Sodium Tungstate for Promoting Mesenchymal Stem Cell Chondrogenesis.
Articular cartilage has a limited ability to heal. Mesenchymal stem cells (MSCs) derived from the bone marrow have shown promise as a cell type for cartilage regeneration strategies. In this study, sodium tungstate (Na2WO4), which is an insulin mimetic, was evaluated for the first time as an inductive factor to enhance human MSC chondrogenesis. MSCs were seeded onto three-dimensional electrospun scaffolds in growth medium (GM), complete chondrogenic induction medium (CCM) containing insulin, and CCM without insulin. Na2WO4was added to the media leading to final concentrations of 0, 0.01, 0.1, and 1 mM. Chondrogenic differentiation was assessed by biochemical analyses, immunostaining, and gene expression. Cytotoxicity using human peripheral blood mononuclear cells (PBMCS) was also investigated. The chondrogenic differentiation of MSCs was enhanced in the presence of low concentrations of Na2WO4compared to control, without Na2WO4. In the induction medium containing insulin, cells in 0.01 mM Na2WO4produced significantly higher sulfated glycosaminoglycans, collagen type II, and chondrogenic gene expression than all other groups at day 28. Cells in 0.1 mM Na2WO4had significantly higher collagen II production and significantly higher sox-9 and aggrecan gene expression compared to control at day 28. Cells in GM and induction medium without insulin containing low concentrations of Na2WO4also expressed chondrogenic markers. Na2WO4did not stimulate PBMC proliferation or apoptosis. The results demonstrate that Na2WO4enhances chondrogenic differentiation of MSCs, does not have a toxic effect, and may be useful for MSC-based approaches for cartilage repair.
1 Department of Biomedical Engineering, New Jersey Institute of Technology , Newark, New Jersey.
Ateka
A
Khader
2 Department of Medicine-Hematology/Oncology, Rutgers-New Jersey Medical School , Newark, New Jersey.
Lauren S
LS
Sherman
2 Department of Medicine-Hematology/Oncology, Rutgers-New Jersey Medical School , Newark, New Jersey.
Pranela
P
Rameshwar
1 Department of Biomedical Engineering, New Jersey Institute of Technology , Newark, New Jersey.
Treena L
TL
Arinzeh
D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects*; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018613:Microscopy, Confocal; D054457:Tissue Scaffolds / Q000737:chemistry; D017973:Tungsten Compounds / Q000494:pharmacology*; D055815:Young Adult
D006025:Glycosaminoglycans; D017973:Tungsten Compounds; C025399:sodium tungstate(VI)
chondrogenesis; human mesenchymal stem cells; insulin mimetic; sodium tungstate