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  • br Results and discussion br Material and

    2018-11-12


    Results and discussion
    Material and methods
    Conclusions There are various applications for cell-based therapies in cartilage repair. For knee cartilage lesion treatment, autologous chondrocyte transplantation has become the principal cell-based approach. The first human autologous chondrocyte transplantation was done by a Swedish group in 1994 (Brittberg et al., 1994). Although this has granted clinical benefits including pain relief with function improvement (Recht et al., 2003; Ferruzzi et al., 2008), it still remains unsatisfactory, mainly because of the morbidity in the donor site caused by the harvesting of the articular cartilage (Hunziker, 2002). It has also been reported that the repair tissue still contains a considerable proportion of fibrocartilage (McNickle et al., 2009). In maxillofacial surgery, the repair and augmentation of craniofacial structures or repair of nose deformities is a challenge for surgeons. The current clinical practice is to treat these deformities with the combination of surgery and the use of autologous tissues. However, grafting autologous tissue is associated with difficulty to obtain a sufficient amount of tissue (Yanaga et al., 2006). Some authors indicate perichondrium as a good cell sources for cartilage repair (Van Osch et al., 2000; Togo et al., 2006), while others do not, claiming inconsistent reproducibility and yield rate of neocartilage (Shieh et al., 2004). Also, the repair tissue formed by these perichondrium cells in vivo is different from the native one (Dounchis et al., 2000) and unstable after long periods (Ostrander et al., 2001). Apart from this discussion, it seems that no study worked specifically with cells of the cartilage superficial zone or perichondrium sphingosine kinase inhibitor layer, suggested to be the source of new cartilage (Upton et al., 1981). Mesenchymal progenitor cells have been reported in normal and osteoarthritic articular cartilage (Alsalameh et al., 2004). The surface of articular cartilage contains pluripotent progenitor cells (Dowthwaite et al., 2004). Although nasoseptal chondrogenic cells were not reported to present such plasticity, they also occupy a surface niche on cartilaginous tissue, belonging to chondrogenic lineage. Further studies are necessary to prove that nasoseptal chondrogenic cells can efficiently generate cartilaginous tissue in vivo and to compare its chondrogenic potential against other progenitor cell types. However, engineering articular cartilage with biomimetic scaffolds is being pointed as a major strategy for success of cartilage engineering in the future (Klein et al., 2009). Therefore, combination of different cell types is an advantage, and nasoseptal chondrogenic cells may occupy the superficial niche in a construct. Finally, nasoseptal chondrogenic cells may not only be used for clinical implants, but also as a model for studying chondrogenesis. The following are the supplementary materials related to this article
    Acknowledgments
    Introduction Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, each of which is derived from the inner cell mass of blastocysts and somatic cells by transducing three or four transcription factors, respectively, can differentiate into various types of cells in vitro. They are thus considered as a valuable model to understand the processes involved in the differentiation of lineage-committed cells as well as an unlimited source of cells for therapeutic applications such as hematopoietic stem/progenitor cell (HSPC) transplantation (Evans and Kaufman, 1981; Thomson et al., 1998; Keller, 2005; Takahashi and Yamanaka, 2006; Takahashi et al., 2007). Differentiation of ES and iPS cells into mature hematopoietic cells, including erythrocytes, myeloid cells, and lymphoid cells, has been performed by embryoid body (EB) formation or coculture with stromal cells (Nakano et al., 1994; Chadwick et al., 2003; Schmitt et al., 2004; Vodyanik et al., 2005). However, the development of an efficient differentiation method for immature hematopoietic cells, including HSPCs, from ES and iPS cells has been challenging. Previously, Daley and his colleagues have shown that enforced expression of HoxB4 in mouse ES cells by a retrovirus vector robustly enhanced the differentiation of ES cells into HSPCs in vitro, and these ES cell-derived HSPCs had a long-term reconstitution potential in vivo (Kyba et al., 2002; Wang et al., 2005). In addition, constitutive expression of HoxB4 was shown to induce the hematopoietic differentiation from human ES cells (Bowles et al., 2006). These findings indicated that manipulation of HoxB4 expression would be effective for production of HSPCs from ES and iPS cells. However, it is known that long-term constitutive HoxB4 expression in HSPCs has an inhibitory effect on the differentiation of certain hematopoietic lineages, such as lymphoid cells and erythroid cells (Kyba et al., 2002; Pilat et al., 2005), and can lead to a significant risk of leukemogenesis in large animals (Zhang et al., 2008). Although a tetracycline-inducible HoxB4 expression system has been utilized to overcome these unwanted effects, this gene expression system is complex, and cannot be directly applied to therapeutic use. Foreign genes can be integrated into the host chromosome in a stable gene expression system that includes a tetracycline-regulated system, and this could cause an increased risk of cellular transformation (Li et al., 2002; Hacein-Bey-Abina et al., 2003; Williams and Baum, 2004). Therefore, to apply ES cell- and iPS cell-derived HSPCs to clinical medicine, development of a simple and transient HoxB4 transduction method in ES and iPS cells is required.