iPS cell technologies: significance and applications to CNS regeneration and disease

The lives of mammals, including humans, begin with the fertilization of an egg by a sperm cell. In humans, a blastocyst composed of 70-100 cells forms by approximately 5.5 days after fertilization. The blastocyst is composed of the inner cell mass, the cell population that has the ability to differentiate into the various cells that constitute the body (pluripotency), and the trophoblast, the cells that develop into the placenta and extra-embryonic tissues and do not contribute cells to the body. In 2006, we demonstrated that mature somatic cells can be reprogrammed to a pluripotent state by gene transfer, generating induced pluripotent stem (iPS) cells. Since that time, there has been an enormous increase in interest regarding the application of iPS cell technologies to medical science, in particular for regenerative medicine and human disease modeling. Three major lines of research led us to the production of iPS cells [5] (Figure 1). The first, as described above, was nuclear reprogramming initiated by Sir John Gurdon in his research of cloning frogs by nuclear transfer in 1962 [2] and by Sir Ian Wilmut, who cloned a mammal for the first time in 1997 [3].

• 1
  When mouse or human iPS cells were induced to form NS/PCs and were transplanted into mouse or non-human primate SCI models, long-term restoration of motor function was induced, without tumorigenicity, by selecting a suitable iPS cell line.
• 2
  Lewy bodies, a pathology characteristic of PD, and their main component, α-synuclein, were investigated in PARK2 patient-derived iPS cells [58]. Based on an analysis of patient brain autopsies, Lewy bodies were found to accumulate in the neurons of patients with sporadic PD.
• 3
  We confirmed that these patient-derived neuronal cells produce twice the normal level of the highly toxic Aβ-42. This result correlated with Aβ accumulation in neural cells derived from living patients with AD.