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Stem Cell Facts and Uses of Organoids in Medical Research

Linda Crampton is a writer and teacher with a first-class honors degree in biology. She often writes about the scientific basis of disease.

An intestinal organoid created from stem cells present in the intestine

An intestinal organoid created from stem cells present in the intestine

The Nature of Organoids

An organoid is a small and simplified version of a human organ that is created in the laboratory from stem cells. Despite its size, it's a very important structure. Medical researchers and other scientists may be able to create new treatments for health problems by experimenting with organoids. The structures may be especially useful if they are made from stem cells coming from the patient who needs to be treated because they will contain the patient’s genes. Treatments could be applied to the organoid first in order to see if they are safe and helpful and then administered to the patient. Organoids may also help us to better understand how a particular organ or disease works.

Though the processes described above may sound wonderful, researchers are facing some challenges. An organoid is isolated from the body and is therefore not affected by body processes in the way that a real organ is. Some organoids have been implanted into living organisms, however, which is helping to solve this problem. Another concern is that an organoid is often simpler than a real organ. Nevertheless, its creation is exciting. As scientists learn how to create better versions of organoids, some significant discoveries may appear. Even today, some of them have microanatomy that resembles that of the real organ. The technology needed to create the structures is advancing rapidly.

What Are Stem Cells?

Since organoids owe their existence to stem cells, it's useful to know some facts about the cells. Stem cells are unspecialized and have the wonderful ability to produce both new stem cells and the specialized cells that we need. The first ability is known as self-renewal and the second as differentiation. Stem cells produce the new stem cells and the specialized ones by cell division. There is a huge amount of interest in understanding their actions and abilities because they could be very useful in treating certain diseases.

Adult or somatic stem cells are found in only certain parts of the body and produce the specialized cells of specific structures. Embryonic stem cells are more versatile, as described below, but are controversial. Induced pluripotent stem cells are often used to create organoids. They are also popular for other purposes because their use avoids some problems associated with adult and embryonic cells. Scientists are investigating the best way to activate desirable genes in the cells. Additional categories of stem cells exist. Even more may be created as research continues.

The blastocyst is fully developed by day five after conception. The cells of the inner cell mass are pluripotent.

The blastocyst is fully developed by day five after conception. The cells of the inner cell mass are pluripotent.

Four Types of Stem Cells

Cells can be characterized by their potency. The zygote or fertilized egg is said to be totipotent because it can produce every cell type in our body plus cells of the placenta and umbilical cord. The cells of the very early embryo (when it exists as a ball of cells) are also totipotent.

Embryonic

The cells of the inner cell mass in the five-day-old embryo are identical and undifferentiated. They are pluripotent because they can create any cell in the body but not placental or umbilical cord ones. The embryonic stage with the inner cell mass is known as the blastocyst. The cells of the trophoblast in the blastocyst produce part of the placenta. When the cells of the inner cell mass are obtained and used as pluripotent stem cells, the embryo will no longer be able to develop. The cells are controversial for this reason.

Embryos for stem cell research are usually obtained from a couple who have used in-vitro fertilization to enable them to produce a baby. Multiple embryos are created from the eggs and sperm in order to help ensure a successful pregnancy. Unused embryos may be frozen or destroyed, but sometimes the couple decide to give them to researchers.

Adult or Somatic

The term "adult" stem cells is not completely appropriate because they are found in children as well as adults. They are multipotent. They can produce a few kinds of specialized cells, but their ability in this area is limited. Nevertheless, they are very useful and are being explored by scientists.

Induced Pluripotent

Researchers have found a way to turn adult cells into pluripotent stem cells. Skin cells are often used for this purpose. This avoids the use of embryos. It also overcomes the fact that adult stem cells are only multipotent. Organoids are often made from induced pluripotent stem cells (iPS cells) obtained from a patient, which means that they are genetically identical to the patient's cells. This makes personalized treatments possible and should avoid the problem of rejection if organoids are placed in the human body.

Human Pluripotent

Another category of stem cell is the human pluripotent stem cell, or hPSC. The cells are either embryonic stem cells or fetal ones. A common form of the fetal version is obtained from the umbilical cord or placenta after a baby is born. Another form comes from the body of a fetus that has been miscarried or aborted. In some cases, a fetal somatic cell is induced to become pluripotent.

Genes and Transcription Factors

In 2012, a scientist named Shinya Yamanaka received a Nobel Prize for his discovery that the addition of four genes or the proteins that they code for could turn a skin cell into a pluripotent stem cell. The genes are named Oct4, Sox2, Myc, and Klf4. The proteins (also called transcription factors) that the genes code for have the same names. The four genes are active in embryos but become inactivated after that stage. Yamanaka made his discoveries in mouse cells and later in human ones.

The genetic code is universal (the same in all organisms), except for a few minor differences in some species. The code is determined by the sequence of nitrogenous bases in a DNA (deoxyribonucleic acid) or an RNA (ribonucleic acid) molecule. Each set of three bases codes for a particular amino acid. The amino acids that are made are joined together to make proteins. A section of DNA that codes for a protein is called a gene.

Transcription is the process in which the code in the gene of a DNA molecule is coped into a messenger RNA or mRNA molecule. The mRNA then travels out of the nucleus and to a ribosome. Here amino acids is brought into position according to the instructions in the gene in order to make a specific protein.

Genes in DNA are active or inactive. A transcription factor is a protein that joins to a specific location on a DNA molecule and determines whether a particular gene is active and ready for transcription or not.

Flattened section of a DNA molecule (The molecule as a whole has a double helix shape.)

Flattened section of a DNA molecule (The molecule as a whole has a double helix shape.)

Transport of Genes to the Nucleus

Since Shinya Yamanaka's original discoveries, scientists have found other ways to trigger pluripotency in cells. A common technique used today to send the required genes into a cell inside a virus. Some viruses deliver the genes to the DNA of a cell, which is located in the nucleus.

A virus contains a core of genetic material (either DNA or RNA) surrounded by a coat of protein. Some viruses have a lipid envelope outside the protein coat. Although viruses contain nucleic acid, but they don't consist of cells and can't reproduce on their own. They require the help of a cellular organism in order to reproduce.

When a virus infects our cells, it uses its nucleic acid to "force" a cell to make new viral components instead of its own versions of the chemicals. The new viruses are then assembled, break out of the cell, and infect other cells.

In some case, the DNA of a virus becomes incorporated into the cell's own DNA located in the nucleus instead of immediately forcing the cell to make new viruses. These types can be helpful in transporting desirable genes to the DNA.

It requires only a handful of genes to reprogram an ordinary cell from the body, such as a skin cell, into what’s known as an induced pluripotent cell (iPS cell). Currently, these genes (Oct4, Sox2, Myc, and Klf4) are most commonly brought into the cell using viruses, but there are newer methods that do not use viruses.

— Boston Children's Hospital

Problems and Concerns

There are many factors for scientists to consider in transporting genes into a cell to trigger pluripotency. It's not as easy as it might sound. Some biologists prefer to eliminate the Myc gene from Yamanaka's original set of four genes because it can stimulate the development of cancer. Some kinds of viruses that have been used to supply the genes to cells can do the same thing. Scientists are working hard to eliminate these problems. If induced pluripotent cells are used to create structures for transplantation into humans, they mustn't increase the risk of cancer.

Some newer methods of inducing pluripotency don't require viruses. In addition, some viruses that carry useful DNA but stay outside the nucleus have been found to be helpful in transforming the cell. These methods are worth exploring.

There are a lot of things for scientists to consider with respect to safety and effectiveness when triggering pluripotency. Many researchers are exploring stem cells and organoids and new discoveries are appearing on a frequent basis, however. Hopefully, concerns linked to the creation and control of iPS cells will soon disappear. The cells offer wonderful possibilities in medicine.

Induced pluripotent stem cells, a subgroup of stem cells, are capable of producing cells that can build entire organs in the human body. But they can do this job only if they receive the right quantity of growth signals at the right time from their environment.

— Mo Ebrahimkhani from the University of Pittsburgh, via The Conversation

Producing Organoids and a Controversy

Once cells have been triggered to become pluripotent, the next task it to stimulate their development into the desired cells. Many steps are involved in making organoids from a pluripotent stem cell. Chemicals, temperature, and the environment in which the cells are growing are all important and often specific to the structure being made. A "recipe" needs to be carefully followed so that the correct conditions are applied at the right time in the organoid's development. If scientists provide the right environmental conditions, the cells will self-organize as they form an organoid. This ability is very impressive.

Researchers are excited about the fact that they may discover new and very effective treatments for people with health problems via studying organoids derived from iPS cells (and from other types of stem cells). As the technology for creating the structures improves, however, some new controversies are arising.

The creation of brain organoids is one area that worries some people. The current versions are no bigger than a pea and have a much simpler structure than a real brain. Nevertheless, there have been some concerns from the public about self-awareness in the structures. Scientists say that self-awareness in not possible in the present brain organoids. However, some scientists say that ethical guidelines need to be established because the methods for creating the organoids and the complexity of the structures will very likely improve.

A Mini-Heart

Researchers at Michigan State University have announced the creation of a mini mouse heart that beats rhythmically. It's shown in the video above. According to the university's news release, the organoid has "all primary heart cell types and a functioning structure of chambers and vascular tissue." It's far from being a blob of heart cells. Since mice are mammals like us, the discovery could be significant for humans.

The heart was created from mouse embryonic stem cells. The researchers provided the cells with a "cocktail" of three factors that are known to promote the growth of the heart. Using their chemical recipe, they were able to create an embryonic mouse heart that beats.

Lung Organoids

The scientist in the video above (Carla Kim) has created two types of lung organoids from induced pluripotent cells. One type has passages for air transport that resemble the bronchi of our lungs. The other type contains branching structures that look as thought they're budding. The structures resemble the air sacs of a lung, or the alveoli.

As Carla Kim says, it's hard to get a sample of a patient's lung cells to study. Inducing pluripotency in a cell and then stimulating the development of lung tissue enables physicians to see the cells, though perhaps not in their current condition in the patient. The researcher hopes that eventually scientists will be able to produce tissue that could be transplanted into the patient when they need it.

Kim is also creating mouse lung organoids to study lung cancer with the goal of developing better treatments for humans with the disease.

Intestinal Organoids

The intestinal epithelium or the lining of the small intestine is impressive. It completely replaces itself every four or five days and contains very active stem cells. The lining consists of projections called villi and pits called crypts. The illustration below gives the general idea of the lining's structure, though it doesn't show the fact that there are more cell types than enterocytes in the lining. Enterocytes are the most abundant type, however. They absorb the nutrients from digested food.

The first intestinal organoids were created from the stem cells that are located in the intestinal crypts. As a result, the researchers were able to grow intestinal epithelium outside the body. The complexity of intestinal organoids has increased rapidly since the earliest experiments. Today their features include "an epithelial layer surrounding a functional lumen and all of the cell types of the intestinal epithelium present in proportions and relative spatial arrangement that recapitulate what is observed in vivo," as the relevant reference below states.

The latest organoids are used to study the effects and benefits of medicinal drugs, cancer, infectious microbes, intestinal disorders, and the action of the immune system. The researchers have been able to create this duplication of the intestine by starting with a pluripotent stem cell instead of one of the stem cells in the crypts.

A simplified section of the lining or epithelium of the small intestine

A simplified section of the lining or epithelium of the small intestine

Creating a Mini-Liver

Scientists have created mini-livers that have extended the lives of mice with liver disease. The researchers in one project created their organoids from stem cells but used different techniques from the ones described above. Their emphasis was on genetic engineering. The reference about mini-livers below refers to “synthetic biology” and “tweaking genes.” The researchers have manipulated DNA in a different way from the other researchers mentioned in this article,

Though we have a lot to learn about human biology and the behavior of DNA, we do understand how a sequence of three nitrogenous bases in a DNA molecule (a codon) codes for a specific amino acid. We also know which codon(s) code for which amino acid. Each base in DNA is bonded to a sugar molecule (deoxyribose) and a phosphate to make a "building block" called a nucleotide.

We have the ability to "edit" the genetic code by altering DNA. We also have the ability to link nucleotides together to create new pieces of DNA. These options for changing the structure and effect of human DNA might eventually become common either on their own or in addition to techniques such as creating iPS cells. "Tweaking genes" seems to have been put to good use by the researchers who created the mini-liver. As in some aspects of stem cell and organoid creation, however, the idea of editing and constructing DNA may worry some people.

A Hopeful Future

Stem cells could provide some wonderful benefits, including the production of useful organoids. Some of the predicted and possible outcomes of organoid research are important and exciting, especially those related to helping people with health problems. Although the technology for creating the structures is sometimes controversial, the results of some of the investigations done so far are impressive. It should be very interesting to see how the technology progresses.

References

  • Information about stem cells and their uses from the Mayo Clinic
  • Adult and pluripotent stem cell facts from the Boston Children's Hospital
  • Stem cell basics from the International Society for Stem Cell Research (ISSCR)
  • Information about fetal stem cells (abstracts) from Science Direct
  • iPS cells and reprogramming from EuroStemCell
  • Transcription factors from PDB (Protein Data Bank)
  • Organoid facts from the Harvard Stem Cell Institute
  • Mounting brain organoid research reignites ethical debate from the ScienceDaily news service
  • Embryonic heart organoids from the phys.org news service
  • A description of Carla Kim's lung research from the Harvard Stem Cell Institute
  • Information about intestinal organoids from Stem Cell Technologies
  • Mini-livers helped mice with liver disease from The Conversation

This content is accurate and true to the best of the author’s knowledge and is not meant to substitute for formal and individualized advice from a qualified professional.

© 2020 Linda Crampton

Comments

Linda Crampton (author) from British Columbia, Canada on January 04, 2021:

I appreciate your comment, Glenn. I hope organoids will be very useful in treating patients. The future developments of the technology should be interesting.

Glenn Stok from Long Island, NY on January 01, 2021:

Linda, I found your article extremely interesting and highly educational. I must admit I didn't know much about stem cells, other than being aware of the technology. And I knew nothing about organoids. Reading what you described has given me a new appreciation for the science behind it.

It's incredible that organoids made from pluripotent stem cells, especially iPS cells, can be used to treat patients because they share the same genes, which avoids rejection. That gives a lot of hope for future developments with treatments, despite the concerns you discussed with triggering pluripotent stem cells.

Linda Crampton (author) from British Columbia, Canada on December 27, 2020:

Thank you very much, Devika.

Devika Primić from Dubrovnik, Croatia on December 27, 2020:

AliciaC You are good at what you do and this is another one of your well-researched hubs. Information you enlighten us about and fascinating in your line of work.

Linda Crampton (author) from British Columbia, Canada on December 23, 2020:

Thank you very much for the visit and the comment, E. Randall.

E Randall from Florida on December 23, 2020:

Thank you for posting this, very insightful.

Miebakagh Fiberesima from Port Harcourt, Rivers State, NIGERIA. on December 17, 2020:

Yes, I agreed.

Linda Crampton (author) from British Columbia, Canada on December 16, 2020:

Thanks for the visit and the comment, MG. I'm hoping the research by scientists will be very helpful.

MG Singh emge from Singapore on December 16, 2020:

This is one of the latest field of research. Fascinating article

Linda Crampton (author) from British Columbia, Canada on December 16, 2020:

Hi, Liza. I think stem cell biology is exciting and very important, as you say. I hope some wonderful benefits for people soon appear as a result of the studies. Thanks for the comment.

Liza from USA on December 16, 2020:

An exciting article, Linda. I'm convinced stem cell research is one of the most important studies in the world of medicine. It's intriguing to learn something like this and the possibilities benefits for the patient. Thank you for the well-written article.

Linda Crampton (author) from British Columbia, Canada on December 16, 2020:

Thanks for the visit and the comment, Mary. Henrietta Lacks and her cells are interesting topics to explore.

Mary Norton from Ontario, Canada on December 16, 2020:

It is exciting to follow all these developments. I am reading a book, The Immortal Life of Henrietta Lacks, whose cells became very important to medicine development. We need to know more about these cells.

Linda Crampton (author) from British Columbia, Canada on December 15, 2020:

Hi, GwennyOh. Yes, though I'm fascinated by the research and very hopeful about its benefits, what you've said worries me, too. I'm hoping for the best.

GwennyOh on December 15, 2020:

Great piece. Science that involves replication of human components though, gives me the chills on some level. Though obviously much of it is done for the greater good, there also exist those without scruples, and there's no way to know what may emerge from it.

Of course such a concern isn't expressed to say that the good could potentially outweigh the bad, but so much in our society now, bypasses due checks and balance.

Linda Crampton (author) from British Columbia, Canada on December 15, 2020:

Saving umbilical cords sounds like a great idea, Peggy, Thanks for commenting and for sharing the information.

Linda Crampton (author) from British Columbia, Canada on December 15, 2020:

Thank you very much, Bill. Medical research is certainly fascinating!

Linda Crampton (author) from British Columbia, Canada on December 15, 2020:

Hi, Manatita. I appreciate your comment. I agree with what you have said. We can certainly learn from other cultures and disciplines beyond our own. I hope you have a very merry Christmas!

Linda Crampton (author) from British Columbia, Canada on December 15, 2020:

Thank you for the comment, Vidya. The technology does hold great possibilities, as you say. The new discoveries should be very interesting.

Linda Crampton (author) from British Columbia, Canada on December 15, 2020:

Hi, Pamela. I'm looking forward to seeing the developments in the near future. There's a lot to think about! Thanks for the comment.

Linda Crampton (author) from British Columbia, Canada on December 15, 2020:

Thank you, Miebakagh. I appreciate your visit and comment.

Linda Crampton (author) from British Columbia, Canada on December 15, 2020:

Hi, Fran. It's very interesting to wonder what developments will happen over the next fifty years. Medical science is a fascinating subject.

Peggy Woods from Houston, Texas on December 15, 2020:

I can understand some of the ethical concerns, but the research and possible benefits of using stem cells to grow new organs are exciting. Some people are now saving umbilical cords in case their children ever need some of those stem cells.

Bill Holland from Olympia, WA on December 15, 2020:

Always a great read, Linda! Thank you, as always, for my education. Medical research is fascinating, and you make it understandable.

manatita44 from london on December 15, 2020:

This is a truly fascinating look at stem cells and organoids. It is one full of potential, or possibilities for the human kingdom of birth and diseases.

Shinya Yamanaka's video was amazing and I kept wondering why he hadn't got the Nobel Prize for it. So my Joy was over-flowing when I eventually got to that part. I found Yamanaka to be open ... broad-minded.

My experience is that people in their specialized field, stick only to what they know. The allopathic 'poo poos' the alternative specialist, and vici-versa. Bruce Lee says no, that we can learn from everything and become stronger by combining them.

I travelled hundreds of miles - away from my own Christianity - to learn, at the feet of an Indian man, that God Itself is constantly in motion ... that the Divine Intelligence is not fixed ... not bound by plans. Yamanaka's ideas are like that, showing the impossible possible, if we are prepared to challenge the old system and dare to look. He was divinely inspired.

Yes, I see ethics being involved, as with so many things. Yet it looks like there's scope for a brighter future too, for many. A most wonderful job done, Alicia. Merry Christmas!

VIDYA D SAGAR on December 15, 2020:

Hi Linda,

A very informative, well-researched article. Stem cell research holds great possibilities. It is a boon to cancer patients. Its use in creating organoids to help in better treatment plans for patients is very interesting.

Pamela Oglesby from Sunny Florida on December 15, 2020:

I agree that this research is fascinating, and the possibilities are excellent as well. It sounds very complicated, and no one wants to increase the risk of cancer. The possiblities of growing ogans for those in need sounds very promising.

Thank you Linda for a well-documented article that was primarily new information to me.

Miebakagh Fiberesima from Port Harcourt, Rivers State, NIGERIA. on December 15, 2020:

Linda, I'm begining to learn more about stem cells and its use in medicine to treat diseases and improve human healh. I hope this well written and informative article find you well online. Much thanks.

fran rooks from Toledo, Ohio on December 15, 2020:

Very, very informative. Medical science is so critical and important and has come a long way in the last 50 years. Wonder what it will be like in another 50 years. Thanks for your article.

Linda Crampton (author) from British Columbia, Canada on December 14, 2020:

I agree, Bill. The research is fascinating. I appreciate your comment.

Bill De Giulio from Massachusetts on December 14, 2020:

Linda, fascinating stuff. Hopefully research advances to the point of being able to create replacement organs. Amazing. Thank you for the education.