Is iPS cell the panacea?

Abstract

SummaryIn 2006, it was reported that transgenic expression of merely four defined transcription factors (c-Myc, Klf4, Oct4, and Sox2) is sufficient to reprogram somatic cells to a pluripotent state. The resulting induced pluripotent stem (iPS) cells ignited intense interest in the field of life science for their promising applications in basic biology, drug development, and transplantation. However, the underlying problems of iPS cells seem to be ignored. This review shed light on the problems pertaining iPS cells, including the elusive origin, risk of tumorgenesis, and its relationship with natural selection.

Multilineage-differentiating stress-enduring (Muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts

“…On the other hand, the elite model proposes that iPS cell generation occurs only from a subset of cells (6). The validity of the elite model is still debated (11,14,15).…”

Do we Still Need Human Embryonic Stem Cells for Stem Cell-Based Therapies? Epistemic and Ethical Aspects

“…For example, some have pointed out that both hES cells and hiPS cells have the potential to form teratomas 4 if transplanted into patients [7,8], the risk of tumorigenesis [7,[9][10][11] as well as the potential of aberrant reprogramming [12]. Others have objected, however, that using for therapies hiPS cells, generated from somatic cells that might have been altered by aging or toxins contrary to a pure unaffected hES cell line, would add unpredictable risks 5 [15].…”

“…If that is the case, this would mean that the difference between hiPS cells and hES cells regarding their possibility to be rejected by the patient's immune defense system would at least become less significant. 7 To support their opinion, some scientists have argued that: a) for patient-specific stem cell-based therapy millions of stem cell lines would be needed [15], b) there is no time to generate the cells if they are needed rapidly, as after a heart attack or spinal injury-it may take several months of really hard work to make a cell line [11,15], c) it is not realistic to repair the disease causing genetic mutations and epimutations in iPS cells and replace with the somatic cells in patients [11], d) it is impossible to treat large tissue degenerations [11]. 8 SCNT is the injection of a nucleus derived from a somatic cell such as fibroblast into an enucleated egg [17].…”

“…On the one hand, some have argued that the notion of generating individually tailored cell populations for every patient, as in "therapeutic cloning" involving hES cells, will not be achieved with either hES cells or hiPS cells, since even with hiPS cells patient-specific therapy is impractical 7 and costly [11,15]. Therefore, some authors have suggested that the most likely approach for stem cell-based therapy will be to create banks of cell lines, generated from donated embryos, iPS cells, or cell lines gained through somatic cell nuclear transfer (SCNT), 8 with different immune properties that would provide acceptable matches with most of the population 9 [15,17].…”

“…SCNT procedure is technically challenging, inefficient and dependent on voluntary donation of a large number of unfertilized oocytes 11 [2], whereas hiPS cell research would not face at least some of these problems. 6 This statement has been contested by Dressel et al who have argued that the adaptive immune system has in principle the capacity to kill pluripotent and teratoma-forming stem cells [18].…”