Future perspectives about clinical trials with stem cells from donors The use of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in clinical trials for treatment of knee OA faces the same challenges as clinical trials with other types of MSC in terms of stem cell handling[43]. There is also the need for more Hedgehog Pathway relevant clinical data, so it would be beneficial to have more clinical trials for knee OA, which utilize hUC-MSCs. Future perspectives
about basic research in knee cartilage regeneration and chondrogenesis in vitro and in vivo Nowadays basic research in chondrogenesis in vitro and in vivo is primarily focus on increasing the efficacy of stem cells in terms of tissue repair[57-62]. However, the issues of stem cell characterization and tumorigenesis in vivo are somewhat overlooked. Until relatively recently, the genomic profile of the stem cell lines maintained in vitro was only assessed in terms of ploidy and karyotype, as it was known that cultured cells may exhibit loss or gain of chromosome fragments or whole chromosomes and/or genomic rearrangements[63-65]. After the introduction of the
concept for individual capacity for DNA repair and for maintenance of genomic integrity in research and diagnostic practice, its applicability as a complex marker for the proliferative potential and/or the differentiation capacity of undifferentiated cells has been extensively discussed[66-69]. Some authors have advised that the minimal panel for characterisation of in vitro maintained pluripotent
cell lines ought to include markers for individual capacity for repair of genotoxic damage and maintenance of genomic integrity[69-71]. Some stem cells types (mesenchymal stem cells, haematopoietic cells from bone marrow and iPSC) have been shown to lose TP53 gene copies during in vitro culturing (detected as loss of heterozygocity for markers at the TP53 locus)[72]. Shetzer et al[72] also reported that the cells with loss of heterozygocity were more often than not identified as the origin of the teratoma-like tumours developing after the cells were transplanted in mice. All those findings in basic stem cell biology will likely influence the Dacomitinib development of more advanced (in terms of cell characterization) stem cell culturing and differentiation protocols and lead to the development of a gold standard in clinical trials with MSCs. Conclusion In conclusion, stem cell therapy may not become a standard treatment for knee OA till the end of the decade due to various aspects regarding the clinical safety (e.g., risk of complications after surgery, compatibility of donor stem cells) and the affordability of this treatment for the general public. Moreover, there is still no sufficient amount of clinical data on the effectiveness of stem cell therapy when compared with pharmacological treatments for this particular disease[47].