Reprogramming of somatic cells into induced pluripotent stem cells (iPSC) at a glance. Major stem cell discovery in regenerative medicine
Regenerative medicine
Regenerative medicine is the area of biomedical science and medicine, focused on development of scientific and clinical approaches and cell therapies to repair or replace pathological cells, tissues or organs (appearing in the body due to disease or injury) by generating and employing stem cells for producing of new tissues and organs.
What are embryonic stem cells?
Due to their unique property of stem cells, regenerative medicine has the great interest in using of these cells. These unspecialized embryonic cells have the inherent unlimited potential to generate into various types of specialized cells of the body: blood cells, nervous cells of brain, skin cells, bone cells, muscle cells etc. The embryonic stem cells don’t possess any specific functions in the body, except just one, but very important – repairing of the body after damage or disease. However, the only natural source of embryonic stem cells are early-stage embryos (also blastocysts), which creates severe ethical issues in the use of human embryos.
Induced pluripotent stem cells
Fortunately, the new option for using stem cells in biology and medicine appeared just 15 years ago. It was the greatest discovery in regenerative medicine of reprogramming of somatic cells, resulted in simultaneous invention and following fast development of the technology of induced pluripotent stem cells (iPSCs) by Takahashi and Yamanaka in 2006 [1]. These brilliant scientists generated embryonic-like pluripotent stem cells from mouse embryonic and adult fibroblasts by introducing just four factors of nuclear content (4 genes), Oct3/4, Sox2, c-Myc, and Klf4, under conditions of embryonic stem cell (ES) culture. They found, that those newly generated iPSCs had the morphology and growth properties of ES cells, including expressing ES marker genes. The great significance of this excellent research has been confirmed by awarding of 2012 Nobel Prize in Physiology and Medicine.
This breakthrough discovery with invention of a new technology allowed indispensable capability of regenerative medicine for reprogramming mature somatic cells into an embryonic-like pluripotent state after transferring four genes, resulting in producing of iPSCs, demonstrating properties of stem-like cells (pluripotency etc).
Advantages and problems of using iPSCs
Due capability of iPSCs for differentiation into variety of cell types in the body, obviously, much less ethical issues should appear in using human somatic cells in comparison with human embryonic stem cells. This provides much more opportunities for using this technology in development of effective therapies of human diseases and pathological conditions.
In the beginning of era of reprogramming of somatic cells, scientists recognized that there is the link between pluripotency and tumorigenicity [2]. Surprisingly, there is no such problem nowadays, mostly due to improvement of quality of all components, employed in the iPSC technology and the working protocol itself.
Due to iPSCs can be prepared from and for patients themselves, iPSC technology provides regenerative medicine with autografts, and allows avoiding any graft rejection reactions. However, this is not true in the case of using iPSC from donors, due to variety of HLA genes (encoding HLA proteins) in population. HLA is an important molecule on cellular surface; it enables the immune system to differentiate between “self” and “foreign” proteins in the body, creating a major problem in employing reprogrammed cells from a donor. However, currently there are two effective approaches to produce universal donors’ iPSCs which are suitable for virtually all recipients: by deleting HLA expression and by suppressing activity of NK cells [3].
The use of iPSCs in regenerative medicine and its perspectives.
Since the revolutionary discovery of phenomena of reprogramming of somatic cells, iPSC technology has greatly advanced regenerative medicine, modeling and drug discovery of poorly understood and poorly treated diseases. There are enormous amount of scientific reports and clinical trials, focused on regenerative cell therapy of various human diseases of central and peripheral nervous system (spinal cord injury, Parkinson's disease, Alzheimer's disease, Huntington’s disease, schizophrenia, dementia, multiple sclerosis, spinomuscular atrophy etc)[4, 5, 6, 7], heart (cardiomyopathy, heart failure) [8,9], eyes (age-related macular degeneration, corneal endothelial dysfunction, retinitis pigmentosa) [10, 11], blood (thrombocytopenia) [12], liver (chronic liver disease) [13, 14], gastrointestinal tract (ulcer) [15], pancreas (diabetes) [16] skin (dystrophic epidermolysis bullosa) [17], bones (bone injury) [18], various types of cancer [19, 20] etc.
References
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