Embryonic Stem Cells – a cure for old age (1)
Prospects for the use of human embryonic stem cells for the treatment of age-related diseases
Review of “The promise of human embryonic stem cells in aging-associated diseases" (Odessa Yabut, Harold S. Bernstein)
published in Aging magazine, volume 3, No. 5 (May 2011).
Translated by Evgenia Ryabtseva
Resume
The cause of the development of age-related diseases is often the progressive death or disruption of the functioning of cells, which ultimately affects the functions of all tissues and organs. The effectiveness of the treatment of such diseases can be improved with the help of cell therapy methods involving the regeneration of lost cells or other approaches to restoring the functioning of tissues. Human embryonic stem cells (CESCS), due to their unique ability for self-renewal and pluripotency, are a promising therapeutic candidate for tools for the treatment of age-related diseases. To date, many cESC lines have been developed and characterized. In this review, we will discuss methods for isolating cESC lines, their molecular and cellular features, as well as characteristics that determine their ability to differentiate into cells of all three embryonic germ leaves. We will also describe the methods currently used to guide their differentiation in a population of functional tissue-specific cells. And finally, we will list the main problems that have yet to be solved and the strategies being developed for creating highly purified populations of cells derived from cESC suitable for use in clinical practice.
I. AGE-RELATED DISEASES AND STEM CELLSTherapy
In 2010, people aged 65 and older accounted for approximately 12.9% and 8% of the population of the United States and the world, respectively [1].
These figures are expected to increase dramatically when millions of members of the baby boomer generation born between 1945 and 1964 reach this age. Therefore, the possibility of preventing and curing age-related diseases is rapidly becoming the main goal of the work of various branches of biomedical science.
Age-related diseases include degenerative diseases that disrupt the functioning of tissues and organs. For example, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS) are conditions characterized by progressive deterioration of the structure and functions of neurons, leading to their death. Macular dystrophy develops as a result of gradual degeneration of retinal macular cells and is the leading cause of vision loss in adults over the age of 55. Diseases such as osteoarthritis and osteoporosis, characterized by degeneration of cartilage and bone tissue, respectively, are the cause of most injuries to the knee, hip and other joints, as well as the spine in elderly people.
Age-related diseases can also be the result of impaired cell function. Such diseases include cancer, heart disease, chronic obstructive pulmonary disease (COPD) and diabetes. The development of cancer is caused by metabolic changes in cells, leading to the appearance of DNA damage, which can cause uncontrolled inadequate cell division. The risk of cancerous tumors increases significantly as the body ages. The cause of the development of heart disease is usually the prolonged functioning of the heart against the background of hypertension, hypercholesterolemia, diabetes and other risk factors for cardiovascular diseases, as well as an age-associated increase in the likelihood of developing left ventricular hypertrophy, diastolic dysfunction and atrial fibrillation [2]. COPD is a group of progressive diseases of the respiratory system, which include emphysema, characterized by the destruction of the alveolar cells lining the pulmonary epithelium; and chronic bronchitis caused by abnormal mucus production in the airways of the bronchi [3]. With type 2 diabetes developing in adulthood, insulin hypersecretion can lead to dysfunction and degeneration of pancreatic beta cells [4].
The prospect of restoring or replacing damaged abnormally functioning or dead cells with new functional cells has shifted the therapeutic paradigm towards restoring the functioning of tissues in individuals suffering from age-related diseases. The main candidate for use in the development of such therapeutic approaches are stem cells, especially human embryonic stem cells (CESCS), which have the ability to infinitely self-renew and differentiate into all tissue-specific cell types (Fig. 1).
Figure 1. Creation of pluripotent human embryonic stem cell lines
The creation of human embryonic stem cell (cESC) lines takes place in several stages. First, by in vitro fertilization or egg activation (parthenogenesis), donor embryos are obtained, which develop in vitro for some time. After that, pluripotent cells are isolated from the internal cell mass of the preimplantation blastocyst or morula at the stage of 4, 8 or 16 cells. At the final stage, the isolated cells are seeded into a special medium for the cultivation of cESC, without or using a layer of feeder cells, for reproduction and isolation of populations of pluripotent cells. The use of this method allowed to obtain cESC lines capable of giving rise to both embryonic cells and tissues of all three germ leaves.
In this review, we will describe the methods of isolation and maintenance of viability, as well as the properties of pluripotent cescs. We will also talk about the methods used to induce the differentiation of CESCS into cells of certain types, paying special attention to the types of cells suitable for studying the mechanisms of pathology, as well as being potential tools for methods of cell therapy of age-related diseases.
Continuation: sources of production, maintenance of viability and basic properties of human embryonic stem cells.
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19.12.2011