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.

very early human embryos, totipotent 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.

IPS cells, induced pluripotent stem cells, Knoepfler lab, stained for TRA-1-60, an ES cell marker., where do stem cells come from?
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.

mesenchymal cells, MSCs, mesenchymal 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.

References

  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. Clinicaltrials.gov 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.

3 thoughts on “Multipotent & totipotent vs pluripotent stem cells”

  1. Difference between pluripotent and multipotent is confusing at present.
    Pluripotent stem cells imply differentiation into 3 lineages ecto-, endo- and mesoderm
    Multipotent stem cells has nothing to do with distinct lineages …
    MSCs differentiate into osteoblasts, chondrocytes and adipocytes (all mesoderm lineages)
    Similarly, HSCs differentiate into lymphocytes, neutrophils, basophils, eosinophils, platelets, RBCs
    Both MSCs and HSCs are lineage restricted but are termed multipotent (nothing to do with pluripotent)

  2. RE: “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.”

    Come on, Admin…say it all.
    And how will those transplanted differentiated cells renew themselves in the many, many cases for which it will be required for a durable treatment (e.g., blood, liver, cornea, pancreas, on and on for renewing tissues).
    Yep, “those differentiated cells [that] will be transplanted” will need to be asymmetrically self-renewing tissue stem cells, aka adult tissue stem cells.
    Oh, did you mention that neither HUMAN ESCs nor HUMAN iPSCs practically “differentiate into ALL the cells in the body,” because, so far, its been a singular challenge to differentiate them into mature adult cell phenotypes instead of fetal cell phenotypes.

    James @ Asymmetrex

  3. my two cents

    A.Blidy
    10-2020

    I am constantly asked to explain stem cells to people trying to understand the science of regenerative medicine ……it is not about believing or not , they exist ….
    What are stem cells, and what do they do?
    Sources
    Types
    Uses
    Donating and harvesting
    Cells in the body have specific purposes, but stem cells are cells that do not yet have a specific role and can become almost any cell that is required. Stem cells are undifferentiated cells that can turn into specific cells, as the body needs them. Scientists and doctors are interested in stem cells as they help to explain how some functions of the body work, and how they sometimes go wrong. Stem cells also show promise for treating some diseases that currently have no cure.
    Sources of stem cells
    Stem cells originate from two main sources: adult body tissues and embryos. Scientists are also working on ways to develop stem cells from other cells, using genetic “reprogramming” techniques.
    Adult stem cells
    Stem cells can turn into any type of cell before they become differentiated. A person’s body contains stem cells throughout their life. The body can use these stem cells whenever it needs them. Also called tissue-specific or somatic stem cells, adult stem cells exist throughout the body from the time an embryo develops. The cells are in a non-specific state, but they are more specialized than embryonic stem cells. They remain in this state until the body needs them for a specific purpose, say, as skin or muscle cells. Day-to-day living means the body is constantly renewing its tissues. In some parts of the body, such as the gut and bone marrow, stem cells regularly divide to produce new body tissues for maintenance and repair.
    Stem cells are present inside different types of tissue. Scientists have found stem cells in tissues, including:
    the brain
    bone marrow
    blood and blood vessels
    skeletal muscles
    skin
    the liver
    However, stem cells can be difficult to find. They can stay non-dividing and non-specific for years until the body summons them to repair or grow new tissue. Adult stem cells can divide or self-renew indefinitely. This means they can generate various cell types from the originating organ or even regenerate the original organ, entirely. This division and regeneration are how a skin wound heals, or how an organ such as the liver, for example, can repair itself after damage. In the past, scientists believed adult stem cells could only differentiate based on their tissue of origin. However, some evidence now suggests that they can differentiate to become other cell types, as well.

    Embryonic stem cells,
    Human Embryonic Stem Cell Lines Generated without Embryo Destruction

    From the very earliest stage of pregnancy, after the sperm fertilizes the egg, zygote is form to blastomere to blastocytes in an embryo form. Around 3–5 days after a sperm fertilizes an egg, the embryo takes the form of a blastocyst or ball of cells. The blastocyst contains stem cells and will later implant in the womb. Embryonic stem cells come from a blastocyst that is 4–5 days old. It has been demonstrated that hESCs can be generated from single blastomeres (Klimanskaya et al., 2006 https://www.sciencedirect.com/…/pii/S193459090700330X). In that “proof-of-principle” study, multiple cells can be removed from an embryo and the embryos can continue to develop. No death of embryo in harvesting cells …..The derivation of hESC lines using a non-embryo destruction (NED) technique , including one without hESC coculture. Single blastomeres are removed from the embryos by using a technique similar to preimplantation genetic diagnosis (PGD). The biopsied embryos were shown to grown to the blastocyst stage and frozen. The blastomeres were cultured by using a modified approach aimed at recreating the ICM niche, which substantially improved the efficiency of the hESC derivation to rates comparable to whole embryo derivations. When scientists take stem cells from embryos, these are usually extra embryos that result from in vitro fertilization (IVF). In IVF clinics, the doctors fertilize several eggs in a test tube, to ensure that at least one survives. They will then implant a limited number of eggs to start a pregnancy.

    Mesenchymal stem cells (MSCs)

    MSCs come from the connective tissue or stroma that surrounds the body’s organs and other tissues.
    Scientists have used MSCs to create new body tissues, such as bone, cartilage, and fat cells. They may one day play a role in solving a wide range of health problems.

    Induced pluripotent stem cells (iPS)

    Scientists create these in a lab, using skin cells and other tissue-specific cells. These cells behave in a similar way to embryonic stem cells, so they could be useful for developing a range of therapies.
    However, more research and development is necessary.
    To grow stem cells, scientists first extract samples from adult tissue or an embryo. They then place these cells in a controlled culture where they will divide and reproduce but not specialize further. Stem cells that are dividing and reproducing in a controlled culture are called a stem-cell line. Researchers manage and share stem-cell lines for different purposes. They can stimulate the stem cells to specialize in a particular way. This process is known as directed differentiation. Until now, it has been easier to grow large numbers of embryonic stem cells than adult stem cells. However, scientists are making progress with both cell types.

    Types of stem cells
    Researchers categorize stem cells, according to their potential to differentiate into other types of cells.
    Embryonic stem cells are the most potent, as their job is to become every type of cell in the body.

    The full classification includes:
    Totipotent: These stem cells can differentiate into all possible cell types. The first few cells that appear as the zygote starts to divide are totipotent.
    Pluripotent: These cells can turn into almost any cell. Cells from the early embryo are pluripotent.
    Multipotent: These cells can differentiate into a closely related family of cells. Adult hematopoietic stem cells, for example, can become red and white blood cells or platelets.
    Oligopotent: These can differentiate into a few different cell types. Adult lymphoid or myeloid stem cells can do this.
    Unipotent: These can only produce cells of one kind, which is their own type. However, they are still stem cells because they can renew themselves. Examples include adult muscle stem cells.
    Embryonic stem cells are considered pluripotent instead of totipotent because they cannot become part of the extra-embryonic membranes or the placenta.

    SCIENCEDIRECT.COM
    Human Embryonic Stem Cell Lines Generated without Embryo Destruction
    To date, the derivation of all human embryonic stem cell (hESC) lines has involved destruction of embryos. We previously demonstrated that hESCs can b…

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