Stem Cells: Daddy or Chips? —An Up-to-Date Review on Ground-Breaking Discoveries in Stem Cell Research, with Special Attention to iPSC Applications in Osteoarthritis

摘要

?“Stem Cells is what stem cells does” ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ??not Forrest Gump In the present day Stem Cells are increasingly becoming popularized as the potential “ultimate” cure for the most challenging maladies… the “Daddy of medical intervention”. Forefront SC research on human induced pluripotent stem cells (iPSCs) and other sub-disciplines, is quickly revolutionizing healthcare towards “Regenerative Medicine”, as beautifully exemplified by the use of iPSCs in treating and possibly curing osteoarthritis, discussed at the end of this publication. This review documents and reflects on the most topical discoveries in SC research, and the challenges researchers in this field nowadays face. Major Findings: 1) In 2006 Yamanaka et al. generated the first iPSCs from mouse fibroblasts, using retroviral transmission of c-Myc, Oct3/4, Klf4 and SOX2 transcription factors. Later, they successfully generated iPSCs from human fibroblasts (2007). 2) Contemporary cultivation methods carry high risks of iPSC genome disruption, possibly leading to tumorigenesis, teratoma formation and reducing iPSC induction efficacy. 3) Many studies on preserving genome integrity and decreasing malignancy in iPSCs, suggest using valiproic acid and protecting tumour suppressor genes. 4) In many malignant tumours only a small minority of cells, called Cancer Stem Cells, metastasise and hyper-proliferate. 5) Not all mature cell sources yield the same [undifferentiated iPSCs: lineage-committed] ratio as others. Feb 2014: Obokata et al. claimed to have generated iPSCs by exposing mature cells to a 25 min, pH 5.7 bath. These iPSCs were termed “Stimulus-triggered Acquisition Pluripotency Cells” (STAP). However by July 2014 this study had been revoked, as the results could not be replicated. Conclusion: Stem cells have enormous potential to offer, especially iPSCs. Although currently not a viable treatment option on their own, for many daunting diseases they will definitely be at the core of multi-disciplined therapies within the near-future, including multi-factorial diseases like osteoarthritis.