title: Suspension-based differentiation of adult mesenchymal stem cells toward chondrogenic lineage.
abstract: Human mesenchymal stem cells (hMSCs) are derived from bone marrow and have the ability to differentiate into cartilage and other mesenchymal cell types found throughout the body. Traditionally, the differentiation of hMSCs toward chondrocytes occurs through a combination of pelleted static cell culture and chemical stimuli. As an alternative to these protocols, we developed an in vitro flow through microfluidic method to induce the differentiation of hMSCs into chondrocytes. Suspensions of unattached hMSCs were exposed to a constant shear flow over a period of 20 minutes, which promoted phenotypic and gene expression changes toward the chondrogenic lineage. These internal and external changes of chondrogenic differentiation were then observed over 3 weeks later in culture, as confirmed through fluorescent immunocytochemical staining and real-time quantitative reverse transcriptase polymerase chain reaction. The increased concentration of Type II collagen on the surface of shear stimulated hMSCs with the upregulation of MAPK1 and SOX9 demonstrated the capabilities of our approach to induce sustained differentiation. In conclusion, our shear stimulation method, in combination with chemical stimuli, illustrates enhanced differentiation of hMSCs toward the chondrogenic lineage.
authors.affiliation: a Department of Bioengineering , Northeastern University , Boston , MA , USA.
authors.forename: Adedayo E
authors.initials: AE
authors.lastname: Adeniran-Catlett
authors.affiliation: b Department of Chemical Engineering , Northeastern University , Boston , MA , USA.
authors.forename: Estelle
authors.initials: E
authors.lastname: Beguin
authors.affiliation: c Biochemistry Program , Northeastern University , Boston , MA , USA.
authors.forename: Fazli K
authors.initials: FK
authors.lastname: Bozal
authors.affiliation: b Department of Chemical Engineering , Northeastern University , Boston , MA , USA.|d Barnett Institute of Chemical & Biological Analysis, Northeastern University , Boston , MA , USA.
authors.forename: Shashi K
authors.initials: SK
authors.lastname: Murthy
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects; D005453:Fluorescence; D020869:Gene Expression Profiling; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013535:Suspensions / Q000494:pharmacology*
chemical_list: D013535:Suspensions
keywords: Chondrocytes; differentiation; mesenchymal stem cells; microfluidics; shear stress