Abstract
BackgroundInduced pluripotent stem cells (iPSCs) exhibit limitless pluripotent plasticity and proliferation capability to provide an abundant cell source for tissue regenerative medicine. Thus, inducing iPSCs toward a specific differentiation direction is an important scientific question. Traditionally, iPSCs have been induced to chondrocytes with the help of some small molecules within 21–36 days. To speed up the differentiation of iPSCs, we supposed to utilize bioactive ceramics to assist chondrogenic-induction process.MethodsIn this study, we applied ionic products (3.125~12.5 mg/mL) of the lithium-containing bioceramic (Li2Ca4Si4O13, L2C4S4) and individual Li+ (5.78~23.73 mg/L) in the direct chondrogenic differentiation of human iPSCs.ResultsCompared to pure chondrogenic medium and extracts of tricalcium phosphate (TCP), the extracts of L2C4S4 at a certain concentration range (3.125~12.5 mg/mL) significantly enhanced chondrogenic proteins Type II Collagen (COL II)/Aggrecan/ SRY-Box 9 (SOX9) synthesis and reduced hypertrophic protein type X collagen (COL X)/matrix metallopeptidase 13 (MMP13) production in iPSCs-derived chondrocytes within 14 days, suggesting that these newly generated chondrocytes exhibited favorable chondrocytes characteristics and maintained a low-hypertrophy state. Further studies demonstrated that the individual Li+ ions at the concentration range of 5.78~23.73 mg/L also accelerated the chondrogenic differentiation of iPSCs, indicating that Li+ ions played a pivotal role in chondrogenic differentiation process.ConclusionsThese findings indicated that lithium-containing bioceramic with bioactive specific ionic components may be used for a promising platform for inducing iPSCs toward chondrogenic differentiation and cartilage regeneration.
Highlights
Induced pluripotent stem cells exhibit limitless pluripotent plasticity and proliferation capability to provide an abundant cell source for tissue regenerative medicine
While there was currently no generally accepted efficient protocol for differentiation chondrocytes from Induced pluripotent stem cells (iPSCs) [4], producing embryoid bodies (EBs) or mesenchymal stem cells (MSCs)-like cells from iPSCs before chondrocytes differentiation were reported as regular methods by previous studies [5,6,7]
After culturing on ultra-low-attachment plates with a concentration of 3000/20 μl, the iPSCs formed a large number of EBs with smooth edges and uniform sizes (Fig. 1c), and these
Summary
Induced pluripotent stem cells (iPSCs) exhibit limitless pluripotent plasticity and proliferation capability to provide an abundant cell source for tissue regenerative medicine. The iPSCs were considered as an attractive cell source for cartilage repair owing to their abundance, autologous nature, and potentiality to generate adequate chondrocytes rather than. While there was currently no generally accepted efficient protocol for differentiation chondrocytes from iPSCs [4], producing embryoid bodies (EBs) or MSC-like cells from iPSCs before chondrocytes differentiation were reported as regular methods by previous studies [5,6,7]. These methods were time-consuming for multiple differentiation steps and would cause adverse effects on the urgency of clinical cartilage repair. To our knowledge, it is unclear whether the biomaterial can observably promote chondrogenic differentiation of iPSCs in vitro
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