The future of regenerative medicine?
Multipotent stem cells from fat cells
All somatic (non-sexual) human cells contain the same genetic material, only it is used differently in different cells. However, with the help of new technologies, they can be turned into "stem cells" capable of generating a variety of cell types. Experiments on laboratory animals using human stem cells "created" from ordinary fat cells allow us to be optimistic about the future of this therapeutic approach.
Press release Scientists are a step closer to developing 'smart' stem cells – and they're made from human fat published on UNSW Sydney, article by Yeola et al. Induction of muscle-regenerative multipotent stem cells from human adipocytes by PDGF-AB and 5-azacytidine – in the journal Science Advances – VM.
Regenerative medicine deals with the restoration of diseased or injured tissues and organs. One of the main areas of research in this area is related to stem cells: these undifferentiated ("immature") cells are the universal source of all specialized cells of the body.
Stem cells are present in large numbers in the tissues of the developing embryo, and in a small number in the adult body. In humans, stem cells are responsible for the normal renewal of tissues (for example, blood cells, bone and cartilage tissues, etc.), but they are not able to repair serious damage. It is not always possible to use the stem cells of the patient himself for therapeutic purposes, and ethical problems arise when using fetal (taken after abortion) stem cells.
Fortunately, technologies for converting ordinary cells into stem cells have been developed for quite a long time; research is also successfully underway to create methods for growing new organs from such cells.
From the somatic cells of the patient, it is now possible to obtain both pluripotent (with "many possibilities") stem cells capable of differentiating into almost all types of cells, and more specific, capable of turning into only a small number of specialized cells. At the same time, the use of both is not without drawbacks: planting pluripotent cells to a person carries the risk of developing tumors, and the benefits of more highly specialized ones will be limited, since the tissues are a complex cellular composition.
Ideally, therapeutic stem cells should respond to local molecular signals, turning into those cells that are needed "here and now", and at the same time not show tumor-like growth. The golden mean, possessing these qualities, can be the so-called multipotent stem cells, capable of giving rise to not all, but many types of cells.
The production of such cells was reported by Australian researchers back in 2016. To do this, they used a culture of mature somatic cells of mouse bone tissue, adding two compounds to the culture medium. The first of them is platelet growth factor AB, which is involved in stimulating cell growth and tissue repair, and the second is azacitidine, which is commonly used in blood cancer.
Azacitidine, which is an altered analog of the cytidine nucleoside, a normal component of the nucleic acid molecule, disrupts transcription and protein synthesis when incorporated into RNA. But in this case, it is important that about 10-35% of this compound is also included in DNA, suppressing its methylation (addition of a methyl group). It is known that cytosine methylation in the regulatory region of genes "turns them off", but if this process does not go on, the cell will lose its specialization and return to its original stem state.
In principle, human treatment with induced multipotent stem cells can be carried out in two ways. In the first case, the patient is simply injected with his own fat cells reprogrammed "in vitro". Another option is to install a mini–pump near the area in need of regeneration, which will inject substances necessary for the transformation of subcutaneous fat cells
Previously, researchers transplanted such "reprogrammed" bone cells to mice, as well as human fat cells, and observed signs of accelerated tissue formation in animals. Now they have optimized the protocol for the transformation of human fat cells – a potential, easily accessible source of cells for clinical practice. When such cells were injected into injured mice, they remained at the implantation site for a long time and provided "repair" of damaged tissue – muscle, bone, cartilage, as well as blood vessels. Importantly, there were no signs of malignant growth or proliferation of injected cells.
Of course, the introduction of the new method into clinical practice is still far away: additional preclinical and clinical trials are required to assess its effectiveness and safety for humans. According to scientists, the implementation of such a project may take up to 15 years.
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