What is the relationship between stem cells and vaccines?

This project focuses on the relationship between stem cells and vaccines. We are aiming to understand the properties of both vaccines and stem cells, how they are similar, and how they may affect each other.
Abigail Xu Sonal Arya
Grade 10

Presentation

No video provided

Problem

Our Main Focus

Stem Cells and Vaccines are growing technologies in the medical field, and our main objective is to delve deep into these topics and understand the lasting impacts that they can have on each other. The technology being produced today is growing at an alarming rate and we wish to understand what advancments are being made to vaccines that can help support stem cells, or if there are any sorts of vaccines that hinder the ability of stem cells to perform their unique functions in the human body. Many people in the world depend on the growing technologies that scientists work on day to day in order to survive. For example, there are many all around the world who are waiting to recieve an organ transplant, which could potentially be made possible through the development of these unspecialized cells. However, we believe that it is important to tie the developments of stem cells into the developments of arguably, the worlds greatest invention, the vaccine. Vaccines are a massive part of day-to-day life, and they strengthen our immune system in a controlled enviornment that is able to prevent intese or fatal effects of certain illnesses. In the medical field, little testing has been done to determine whether or not organs grown from stem cells will react differently to stem cells, which is why in this project we will attempt to get to the bottom of this underlying issue, and understand whether or not people with stem cell grown organs will be more susceptible to diseases or not. 

The Big Question

Do vaccines hinder or facilitate the use of stem cells? Or, can stem cells be used as a way to promote vaccine development?

Our Hypothesis

We believe that the vaccines ability to enhance and strengthen the immune system will have a positive affect on stem cells and their uses in the human body. This is because through the vaccines abilities to prevent infectious diseases, stem cells have the potential to be assigned and act similarly to specialized cells. Meaning that there is no difference between the reactions caused from a person with stem cell grown organs and non-stem cell grown organs. 

Method

Steps for Research and Finding a Solution

1. Begin with a brief google search to discover if any articles delve into our topic at a surface level. Read through these articles and record down website links and research in log book. Start to find background information on the subejct. Remember to keep all research organized. 

2. To furthur understand topic throuoghly research stem cells and vaccines. Divide and conquer research, share findings within group.  This information will be summarized as research on the online platform, with changes being made to logbook as further research is conducted.

3. After baseline research is conducted begin to focus on the main issue presented in the problem section. Begin to understand the history of vaccines and stem cells and when they begin to overlap with each other. 

4. Now begin to narrow down research to specific vaccines and stem cells. Choose a specific vaccine and its effects on a specific type of stem cell.

5.  Research case studies and form a potential solution to the related problem which will be relayed in the conclusion section. 

Research

Background Information

Stem Cells

Stem cells are the root of cell growth in a multi-cellular organism, they are a type of cell with two special properties, 1. Make more cells like themselves (self-renewing), 2. They can develop into other cells the body needs based on signals from surrounding cells and their environment, these signals regulate which genes will be present, determining the future cells' function. These cells are vital to the maintenance of tissue as well as the repair of the body after injury.

In the human body, there are around 5 types of different stem cells, in our research we will focus on embryonic cells and somatic stem cells, commonly known as adult stem cells, with a brief mention of induced pluripotent stem cells. But what makes them different? Pluripotent cells are what are what most people would think of when they think of stem cells, these cells can turn into any cell type in the body without limitations, an embryonic cell is pluripotent. Meanwhile somatic stem cells are multipotent, meaning that they are limited, only becoming the different cells of their tissues. (Somatic cells and somatic stem cells are different things, Somatic stem cells are already there, while somatic cells develop through the process of mitosis) Induced pluripotent cells are a different case fusing the two ideas of multipotent and pluripotent. They are cells taken from blood or skin cells which then go through a process in which they insert 4 genes(Sox2, Oct4, Klf4|,cMyc) which results in the cells becoming genetically modified and reprogrammed back into an Embryonic pluripotent stage where they can become any cell type without limitations.

The development of stem cells depends on where the stem cells are located. A specific example is hematopoietic stem cells which can be found in the bone marrow, These cells then develop into various types of blood cells depending on the need. The majority of stems have low regenerative abilities only able to repair and maintain tissue in organs instead of growing into a completely new cell.

What's the Difference?

T cells

T cells, along with b cells, are a type of lymphocyte cells and lymphocyte cells are one of the 5 types of white blood cells.  Lymphocyte cells play an important role in your immune system and focus on protecting against viral infections and produce proteins to help anitbodies fight aginast infections.There are two main types of T cells, which are the helper T cells or the cytotoxic T cells. Cytotoxic cells aim to kill cells infected with viruses and bacteria or destroying tumur cells. helper cells are different in the fact that they dont aim to kill infected cells directly , instead sending signals to other cells on how to attack the pathogens, helping out fellow cytotoxic cells, b cells, and macrophage. These cells play a crucial role in your bodies adptive immues responses, your responses constantly monitor for danger or sudden pathogens and once located, the adaptive immune responses build customized offences that send in specilaized t cells. Effector t cells like cytotoxic cells fight agaisnt the pathogen and after the pathogen is gone, some effector t cells morphe into memore t cells, that memorizes the pathogen to quickly defend and recognize it if the pathogen invades again.

How are they created?

The T cells in the human body are developed through a process called hemopoisis that uses hempoetic stem cells, which produces the bodies blood and bone marrow cells. Hempoetic stem cells go through many developmental stages to either become a myeloid stem cells or a lymphoid stem cell. Myeloid stem cells go on to change into red blood cells, while lymphoid stem cells will become lymphocyte cell, which includes the t cell. However, T cells do not finish maturing in the bone marrow as they leave as thymocytes to finish devloping in the thymus. The thymus attracts the immature T cells by releasing chemicals called chemokines, once in the thymus, the outer layer stimulates t cells to produce t cell receptors(TCR) and double postives that recognize crucial molecules, falilure to bind to the molecules kills the t cells off, this process is called postive selction. T cells now move onto medulla of the thymus, here they are exposed to self antigens and the ones that bind to them are killed off , this process is called negative selction. This happens so t cells dont start to attack ones own tissues. After these two processes happen, t cells will be exposed to other body cells which will develop the t cells into their two types, either helper t cells(presence of CD4) or cytotoxic cells(presence of CD8). They are finally released into the lymphatic system.

How are they different from stem cells?

Stem cells are cells that have yet to have any specific function, except for dividing into specilaized cells, like t cells. T cell are specialized and have a function to fight against pathogens in your bodies immune system.

Hormones

Hormones are chemicals that send messages throughout the body and its organs, these messages regulate and control functions of the body, such as, metabolism, growth and development, sexual function, and more. Hormones are created by the organs and glands that make up an individuals endocrine system, some main ones are the pancreas organ and the pineal gland. Some tissues also create hormones, but many have other main functions that play a bigger role, so they are mainly not considered in the endocrine system. 

Hormone communication

The human body uses hormones for two types of communication. The first type is communication between the endocrine glands, this happens when the body needs to regulate hormone production. One gland will release a hormone, which in turn signals the other gland to alter its hormonal levels to maintain hormonal balance. The second type of communication is between an endocrine gland and a target organ, an example would be the release of insulin from your pancreas which then signals your liver to produce glucose.

How are they different?

Hormones are chemical messengers and they are not cells. They send signals to the many different parts of the body, controlling the functions of ones body. Stem cells are unspecialized cells that only develop into new cells, they do not control the functions of the body. Hormones do affect stem cells as they control and regulate the cells ability to regenerate and grow into other cells, this happenes because hormones can control their function in various tissues and organs through messages.

 

Vaccines

Vaccines are arguably one of mankind's greatest inventions. Protecting us from bacteria, illnesses, pathogens, and other harmful foreign microbes that may enter our bodies. When the body suffers from a disease caused by a particular strain of pathogen (a pathogen is a microorganism that contains fungus, bacteria, viruses, etc, that develop into fully blown illnesses within their host), it will release a few lines of defence to rid itself of the disease. White blood cells and anti-bodies work in synchronous to heal the body, and signs that they're working are coughing, sneezing, and high fevers that appear when sick. However, the body keeps track of the pathogens that they destroy and the methods they use to destroy them. This information is stored within B-Cells and T-Cells, which work together as the body's second line of defence when it comes to eradicating illness. However, the development of vaccines works to allow us to eliminate these diseases quickly, by allowing us to expose our bodies to these pathogens prematurely, in a controlled environment. Vaccines work by triggering the body's autoimmune response to prepare for the invasion of harmful pathogens.

There are 4 major types of vaccines available, these vaccines are: Live attenuated vaccines, Inactive vaccines, Subunit vaccines, and DNA vaccines. Live attenuated vaccines are vaccines that contain a weaker version of the live pathogen. They are extremely effective at disease prevention by triggering the immune system and usually, just 1-2 shots of these types of vaccines can provide immunity for life, but they cannot be given to those with debilitated immune systems as extreme harm could potentially be caused. Examples of live attenuated vaccines are measles, smallpox, and chickenpox.  Inactivated vaccines are vaccines that contain dead or inactive pathogens. They are effective at provoking an immune response within the body but they are not as long-lasting as active vaccines. Usually booster shots are necessary for immunity to a specific pathogen. Types of inactivated vaccines are the flu shot, hepatitis A, and rabies. Subunit vaccines are created by using a specific part of a pathogen, this could be a protein, sugar, or capsid. These vaccines provide a strong response to a major part of the germ and can be used by almost everyone (no restrictions regarding immune system strength). However, booster shots are necessary for ongoing protection. A few specific examples of subunit vaccines are hepatitis B, whooping cough, and human papillomavirus. Finally, the last major type of vaccine is the DNA vaccine. DNA vaccines are a newer type of vaccine, they use engineered DNA to trigger the immune system and allow it to recognize specific antigens in host cells, so it may fight off entire pathogens. These vaccines are currently being developed for cancer treatments, Influenza, HIV, and Ebola. 

Development of the First Vaccine

What is smallpox?

Smallpox is a contagious disease that ravaged many civilizations, including China, Africa, India, etc. Its emergence was believed to be in around 10,000 B.C. after the first agricultural settlements began to pop up in North East Africa. Smallpox spread around the world as trade routes grew and expanded killing around 30% of the people that contracted it, devastating populations. When an infected person coughed, sneezed, or talked, they risked spreading this disease as they would release virus-containing droplets in the air, and the people around them could inhale those droplets. Once inhaled, Smallpox attacks the cells in your mouth and throat making its way to your lymph nodes, after 12-14 days symptoms start to appear as the virus enters your bloodstream, these symptoms usually include fever, muscle ache, fatigue, and vomiting. Red spots then start to appear on the mouth and throat, spreading to the skin shortly and forming rashes that develop into blisters filled with pus. These sores are called pustules and scabs form 8 or 9 days after falling off and leaving scars.

Who created it and what impacts did they leave?

The earliest form of vaccine against smallpox, was not yet called a vaccine but instead by the name variolation. Variolation is the process of taking pus or powdered scabs from an infected individual and inserting them into a healthy person's open wounds. The term variolation was named after the variola virus which causes smallpox. This practice arose independently as many nations got hit by smallpox outbreaks. By the 18th century, the process of variolation spread to the Ottoman Empire where Lady Worley Montague observed that the Turkish people using the process were not affected by smallpox anymore. She wanted to bring this process to Europe, so she decided to arrange an experiment with the Princess of Wales to variolate prisoners and orphans, the variolated people were then exposed to smallpox shortly after and no big signs of infection could be seen. The royal family got variolated following the success. However, a downside was that Variolation was only accessible to the rich as it was very expensive and a variolated person would need time to quarantine, which required time off work and a caretaker. However, this process could be made safer and more accessible with a milder version of the Pox disease and that is where Edward Jenner comes into the picture. Jenner found a safer version of variolation, that would later go on to be named vaccination, where instead of using the smallpox vaccine to variolate he decided to use cowpox instead. This idea was based on the knowledge of milkmaids being immune to smallpox. He decided he would test this method of cowpox variolation on his gardener's 8-year-old son.  Later when the boy was exposed to smallpox, he didn't get sick, proving that Jenner's method of vaccination with cowpox was successful. He would coin the word vaccination which stems from the Latin word Vaca meaning cow.  This vaccination method was proved even more efficient as cowpox would transfer from person to person making vaccination easier. Yet, many opposed his vaccine initially due to many reasons, recreations of his process spread other diseases or did not succeed, likely due to contamination and no standardization. Some protested due to religious beliefs and some other doctors disliked this new cheaper method as variolation was a lucrative practice producing a lot of profit. Despite so many objections, Jenner did not back down working tirelessly to promote vaccines as safe and important. His efforts paid off, as in 1802 parliament granted him 10,000 pounds for his work. In 1813, The US Congress passed legislation ensuring public vaccination. Edward Jenner passed away on January 26, 1823, leaving behind an important legacy that would go on to impact the medical world surrounding vaccines heavily. His smallpox vaccine would be the first heavily documented and advocated vaccine and it would go on to usher and lead the world into an era of preventative measures against diseases. His smallpox vaccine would also go on to exterminate all naturally occurring smallpox viruses.

The process of vaccination/variolation

People would dip a needle into a solution containing the virus or directly poke it into a pustule. Then they would open a small wound or cut in the person receiving the vaccine and insert the needle into the wound. A wound was created as it was the best way to transfer material underneath the skin of an uninfected person. After the process, the side effects might have included a small fever, but this would be taken as a sign of a successful procedure.

The Relationship Between Stem Cells and Vaccines 

Through many trials, it appears that vaccines have no abnormal effects on stem cells. Stem cells that have adapted to the body react the same way to vaccines as any other sort of cell would. However, there is a large development of stem cells being used to create vaccines. In multiple case studies (referenced in the citations section), mesenchymal stem cells are used to develop vaccines that have the potential to cure infection diseases. Mesenchymal stem cells contain a large number of extracellular vesicles (vesicles produced by cells that are the main facilitators of communicators between molecules), which is something that creates a sign of promising vaccine development. Mesenchymal stem cells are cells that are produced in all tissues and are used to repair tissues when any sort of injury occurs. Mesenchymal stem cells are amazing at reducing inflammation and their secretion of extracellular vesicles has been proven to work in Pnenomia patients. This makes stem cells a great contender for being used in vaccines. 

Case study

Mesenchymal cells and vaccines inhibting covid 19 disease

This case study focuses on comparing the impatcs of Mesenchymal stem cells(MSCs) with the impacts of vaccines and drugs against covid 19. MSCs are a type of multipotent stem cell and it can develop into many different types of cells, that include bone cells, muscle cells, and cartilage cells. This stem cell has also been found to have anti-inflammatory properties and  immunomodulatory properties. In this case study, MSCs have been found to improve the respiratory abilities of people affected by covid 19. Severe covid 19 can lead to respiratory failure that can be fatal, so if MSCs can prevent these issues from becoming so severe, then these stem cells can be a vital part of treating and decreasing covid 19 and the severity of possible symptoms. These anti inflammatory ablities can become a major tool for anti viral drug delivery, that can prevent the covid 19 virus from replicating and worsening. In a study that used MSCs in covid 19 patients, the patients were seen to be recovering and fighting off covid 19 induced pneumonia with exceptional results. MSCs can exert anti viral effects on covid 19 and unlike other stem cells, MSCs can continoulsy activate a large number of anti-virus genes. These stem cells can also produce an indirect antiviral effect by controlling the coordination of the pro-inflammatory and anti-inflammatory parts of the patient’s immune system and it can also promote the activity of the phagocytes. These functions are similar to vaccines as they introduce the pathogen to the bodies immune system in small amounts. As the virus enters the body through vaccination, it is enough to tigger a immune response but not enough to take over, resulting in increased phagocyte activity and the covid 19 antigen being memorized incase of future need. The results of the MSCs inflammatory abilities paired with the results of vaccines could inhibit covid 19 effectively.

 

 

Data

Schematic diagram illustrating the stem cell hierarchy. Embryonic stem... |  Download Scientific Diagram

Stem cell diagram shows how stem cells form and differentiate into different types.

"Figure 2. Schematic diagram illustrating the stem cell hierarchy. Embryonic stem cells (ESCs) are pluripotent, and have the capacity to

differentiate into cells of all three dermal layers, that is, endoderm, mesoderm and ectoderm. Adult stem cells are multipotent, and have a more

restricted ability to differentiate, being committed to a specific lineage."

This was taken from the article, https://www.researchgate.net/publication/221712545_Clinical_review_Stem_cell_therapies_for_acute_lung_injuryacute_respiratory_distress_syndrome_-_hope_or_hype

diagram showing developmental journey of Hematopoietic stem cells

"All blood cells are produced and derived from cells in the bone marrow known as hematopoietic stem cells (HSCs). HSCs have the ability to proliferate and differentiate into any type of blood cell."

This diagram was found in the article,https://researchfeatures.com/steady-state-hematopoietic-stem-cells-transplantation/ 

Measuring vaccine effectiveness from limited public health datasets:  Framework and estimates from India's second COVID wave | Science Advances

Vaccine effectiveness based on age

"Before vaccination, protective antibody levels were found for tetanus in 95% of patients (geometric mean concentration [GMC], 0.07 IU/mL; 95% CI, 0.05–0.1 IU/mL), for Hib in 63% (GMC, 0.34 µg/mL; 95% CI, 0.21–0.57 µg/mL), for measles in 60% (GMC, 102 mIU/mL; 95% CI, 41–253 mIU/mL), for meningococcus C in 11% (geometric mean titer [GMT], 1 : 4; 95% CI, 1 : 2–1 : 8.4), for all 3 poliovirus serotypes in 29%, and for all 9 pneumococcal serotypes in 0%. Vaccination resulted in a significant increase (P ⩽ .05) in antibody levels to each vaccine antigen studied, with 100% of patients achieving protection against tetanus (GMC, 2.2 IU/mL; 95% CI, 1.8–2.7 IU/mL), 100% achieving protection against Hib (GMC, 8.4 µg/mL; 95% CI, 7.6–9.3 µg/mL), 100% achieving protection against measles (GMC, 2435 mIU/mL; 95% CI, 1724–3439 mIU/mL), 100% achieving protection against meningococcus C (GMT, 1 : 5706; 95% CI, 1 : 3510–1 : 9272), 92% achieving protection against the 3 poliovirus serotypes, and ⩾80% achieving protection against each of the heptavalent pneumococcal conjugate vaccine–associated serotypes. No factors relevant to age, underlying disease, or treatment type were found to significantly influence responses." 

This is data taken directly from https://academic.oup.com/cid/article-abstract/44/5/625/347552?redirectedFrom=fulltext regarding the case study mentioned in the research section. 

Conclusion

When regarding the issue of stem cells and vaccines and how they affect each other, we were able to come to the conclusion popular vaccinations have been proven to have no major external effects on recipients of stem cell transplants. But, they have been an extremely useful contender in vaccine development. This is due to the nature of stem cells and their uses within the human body that allow for repair and regeneration. It is important to note that the use of developing medical technology with stem cells is a growing field that has only just begun to be seriously developed globally and that vaccines are constantly being adapted and changed to better-fit humanity's expanding knowledge. When taking this into account and only looking at the science that has been done up to date we can begin to understand the implicated effects, and these case studies need to be done on a larger scale to begin seeing the patterns and effects that can be had on the general populous. This conclusion is drawn from data garnered from case studies and inferences drawn from background knowledge about both stem cells and vaccines. 

Citations

https://www.mayoclinic.org/diseases-conditions/smallpox/symptoms-causes/syc-20353027 (Small-Pox research)

https://www.youtube.com/watch?v=rb7TVW77ZCs  (Vaccines)

https://www.immunize.org/ (Vaccines)

https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/candida-cleanse/faq-20058174 (Vaccines)

https://www.niaid.nih.gov/research/vaccines (Vaccines)

https://www.who.int/health-topics/vaccines-and-immunization#tab=tab_1 (Vaccines)

https://www.cdc.gov/vaccines/basics/index.html (Vaccines)

https://pubmed.ncbi.nlm.nih.gov/?term=vaccines+and+stem+cells (Vaccines and Stem-Cells)

https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/immune-system (Vaccines)

https://www.mdanderson.org/cancerwise/t-cells--b-cells-and-the-immune-system.h00-159465579.html#:~:text=T%20cells%20can%20wipe%20out,of%20protein%20called%20an%20antibody. (Vaccines)

https://my.clevelandclinic.org/health/body/24630-t-cells(t cells)

https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117(stem cells)

https://stemcells.nih.gov/info/basics/stc-basics(stem cells)

https://my.clevelandclinic.org/health/articles/22464-hormones(hormones)

https://www.hhs.gov/immunization/basics/types/index.html#:~:text=Inactivated%20vaccines%20use%20the%20killed,Rabies (Vaccines)

https://www.who.int/teams/health-product-policy-and-standards/standards-and-specifications/norms-and-standards/vaccines-quality/dna#:~:text=DNA%20vaccines&text=Recently%2C%20a%20radically%20new%20approach,production%20of%20the%20target%20antigen (Vaccines)

https://link.springer.com/article/10.1007/s00262-010-0899-9?utm (Stem Cells and Vaccines)

https://www.cell.com/cell-stem-cell/fulltext/S1934-5909%2818%2930016-X?sf186924848=1&utm (Vaccines and Stem Cells)

https://cancerci.biomedcentral.com/articles/10.1186/s12935-024-03624-7?utm (Vaccines and Stem Cells)

https://link.springer.com/article/10.1007/s12026-015-8631-7?utm (Vaccines and Stem Cells)

https://www.mdpi.com/2076-393X/11/11/1631?utm (Vaccines and Stem Cells)

https://academic.oup.com/cid/article-abstract/44/5/625/347552?redirectedFrom=fulltext (Vaccines and Stem Cells)

https://pmc.ncbi.nlm.nih.gov/articles/PMC7505274/ (case study)

https://my.clevelandclinic.org/health/body/21196-immune-system (immune system)

https://youtu.be/3IQT9KsrO6M?si=Jg8MI748Wx3WOZEv (t cells)

https://www.youtube.com/watch?v=jtqAqL3fn64 (small pox)

https://www.youtube.com/watch?v=Ke6tT3_QTuM&t=157s(small pox)

Acknowledgement

We would like to extend a huge thanks to our teacher Mr. Buhler for organizing our participation in the science fair and giving us tons of oppourtunity to learn and grow from this experience! We would also like to acknowledge the unwavering support of our family and friends as we spent countless hours pouring over reasearch for this project. Finally, we would like to thank the Calgary Youth Science Fair for organizing this event and giving us the oppourtunity to participate in something like this.

Attachments

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