We often talk about stem cells but there are some pretty basic, important questions that often go unanswered like ‘where do stem cells come from?’
It’s a more complicated and interesting question than you might think, and some of the answers point to novel ways in which stem cells may be used to treat human diseases. Note that if you are looking for information in a language other than English, my stem cell outreach pages have key facts about stem cells in dozens of languages. The website A Closer Look at Stem Cells is also a good resource.
As a stem cell biologist myself and professor of a research lab working on stem cells for 14+ years, the origins and properties of stem cells are questions I’ve been thinking about for a few decades. I enjoy discussing these issues. This post is likely to be of special interest to people or patients interested in stem cells, other stem cell biologist, scientists more generally, and students who want to learn more, perhaps for an upcoming test that will include questions on stem cells and their origins. In a broad sense many stem cells can be found in what’s called ‘the niche’, which is kind of akin to their nest inside each particular tissue, but this post is more focused on their sourcing from different tissues.
Adult stem cells intro
Let’s start by discussing the adult sources of stem cells, which have great medical promise. In the old days people would widely classify stem cells as “adult” or “embryonic”, but this binary way of thinking was in part driven more by antiquated views of “good” and “bad” stem cells than by science. For instance, since induced pluripotent stem cells or IPS cells (more on them below) were not made from embryos they were sometimes classified as adult stem cells, which to me doesn’t make sense.
Where can adult stem cells come from?
For today’s article, we’ll classify adult stem cells as stem cells that are from individuals who are already born but may still be children. In this sense, the term “adult” is a bit odd, but it seems like the best classification approach. So, for example, stem cells from the bone marrow of a six-year-old girl would be considered “adult” stem cells.
In adults, where do stem cells come from?
- Bone marrow. From a historical perspective, in a way bone marrow was the original source of some of the key concepts and data about stem cells. Bone marrow stem cells also arguably are the main success story of the stem cell or regenerative medicine field as well. They are the basis for bone marrow transplants, now sometimes called hematopoietic stem cell transplants, which have saved hundreds of thousands of lives. For instance, bone marrow stem cells can regrow the entire immune system after chemotherapy is used to wipe out blood cancers. Bone marrow also contains so-called mesenchymal stem/stromal cells or MSCs. While MSCs are now widely accepted to not necessarily be pure stem cells, depending on how they are produced they can be at least enriched for true stem cells along with other supportive cells like stromal cells. By stromal cells we mean those that are in the tissue surrounding the actual stem cells.
- Blood. Another source of hematopoietic stem cells is blood. At any one given time most of the hematopoietic stem cells are hanging out in the bone marrow, but some circulate through the blood. In addition, the number of stem cells in the blood can be increased greatly by treatment with certain mobilizing factors, like Neupogen, prior to donating such stem cells either for one’s own use or for another person. See a picture of a wonderful person donating stem cells above. Within the Blood category, we should also include umbilical cord blood, which is a somewhat unique source of stem cells. Umbilical cord blood stem cells seem to be more flexible in their functions as compared to typical stem cells found in regular blood.
- Fat. Adipose or fat tissue is a good source of MSCs. Fat MSCs are being studied in many clinical trials for almost any disease you can think of, but they are also already being marketed as treatments for many conditions too despite there being little evidence to support such offerings. Usually those selling fat MSCs, which sometimes go by the name stromal vascular fraction or SVF, operate out of small “stem cell clinics”. Many of these have run into trouble with the FDA.
In addition to the examples above, one theory is that every adult tissue or organ has its own population of stem cells. In this sense, there may be stem cells right now in every part of your body including your brain, kidney, liver, lungs, etc. Scientists periodically debate whether certain organs have meaningful populations of stem cells and it seems like the topics of adult human brain stem cells and heart stem cells are particularly contentious. My own sense is that nearly every adult organ has stem cells, but in some cases like in the heart they may either be absent or present in such small numbers that they do not seem at this time to have much significance for health.
These adult stem cells are there for two main reasons. First, they help to maintain that particular tissue or organ. Every day some of the cells in our bodies randomly die even under normal conditions and the adult stem cells help replace those. Second, should a tissue or organ get damaged or become infected, the adult stem cells in it will help it heal.
Where do embryonic stem cells come from?
As their name suggests, embryonic stem cells are largely generated using embryos. In the case of human embryonic stem cells, they are derived from human embryos left over from IVF procedures done to help infertile couples have babies.
These human embryos are at a very early stage of development only a few days after fertilization and have around 100 cells.
They have no specific tissues or organs yet, as those will come much later. Instead they are essentially a ball of mostly uniform cells.
While years ago human embryonic stem cells were the source of quite a bit of debate, today they are much more widely accepted by the public including in the U.S.
Still, some folks are opposed to making or using human embryonic stem cells.
Cloning stem cells
Embryonic stem cells can also be made through a process called somatic cell nuclear transfer or SCNT. In this process, the nucleus of an adult cell is transferred into an egg (or one-cell embryo) that has had its own nucleus removed. Sometimes if this all goes right the hybrid cell will go on with development normally even though it has the nucleus from another cell.
Such cloning is widely used to make more farm animals. To my knowledge it has never been used to make a human clone, but the topic often comes up. If the SCNT procedure is done with human cells, instead of trying to make a cloned person those early embryos can instead be used to make human embryonic stem cells, which could be very useful in medicine. For this reason, this process is sometimes called therapeutic cloning. It remains unclear whether SCNT-derived human embryonic stem cells are really needed given the innovation of IPS cells, which I’ll now discuss.
Induced pluripotent stem cells or IPS cells were first reported using mouse and human cells in 2006 and 2007, respectively. Where do IPS cells come from? They are made through a process called reprogramming, which in a nutshell means that adult cells are transformed into IPS cells using specific molecules that have the power to “convince” cells they are like embryonic stem cells.
One analogy is that cellular reprogramming is sort of like installing a new operating system on your computer to make it function differently, but in the case of cells this new “operating system” does physically changes the resulting cells as they make new proteins, RNAs, etc.
The bottom line is that the resulting IPS cells act just like embryonic stem cells, but no embryo is needed to make them. The IPS cells can be differentiated into just about any cell type for use as therapies including making adult stem cells.
An increasing number of clinical trials are ongoing using IPS cells across the globe including both here in the US and in Japan, just to name two hubs of IPS cell work.
A related method called direct reprogramming is also in the mix. Direct reprogramming (also called dedifferentiation) in a way skips the IPS cell step.
In this way, typical adult stem cells like from blood can be directly changed into totally different kinds of cells like brain cells without having to go through the IPS cell step.
Where do stem cells come from in other animals?
Yes, us humans are amazing in some ways with our big brains and such, but when it comes to stem cells some other animals are way cooler than us. Certain species have far more stem cells than we do and even what seem like non-stem cells in these animals can convert to a stem cell-like state under stress. While some researchers believe that in humans some non-stem cells can change into stem cells under stress like disease, this remains a more controversial idea.
One of the more amazing creatures from a stem cell perspective is the type of amphibians called axolotls. You can see a picture of an axolotl above. If they are attacked by a predator deep within their habit like a pool in a cave in Mexico and lose an arm or a leg, they have so many stem cells that they can regrow a new arm or leg. They could also regrow a new part of their head or of a damaged organ in some cases. By doing research on such creatures the hope is that it will unlock the stem cell-based regenerative potential of humans too.
What’s a more important question than ‘where do stem cells come from?’
In a way, what’s more important than where particular stem cells come from is what those stem cells can do. A second important question goes hand-in-hand and that is what risks particular stem cells might pose. Overall, what biomedical scientists and patients should focus on is the ratio of potential benefit to potential risk. still, I understand that the source of stem cells is an important issue as well to many people.