An insider’s guide: what are iPS cells?

What are iPS cells?

We talk about iPS cells all the time. We are very excited about them.

Heck, the web address for this blog is

But what are iPS cells, really?

A simple definition of iPS cells is the following:

Embryonic stem cell-like cells that are made from non-stem cells in a lab.

But does that definition do them justice?  In fact, there is a lot more to know about iPS cells and more complete ways of defining them such that when we talk about iPS cells we really know what we mean.

The acronym “iPS” was coined by their discoverer, Shinya Yamanaka, to stand for “induced Pluripotent Stem” cells.

One way we can understand what iPS cells are more clearly is by breaking apart their name. Why did Yamanaka choose that name? For good reasons outlined below

Induced. Unlike all other known stem cells, by definition, iPS cells are not naturally occurring stem cells, but are rather “induced”.

What this means is that iPS cells are designed and made in a lab from non-stem cells. We all carry around inside of us various types of stem cells in every organ, but you won’t find iPS cells in a person or any other animal. They are induced from non-stem cells, what we sometimes can “somatic cells”, using a combination of factors. These inducing factors include many different types of cellular factors. The original 4 factors that Yamanaka used were Oct4, Sox2, Klf4, and Myc.

Pluripotent. Pluripotency is a term used to describe the ability of stem cells to turn into (i.e. differentiate) all known types of cells, except extraembryonic tissues such as placenta. The pluripotency of iPS cells and embryonic stem cells gives them dramatically more potential power for medicine than adult stem cells. What this means is that iPS cells are pluripotent (aka powerful) in much the same way as ES cells.


iPS cells were discovered by Shinya Yamanaka using a mouse model system in 2006. They were subsequently made in human cells by Yamanaka as well as a bunch of other researchers. Jamie Thomson made iPS cells using Oct4, Sox2, Lin28, and Nanog, while most other researchers used Yamanaka’s protocol.

Human iPS cells are intrinsically far more difficult to make than mouse iPS cells.


iPS cells versus human ES cells: what’s the reality?

When iPS cells were discovered, there was a great deal of enthusiasm because they were not derived from embryos and since they could be made from a patient’s own skin, in theory they could be used for a transplant from a patient to themselves with no worries of immunorejection. Some anti-embryonic stem cell research folks started chanting a mantra that you still hear to this day: iPS cells makes ES cells “obsolete”. However, ask anyone in the stem cell scientific community about this, and they will say that that is not accurate.  I blogged before on the 5 most serious challenges facing iPS cells in order to get them to the clinic.


Disease in a dish

We are coming to realize that iPS cells, beyond their potential use in regenerative medicine, are extremely powerful for their ability to be used to model complex human diseases in a dish. For many diseases, particularly neurological disorders, there is simply no way to study the cells involved to gain a better understanding of the pathogenesis and potential treatment of the disease. iPS cells change all that. By simply growing skin fibroblasts from any given patient (with their consent of course), iPS cell technology allows for the making of specific differentiated cell types from the patient. For example, for a patient with Parkinson’s, you can grow skin fibroblasts, make iPS cells from them, make neurons from the iPS cells, and then study them in a dish. This is a tremendously powerful way to understand diseases and screen for new drugs that might be the basis of novel treatments.


iPS cells behind the scenes: some realities coming into focus

Anectodal evidence suggests that Yamanaka’s cocktail of 4 factors works with a much higher efficiency than Thomson’s, particularly for human cells.

Making iPS cells without Myc is a challenge.  When Yamanaka first reported making iPS cells, he said that they could not be made without Myc. As it turns out, they can be made without Myc, but it is a very low efficiency process. In some cases, adding Myc boosts efficiency up to 100 fold.

Making iPS cells using just RNAs or proteins is, at least at this point, extremely difficult and most often fails to work to make “real” iPS cells.

Most colonies that sprout up in any given iPS cell experiment are not real iPS cells. They are a hodgepodge of partially reprogrammed colonies and other, clinically unhelpful cell types. What this means is that validation of iPS cells is incredibly important.


Other definitions out there on the web:

WISC definition (caution PDF)

BUMC Center for Regenerative Medicine



The future of iPS cells

At this moment in mid-April 2011, the most concrete, promising aspect of iPS cell technology for human health is their power to model complicated diseases. Through this approach, it is possible that new treatments and perhaps even cures for currently untreatable diseases will be discovered.

As a stem cell scientist, I still hold out hope that iPS cell technology will continue to develop at a rapid clip leading to their eventual use in patients for regenerative medicine therapy. There are difficult roadblocks between us and that potential reality, but I for one have optimism that we will get there.

The discovery of iPS cells has energized and excited the stem cell field. It has opened the door to new ideas and I would argue, has made scientists think more creatively. For example, iPS cells made transdifferentiation technology (whereby you skip the iPS cell step and directly change one cell type into another) a reality and I think this approach will produce clinically important drugs. Yamanaka’s discovery of iPS cells was a transformative event that opened people’s minds about and directly catalyzed the advances in transdifferentiation.