From Stem Cells to Cancer Cures: Reprogramming is the Way of the Future

By: Nina Paletta

The media loves to sensationalize stories of medical marvel – from movies and TV specials to magazine articles and aggrandized Facebook posts, it seems as though the science fictional nature of modern medical advancements is a topic that both fascinates and mystifies the public. The line between fact and fiction, however, is difficult to discern because of this; facts can get distorted or exaggerated in order to craft a more appealing outlook, or details may be fabricated, overly simplified, or even omitted entirely to ensure that the layman can understand the underlying concept. What the media fails to realize is that this glorified presentation of information gives the public a fantasized and incorrect view of the true medical advancements of the time. By both appealing to the political and social views of the time, the media’s influence on the public’s reception of medical advancement is more detrimental than beneficial. For the past decade, issues such as stem cell research and modernized cancer treatments have been topics of heated debate. Because of past media stigma and great selectivity in the presented details, however, many people have been reluctant to further explore or accept these advancements. What these people do not know is that both stem cells and modern cancer treatments have something in common – a new and emerging technology called “reprogramming.” By looking at the entirety of the situation, it is easy to see that reprogramming is the way of the future.

When some people hear the words “stem cells,” they automatically think of embryonic stem cells; and the ethical backlash can be brutal because of the controversial way of obtaining them through undeveloped embryos. What most people fail to realize, however, is that in scientific experiments, a new type of stem cell has been developed in order to bypass using embryonic stem cells. This new technology is called induced pluripotent stem cells, or iPSCs. Induced pluripotent stem cells were first discovered in 2006 when Shinya Yamanaka of Kyoto University experimented with mouse skin cells. In his experiment, Yamanaka was able to reprogram the mouse skin cells into a sort of pluripotent stem cell that could be converted into any type of cell – just as a naturally occurring pluripotent stem cell would be able to do. In 2007, Yamanaka was able to recreate his mouse experiment with human cells. In his process, the cells were exposed to a retrovirus – an RNA virus, like HIV – that contained four genetic reprogramming factors; once infected, the reprogramming factors would integrate into the cell’s DNA. The cell would then be reprogrammed to function as an induced pluripotent stem cell. Even though it was the most effective way of reprogramming cells, there were a few problems with Yamanaka’s methods. First, the use of a retrovirus to introduce the reprogramming factors can be damaging to the cells. Because the DNA of the reprogramming factors is integrated into the DNA sequence of the host cell, there could be problems with integrating in a coding region; if this is the case, the integration of this DNA could cause cancer. In addition to the DNA integration causing cancer, some of the reprogramming factors themselves are carcinogens. Because of these limitations, scientists worked towards developing methods to reprogram the cells without the use of a retrovirus.

Today, researchers at Johns Hopkins have not only successfully employed a virus-free induced pluripotent stem cell development technique but have also used these stem cells to repair retinal tissue in mice. Dr. Zambidis and his research team used stem cells taken from human cord blood and genetically reprogrammed them with DNA plasmids – small, round fragments of DNA that replicate independently of nuclear DNA in the cell and degrade after short periods of time. This method of reprogramming eliminates the use of carcinogenic reprogramming factors and yields a more stable cellular product. After these cells were reprogrammed, the cells expressing the correct cell surface proteins were selected for and grafted into the blood vessels of mice with damaged retinas. The results were astounding – most of the mice that were injected developed normally functioning retinal vascularity. When compared to an embryonic stem cell control, the induced pluripotent stem cells yielded augmented success.

Many labs across the country are now using these techniques in order to study induced pluripotent stem cells. The implications of these successful findings are limitless – by developing a safe and effective way to reprogram cells into pluripotency, researchers can not only develop human models for testing drugs and other treatment options for currently untestable diseases but they can also develop artificially grown organs to monitor abnormal function. For example, until this point, in order to study Alzheimer’s disease in a live environment rather than a postmortem autopsy, a viable disease model is needed in order to ethically and efficiently tests these neurons. In just the past few years, induced pluripotent stem cells have been utilized to grow Alzheimer’s diseased neurons in a Petri dish. In an experiment done at the University of California, San Diego by Larry Goldstein, skin cells from three different risk groups – people with familial Alzheimer’s disease, people with sporadic Alzheimer’s disease, and people with a normal genotype without dementia – were transformed into induced pluripotent stem cells. These iHPS cells were transformed into neurons that mimicked the Alzheimer’s disease (or lack thereof) in the patients; the neurons produced by this culture were used in order to compare the live models of the different types of disease as well as diseased tissue to genotypically normal tissue. Up until this point, Alzheimer’s diseased neurons had not been able to be produced purely in a laboratory setting. By using these induced pluripotent stem cells, areas of medicine that have stagnated due to ethical concerns can now be reignited.

In addition to stem cell reprogramming, there have been many reports circulating recently about a seven year old girl dying of leukemia who was cured after being injected with the HIV virus. This dramatized story spread like wildfire on social networks such as Facebook and Reddit over the past few months – people were outraged by the fact that a virus as dangerous and as taboo as HIV was willingly used on a dying child. What these aggrandized stories did not fully disclose, however, were the methods and protocols that the doctors working on this experimental treatment followed. Dr. Stephan Grupp at the Children’s Hospital of Philadelphia aided in developing a technique called CTL019, or CART19, since 2011. CTL019 is a T cell modifying procedure in which a lentivirus is injected into the T cell and incorporates its DNA into the host cell’s DNA – similar to the retrovirus induced pluripotent stem cell reprogramming methods. The T cells are modified to attack the acute lymphoblastic leukemia cells; with the two trials done at the Children’s Hospital of Philadelphia, one of the children – Emma Whitehead from the story  – had sustained complete remission. From this success story, the media latched onto controversial buzzwords like “lentivirus” and spun the report around that. Although HIV is in the lentivirus family, Grupp and his team used a modified virus from that family that was equipped with self-regulating mechanisms. Although the mechanism employed by the virus was similar to that of the HIV virus, it was not the infectious agent itself. Instead of reporting a controversial view of the story, the media should have focused on the reprogramming mechanisms that were developed. By reprogramming immune cells to recognize specific cancerous cells, new treatments for many inoperable or currently untreatable cancers could be developed in the near future, changing the face of oncology altogether.

New technological advances in the medical field are swiftly changing the way doctors are thinking about treatment plans for their patients. Once stagnated areas of research are now becoming more feasibly available to lab researcher teams. By harnessing different cellular reprogramming technologies, diseases like cancer, Alzheimer’s, Parkinson’s, Huntington’s and others can be ethically studied and experimentally tested and manipulated. In addition, breakthrough transplant technologies are being redeveloped – if new organs can be grown in a lab using the patient’s own cells, the problem of finding a transplant match would become an obsolete problem; and rejection would be less of a worry. Even with the stigmas associated with these new technologies, the medical field is being revolutionized by reprogramming – the medicine of the future.