Biologists have long touted the promise of embryonic stem (ES) cells.  These cells are pluripotent, meaning they can be coaxed to form nearly any cell type of the body.  However, the enormous promise of these cells is overshadowed by moral and technical difficulties.  Human ES cells are derived from very early stage embryos which otherwise have the potential to develop into a fully-grown human being, so many find their use ethically questionable.

Figure 1: Embryonic stem cells (green) are pluripotent, meaning they have the potential to form all of the cell types of the body.  As an embryo develops, the ES cells differentiate, forming intermediate cell types (yellow) like endoderm, mesoderm, and ectoderm cells, and eventually differentiated cell types (orange) that have a specialized role, but no potential to form other cell types.  Yamanaka discovered that if you add important stem cell factors to differentiated cells, you can induce pluripotency in them, turning them back into cells with high potential, called iPS cells.

Biologists’ obsession with stem cells comes from an old dogma which says that, during embryonic development, cells resemble pebbles rolling downhill (Figure 1).  An ES cell sits at the top of the hill, with the potential to take any path down and therefore become any type of cell.  As cells roll down through developmental time, they take paths that determine their future fate.  This process is called differentiation.  Scientists long believed that once cells had taken on a particular fate, say to become a skin cell or blood cell, they could not move back uphill and regain the potential to become other cell types.  Luckily, a few scientists challenged this view and worked to push differentiated cells uphill.

“Reprogramming” stem cells

In the 1960’s, John Gurdon, a scientist then working at the University of Oxford in England, took the nucleus out of a mature frog intestine cell.  The nucleus contains the cell’s DNA and presumably was already “programmed” to be an intestine cell.  He placed it instead into a fertilized egg cell whose nucleus had been removed.  He found that this new cell with a mature nucleus still developed into a normal tadpole!  This suggested that there was something in the egg cell that was able to reprogram the mature nucleus and return it to a pluripotent state, which went on to make all of the different cells of the tadpole, instead of just intestine cells.  This same technique was much later used to clone Dolly the sheep [].

Biologists have since wondered what was responsible for that reprogramming event.  In 2006, Shinya Yamanaka, then a researcher at Kyoto University in Japan, became interested in the genes turned on in ES cells, but turned off in differentiated cells.  He turned on many different combinations of these genes in mouse skin cells.  He found that one combination of four genes successfully “reprogrammed” the skin cells back into stem cells, which he called induced pluripotent stem cells, or iPS cells.  This new cell type proved to be very similar, though not identical, to mouse ES cells.  They could reproduce indefinitely in a petri dish, and they had the potential to form many different cell types.  Shortly afterwards, other scientists adapted his methods and created human iPS cells.

Yamanaka’s research revolutionized stem cell biology, and fast.  Gurdon and Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine, just six years after Yamanaka’s discovery [].  For comparison, this year’s winners in Physiology or Medicine performed their major experiments in the 1980’s.  iPS cells are a booming field because they can be made from anyone’s cells, which gives them great potential in the realms of disease modeling, drug discovery, and stem cell therapeutics [].

Figure 2: Patient-derived iPS cells.  To better understand a specific patient’s disease, we can take their own skin cells, and turn those into iPS cells.  Since iPS cells have the potential to form many different cell types, we can differentiate them into the cell type affected in the disease, for example a neuron.  Now we have patient-specific neurons, without having taken any neurons from the patient!  We can use these to study the disease, test drugs, or develop new therapies.

iPS cells in disease modeling

Before we can develop therapies for a disease we need to know what goes wrong in the affected cells. Determining this usually requires many cells, more than we can safely take out of a patient to study.  Instead, scientists typically study mice or rats that have a condition resembling a particular human disease.  However, rodents are not people, and there are many physiological differences between the two.  This is especially true for neurological disorders, since the human brain is quite unique, and for complex diseases that have no single cause.  Now, scientists can take skin cells from an Alzheimer’s patient, reprogram them into iPS cells, and then differentiate them into neurons (brain cells) (Figure 2).  Scientists then have a vast supply of patient-specific neurons, and can understand the defects present specifically in that patient’s cells.  We’ve learned this way that defects associated with Alzheimer’s arise very quickly at the cellular level, likely long before cognitive difficulties are noticed in a patient.  This suggests that early, preventative therapies could be useful in this disease [].

iPS cells in drug screening

Once you understand how a disease works a common next step is to conduct a drug screen, where scientists test potential drugs for their ability to alleviate disease symptoms at the cellular level.  The hope is that if a drug can cure a diseased cell, it can also cure a whole person with that disease.  Drugs screened in mice or other model organisms often do not work on human patients and fail in clinical trials.  iPS cells allow us instead to get nearly unlimited cells from human patients for screening.  Several groups have taken this approach to look for treatments for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.  Patients with this disease suffer from progressive motor neuron degeneration that is eventually fatal.  One group recently tested several drugs on neurons made from patient-derived iPS cells, and found one that decreased the levels of an ALS-associated protein [].

iPS cell therapies

Perhaps the most enticing promise of iPS cells is their potential use in cell or tissue therapies.  If a patient needs a particular cell type, for example motor neurons for ALS patients, scientists could theoretically make this cell type from the patient’s other cells.  The patient’s immune system would even recognize and accept the cells.  Several obstacles remain, however.  The first is safety: the four reprogramming genes turned on in iPS cells have been linked to cancer, raising worries that iPS cell therapies could cause cancers.  Additionally, for many conditions, we would need to fix the cells before returning them to patients.  Without fixing the underlying genetic problem, motor neurons derived from the iPS cells of ALS patients would eventually degenerate.  Delivery of the cells to the exact right location in the body, so that they form all of the correct relationships with surrounding cells, is another large challenge.  Despite these difficulties, scientists are working towards iPS cell therapies.  The first clinical trial is set to start next year in Japan, where scientists will grow new retinas from iPS cells for patients suffering from a form of blindness called macular degeneration [].

The discovery of induced pluripotency turned biological dogma on its head and opened a whole new realm of study in both basic biology and disease.  The first medical breakthroughs from this technology have not yet been seen, but we can soon expect many advancements from this dynamic field.

Jamie Lahvic is a student in the Biological and Biomedical Sciences Ph.D. program at Harvard Medical School.


1. The Nobel Prize in Physiology or Medicine 2012.

2. Christopher Unger and Peter Andrews. “New tools for disease research: reprogrammed cells in disease modelling.” Euro Stem Cell.  <>

3. “Researchers Induce Alzheimer’s Neurons from Pluripotent Stem Cells.” UC San Diego Health System. <>

4. Michelle Pflumm. “iPS: ready, set, screen?” ALS Therapy Development Institute. <>

5. James Gallagher. “Pioneering adult stem cell trial approved by Japan.” BBC News. <>

2 thoughts on “Do-it-yourself stem cells: the story of induced pluripotency

  1. I have read through three articles laiming that we can do stem cell therapy at home, but noen of the fucking articles tell us how to do this. I am pissed off.

    1. I want to reverse Lupus but none of the DIY stems cells blogs tell us how to do it,its only complicated biological stories

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