By: Israh Ghobbar
An option for a medical patient with an ageing disease to turn back the developmental clock is using a medical therapy. This includes reprogramming mature cells into immature cells. Pluripotent cells give rise to all of the cell types which make up the body. A mature cell is a specialized cell that is designed to carry out a specific function in the body. For example, nerve cells and immature cells are capable of developing into any tissue of the body. This is because the DNA of mature cells have all the information needed to develop any cells in the body.
Since everyone has developed from a fertilized egg cell, the embryo, the early stage development of a human consists of immature cells which are capable of developing into all the cell types that form the adult organism. These include and are not limited to nerve cells, blood cells, muscle cells and epithelial cells. The process of reprogramming mature cells into pluripotent cells was originally done by the removal of the cell’s nucleus from a mature cell (specialized cell) which controls the cell’s contents and contains chromosomes (genetic information) with a pipette which is then inserted into other cells. Evidence for this was performed by John B. Gurdon in 1962 at the University of Oxford. However, in 2006 four genes were identified by Shinya Yamanaka at Kyoto University in Japan which keep embryonic stem cells immature. These genes were introduced into different combinations of mature cells to see whether any of them could reprogram mature cells into pluripotent stem cells.
This means that although the genome, the complete set of genes present in an organism, undergoes modifications during development, these modifications are not irreversible. Consequently, skin cells can be obtained from a patient with an ageing disease and reprogrammed to become an induced pluripotent stem cell (iPS cell) and used to grow neurons in order to treat the disease. They are known as iPS cells as they are being artificially generated.
As these cells are derived from the same patient’s body, they are a healthy treatment option that won’t be rejected by the immune system. This removes the need for the patient to take immune-suppressing drugs that are needed when using embryonic stem cells from a donated early embryo. There are also no ethical issues concerned with using iPS cells as a form of treatment as there is no longer a need for the use of human embryos. iPS cells are important for discovering how a disease unfolds as doctors are able to track the origin of the disease-causing cell and serve as an effective model to research to understand the mechanisms of diseases alongside treatment. Using this information, doctors may be able to intervene and correct the genetic defect before the disease advances. iPS cells can help a patient’s health indirectly in drug discovery by providing relevant cells in research alongside reprogramming for toxic compound identification which can also help in generating patient specific cell types. This has been performed at Boston Children’s Hospital, where patients have been treated to solve progressive blindness by producing retinal cells, preventing muscle degeneration.
The use of iPS cells has disadvantages related to current reprogramming methods, including the integration of multiple viruses into iPS cell genomes, resulting in tumorigenesis, the formation of a tumor due to genetic abnormalities in the cell. The efficiency of the reprogramming of iPS cells is low. For example, the reprogramming from fibroblasts is less than 0.02% of a cell, leading to an expensive process for the patient and hospital. Additionally, the reactivation of a silenced Myc gene might cause the iPS cells to become cancer cells. Reprogramming can induce genetic and epigenetic abnormalities in these cells due to the failure of complete cell reprogramming.
Therefore, iPS cells have a positive impact on modern day medicine, reducing the need for immune-suppressing drugs and helping doctors research the mechanisms of disease. However, more research is necessary to understand and improve the reprogramming process and the biological consequences of the genomic and epigenomic changes need to be investigated and minimised.