March 16, 2021

Multipotent & totipotent vs pluripotent stem cells

Multipotent & totipotent vs pluripotent stem cells

What’s the difference between multipotent stem cells, totipotent stem cells, and pluripotent stem cells?

The goal of today’s post is to help you learn and be clear on the differences.

What’s in this article

Definition of stem cells |Totipotent vs pluripotent stem cellsPluripotent stem cellsMultipotent stem cells | The best kind of stem cell | References

Definition of stem cells

Too often we hear about “stem cells” as though they were all pretty much the same, but they in reality come in those three main types.

The distinctions are important both for understanding our own biology and for stem cell clinical trials.

Here at The Niche is a great place to learn about these stem cell types because my own lab, the Knoepfler lab at UC Davis School of Medicine, routinely grows stem cells.

Multipotent & totipotent vs pluripotent stem cells
Photomicrograph of early human embryo development. An arrow in the inset higher magnification view of the hatched blastocyst (breaking out of the zona pellucida) indicates the inner cell mass (ICM) that can produce embryonic stem cells when cultured. In terms of totipotent vs pluripotent stem cells, the early embryos shown here are totipotent, while later the ICM has pluripotent stem cells in it. Photos courtesy of Meri Firpo.

Totipotent vs pluripotent stem cells

I have a whole post on totipotent stem cells so I encourage you to dig into that. These cells got the name “totipotent” because that in a sense means “all powerful”.

Ironically despite all that power, there aren’t any therapies that I know of being developed from these cells in clinical trials yet.

Totipotent stem cells can make any other kind of cell in the body. So, for example, totipotent stem cells can make more of themselves or pluripotent stem cells. They can also make the entire embryo that will develop into the final organism, whether it is a person, an elephant or a mouse.

The best example of totipotent cells is the fertilized egg or zygote (1-cell embryo). See an image of totipotent stem cell-containing human embryos above.

Finally, these cells can also make the placenta and umbilical cord that are so important for development.

Pluripotent stem cells are a tad more limited in potential. Let’s talk about them next.

Multipotent & totipotent vs pluripotent stem cells
IPS cells, induced pluripotent stem cells, Knoepfler lab, stained for TRA-1-60, an ES cell marker.

Pluripotent stem cells

What are pluripotent stem cells? These are the next most powerful stem cells and are sometimes called PSCs. They can form the entire embryo of a developing organism. However, unlike totipotent cells, PSCs cannot form placenta and umbilical cord. They also cannot make totipotent stem cells.

The two most well-known types of PSCs are embryonic stem cells (see a primer on them here) and induced pluripotent stem cells or iPS cells. You can learn more about iPS cells here.

You might enjoy my video on embryonic stem cells below too. While you’re watching please consider subscribing to The Stem Cell Channel on YouTube.

PSCs are involved in a number of clinical trials. These include trials for diabetes, spinal cord injury, Parkinson’s and vision loss. I expect many more trials in coming years.

Multipotent & totipotent vs pluripotent stem cells
Human MSCs or mesenchymal cells grown in the Knoepfler lab. Some of the cells are multipotent stem cells.

Multipotent stem cells

The next category of stem cells is kind of a grab bag of cells that have what we call “multipotency”. Multipotent stem cells make up just about all other kinds of stem cells beyond the first two types. These are sometimes called oligopotent, but we stem cell biologists actually don’t use that term almost ever.

In a nutshell, multipotency means being able to make more than one kind of cell.

Multipotent stem cells include almost every kind of adult stem cell.

It is thought that most if not all of the different organs and tissue types in the human body have some population of multipotent stem cells. These are present to help maintain the tissues and in some cases respond to injury by making more cells.

There is still some debate about whether the heart has true stem cells in it or not. While there was debate in the past about whether the adult human brain has stem cells, I’m convinced that it does based on numerous research papers, over the past decade especially.

Where they do exist, pure adult stem cells are hard to isolate. Many things that are called adult stem cells like mesenchymal stem/stromal cells or MSCs, may often not contain almost any stem cells, depending on how they were processed. See an image of MSCs above.

There are hundreds of clinical trials ongoing with multipotent stem cells so there is real promise here. A few have even been approved in different countries.

A cautionary note. It’s important, however, to be cautious in exploring clinical trials and offerings related to multipotent stem cells from unproven clinics as some are not even real stem cells. Other offerings have no living cells of any kind in them. There are risks to consider. Check out what the FDA has to say about this.

What is the best kind of stem cell?

The “best” entirely depends on content. For some types of therapies, for instance, adult stem cells are going to be ideally suited and they have a low risk of causing cancer as a side effect.

For some diseases pluripotent stem cells are likely the best way to go as a basis for treatment, but we won’t be directly using them in the clinic. Instead, they will be made into more specialized cells like beta cells of the pancreas, retinal cells of the eye, or nervous system cells. Then those differentiated cells will be transplanted.


  1. Medicinal signalling cells: they work, so use them, Arnold Caplan, Nature, 2019.
  2. The ‘unwarranted hype’ of stem cell therapies, Jules Montague, BBC, 2019.
  3. Clear up this stem-cell messConfusion about mesenchymal stem cells is making it easier for people to sell unproven treatments, warn Douglas Sipp, Pamela G. Robey and Leigh Turner, Nature, 2018.
  4. Embryonic stem cell lines derived from human blastocysts, Science, 1998.
  5. NIH Human Embryonic Stem Cell Registry, NIH Registry of human ES cell lines, updated 2/25/2021
  6. Human embryonic stem cell lines derived from single blastomeres, Nature, 2006.
  7. search for embryonic stem cell trials. Source NIH. February 25, 2021.
  8. Induced Pluripotent Stem Cells: Past, Present, and Future, Shinya Yamanaka, Cell Stem Cell, June 24, 2012.
  9. Global trends in clinical trials involving pluripotent stem cells: a systematic multi-database analysis, NPJ Regenerative Medicine, 2020.

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