Jyotsna Joshi’s Study
In order to determine the practicality of iPSCs in medicinal research, Jyotsna Joshi and her associates began experimentation as to how effectively iPSCs can create heart muscle tissue (cardiomyocytes) for the purpose of treatment research for arrhythmia. Dr. Joshi and her colleagues were able to determine that the iPSCs were able to create tissue suitable for experimentation and that would react similarly to that of cardiomyocytes. Jyotsna concludes her research by stating the potential harms of iPSCs and by explaining the benefits that iPSCs can give to research in arrhythmia.
What are hPSCs and iPSCs?
A human Pluripotent Stem Cell (hPSC) is a cell capable of not only copying itself through mitosis but also synthesizing cells that are different from the original Stem Cell. For example, an hPSC is capable of dividing and one of the sister cells could be a skin cell, an epithelial cell, or any other cell that the body requires. hPSCs are mostly present during the pre-embryonic stage of human development where the developing organism is a blastocyst. These cells are responsible for creating cellular variation in the fetus that is necessary for early growth but becomes less essential to humans as they grow in size as the cells derived from hPSCs can undergo mitosis. This leads to many hPSCs being discarded as the human grows into adulthood with very few remaining as Adult Stem Cells (ASCs). An induced Pluripotent Stem Cell (iPSC) is a somatic cell that has been genetically re-engineered (likely using CRISPR technology) to have the same attributes as an hPSC. This is done by reintroducing pluripotent associated genes into a skin or blood cell, making it able to perform the same functions that an hPSC is capable of.
What is the Problem?
For scientific research in cardiovascular tissue scientists often need cardiomyocytes to undergo experimentation. However, any cells in the adult human body are incapable of undergoing mitosis including muscle tissue. This can be due to a multitude of reasons such as nerve cells being incapable of undergoing mitosis due to the unique shape of the cells with their long axons preventing telophase from being able to occur. In the case of muscle tissue, such as that in the heart/cardiovascular system, they are incapable of undergoing cell division due to how highly specialized their function is as a cell and as a mass of tissue. Simply put, a muscle cell is incapable of undergoing mitosis because its contractile nature makes the process incapable of occurring. In muscle tissue, to prevent mitosis from occurring, these cells do not pass through the G1 DNA checkpoint and are perpetually stuck in the G0 phase. This means that grown adults who do not have the ASCs required to rebuild cardiovascular tissue will receive permanent damage if cardiomyocytes were to become damaged in some way (such as alterations in the genomes of the cells). This makes extracting this tissue via biopsies for research purposes very dangerous and very limiting in the amount of tissue that can be taken.
The Problems with Modern Stem Cell Experimentation:
The potential methods by which scientists can get a hold of heart muscle cells (Cardiomyocytes/CMs) are either through direct extraction or synthesizing tissue using laboratory stem cells. As stated before hPSCs are only abundant in the human body during the pre-embryonic faze of human development and are scarce as humans reach adulthood. Therefore the main component in stem cell transplants (such as in the case of fixing chronic arrhythmia), those being the stem cells themselves, are incredibly difficult to come across. Scientists have proposed multiple different answers to this problem, but most of them are unsatisfactory. For example, it is an option to extract embryonic hPSCs from a mother’s umbilical cord and store those hPSCs for the future use of the offspring. Another option is to extract ASCs from a patient (or a donor with similar DNA to a sibling) and replicate them in a lab through mitosis and reintegrate the new and previous stem cells back into the patient. The problem with these systems is that as time goes on stem cells in laboratories have tendencies to behave similarly to cancer cells in that their behavior and replication become more sporadic than when it was inside the body. Therefore, such stem cells are often wastefully discarded. Another major flaw of stem cell transplants is the limited number of them in the adult human body to be extracted and genetically modified. This drastically decreases the practicality of stem cells. The process is also very expensive as extraction and genetic modification are both very difficult and require a lot of resources to pull off.
The introduction of iPSCs in treatment is able to mitigate these problems in modern stem cell transplants. For starters, iPSCs are not ASCs being extracted from the body and being modified, but rather blood and skin cells that have undergone genetic engineering. This means that doctors are no longer restricted to procedurally removing ASCs from the body to create useful stem cells which will reduce overall cost and patient safety in that aspect. The potential abundance of iPSCs also alleviates the need for long-term stem cell storage.
iPSCs in Treating Chronic Heart Arrhythmia:
Arrhythmia occurs when a person’s heartbeat behaves abnormally. This disease can be caused by the cardiomyocytes responding incorrectly to a signal from associated neurons. Chronic Heart Arrhythmia causes significant pain in the patient, greatly increases the likelihood of heart attacks, can affect blood pressure, and increases the likelihood of stroke. To treat this disorder, researchers must have heart tissue to determine what treatment options work most effectively at correcting the patient’s heartbeat. iPSCs provide cardiomyocytes in mass quantities as iPSCs can perform mitosis and become factories for these cells and only require blood or skin cells for reprogramming. This heavily speeds up research for more effective treatments for arrhythmia as more resources are readily available and easy to produce. iPSCs are a pathway to more effective treatments for the future and more efficient and available experimentation in cellular biology.
What Does This Mean?
I believe that iPSCs’ potential is not limited to just heart arrhythmia, but can be applied to any cell that is difficult to acquire naturally (i.e. neurons). iPSCs, especially as scientists begin to maximize their similarities to hPSCs, are going to pave a path to the future of biological experimentation in a similar way that HeLa cells did for cancer research; By providing cells in mass that can represent tissue matter scientists wish to experiment on, iPSCs are going to be able to make experimentation much cheaper, simpler, safer, and practical. We still have to inquire further about the negative consequences of iPSCs, as the technology to create them and their existence is still very recent (first developed around 2007). Looking further into the future still, there is a potential that these iPSCs can functionally replace stem cells, however, this is still a point of contention among scientists as to its plausibility. Do you think iPSCs could potentially be used in practical medicine beyond research? If this is the case, would you trust iPSCs to function as a normal PSC would be able to?
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