ABSTRACT
BACKGROUND: Stem cell-based therapy has been proposed for the treatment of osteoarthritis (OA) and induced pluripotent stem cells (iPSCs) are becoming a promising stem cell source as they have strong proliferation and differentiation potentials and no ethics problem. OBJECTIVE: To explore an effective method of iPSCs differentiating into chondrocytes and to study the therapeutic effect of iPSCs derived chondrocytes on osteoarthritis. METHODS: In this study, three steps were developed to induce human iPSCs to differentiate into chondrocytes which were then transplanted into rat OA models induced by monosodium iodoacetate (MIA). There were four groups in the experiment: control group with normal saline injection, model group with MIA injection, iPSCs group with iPSCs transplantation following MIA injection, and differentiated iPSCs group with transplantation of iPSCs derived chondrocytes following MIA injection. At 15 weeks after transplantation, micro-CT was used and histological analysis of the knee joint was performed. RESULTS AND CONCLUSION: Compared with the iPS group, the expression of chondrocyte specific genes and proteins (Col2A1, GAG and Sox9) were significantly increased in the differentiated iPSCs group after 6 days of embryoid formation and after 2 weeks of cell differentiation. At 15 weeks after cell transplantation, no immune responses were observed, micro-CT showed an improvement in subchondral bone integrity, and histological examinations demonstrated the production of articular cartilage matrix. iPSCs derived chondrocytes showed better effects on articular cartilage repair than the iPSCs. To conclude, iPSCs derived chondrocytes can be effective via transplantation approach for cartilage tissue regeneration in OA rats.
ABSTRACT
Objective To investigate the clinical and genetic characteristics of a case with non-classical 21-hydroxylase deficiency(210HD).Methods Clinical features and laboratory data were obtained from a patient with non-c]assical 21OHD,and the promoter and coding areas of CYP21 gene were sequenced.Results The old female patient presented with hypertension.The laboratory examinations showed that plasma androstenedione, testosterone,progesterone and 17-hydroxy progesterone(17OHP)were increased.CT scan revealed bilateral adrenal nodular enlargement.Furthermore,rapid ACTH stimulation test showed that the plasma 17OHP concentration was further increased up to 68.3?g/L.Sequencing analysis showed a C1187T(R356W) substitution at exon 8 and the C-125T,G-112A,T-109C variations in the promoter of CYP21 gene,which was not previous reported.Conclusion The combined heterozygous mutations,Cl187T at exon 8 and C-125T,G -112A,T-109C in promoter,seem to be associated with non-classical 21OHD phenotype.