therapeutic efficacy of hMSCs faces the problem of donor variability. In bone tissue engineering, no reliable markers have been identified which are able to predict the bone-forming capacity of hMSCs prior to implantation. To this end, we isolated hMSCs from 62 donors and characterized systematically their in vitro lineage differentiation capacity, gene expression signature and in vivo capacity for ectopic bone formation. Our data confirms the large variability of in vitro differentiation capacity which did not correlate with in vivo ectopic bone formation. Using DNA microarray analysis of early passage hMSCs we identified a diagnostic bone-forming classifier. In fact, a single gene, CADM1, strongly correlated with the bone-forming capacity of hMSCs and could be used as a reliable in vitro diagnostic marker. Furthermore, data mining of genes expressed correlating with in vivo bone formation represented involvement in neurogenic processes and Wnt signaling. We will apply our data set to predict therapeutic efficacy of hMSCs and to gain novel insight in the process of bone regeneration. Our bio-informatics driven approach may be used in other fields of cell therapy to establish diagnostic markers for clinical efficacy.
authors.affiliation: University of Twente, MIRA Institute for Biomedical Technology and Technical Medicine, Department of Tissue Regeneration, Drienerlolaan 5, 7522 NB Enschede, The Netherlands.
authors.forename: Anouk
authors.initials: A
authors.lastname: Mentink
authors.forename: Marc
authors.initials: M
authors.lastname: Hulsman
authors.forename: Nathalie
authors.initials: N
authors.lastname: Groen
authors.forename: Ruud
authors.initials: R
authors.lastname: Licht
authors.forename: Koen J
authors.initials: KJ
authors.lastname: Dechering
authors.forename: Johan
authors.initials: J
authors.lastname: van der Stok
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Alves
authors.forename: Wouter J
authors.initials: WJ
authors.lastname: Dhert
authors.forename: Eugene P
authors.initials: EP
authors.lastname: van Someren
authors.forename: Marcel J T
authors.initials: MJ
authors.lastname: Reinders
authors.forename: Clemens A
authors.initials: CA
authors.lastname: van Blitterswijk
authors.forename: Jan
authors.initials: J
authors.lastname: de Boer
mesh_terms: D000818:Animals; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009999:Ossification, Heterotopic / Q000209:etiology; D010012:Osteogenesis; D010641:Phenotype; D023822:Tissue Engineering
chemical_list: C403514:CADM1 protein, human; C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins