Science as We Know It

Everything is connected: Neuroimmunology

By Niklas Krausse

Neuroimmunology combines neuroscience with immunology to better understand the interactions of the two systems.

How does our immune system control our behavior?

The immune system is the body’s defense system, whereas the central nervous system is the control unit. It is easy to think about them as separate and isolated – but they are much more closely interwoven than one would think.

Pathogens have always been a driving force in human evolution. Harmful viruses, bacteria and parasites have forced us to adapt and develop better defense strategies. One theory suggests the co-evolution of the immune and the central nervous system. At least partly, our cognitive development could be the result of pathogen evading strategies. The never-ending arms race between pathogens and our immune system may also have influenced our highly adaptive central nervous system. New behavior strategies could have evolved to prevent the spread of infections. In turn, the immune system might have evolved ways to communicate with the nervous system in order to respond to a threat. Undoubtable, however, are the similarities between the molecular and cellular features of the two systems¹^,².

In a study from 2016, researchers found that mice without an adaptive immune system (which mostly consists of B and T cells) showed despaired social behavior³. They observed that these immune-deficient mice lacked a social preference for another mouse over an object, unlike wild-type mice which always chose to socialize with other mice. Interestingly, this disturbed social behavior could be reversed by simply injecting immune cells in the immune-deficient mice.

The same group of researchers were able to show that loss of meningeal T cells causes the disturbance in social behavior. The “meninges” are the three membranes that enclose and protect the brain and the spinal cord⁴. These membranes, and the spaces between them, harbor a variety of immune cells that are in close contact with the central nervous system without actually infiltrating it – communication between the two systems takes place via soluble molecules known as cytokines. Consequently, the research team identified the T cell-derived cytokine “interferon-gamma” (IFN-γ) as the mediator between immunity and the neuronal connections that control social behavior.

In an earlier study from 2010, researchers had found a similar connection between meningeal T cells and the regulation of learning and memory behavior in mice⁵. They showed that the number of T cells increased in the meninges of mice trained in a learning and memory test. Depletion of these cells caused mice to perform worse in the same test. The learning and memory performance was regulated by another cytokine secreted by meningeal T cells, “interleukin-4” (IL-4). Besides other effects, IL-4 was increasing the production of a molecule in neural cells that is key for learning and memory processes.

It is easy to think of an organism as the sum of different, strictly separated systems – all required for a specialized task, but living organisms cannot be described in the same way as artificial objects. There is much more exchange and interaction between the different parts. Neuroimmunology is a great example how the combination of different research fields may help to better understand complex biological processes such as learning and memory, social behavior, and the development of neurodegenerative and autoimmune diseases.

2021-05-05

Science As We Know It

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How stressed out stem cells make your hair go gray

By Maria Jassinskaja

A friend of mine who recently went through a long period of uncertainty regarding his work situation noted an undesired side effect of this stressful time – his hair was going gray, way too fast to be considered normal aging. Indeed, the phrase “You’re going to give me gray hair!” implies a connection between someone stressing you out and premature loss of hair pigmentation. Plenty of anecdotal evidence exist for this phenomenon, but the biology behind it has long remained a mystery. Recently, a group of researchers at Harvard University set out to solve this long-standing question, and published their findings in the prestigious scientific journal Nature in January 2020¹. The answer? Stressed out stem cells.

After a bad haircut, one can often find some consolation in the fact that hair (usually) grows back. Just like in many other tissues where we see this kind of regeneration (such as blood or skin), hair regrowth is made possible by stem cells – in this case, hair follicle stem cells (HFSCs). However, while HFSCs ensure that we don’t go bald, they have little to do with the actual color of the hair. The color, or pigment, in hair comes from another set of stem cells – the melanocyte stem cells (MeSCs). Just like most other adult stem cell types, MeSCs are normally in a resting stage, which protects the cells and ensures their longevity. MeSCs are activated during hair growth to divide and produce mature pigment cells (melanocytes) which give our hair (and skin) its color². Depletion of MeSCs with age has been suggested to be the reason behind why humans (as well as other animals) go gray as we approach our golden years³.

In the Nature study¹, Zhang and colleagues found that stress caused the fur of black mice to become white significantly faster than in non-stressed animals. This effect was most pronounced when the stress was caused by pain, but was also evident when the stress was caused by restraining the animals or subjecting them to so called chronic unpredictable stress, such as quick switches between isolation and crowding. Upon closer examination of the cells responsible for hair growth and pigmentation, the researchers found that while HFSCs were unaffected by stress, MeSCs were quickly depleted from the hair follicle. In other words, the hair of the stressed mice grew out as normal, but had lost its black color. This was due to an abnormal increase in the rate at which the MeSCs divide, which caused the pool of stem cells to gradually become depleted and finally disappear. This in turn lead to a complete and permanent loss of pigmentation in the affected hairs. The main culprit behind this effect turned out to be noradrenaline, which is the hormone responsible for initiating a fight-or-flight-response in animals faced with danger. The secretion of noradrenaline was caused by stimulation of the sympathetic nervous system, which is part of the autonomous (unconscious) nervous system and is responsible for sensing and responding to danger. Molecularly, human MeSCs responded similarly to the mouse cells, indicating that noradrenaline may have a similar effect on human hair pigmentation as it has in mice.

Although there is a lot of evidence that these biological processes occur also in humans, one should keep in mind that this study was done mainly in mice. It is difficult to translate the stress experienced by the mice into human stress factors. Are a couple of bad weeks at work enough to damage human melanocyte stem cells permanently, or is a much more severe type of stress required to produce this, often undesired, effect? Regardless of the exact mechanism, stress has previously been shown to negatively affect other adult stem cell types, such as hematopoietic stem cells⁴, which can potentially lead to much more severe side effects than a couple of unwanted gray hairs. With that in mind, enjoy a lazy summer vacation this year – your stem cells could really use a break.

2020-08-18

Science As We Know It

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SARS-CoV-2 vaccination: In search for the holy grail

By Niklas Krausse

The current COVID-19 pandemic is still overshadowing many aspects of our lives. The fastest exit out of this situation seems to be the approval of a safe and effective vaccine. Scientists all over the world are eagerly looking for the holy grail – a protective vaccine – but how far have we come along?

Before we dive into ongoing clinical trials, let’s step back and reconsider the basic idea of vaccines again. A vaccine contains killed, weakened, or parts of a disease-causing pathogen (virus or bacteria). The vaccine educates our immune system to memorize the germ, without actually causing the disease. Once immunized against a disease through vaccination, the encounter with the real germ will evoke a much faster and stronger response of the immune system and prevent us from getting sick. That’s what makes vaccines so great, they do not treat a disease, but prevent the outbreak of the disease in the first place¹.

Unfortunately, there is no approved vaccine available against coronaviruses yet. However, there is plenty of research under way, from pre-clinical studies (basic research performed before the drug is tested in patients) to clinical trials (drug testing in human patients). Let’s focus on some of the ongoing clinical trials (a more comprehensive list of ongoing studies can be found on the WHO website²).

A group at Oxford University in the UK is working together with the pharmaceutical company AstraZeneca on a viral vector-based vaccine (see Infobox) called ChAdOx1-S. Here, researchers try to deliver the gene for the SARS-CoV-2 spike protein (see earlier blog post) to the patient’s cells. Once the cells produce the spike protein, the immune system generates a response against it. If sufficient immunity has been established, the patient is protected against an attack of the actual virus. So far, this vaccine platform has been successfully tested with the highly related middle east respiratory syndrome (MERS) virus in mice³ and monkeys⁴. Currently, a study from the group in Oxford using the vaccine platform to deliver the SARS-CoV-2 spike gene in monkeys is under review⁵. A similar vaccine approach has been developed by the Beijing Institute of Biotechnology and CanSino Biologics, both located in China. Their adenovirus type 5 vector has also entered clinical trials⁶.

Another approach has been pursued by Sinovac, the Wuhan Institute of Biological Products, and the Beijing Institute of Biological Products. All three have manufactured an inactivated vaccine for COVID-19⁶ that has entered clinical trials by now. In this case, the actual virus is killed with heat or chemicals before it is used as a vaccine. Usually, these types of vaccines generate a strong protection against the intact pathogen. On the downside, the required safety precautions for the production and administration of such vaccines are naturally much higher.

The American biotech company Moderna, Inc. has launched clinical trials for their messenger RNA (mRNA) based vaccine against COVID-19⁷. Here, mRNA molecules were artificially designed to contain only the building instructions for the SARS-CoV spike protein. The designed mRNA molecules were then encapsulated in nanoparticles for further delivery into the cells. Once in the host cells, the mRNA instructions are used to generate the viral protein, which then triggers the immune system to initiate a response. Similar technologies from other companies have entered the phase of clinical trials as well.

Among all the excitement and hope raised in finding an effective vaccine, it is important to keep a clear head. Vaccine development and testing takes time – and for good reason. The desired long-term effects of vaccines have to be carefully evaluated in terms of safety and efficient immune protection.

Infobox: Different types of vaccines
Live attenuated vaccines: These vaccines contain a weakened version of the actual disease-causing germ. They usually provide strong and long-lasting immunity, but are not feasible for people with a weakened immune system, since they might cause the disease in these people. Inactivated vaccines: This type of vaccine contains whole germs that were killed before delivery to the patient. They are less efficient in generating immunity compared to live attenuated vaccines, but safer. Subunit vaccines: Subunit vaccines are another type of inactivated vaccines. Instead of the whole pathogen, subunit vaccines contain only a part of the germ (usually the part our immune cells recognize). Subunit vaccines are even safer than the previously mentioned vaccines, but usually elicit a weaker immune response. Nucleic acid vaccines: Nucleic acids such as DNA or RNA contain the building instructions for proteins. All cells have the machinery to translate these instructions into the actual proteins. Nucleic acid vaccines deliver the instructions for only some parts of the germ. Once built by the cell, the immune system recognizes the foreign proteins. However, the germs never get fully assembled, since only partial instructions were provided, thereby increasing safety. Viral vector vaccines: Here viruses themselves carry the vaccine. Harmless viruses are genetically modified to transport the vaccine to our cells (for example in the form of nucleic acids). One variation of this delivery platform are virus-like particles. In this case, harmless viruses carry proteins of the disease-causing pathogen on their surface. Tricked by this disguise, our immune system mounts a response against the displayed proteins.

Infobox: Different types of vaccines

Live attenuated vaccines: These vaccines contain a weakened version of the actual disease-causing germ. They usually provide strong and long-lasting immunity, but are not feasible for people with a weakened immune system, since they might cause the disease in these people.

Inactivated vaccines: This type of vaccine contains whole germs that were killed before delivery to the patient. They are less efficient in generating immunity compared to live attenuated vaccines, but safer.

Subunit vaccines: Subunit vaccines are another type of inactivated vaccines. Instead of the whole pathogen, subunit vaccines contain only a part of the germ (usually the part our immune cells recognize). Subunit vaccines are even safer than the previously mentioned vaccines, but usually elicit a weaker immune response.

Nucleic acid vaccines: Nucleic acids such as DNA or RNA contain the building instructions for proteins. All cells have the machinery to translate these instructions into the actual proteins. Nucleic acid vaccines deliver the instructions for only some parts of the germ. Once built by the cell, the immune system recognizes the foreign proteins. However, the germs never get fully assembled, since only partial instructions were provided, thereby increasing safety.

Viral vector vaccines: Here viruses themselves carry the vaccine. Harmless viruses are genetically modified to transport the vaccine to our cells (for example in the form of nucleic acids). One variation of this delivery platform are virus-like particles. In this case, harmless viruses carry proteins of the disease-causing pathogen on their surface. Tricked by this disguise, our immune system mounts a response against the displayed proteins.

2020-07-22

Science As We Know It

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The other side of CRISPR: Diagnostic tests for COVID-19 and beyond.

By Pia Johansson

CRISPR (Clustered Regulatory Interspersed Palindromic Repeats) is a new gene-editing tool that has created great potential for curing some human genetic diseases. It has been featured extensively in the press as both the tool for Armageddon and the Corrector-of-all-disease. Both of these depictions are exaggerated and inaccurate (but that is a story for another time). However, there are other technologies, stemmed from the CRISPR discovery, that are much less controversial. One of these new technologies is a fast and simple method for pathogen detection that has recently been applied to COVID-19.

Just like humans, bacteria can be infected by viruses. CRISPR is actually a form of bacterial immune system that recognizes nucleic acids from invading viruses.¹ The CRISPR system consists of two steps; 1, the recognition of specific stretches of nucleic acids using a specialized RNA sequence and 2, the cutting of these stretches with a CRISPR-associated (CAS) protein. The most commonly used form of CRISPR is based on the CAS protein found in Streptococcus pyogenes, called spCas9. There are other CAS proteins in other bacteria, and it is by studying the properties of these variants that new diagnostics tools have arisen.^2-4

All artificial CRISPR works by designing a short RNA sequence that recognizes the DNA that you want to target. This RNA sequence (a.k.a guideRNA) guides the CAS protein to the target region where it binds and cuts the DNA.¹ Interestingly, some CAS variants do not stop there. They continue to be active and start to shred other DNA (or RNA) indiscriminately. This is not very useful when it comes to finding precise and scarless gene-editing methods – but turned out to be important when it comes to diagnostic tests.

The diagnostic test kit contains a guideRNA that recognizes COVID-19, a CAS variant, and control DNA. In the presence of COVID-19, the CAS protein binds to the specific target site and then cleaves the control DNA (as part of the random cutting described above). The cleavage of the control DNA, which only occurs in the presence of the virus, leads to changes that can now be visualized via fluorescence or antibody capture. The actual procedure takes about an hour and, in its simplest form, goes more or less as follows:^3-7

Step 1: The primary target is the COVID-19 RNA, so viral RNA is extracted from a patient sample (e.g. a mouth swab).

Step 2: The extracted viral RNA is mixed with the kit reagents and heated.

Step 3: The diagnostic paper strip (also in the kit) is dipped in the test solution (the RNA/kit mix from Step 2) and, a bit like a home-pregnancy test, a band will show you if you are positive or not.

The nice thing about these diagnostic tests is that they can be done quickly, do not require expensive machines and can be performed by most laboratories. The downside is that they can’t handle a lot of samples at once. In regard to COVID-19 and the current high demand for testing, it will most likely be used in combination with the already existing COVID-19 testing methods.

As with all things CRISPR, several labs have been working on this and the CRISPR pioneers (and others) have come out in force and done a great job developing these tools and applying them to COVID-19. Two major kits/approaches have been developed: DETECTR (from Mammoth Biosciences and the Jennifer Doudna lab)^{2, 3} and SHERLOCK (from SHERLOCK Biosciences and the Feng Zhang lab)^{4, 5}. Initial reports show that the efficiency and reliability of these tests are very high, with a detection rate of around 95% and almost no false positives. The SHERLOCK kit was recently approved by the American Food and Drugs Administration (FDA) for use as “emergency testing”.⁸

In addition to COVID-19, these systems can test for the presence of other pathogens, such as Zika, HIV and HPV.^{2, 4} Importantly, their simplicity means that they can be used “in the field”, so to speak – in places where access to big lab equipment and diagnostic tests is limited or when time is of the essence. These test kits will instead contain a guideRNA specific to another virus and will then react only to that virus. In addition, using a slightly different detection method it is possible to test for, and discriminate against, multiple viruses at once with multiple guide RNAs and multiple CAS variants.⁵ It can also be used to detect mutations or common variants in the human genome. In recent interesting developments, CRISPR diagnostics have been applied to ecological research in terms of species identification, where the SHERLOCK system was used to identify closely related species that are easily mis-identified in the field.⁹

In summary, CRISPR can be used for fast and easy diagnostics and identification purposes using specialized detection kits. This novel technology and its applications will likely become a very useful addition to the diagnostics toolkit in human health and disease, as well as in agriculture and ecology. Who would have thought all this could come from bacteria?

Lessons learned from SARS-CoV: A molecular handshake with consequences

Virus entry depends on spike protein and cell surface receptor compatibility

By Niklas Krausse

It is early spring 2020. What has started as a local outbreak in China has by now paralyzed many countries in Europe and the rest of the world. In one way or another, most of us have been affected by the recent coronavirus disease (COVID-19) pandemic. There is still a lot unknown about the pathogen itself, and despite tremendous efforts from scientists all over the world, a safe and effective vaccine is still some way off. But perhaps a look back into the past could provide some insights into how viruses from the same group infect cells and which intervention strategies are suggested. After all, this is not the first encounter humans have experienced with coronaviruses.

In 2002, an outbreak of severe acute respiratory syndrome (SARS) was reported. A virus that was designated SARS-CoV had crossed the species-boundaries (a process called zoonosis) and was identified as the cause of the disease. The pathogen responsible for the current outbreak (SARS-CoV-2) belongs to the same group of viruses as SARS-CoV, which are called Coronaviridae. In general, members of the Coronaviridae family consist of three structural components (proteins): spike (S), envelope (E), and membrane (M). These three proteins make up the outer structure of the virus, the so-called virus envelope. The genetic material (single stranded RNA in this case) is wrapped around the nucleocapsid (N) protein and located in the virus envelope. All viruses have to find a way to infiltrate their target cells in order to make use of their host’s internal protein-making machineries (ribosomes) to produce more virus particles. Understanding exactly how the virus enters the host provides vital information regarding the virus life cycle, and may help to stop the progression of the virus.

In 2003, Li and colleagues addressed this question in their work “Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus”, which they published in the prestigious scientific journal Nature.¹ Previous studies had identified the S protein as the part of the virus that interacts with its target cells, similarly to a key in a lock. In order to identify the corresponding counterpart of the S protein on the host cell, they created a fusion protein with parts from the viral S protein and parts from human antibodies (important for detection of the fusion protein later in the study). Replicating the “key” of the virus, they managed to capture the “lock” on cells accessible to the virus. The “lock” turned out to be Angiotensin-converting enzyme 2 (ACE2). To further prove that the correct receptor had been identified, they artificially expressed ACE2 on cells that usually do not express it. And voilà – the fusion protein recognized the cells that were previously invisible to the virus again. Interestingly, they also found that adding a soluble version of the ACE2 receptor to cells vulnerable to viral infection prevented virus uptake by intercepting the virus. Blocking the ACE2 receptor with an antibody also hindered the virus from entering the cells. These effects were specific to ACE2, since the same experiments were performed with the closely related ACE1 receptor and did not prevent virus entry. In their work, they identified ACE2 as the functional receptor for SARS-CoV. Importantly, it has been shown before that ACE2 is expressed on a variety of different tissues in humans including the lungs, the heart, the kidneys and the gastrointestinal tract.

Seventeen years later, Hoffmann and colleagues were wondering if the newly emerged SARS-CoV-2 virus uses the same entry route as SARS-CoV.² The S-proteins of both viruses are approximately 76% identical, and both viruses seem to affect the same spectrum of cell lines. Besides many structural similarities, ACE2 was indeed used by SARS-CoV-2 to enter the host cells. They performed the same trick as Li et al. and artificially expressed ACE2 on cells that then became susceptible to infection by SARS-CoV-2. Furthermore, they showed that virus entry depends on yet another protein located on the host cell. The enzyme, with the fancy name TMPRSS2, primes (or activates) the S-protein of the virus. Upon activation, the S-protein is cleaved into two subunits. Subunit 1 of the cleaved S-protein interacts with the target receptor on the host cell (ACE2) and establishes the first contact, almost like a molecular handshake between the virus and the cell. Subunit 2 of the cleaved S-protein then fuses the viral and host membrane together and completes the entry.³ One possible treatment approach would be to block the activity of the priming enzyme, and Hoffmann et al. have already shown that the clinically proven inhibitor “camostat mesylate” partially blocks S-protein driven entry of SARS-CoV-2.

This is just one example how research conducted almost 20 years earlier on a related virus has helped to accelerate the efforts made in understanding the biology behind a present threat. If you are interested to find out more about past and present vaccination approaches against SARS-CoV and SARS-CoV-2 stay tuned for our next blog post!

2020-04-14

Science As We Know It

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Neural Stem Cells

By Jonas Fritze

Neural stem cells exist both in the developing and in the adult brain of mammals. Just like other stem cells, they can divide limitless to make copies of themselves and turn into other cell types. Neural stem cells are restricted to cell types found in the central nervous system, and are therefore considered multipotent stem cells.

During embryonic and fetal development, neural stem cells contribute to a massive production of different brain cells to build up the brain. In the adult brain it is quite different. There, neural stem cells are very few in number, mainly inactive, and exist only in certain areas of the brain. Still, they are essential for some tasks. Since neurons are unable to divide, neural stem cells are the only source of new neurons.¹ When the brain is injured from stroke, and neurons die, neural stem cells are activated to produce new neurons to repair the damaged part of the brain.²

The birth of new neurons from neural stem cells is called neurogenesis and is important for creating new memories. Neurogenesis continues throughout life but becomes less efficient with age and in some age-related dementia diseases, such as Alzheimer’s and Parkinson’s disease.³ One way to improve neurogenesis is with physical activity⁴, which can also be beneficial for healthy aging.⁵

Neural stem cells have the potential to repair the brain and improve memory and are therefore the target for a lot of research. Knowledge from studying neural stem cells has made it possible for scientists to produce neurons from induced pluripotent stem cells, which will soon be used in clinical trials as a therapy for Parkinson’s disease.⁶

2020-03-05

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Hematopoietic Stem Cells

By Maria Jassinskaja

Everyone who has donated blood or had a deep cut knows that losing blood can make you feel dizzy and weak for a while. Usually this feeling doesn’t last for too long, and we have the hematopoietic stem cells (HSCs) to thank for that. Their name is derived from the Greek word “hematopoiesis” which quite literally means “to make blood”. HSCs are multipotent and can produce red blood cells, platelets and immune cells (white blood cells). Like all stem cells, HSCs have the capability to self-renew by creating copies of themselves, which enables them to sustain life-long blood production. HSCs appear in the embryo at around week four of human pregnancy. They are formed from epithelial (“skin-like”) cells in the aorta of the embryo through a process called endothelial-to-hematopoietic transition. After this, the newly formed HSCs join the blood circulation and begin to divide and grow in numbers to build up the blood system of the embryo. In adult mammals, HSCs can be found in the bone marrow. Like most other adult stem cells, HSCs in the bone marrow are normally in a resting state where they don’t divide that much, but can be activated in response to blood loss or infection to produce the cells required to deal with the injury.¹

HSC transplantation (sometimes referred to as bone marrow transplantation) is the only stem cell therapy that is used regularly in the clinic. The first HSC transplantation was performed already in the 1950s. HSC transplantation is used to treat a number of different conditions, such as blood cancer (leukemia), blood deficiency (anemia) and some autoimmune diseases. The most common way of performing HSC transplantation is to give the donor a drug that makes HSCs exit the bone marrow and circulate in the blood. The blood is collected and given to the patient who has been pre-treated with radiation to remove their own, diseased, HSCs. Through a process called homing, the donated cells find their way to the bone marrow where they go on to rebuild a new and healthy blood system in the patient. HSC transplantation is a life-saving procedure and for some severe diseases, it is the only treatment option. Like in all other types of organ donations, it is important that the donor and the patient’s immune systems are compatible with each other. If not, the newly transplanted cells can begin to attack the patient’s body and cause a disease called Graft-versus-Host.² For this reason, it is important that there are many bone marrow donors available to choose from to be able to find the right match for each patient. In Sweden, people interested in donating bone marrow can register themselves at Tobiasregistret.

2020-03-05

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Stem Cells For Beginners

By Niklas Krausse, Magdalena Madej and Ouyang Yuan

Have you ever wondered where the new cells come from after an injury? How is it possible, that a scratch on our skin is replaced with new skin after a couple of days? It is said that time heals all wounds, but stem cells play a big role in many cases too.

Stem cells do much more than repair scratches though. Did you know that:

• 100 million new red blood cells are generated in our body every minute?¹

• The lining of the small intestine is fully exchanged every 4 days?²

• The human epidermis (skin) is entirely replaced in 27 days on average?³

Maintenance (homeostasis) is one of the most important functions of stem cells, which help us keep our bodies in good shape and jump in when necessary, for example following injuries or infections. So, let’s take a closer look at these fascinating cells. In order to be classified as a stem cell, two fundamental criteria have to be met:

1. The cell is able to make new cells of their own kind (self-renewal)

2. The cell can change into a different cell type (differentiation)

Usually, stem cells live in a certain location in our body, called the niche or microenvironment. The niche consists of other cell types that protect and maintain the stem cells. Often, the niche cells communicate with the stem cells and provide instructions about what mature cell types are currently needed. However, if there is no urgent need for new supply, most stem cells tend to be in a non-active or dormant state. Stem cell dormancy helps to protect and prolong the life of these precious cells. Any kind of error in stem cells can have devastating consequences, since they can pass that error on to descending cells. These mistakes can be passed on to either new stem cells made by self-renewal, or differentiated cells originating from the “faulty” stem cell.

Stem cell types

Stem cells come in different flavors. Broadly, they can be categorized into three different types: Embryonic stem cells, adult stem cells, and induced pluripotent stem cells. They differ in their origin as well as how restricted they are in their potential to give rise to other cell types. In other words, their potency.

Embryonic stem cells (ESCs)

Just like a human life, the stem cell story has its beginning with the union of a human sperm and egg. This leads to the formation of the most potent cell in human body, a zygote. The zygote is totipotent, which means that it is capable of creating any cell type in an organism, as well as extraembryonic tissues such as the placenta. The totipotent state lasts for 4 days until the zygote has developed into a blastocyst, which could be described as a tiny ball with embryonic stem cells inside. The embryonic stem cells are pluripotent, which means that they can give rise to all cell types of the body, but no extraembryonic tissues. During embryo development, embryonic stem cells soon lose their pluripotency as they begin to differentiate into other tissues. Since the 1990s, scientists have been able to extract human embryonic stem cells from the inner cell mass of the blastocyst and grow and study them in the lab.⁵ This has led to many important discoveries about human embryonic development. Research on human embryos is a matter of constant ethical debate and is even illegal in some countries. In Sweden, many embryonic stem cells used in research come from leftover embryos from in vitro fertilization (IVF) treatments. Researchers are only allowed to use the embryos until they are 14 days old, after which they must be destroyed to stop further development.⁶

Induced pluripotent stem cells (iPSCs)

It was believed for a very long time that once a cell becomes fully mature, it can never revert back to a stem cell stage. However, in 2006 a group of Japanese scientists discovered that by turning on just four genes, it is possible to create a cell very similar to an embryonic stem cell from a mature cell through a process called reprogramming.⁷They named these reprogrammed cells induced pluripotent stem cells, and were awarded the Nobel Prize in 2012 for their ground-breaking research. The ability to create pluripotent stem cells from any kind of mature cell type has led to a lot of new possibilities for researchers to study development without having to use human embryos. Induced pluripotent stem cells can also be used to study disease development and for testing new drugs. In the future, scientists and medical doctors hope to be able to use induced pluripotent stem cells to treat diseases caused by loss of/injury in a particular tissue, such as Parkinson’s disease, multiple sclerosis (MS) and heart failure. However, so far, the use of induced pluripotent stem cells in the clinic is extremely limited and much more research is required before induced pluripotent stem cells can be used to their full potential.

Adult stem cells

These cells reside in different tissues and supply the organism with new cells. They are multipotent, which means they can only differentiate into cells that make up the tissue where they belong. Therefore, they are less potent than embryonic stem cells. An example of adult stem cells are hematopoietic (blood) and neural stem cells.

Read more about hematopoietic stem cells here