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.


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  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2008-01
Sub-type Article
DOI 10.1002/art.23143
Volume number 58
Issue number 1
ISSN 0004-3591; 1529-0131
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 Objective
To develop a biomarker-based model to predict osteogenic potency of human mesenchymal stem cells (MSCs) from synovial membrane and periosteum.
Methods
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.
Results
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.
Conclusion
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

Document type: Journal Article
Sub-type: Article
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 35 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 41 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Access Statistics: 185 Abstract Views  -  Detailed Statistics
Created: Tue, 30 Mar 2010, 16:04:26 EST by Ms May Balasaize on behalf of Faculty Of Health Sciences