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Stem cells are the outline on which all the specialized cells of our body are built and they form the basis of every organ and tissue in the body.
Recent research conducted by Professor G.V. Shivashankar of the Mechanobiology Institute (MBI) at the National University of Singapore (NUS) and the FIRC Institute of Molecular Oncology (IFOM) in Italy, revealed that mature cells can be reprogrammed into stem cells re-deployable without direct genetic modification – confining them to a defined geometric space for a long period of time.
"Our breakthrough results will usher in a new generation of stem cell technologies for tissue engineering and regenerative medicine that can overcome the negative effects of geological manipulation." Prof. Shivashankar
Withdrawal of the Cell Clock
More than 10 years have passed since scientists have shown that mature cells can be reprogrammed in the laboratory to become pluripotent stem cells able to be developed. in any type of cell in the body. In these early studies, researchers genetically modified mature cells by introducing external factors that reinitialize the genomic programs of cells, essentially returning time and bringing them back to an undifferentiated or non-specialized state. The cells obtained in the laboratory, known as Induced Pluripotent Stem Cells (iPSCs) can then be programmed into different types of cells for use in tissue repair, drug discovery and even to grow new organs for transplantation. . It is important to note that these cells do not need to be harvested from embryos
. However, a major obstacle is the tendency of any specialized iPSC cell to form tumors after being introduced into the body. To understand why this happened, researchers focused on regulating the differentiation and growth of stem cells in the body, and in particular on how cells naturally return to the state. immature stem cells.
Dr. Shivashankar's team of researchers has shown that mature cells can be reprogrammed, in vitro, into pluripotent stem cells without genetically modifying mature cells, simply by confining cells to a defined area for growth. . 19659003] Resetting Mature Cells
When fibroblast cells (a type of mature cells found in connective tissue such as tendons and ligaments) were confined to rectangular areas, they quickly took the form of the substrate. . or means to which the cells are attached). Based on previous work from the Shivashankar laboratory, this indicated that the cells measured and responded to the physical properties of their environment, and passed this information to the nucleus where the DNA packaging and genome programs were carried out. adapt accordingly.
cells over 10 days until they form spherical clusters of cells. Genetic analysis of cells within these groups revealed that the specific characteristics of chromatin (the condensed form of conditioned DNA) normally associated with mature fibroblasts were lost by the sixth day. By the tenth day, the cells expressed genes normally associated with embryonic stem cells and iPSCs. Researchers have now learned that by confining mature cells for a long period of time, mature fibroblasts can be transformed into pluripotent stem cells.
To confirm that fibroblasts had been reprogrammed into stem cells, the researchers then oriented their growth, with great efficiency, in two different types of specialized cells. Some cells have also been redirected to fibroblasts
Redefining stem cell technologies
The physical parameters used in the study reflect the transient geometric constraints to which cells may be exposed in the body. body. For example, during development, the establishment of geometric patterns and niches is essential to the formation of functional tissues and organs. Likewise, when the tissue is damaged, either as a result of an injury or a disease, the cells undergo sudden alterations of their environment. In each case, mature cells can revert to a pluripotent stem cell state, before being redeployed as specialized cells for tissue repair or maintenance
"Although it is well established that confining defined-geometry stem cells to models and properties of substrates can direct their differentiation into specialized cells, this study shows for the first time that mechanical signals can reset genomic programs of mature cells and return them to a pluripotent state " , says Professor Shivashankar
. The use of geometric constraints to reprogram mature cells can better reflect the process that occurs naturally in the body.More importantly, our discoveries allow researchers to generate stem cells from mature cells with great efficiency and without modifying them ge ninetily. "
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