A biomarker-based mathematical model to predict bone-forming potency of human synovial and periosteal mesenchymal stem cells

De Bari, Cosimo, Dell'Accio, Francesco, Karystinou, Alexandra, Guillot, Pascale V., Fisk, Nicholas M., Jones, Elena A., McGonagle, Dennis, Khan, Ilyas M., Archer, Charles W., Mitsiadis, Thimios A., Donaldson, Ana Nora, Luyten, Frank P. and Pitzalis, Costantino (2008) A biomarker-based mathematical model to predict bone-forming potency of human synovial and periosteal mesenchymal stem cells. Arthritis & Rheumatism, 58 1: 240-250. doi:10.1002/art.23143

Author De Bari, Cosimo
Dell'Accio, Francesco
Karystinou, Alexandra
Guillot, Pascale V.
Fisk, Nicholas M.
Jones, Elena A.
McGonagle, Dennis
Khan, Ilyas M.
Archer, Charles W.
Mitsiadis, Thimios A.
Donaldson, Ana Nora
Luyten, Frank P.
Pitzalis, Costantino
Title A biomarker-based mathematical model to predict bone-forming potency of human synovial and periosteal mesenchymal stem cells
Journal name Arthritis & Rheumatism   Check publisher's open access policy
ISSN 0004-3591
Publication date 2008-01
Sub-type Article (original research)
DOI 10.1002/art.23143
Volume 58
Issue 1
Start page 240
End page 250
Total pages 11
Place of publication Hoboken, N.J., U.S.A.
Publisher John Wiley & Sons
Language eng
Subject 1103 Clinical Sciences
Formatted abstract
To develop a biomarker-based model to predict osteogenic potency of human mesenchymal stem cells (MSCs) from synovial membrane and periosteum.
MSC populations were derived from adult synovium and periosteum. Phenotype analysis was performed by fluorescence-activated cell sorting and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Telomere lengths were determined by Southern blot analysis. In vitro osteogenesis was assessed quantitatively by measurements of alkaline phosphatase activity and calcium deposits. To investigate bone formation in vivo, MSCs were seeded onto osteoinductive scaffolds and implanted subcutaneously in nude mice. Bone was assessed by histology, and the human origin investigated by in situ hybridization for human Alu genomic repeats. Quantitation was achieved by histomorphometry and real-time RT-PCR for human osteocalcin. Analysis at the single-cell level was performed with clonal populations obtained by limiting dilution. Multiple regressions were used to explore the incremental predictive value of the markers.
Periosteal MSCs had significantly greater osteogenic potency than did synovial MSCs inherent to the single cell. Bone was largely of human origin in vivo. Within the same tissue type, there was variability between different donors. To identify predictors of osteogenic potency, we measured the expression levels of osteoblast lineage genes in synovial and periosteal clonal MSCs prior to osteogenic treatment. We identified biomarkers that correlated with osteogenic outcome and developed a mathematical model based on type I collagen and osteoprotegerin expression that predicts the bone-forming potency of MSC preparations, independent of donor-related variables and tissue source.
Our findings indicate that our quality-control mathematical model estimates the bone-forming potency of MSC preparations for bone repair.
Keyword Bone repair
In vivo
Mesenchymal stem cell
Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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