I’ve been lecturing on stem cells as a professor here at UC Davis School of Medicine for many years so I can answer common questions such as “What are stem cells?” The medical students ask many great questions. They are always interested in clinical applications.
The goal of today’s article is to help you have a much clearer understanding of stem cells.
You might also enjoy our Stem Cell Channel on YouTube.
The short answer is that stem cells are undifferentiated cells with power to make other kinds of cells. Most cells cannot do that as they can only make more of themselves. What this means is that stem cells can be used to make specialized cells. These include neurons, heart cells, and more. Such cells are used in research or in the clinic in the future. Bone marrow transplantation is the best example of a proven stem cell therapy.
What’s in this article?
What are stem cells? | Why are stem cells important? | Types of stem cells | What are iPS cells? | Future of stem cell therapies | Risks of stem cells | References
What are stem cells?
Stem cells are defined as undifferentiated cells, which can become one or more other kinds of cells.
The human body contains hundreds of different types of cells that are important for our daily health. These cells are responsible for keeping our bodies running each day such as making our hearts beat, brains think, kidneys clean our blood, replace our skin cells as they shed off, and so on. The unique job of stem cells is to make all these other types of cells. They are the suppliers of new cells. When stem cells divide they can make more of themselves or more of other types of cells. For example, stem cells in skin can make more of themselves or they can make differentiated cells of the skin that have specific jobs of their own such as making the melanin pigment.
Why are stem cells important?
When we get injured or sick, our cells also are injured or killed. When this happens, stem cells become active. Stem cells have the job of fixing our injured tissues and of replacing other cells when they routinely die. In this way our stem cells keep us healthy and prevent us from prematurely aging. Stem cells are like our own army of microscopic doctors.
Stem cells come in many different forms. Scientists think that every organ of our body has its own specific type of stem cells. For example, our blood is made from blood (also known as hematopoietic) stem cells. However, stem cells are also present from the earliest stages of human development, and when scientists grow these, they are called “embryonic stem cells”.
Stem cells likely also play roles in aging. I proposed a stem cell theory of aging in my book. I’ve included an illustration from it by my student Taylor Seamount above.
Types of stem cells
The reason scientists are excited about embryonic stem cells is that the natural job of embryonic stem cells is to build every organ and tissue in our bodies during human development.
What this means is that embryonic stem cells, unlike adult stem cells, can be coaxed into potentially forming almost any other of the hundreds of types of human cells.
For example, while a blood stem cell can only make blood, an embryonic stem cell can make blood, bone, skin, brain, and so on.
In addition, embryonic stem cells are programmed by nature to build tissues and even organs, while adult stem cells are not. What this means is that embryonic stem cells have a greater natural capacity to fix diseased organs.
Embryonic stem cells are made from leftover embryos from fertility treatments that are only a few days old, that were made in a dish in a laboratory, and that would otherwise be thrown away. These embryos have 100 or less cells in the case of human ES cells.
In rarer instances ES cells can be made by somatic cell nuclear transfer. This “cloning” process involves moving nuclei from one cell to another.
What are iPS cells?
Scientists and doctors are excited about this new type of stem cell called induced pluripotent stem cells or “iPS” cells. We are excited about these cells because iPS cells have almost all the same properties as embryonic stem cells, but are not made from an embryo. (Note you can watch a video about all you need to know about embryonic stem cells above on our YouTUbe channel.)
Thus, there are no ethical concerns with iPS cells. In addition, iPS cells are made from a patient’s own non-stem cells, meaning that iPS cells could be given back to a patient without risk of immune rejection, an important issue with any stem cell transplant.
Future of stem cell therapies
Because by nature stem cells have the job of replacing sick or old cells, scientists have conceived the idea of using stem cells as therapies for patients with a wide variety of medical conditions. The idea here is that by giving a sick patient stem cells or differentiated cells made from stem cells, we can make use of the stem cells’ natural ability to heal to make the patient healthy again.
For example, if a patient has a heart attack, by giving that patient a transplant of stem cells as a therapy our goal is to have the transplanted stem cells repair the damage to the heart. The natural populations of stem cells that we all possess have only a limited capacity to fix injuries to our bodies. Going back to the example of the heart, the heart’s own stem cells are just not up to the task of fixing the damage from a heart attack, but a transplant of millions of stem cells would be far more powerful.
Stem cells for heart disease or other conditions?
Therefore by giving patients transplants of stem cells we boost the body’s ability to heal beyond the capabilities of the limited number of naturally occurring stem cells. I still see some challenges before stem cell therapies become more common including safety, as stem cells can potentially form tumors, and immune rejection. Even so, stem cells are likely to transform medicine and in perhaps just one or two decades most of us will know someone, perhaps even ourselves, who has had a stem cell transplant. Stem cells hold promise to treat most of the major diseases that people face including cancer, heart disease, Parkinson’s Disease, Multiple Sclerosis, Stroke, Huntington’s Disease, spinal cord injury, and many more.
Risks of stem cells
Currently, there are few stem cell transplants available that are proven by scientists to be both safe and effective. The best example is bone marrow transplantation. However, clinics are selling many unproven stem cell treatments around the world. Often these treatments get a lot of attention in the media. Frequently celebrities such as sports stars buy these treatments. Generally, scientists and doctors in the stem cell field caution patients against such treatments. Why? It is unclear whether these treatments actually work and whether they are safe. Patients have died from such treatments. While it is reasonable to consider all options when facing a potentially incurable condition or disease, we recommend caution. One should only consider such treatments as a last resort and only after talking with your personal physician.
The FDA has even issued warnings about stem cells, which are worth a read.
This post is part of our SCOPE stem cells not lost in translation project. It’s all about educational outreach. You can learn more about the project and read the other 34 languages on that page.
You may also be interested in my new post on stem cell therapy cost.
References
- EuroGCT
- About Cells resource page from ISSCR
- Stem Cells: An Insider’s Guide, Paul Knoepfler, 2013.
- Essentials of Stem Cell Biology, Ed. Robert Lanza.
- Adult stem cells and regenerative medicine-a symposium report. 2020.
- FDA warning about stem cells.
- NIH resource page on stem cells.
Paul,
If what you say is correct that adult tissues do not contain connective tissue-resident telomerase positive pluripotent stem cells or totipotent stem cells, for that matter, please explain our results.
In IRB-approved clinical studies we utilized telomerase positive totipotent stem cells, pluripotent stem cells, and mesodermal stem cells that were previously characterized as such by a myriad of different histological, histochemical, immunochemical, immunocytochemical, biochemical, molecular, genetic, differentiation potentials, presence of telomerase, and functional in vitro and in vivo assays. The aforementioned telomerase positive stem cells were isolated (via size, zeta potential, differential density gradient centrifugation, CD marker fingerprint, etc.), activated to respond to local environmental cues (cell-specific exosomes), and used (either as autologous and/or matched allogeneic) to partially to completely reverse the signs and symptoms (safe to transplant with an average efficacy of 83%) of Parkinson disease, age-related dry macular degeneration, traumatic spinal cord injury, complete traumatic blindness, Alzheimer’s disease, chronically inflammatory demyelinating polyneuropathy, stroke, traumatic brain injury, multiple sclerosis, myocardial infarction, systemic lupus erythematosus, celiac disease, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and joint damaged caused by osteoarthritis.
Papers have been published and can be accessed at ResearchGate under my name.
Paul,
Skin is a bilaminar structure, encompassing the epidermis and the dermis.
Surface ectodermal stem cells give rise to epidermis of skin, hair, nails, glands that exit to the outside and the enamel of teeth.
Mesoderm gives rise to the dermis of the skin, dentin of teeth, the connective tissue and blood vessels of the pulp cavity, cementum, and the jaw in which the teeth attach.
Neural ectoderm gives rise to neural crest cells that form sensory nerve endings, Schwann cells, nerve fibers in the pulp cavity, and melanocytes that synthesize melanin.
I expected a lot more from you than making such a generalized statement that “skin stem cells” make cells that form melanin. You are glossing over a very important subject. If one does not understand the normal differentiation potential of a particular stem cell, how would anyone hope to use the correct stem cell to generate the differentiated cell of choice.
Suggest you check out the “Lineage Map” at ResearchGate Website under my name.
Is there a treatment for osteoporosis the hip
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My wife was diagnosed in the year 2000 with the beginning of wide angle Glaucoma. She has shunts in both eyes to maintain the pressure.
Her Optic nerves are dying at a fast pace. She takes special eye drops, morning and night to try and maintain what sight she has.
Her Optic nerves are dying at a fast pace. She is almost completely blind. Please let me know if there is any stem cell study, that can help reverse the progress and get her eye sight back? I am her husband Harry Meyer. Her Durable Power of Attorney.
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Dear Paul,
Another way to look at endogenously occurring natural adult stem cells is whether or not they contain telomerase, the enzyme that adds telomeres to the ends of chromosomes during cell division. Most adult stem cells fall into the category of being telomerase-negative (approximately 40% of all cells in the body). They have defined life spans, conforming to Hyflick’s Limit, and are usually committed to forming particular cell and tissue types. Examples of these types of adult stem cells are MSCs, MAPCs, etc. The other population of adult stem cells are those that are telomerase-positive (approximately 10% of all cells of the body). Since they contain telomerase and do not conform to Hayflick’s Limit. They have essentially unlimited life spans until they differentiate into telomerase-negative stem cells and then into differentiated stem cells. These particular adult stem cells are cell- and tissue-uncommitted. Examples of these adult stem cells would be pluripotent stem cells, ectodermal stem cells, mesodermal stem cells, and endodermal stem cells.
Thank you, Dr. Knoepfler, for this project and thanks to all of the translators for their work. I teach Science and English in a Japanese high school. This should help my English students get a better grasp of how stem cells work. By the way, there is a minor spelling error: …most of us will known someone…
I also appreciate the time and effort you put into your blog. The whole site is a wonderful source of information.
Have a great day,
Kento
Thanks, fixed!
I totally agree with everything that you posted on your blog. In my opinion I think stem cells are the key to moving forward and advancing in the field of medicine. Scientists stated that stem cells can be found in the skin, blood, gut and muscles. However these stem cells are specialized and specific to only these parts of the body. For example, the cells of the skin can only make cells of the skin. One skin stem cell, alone can produce enough specialized skin cells to cover the whole body. Because of this scientists found the breakthrough in the treatment of serious burns. “When an individual is burned, scientists take a sample of their unaffected skin and take it apart in order to obtain the stem cells. They put the cells into a culture flask and feed the cells a special liquid made up of proteins and sugars. Eventually the cells would multiply and cover the entire base of the flask. Scientists would then remove the cells using a chemical, then obtaining a sheet of cells which they then carry into the surgery room and transplanted onto the affected area of the patient” said Professor Yann Barrandone Lausanne.
There is also the topic of embryonic stem cells which are even more special because they can become any type of specialized cell. These stem cells are obtained from blastocysts, the stage before implantation into the uterus. When these embryonic stem cells are isolated from the blastocyst, via removal of the trophectoderm, and then grown in culture, they will grow in large numbers and still be able to form any tissue at all for the body. Embryonic stem cells can become heart, blood, brain or skin cells depending on how they are grown.
Dear Paul,
I forgot to add the following during my previous post outlining some of the experiments that were performed to demonstrate the primitive nature of the adult-derived stem cells. All Lac-Z-labeled stem cell clones that were utilized for the Parkinson studies (animal and human), Myocardial Infarction, Pulmonary, and Pancreatic studies were undifferentiated naive stem cells. We allowed local environmental cues to dictate the differentiation of the primitive stem cells rather than inducing them along a particular lineage prior to transplant.
The adult stem cells utilized for these studies do not spontaneously differentiate, as do ESCs and/or iPSCs to form teratomas. Rather the adult-derived stem cells just sit in the culture dish and do nothing unless acted on by bioactive agents, such as factors that stimulate cellular proliferation, induced differentiation or inhibition.
Henry
Dear Paul,
I agree with you that marker staining is not sufficient for a thorough analysis of cell types. However, it is a “Q/D” method to demonstrate existence of the cells in adult tissues.
I apologize for not describing in detail our further analysis of the cells. We discovered three distinct populations of cells that were located in niches within the connective tissues throughout the body. They were initially identified by unique glycoprotein cell-surface staining. Later, we identified the cells by size, staining with Trypan Blue, cryopreservation, and staining with CEA-CAM, SSEA, and Thy-1. We isolated and/or cloned the cells from multiple mammalian species using repetitive single-cell clonogenic analysis. We genomically-labeled the clones with Lac-Z so that they could be tracked in vivo as well as allowing double antibody staining in vitro. We performed exhaustive growth factor-induced in vitro differentiation, proliferation, karyotypic, and molecular analyses.
The CEA-CAM+ cells demonstrated the ability to form 66 separate and distinct cell types across all three primary germ layer lineages (i.w., ectoderm, mesoderm, and endoderm). They proliferated well past 300 population doublings without loss of differentiative capabilities or change in karyotypic expression. While they were absent of MHC Class-I expression, they did express Nanog, Nanos, Bcl-2 and telomerase.
The SSEA+ cells demonstrated the ability to form 63 separate and distinct cell types across all three primary germ layer lineages. They proliferated well past 400 population doublings without loss of differentiative capabilities or change in karyotypic expression. While they were absent of MHC Class-I expression, they did express Oct-3/4 and telomerase.
The Thy-1+ cells demonstrated the ability to form 39 separate and distinct cell types solely within the mesodermal germ layer lineage. The proliferated well past 690 population doublings without loss of differentiative capabilities or change in karyotypic expression. They expressed BOTH MHC Class-I and telomerase.
We used clones of the CEA-CAM+ and SSEA+ cells to test their function when transplanted into animals models of induced Parkinson Disease (ectoderm-derived cells), Myocardial Infarction (mesoderm-derived cells), and Pulmonary Disease (endoderm-derived cells). In each animal model the Lac-Z labeled primitive stem cells incorporated into damaged tissues undergoing repair and actually formed more cell types than what we had originally hypothesized. For example, in the Parkinson model we had hypothesized that the cells would form neurons. The labeled cells actually formed dopaminergic neurons, pyramidal neurons, interneurons, glial cells, and blood-filled capillaries. In the Myocardial Infarction model we had hypothesized that the cells would form cardiac myocytes. The labeled cells actually formed cardiac myocytes, the cardiac skeleton, and new vasculature. In the pulmonary model we had hypothesized that the cells would form pneumocytes. The labeled cells formed pneumocytes, portions of the bronchial tree, and new vasculature.
We used clones of the CEA-CAM+ and SSEA+ cells to form a composite pancreatic organoid that secreted 77 times the amount of species-specific insulin per microgram DNA compared to the amount of insulin secreted by native islets when challenged with glucose.
We also performed an IRB-approved Parkinson Disease clinical trial using freshly isolated autologous primitive stem cells. At two months post-transplant, all participants in the trial were doing better than when they had started the trial. At the 14th month follow-up post-transplant, 75% of the participants were either stable (50%) or getting better (25%), while 25% of participants started to decline, but at a much slower rate than before the trial started.
While this is not all the studies that were performed with these cells, all the above has been published and can be downloaded from the Research Gate website.
Henry
Dear Paul,
I am disappointed that most stem cell biologists that you know do not believe that adult mammals, humans included, have primitive stem cells. Of course, if it were more common knowledge, then iPSCs would be a moot point. However, my hypothesis is relatively easy to test. Just stain cryosectioned normal healthy adult tissue with antibodies to SSEA (stage-specific embryonic antigen) and CEA-CAM (carcinoembryonic antigen-cell adhesion molecule). We found SSEA+ cells and CEA-CAM+ cells in 11 species of healthy adult mammals, including humans.
With respect to the lay audience, I am finding that they are becoming more and more sophisticated in their knowledge than when I started in this business 40+ years ago. And I believe they would understand that there is a distinct difference in invasive properties between basal cell carcinoma (surface ectoderm-derived) and melanoma (neural crest-derived).
Henry
Marker staining is not sufficient.
One would have to isolate and conduct rigorous functional assays as well on these proposed cells. These studies would include quantitative in vitro differentiation assays as well as teratoma assays and in the mouse context use the isolated cells for embryo germline contribution assays.
For the human cells do RNA-Seq and rigorously compare the data to hESC and hIPSC data. Comparisons here could be useful: https://www.pluritest.org.
Analyzing the global epigenetic state would also be useful such as by ChIP-Seq for H3K4me3 and H3K27m3, and possibly DNA methylation status.
If all this supports the pluripotent state of these cells, then I’d have to reevaluate my thinking on them.
Dear Paul,
While I applaud your description of “What are stem cells?”, you glossed over a category of primitive adult stem cells. Adult individuals contain primitive stem cells with functions very similar to embryonic stem cells. These primitive adult stem cells are found throughout the body residing in connective tissue niches. They are telomerase positive, having essentially unlimited proliferation potential until they lose their telomerase due to subsequent differentiation into organ-specific stem cells and differentiated cell types. These primitive adult stem cells will form all cell types derived from the germ layer lineages: ectoderm, mesoderm, and endoderm. Additionally, they are programmed with the normal checks and balances to keep them from going rogue, as can occur with iPSCs.
And by the way, the melanin pigment is formed by melanocytes, which are derivatives of neural crest, which are derived from neural ectoderm, which is derived from ectoderm. Skin cells, such as epidermis, hair, nails, are derived from surface ectoderm, which is derived from ectoderm. So in essence, the cells forming melanin (melanocytes) and skin cells come from the same early embryonic tissue (ectoderm), they just branch off from each other (neural ectoderm and surface ectoderm) earlier than you intimated in your description.
@Henry,
Most stem cell biologists I know do not believe that adult human tissues have pluripotent stem cells, excluding of course germ cells in the testes and ovary, which are a different matter from what you suggest exists.
As to the melanin, I wrote this for a lay audience.
Paul
What are the top 3-5 legitimate, highly-rated, scientific sites with information on CURRENT stem cell regenerative therapies and their successes/pitfalls?
Probably depends a lot on who you ask.
I think this site is one of them, but I’m biased.
CIRM’s blog is really good as is EuroStemCell.
http://stemcellassays.com was one of the best, but is no longer updated.
There’s stem cell podcast.
This post with a list of sites is a little out of date, but still useful: https://ipscell.com/2015/06/top-10-stem-cell-websites/
Have you found others that you like, Sherri?
Can you treat injured/shortened skeletal muscles with skeletal stem cells?
What about sheep stem cells used in humans? This clinic in Germany is using sheep cells for therapy: http://frischzellen-kuren.de
They do not offer “stem cells”. They inject mashed up sheep embryos into the muscle. At best you get a mild immune response and at worse you die of an acute allergic cascade.
This is about as snake-oily as it gets.
very useful
what about aliens
What about “Plant stem cells”? Such as GRAPE and APPLE?
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