In recent years, stem cell research and therapy have become a very promising and advanced scientific research topic for the scientists in order to develop possible treatment methods for untreatable diseases, such as Parkison’s disease or Lou Gehrig’s disease. This essay focuses on how the scholars worked on their projects mainly granted by California Institute for Regenerative Medicine (CIRM) to utilize human embryonic stem cells to look for a cure for one of the most common diseases in the world, which is Diabetes mellitus. The available treatment methods nowadays can neither cure nor completely control the complications of this disorder. But, scientists have been trying to treat the disease with stem cell therapies in recent years, and it looks like the most likely future success.
Diabetes mellitus is a life-threatening disease with the rapid increase of diagnosed cases worldwide. According to the statistics provided by the International Diabetes Federation (IDF), as of 1997, only “124 million people” out of around 5.873 billion people had diabetes. As of 2017, an estimated “425 million adults” out of 7.256 billion people worldwide had diabetes. Within these twenty years, the total number of people diagnosed with diabetes increased by 240.3 percent. In addition, the proportion of people with diabetes relative to the whole world population of that year increased by 3.71 percent from 2.11 percent to 5.82 percent.
Furthermore, as of 2020, the national report states that “1 of 11” adults would have diabetes with approximately “463 millions people”, and “1 of 2 adults with diabetes are undiagnosed”, which means that the actual incidence of diabetes will be higher than currently estimated because many people have not yet been diagnosed. Most importantly, the organization predicts that “there would be one death every eight seconds”. Furthermore, from Figure 1 shown in Appendix A, even though Type 1 Diabetes (T1D) has much lower prevalence than Type 2 Diabetes (T2D), but the age at onset for T1D is much younger than T2D because T1D happens mostly in children, and thus T1D is also known as juvenile-onset diabetes. Based on these data, it explains why it is important for the scientists to actively research and work for treatment solutions for diabetes mellitus.
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People are normally aware that T1D results in the sugar building up in the blood vessels and requires injecting insulin chronically to sustain life, which is known as insulin-dependent diabetes. However, a few people except for biological experts know that the majority of T1D is “of the immune-mediated nature” in which a “T cell-mediated autoimmune attack” leading to destroy it healthy beta cells in the pancreas that make the hormone insulin and thus absolutely reducing the produced level of insulin. Due to the serious deficiency of insulin, this explains why the patients diagnosed with T1D needs to inject insulin usually starting with “two injections of insulin per day of two different types of insulin and generally progress to three or four injections per day of insulin of different types. The types of insulin used depend on their blood glucose levels”.
However, according to the passage from the “Stories of Hope” program by CIRM, the staff interviewed a woman called Maria who has suffered from diabetes for 20 years. She stated that she needs to inject the hormone five times a day and must often measure her blood sugar levels even more frequently, but insulin is not a cure. Even with the regular injections, she would still face dramatic mood swings and more serious complications as glucose levels keeps rise and fall frequently. In addition, the study also states that it is very difficult to maintain blood glucose at safe levels by only utilizing the method of self-administer insulin, and too high glucose level in bloodstreams chronically can lead to “blindness, kidney failure, nerve damage, and heart problems, and too low can cause coma or death”.
As a result, the scientists found that they needed to find another treatment that would actually cure diabetes, instead of not only failing to control it completely, but also potentially leading to other risks, such as cardiovascular disease. Then, through a large body of research, they indicate that replacing the destroyed beta cells of the “endocrine pancreas would represent a substantially more effective approach to treating type 1 diabetes”. Therefore, to address this need, a San Diego-based company named ViaCyte is developing a cell replacement therapy for T1D. At first, the scientists proposed this promising strategy by transplanting new beta cells to replace the ones they lost for patients with T1D.
However, the process of turning human embryonic stem cells into insulin-producing beta cells by absolutely “replicating the exact signals” was very challenging. With more than $72 million in funding from CIRM, in 2008, ViaCyte succeeded, but with a “clever twist” through creating human pancreatic “progenitor cells transplanted under the patient’s skin, known as PEC-01™ cells” which are “one step shy of mature beta cells”. These transplanted cells are “partially matured into becoming pancreatic tissues (the type destroyed in T1D)” and then will “develop into fully matured beta cells that secrete the hormone insulin”.
By having this technology and knowledge, it means that the patients with T1D could increase their body’s ability to produce enough insulin, lower blood sugar levels maintained in a healthy level, and alleviate the need for injections. With the fundings granted by CIRM, the main investigator, Howard Foyt from ViaCyte, researched two Phase 1/2 trials testing different product candidates, VC-01 and VC-02. The first product, VC-01 (also known as PEC-Encap), encapsulates the cells and protects them from the patient’s immune system. At STEP ONE study, “ten T1D patients had been enrolled in Cohort 1 and implanted with the VC-01 product candidate at a sub-therapeutic dose of cells”.
The reason that they only enroll ten patients and implant at a relatively lower level of dose of cells is because even the experts from this study could promise the implanted cells would have 100 percent no harm for the patients with T1D. After compiling and reporting Cohort 1 to the Data Safety Monitoring Board (DSMB), the observations suggest that the “VC-01 product candidate is safe and well-tolerated” by patients with T1D, and there is “no adverse events related to the implanted cells have been reported”.
In the last year of this trial, ViaCyte decided to pursue and optimize the VC-01 product modifications because they found out that in some cases there is a limited potential for prolonged cell survival and differentiation to insulin-expressing beta cells in patients with T1D caused by a foreign body response which negatively impacts engraftment. For testing their second product, VC-02, which “allows the patient’s blood vessels to make direct contact with the implanted cells and helps the patients with high-risk T1D”, there is limited information about this clinical trial stage project since this project is still active and ongoing. Now, the researchers only announce that they will put “pancreatic progenitor cells in a delivery device that allows direct vascularization of islet cells”.
Because everyone’s constitution is different, the process of implanting a new thing into a person’s body is risky and unable to forecast. For instance, even though a bone marrow transplant is matching the same blood type, there will still be rejection, which helps explain why scientists first starting from small-scaled clinical trials to observe the subjects and record their relative data.
The process to find a perfect cure is very time-consuming, and only when a large number of field trials have been conducted to discover the feasibility of the PEC-Encap, then the technique will be considered as a real treatment for diabetes. But, according to current data, VC-01 is feasible to “cure” diabetes in a short-term with less need of injection, but in a long run, the implanted cells differentiated to insulin-expressing beta cells cannot live very long and easily die caused by negative foreign body response.
It is also hard for researchers to find effective cures for the patients with T2D who have normal or even higher levels of insulin produced and mainly result from cells failing to respond to insulin properly known as insulin resistance. This is because, in addition to genetic factors, the most primary cause of T2D is a combination of acquired factors, such as excessive body fat, insufficient exercise, poor diet, or urbanization.
The investigation of “excess body fat is associated with 30% of cases in people of Chinese and Japanese descent, 60–80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders” shows that the proportion of diabetes caused by excess body fat varies from country to country. It might be because different countries have developed their own unique food cultures and way of life in the long-term, which is rooted and hard to change, and makes people challenge the authority of knowledge.
Take China and Japan as examples, even though experts say that eating too much white rice will increase the risk of diabetes, people especially the adults would still eat due to their fixed dietary habits. However, the reason that rates of diabetes due to excessive body fat in China and Japan are much lower than other countries is because they rarely eat fatty foods such as fried chicken or hamburgers.
Especially in Japan, because of its location near the sea, they like to eat raw seafood which is high in protein but low in trans fat. Furthermore, even though scientists provide suggestions to help slow down the progress for worsening T2D, like eating a healthy diet and keeping exercise, it is hard to apply to all people due to many socioeconomic factors. For instance, either a stressed white-collar worker won’t give up his city job due to necessity of life or a low-income family won’t quit fast food since they don’t have enough money to purchase organic food.
However, in social aspects, humans cannot easily change their original life habits, but in the science aspects, scientists have found out the possible treatment for obesity with stem cell therapy. “Of the 578 articles retrieved, seven studies met the inclusion criteria, and their analysis revealed several main findings” with the “positive effect of the adipose-derived mesenchymal stem cells (AD-MSCs ) in obesity treatment in terms of body weight” and other obesity-related diseases.
Moreover, a few latest studies for a “significant effect of AD-MSCs transplantation on the improvement of obesity-related hormonal status, like leptin and body composition patterns, though these investigations may need further replication”. But nowadays, scientists research on the effects of AD-MSCs transplantation on obesity, in terms of weight loss and obesity related diseases only in animal models, they still need time to prepare clinical trials on humans to observe and conclude the results.
Therefore, stem cell therapy has been a promising and advanced way of research in both type 1 and type 2 diabetes. Before moving forward to assess VC-01 as a potential method for developing prolonged, healthy beta cells differentiated from the human pancreatic progenitor cells or AD-MSCs as a potential strategy for human obesity management, scientists will still need a further study “the mechanism of action and to overcome some methodological limitations such as the small sample sizes and risk of bias evidenced in the systematic review.”
