Embryonic stem cells – a cure for old age (5)
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V. THERAPEUTIC BENEFITS OF cESC COMPARED TO STEM CELLS FROM OTHER SOURCESHuman stem cells isolated from other sources, which are not the subject of discussion in this review, are also considered as material for use in clinical practice.
These include adult stem cells and induced pluripotent stem cells (iPSCs). Unlike cESC, these stem cells can be isolated directly from the body of a patient in need of treatment. Therefore, their therapeutic use avoids issues of immune compatibility that prevent the introduction of many methods of non-autologous transplant therapy. Moreover, the use of these cells in clinical and fundamental research does not raise ethical and political issues that invariably accompany the use of embryonic stem cells. However, the use of adult stem cells and iPSCs also has a number of limitations, which today can be circumvented by using cESC.
Just like cESC, adult stem cells are capable of self-renewal. However, unlike CESCS, they have limited potential and are able to differentiate only into cells of the tissue in which they are localized. In some cases, adult stem cells are not able to give rise to all types of cells that are part of this tissue, and over time lose the ability to divide. The latter problem is more typical for stem cells isolated from the tissues of elderly individuals [95, 96].
iPSCs are created by reprogramming differentiated somatic cells into a pluripotent state. This can be achieved by inducing the expression of three main reprogramming factors – Oct4, Sox2 and Nanog. Several methods are used to ensure the expression of these factors and the induction of pluripotency. These include transduction by retroviruses, lentiviruses and adenoviruses associated with the risk of irreversible dangerous integration of viral genetic material into the genome of cells. Indeed, some existing IPSC lines demonstrate genetic instability, manifested by large-scale genomic rearrangements, variations in the number of gene copies and abnormal karyotype even at early passages [97, 98]. To minimize the possibility of mutagenesis caused by the methods used to introduce reprogramming factors into the cell and to ensure the expression of these factors and the induction of pluripotency, plasmid-free/non-integration strategies were used, such as transduction using RNA viruses or the introduction of purified recombinant proteins capable of penetrating into cells [99, 100]. However, these methods of creating reprogrammed pluripotent stem cells are significantly less effective than methods of viral integration. Moreover, high levels of mutational changes are still observed in some IPSC lines reprogrammed using the non-integration viral method [97].
Recent studies have also revealed that, in addition to genome changes, iPSCs have epigenetic characteristics that indicate incomplete or abnormal reprogramming. In particular, the DNA methylation profiles of iPSCs are often similar to the methylation profiles of somatic cells from which they were obtained [101], which indicates incomplete reprogramming of iPSCs into the initial pluripotent state characteristic of CESCS. It is not yet clear whether the observed genetic instability and epigenetic imprinting are heating up during reprogramming or whether they are characteristic of somatic cells from which iPSCs are obtained. However, patient-specific iPSCs may be less suitable material for the treatment of age-related diseases, since the somatic cells of elderly individuals are more characterized by genomic mutations and unfavorable epigenetic programs. Thus, the safety and effectiveness of the therapeutic use of iPSCs obtained using modern methods are subject to clarification.
VI. ConclusionWith the development and improvement of methods of cell replacement therapy, its use in the treatment of age-related diseases is becoming an increasingly attractive prospect.
cESC offers great promise as a potential tool for appropriate therapeutic approaches and drug testing methods. It is obvious that today there are still a number of unresolved scientific issues, as well as ethical and legislative problems. However, great hopes are inspired by the fact that clinical trials using CESCS have already begun, as well as the fact that active work continues on the creation of methods for effective and safe differentiation of CESCS into certain types of cells. These studies will pave the way to the maximum realization of the therapeutic potential of cESC in regenerative medicine and, in particular, in the treatment of age-related diseases.
The list of references is given in a separate file.
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19.12.2011