Pleuripotent stem cells hold the hope of cure for people suffering from complex genetic disorders like Parkinson’s Disease (PD). Although Embryonic Stem Cells or ESCs are very promising, their use is frought with ethical concerns and is tied up the non availability of federal funding for such research.

In the last two years, several groups came up with non- embryonic induced pleuripotent stem cells (iPS). iPS cells acquire pleuripotency by retroviral indtroduction and expression of three or four transcription factors (Oct-3/4, Sox2, KLF4 and c-Myc- which are known to be highly expressed in  ESCs) into somatic cells like fibroblasts.  iPS cells are similar to ESCs in morphology, proliferation and pleuripotency. More importantly, iPS cells can be derived from human somatic cells, for example a PD patient. iPS cells could be used for autologous cell replacement therapy, reasearch on pathology or drug screen.

Authors of a recent study to be published in Cell managed to make iPS cells from patients suffering from monogenetic and as well as multifactorial  diseases - Parkinson’s disease, Down’s syndrome, denosine deaminase deficiency-related severe combined immunodeficiency, Shwachman-Bodian-Diamond syndrome, Gaucher disease type III, Duchenne and Becker muscular dystrophy, Huntington disease, juvenile-onset, type 1 diabetes mellitus.

Lou Gherig disease or Amyotropic Lateral Sclerosis (ALS) is yet another neurodegenerative disease which could benefit from iPS cells. ALS symptoms are caused by loss of motor neurons and therefore loss of control over muscles involved in walking, swallowing, speech, breathing, circulation and so on which leads to death, typically in 3 to 5 years of diagnosis. Although the genetic basis of sporadic ALS is yet to be found, most familial cases of ALS carry mutations in an enzyme- Cu, Mn-Superoxide dismutase, which tends to form protein aggrgates in motor neurons leading to cell death.

In yet another landmark paper in Science, authors used fibroblasts from a 92 year old familial ALS patient to generate iPS. They show that fibroblast can not only be reprogrammed to become pleuripotent (i.e they give rise to all three germline layers- endoderm, mesoderm and ectoderm) but they could be terminally differentiated into motor neurons using appropriate cues (as shown in the schematic) . Such motor neurons could potentially be used for replacing lost neurons in ALS patients.

Authors of both these and other such studies caution, that although it is possible to generate patient and disease specific iPS cells, we are far from using them in cell replacement therapies for treating the disease itself. At the moment, retroviruses are used to express transcription factors to generate iPS cells, which would not be suitable for direct injections in the patients. So the stem cell biologists would have to come up with a more suitable way of reprogramming. The present day iPS cells are indeed very useful for research on the pathology of the disease or screen for drugs. 

It is a beacon of hope for stem cell biologists and patients. Hopefully it would also attract more funding support from all sources.

Sources: Science 29 August 2008: Vol. 321. no. 5893, pp. 1218 – 1221

               Park et al. Cell. 2008 Aug 6 (online-ahead of print)

               Reviews on iPS cells

Figure. Schematic of somatic cells  reprogramming  to form inducible Pleuripotent stem cells. iPS cells  could be terminally differentiated into cells of interest e.g motor neurons by providing appropriate cues.