The genetic reprogramming technology allows one to generate pluripotent stem
cells for individual patients. These cells, called induced pluripotent stem
cells (iPSCs), can be an unlimited source of specialized cell types for the
body. Thus, autologous somatic cell replacement therapy becomes possible, as
well as the generation of in vitro cell models for studying
the mechanisms of disease pathogenesis and drug discovery. Amyotrophic lateral
sclerosis (ALS) is an incurable neurodegenerative disorder that leads to a loss
of upper and lower motor neurons. About 10% of cases are genetically inherited,
and the most common familial form of ALS is associated with mutations in the
SOD1 gene. We used the reprogramming technology to generate
induced pluripotent stem cells with patients with familial ALS.
Patient-specific iPS cells were obtained by both integration and transgene-free
delivery methods of reprogramming transcription factors. These iPS cells have
the properties of pluripotent cells and are capable of direct differentiation
into motor neurons.
Cytogenetic analysis of karyotypes of hESM01-hESM04 human embryonic stem cells and substrains derived from these strains showed that all these strains retained normal karyotype during long-term culturing. Two substrains of embryonic stem cells with chromosome aberrations indicating clonal origin of these strains were detected. The potentialities of using analysis of chromosome variability of embryonic stem cells for evaluation of predisposition of the corresponding genotypes to the formation of chromosome abnormalities are discussed.
Induced pluripotent stem cells (iPSCs) have the capacity to unlimitedly
proliferate and differentiate into all types of somatic cells. This capacity
makes them a valuable source of cells for research and clinical use. However,
the type of cells to be reprogrammed, the selection of clones, and the various
genetic manipulations during reprogramming may have an impact both on the
properties of iPSCs and their differentiated derivatives. To assess this
influence, we used isogenic lines of iPSCs obtained by reprogramming of three
types of somatic cells differentiated from human embryonic stem cells. We
showed that technical manipulations in vitro, such as cell
sorting and selection of clones, did not lead to the bottleneck effect, and
that isogenic iPSCs derived from different types of somatic cells did not
differ in their ability to differentiate into the hematopoietic and neural
directions. Thus, the type of somatic cells used for the generation of fully
reprogrammed iPSCs is not important for the practical and scientific
application of iPSCs.
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