Induced Pluripotent Stem Cells

Now, Cellular Dynamics International (CDI) is utilizing that technology to offer, via the company’s MyCell Services, iPSC lines from any patient of interest, as well as differentiated cell lines derived from the iPSCs.

“[Customers] don’t have to be stem-cell biologists to leverage this technology,” says Chris Parker, CDI’s chief commercial officer. “They can simply be interested in a disease state and get the human cells they need to answer appropriate questions.”

...The iPSC lines are derived from CD34 cells in blood samples sent in by customers, and returned as 96-well plates of a cell type of interest. To create an iPSC line from a patient sample costs $15,000 and takes about 6 months, Parker says, but once the iPSC lines are established, it takes just 1 to 2 months to order more specific cell types derived from that line.

The objection of course is that by using HEK 293 to grow virus used in the technique, all iPSC research is morally tainted. To some extent that is true for early research, but scientists are getting away from using viruses for the reprogramming, so iPSC research can be free of this particular stain. Analogously, vaccinations are commonly grown in 2 cell lines derived decades ago from aborted fetuses. Since no new abortions are needed to keep these cell lines going and vaccines are generally seen as vastly improving public health, Catholics can vaccinate their children if they ask for alternatives and voice their objections.

It is my opinion that the same applies here. I object to the use of HEK 293 for research period. Please, scientists, find a suitable alternative. That being said, it is possible that iPSCs in the future can be free from any moral taint coming from DNA or cell lines derived from illicit origin.

There has been a lot of talk about Dr. Yamanaka and his work on induced pluripotent stem cells (iPSCs) since he won the Nobel Prize earlier this week.  There have been some rumblings that pro-lifers should not be so happy about iPSCs since they are not "100% pro-life."

Before I list the objections that some pro-lifers are having with this new technology, let me give you a quick refresher on what iPSCs are and how they are made. Pluripotent cells are cells that can become most or all of the 200 cell types of the body, but they cannot become other tissues like placenta. So pluripotent cells, alone without further manipulation, cannot implant and grow into a fetus, baby etc.

Before Dr. Yamanaka's work, scientists would get pluripotent stem cells from the inner stem cell mass of an embryo. Dr. Yamanaka, realizing that we cannot continue to destroy embryos for stem cells, envisioned a way to reprogram an adult cell back to a pluripotent state. Yamanaka used a virus to deliver pieces of genetic material into an adult cell that "rebooted" that cell back to pluripotency so it can be coaxed into becoming another of the body's cell types. Now scientists can take a skin cell, reprogram it and then grow lung tissue, neurons, or other tissue they want to study. Induced pluripotent stem cells are an alternative to cloning because you get stem cells that are a genetic match to a patient, but without creating and destroying a cloned human embryo.

So what are some of the pro-life objections I have been reading? First, there is a concern that iPSCs are dangerous because it is possible they can be used for cloning purposes. The concern stems from work where scientists, testing the pluripotency of the cells, were able to grow a mouse from just iPSCs suggesting that induced pluripotent stem cells are just like cloning, on their own able to produce a human being. But looking closer you find that the scientists had to manipulate some of the iPSCs with something called tetraploid complementation, so that the iPSCs could become the extra-embryo tissues like placenta. So while cloning creates a complete human embryo capable, at least some percentage of the time, of implanting in a uterus and continuing to grow, reprogramming adult cells back to pluripotency (upon my reading) only creates stem cells, not a complete organism.

Second, there is an objection that the viruses used for the reprogramming were grown in a cell-line called HEK 293.  Cell line HEK 293 was derived from the kidney tissue of a boy aborted in the 1970s.  HEK stands for "human embryonic kidney."  The HEK 293 line was subsequently genetically engineered with viral DNA and is now available for sale from a common chemical supply. While I have never personally worked with HEK 293, I understand that this cell line is commonly used just about everywhere, which of course does not negate the ethical implications, but does shed some light on why HEK 293 was used in developing iPSCs.

The objection of course is that by using HEK 293 to grow virus used in the technique, all iPSC research is morally tainted. To some extent that is true for early research, but scientists are trying to get away from using viruses for the reprogramming, so iPSC research can be free of this particular stain. Analogously, vaccinations are commonly grown in 2 cell lines derived decades ago from aborted fetuses. Since no new abortions are needed to keep these cell lines going and vaccines are generally seen as vastly improving public health, Catholics can vaccinate their children if they ask for alternatives and voice their objections.

It is my opinion that the same applies here. I object to the use of HEK 293 for research period. Please, scientists, find a suitable alternative. That being said, it is possible that iPSCs in the future can be free from any moral taint coming from DNA or cell lines derived from illicit origin.

Another objection is the iPSCs are just like embryonic stem cells and so are no good for treating patients. It is true that because iPSCs are pluripotent like embryonic stem cells they will likely have many of the same safety issues for transplantation. More research is needed. What iPSCs are good for is creating model tissues for scientists to use to study disease progression and treatment. As I have written before, previous to iPSCs, scientists would have to create a mouse or other animal that exhibited the symptoms of a human disease that they were interested in studying.  Now they can take a skin cell from a person with a disease, reprogram that cell back to a pluripotent state, and then differentiate them into cells of interest whether they be neurons or fat cells.  iPSCs can continue to grow in culture and be frozen giving researchers a nearly limitless supply of diseased cells to work on.  This is especially useful in brain disorders because isolating neurons from the brain of a patient is dangerous.  Scientists can use the iPSCs to generate tissue used for testing new drugs or other methodologies in the fight against disease.

Another objection is that iPSCs have been used to generate gametes for IVF in animal models. This is true. Scientists have created mouse egg and sperm with this technology and then used them to create mice. Some pundits are talking about using this technique to allow gay couples to have genetically related children. I see this as a problem not with iPSC technology per se, but as a problem with the fertility industry that has an anything goes attitude toward procreation. Get the fertility industry under control with some regulations prohibiting genetically modifying or manipulating gametes and embryos and this objection evaporates.

Stepping back and looking at the big picture, iPSCs I believe are something pro-lifes can be happy about with the knowledge that their history is not perfect. Remember that before iPSC technology, the talk was of nothing other than destroying IVF embryos and creating and destroying embryos through cloning as the "best" ways to develop stem cell cures. Now there is an alternative developed directly as a way to avoid creating and destroying embryos. Which is why moral theologian Father Thomas Berg said the work of Dr. Yamanaka helped to “put human embryonic stem-cell research largely out of business.”

I think that is reason to celebrate.

Clarification:

In the above piece I used an analogy to vaccines that are produced in cell lines of illicit origin where I did not articulate well enough. I wrote:

The objection of course is that by using HEK 293 to grow virus used in the technique, all iPSC research is morally tainted. To some extent that is true for early research, but scientists are getting away from using viruses for the reprogramming, so iPSC research can be free of this particular stain. Analogously, vaccinations are commonly grown in 2 cell lines derived decades ago from aborted fetuses. Since no new abortions are needed to keep these cell lines going and vaccines are generally seen as vastly improving public health, Catholics can vaccinate their children if they ask for alternatives and voice their objections.

It is my opinion that the same applies here. I object to the use of HEK 293 for research period. Please, scientists, find a suitable alternative. That being said, it is possible that iPSCs in the future can be free from any moral taint coming from DNA or cell lines derived from illicit origin.

The man that envisioned a better way than destroying human embryos to get embryonic-like stem cells has won the Nobel Prize for Medicine. Dr. Shinya Yamanaka developed the technique to take an adult cell and reprogram it to an embryonic-like state as a way to avoid the destruction of human embryos. Dr. Yamanka's reprogrammed adult cells are called induced pluripotent stem cells (iPSCs) and have become a boon for the stem cell field allowing researchers to create new pluripotent stem cell lines for study without creating or destroying embryos.

In the New York Times, Dr. Yamanaka stated, “When I saw the embryo, I suddenly realized there was such a small difference between it and my daughters,  I thought, we can’t keep destroying embryos for our research. There must be another way.”

Induced pluripotent stem cells are the perfect alternative to therapeutic cloning or somatic cell nuclear transfer (SCNT). SCNT creates a cloned embryo that would be destroyed for the pluripotent stem cells inside.  Many scientists have called SCNT "the most promising" way to make pluripotent stem cells because it would create embryonic stem cells that are a genetic match to a patient.  The problem with SCNT is that to make pluripotent stem cells that are a genetic match, human eggs are needed and a cloned embryo is created and destroyed.  Induced pluripotent stem cells also creates pluripotent stem cells that are a genetic match to a patient because the reprogrammed adult cell is from the patient.  But iPSCs technology does not require eggs or cloned embryos to do it.

And now iPSCs are coming into their own proving that ethics and science make good partners.  Researchers are finding that iPSCs are great for creating models of disease.  Previously, scientists would have to create a mouse or other animal that exhibited the symptoms of a human disease that they were interested in studying.  Now they can take a skin cell from a person with a disease, reprogram that cell back to a pluripotent state, and then differentiate them into cells of interest whether they be neurons or fat cells.  iPSCs can continue to grow in culture and be frozen giving researchers a nearly limitless supply of diseased cells to work on.  This is especially useful in brain disorders because isolating neurons from the brain of a patient is dangerous.  

The Scientist reports on the award shared with Dr. John Gurdon:

John B. Gurdon of the Gurdon Institute in Cambridge and Shinya Yamanaka of Kyoto University in Japan have won the 2012 Nobel Prize for Physiology or Medicine for finding that cells of an adult organism—once thought be terminally locked into their developed state—can start anew. The discoveries, awarded the prize this morning (October 8th) by The Nobel Assembly at Karolinska Institute in Stockholm, have ignited research in areas ranging from cloning to cancer treatment.

“Gurdon and Yamanaka fundamentally changed the way we all think about the specialized state of cells,” George Daley, director of the Stem Cell Transplantation Program at the Harvard Medical School, wrote in an email to The Scientist. “Collectively they taught us that the identity of a cell can be re-engineered—that an adult cell can be reverted to its embryonic state. This paradigm-shifting concept has opened up whole new avenues of research."

...Since the discovery, other scientists have generated iPS cells from humans—a feat which some argue reduces the need for controversial and difficult to acquire embryonic stem cells. These iPS cells allow researchers to study disease and development in the lab by, for example, generating disease models from the skin of patients with neurodegenerative disorders. The cells are also showing promise for cell replacement therapies to treat various illnesses.

“Induced pluripotent stem cells have already begun to revolutionize medicine,” Paul Fairchild, director of the Oxford Stem Cell Institute, said in an email. They provide “much-needed models of rare and complex disease states while providing sources of cells that may one day be used to replace those that are either worn out or compromised by degenerative diseases.”

Atticus Shaffer

One of my favorite actors is Atticus Shaffer.  He plays the lovably eccentric Brick on my family's guilty pleasure The Middle.  Besides having an awesome first name, Atticus also has osteogenesis imperfecta (OI) a genetic disorder where there is a mutation in the gene for collagen, an important building block for bones and ligaments.  People with OI make fragile bones that break easily.  You may remember OI depicted in the M. Night Shyamalan movie "Unbreakable."

Osteogenesis imperfecta (OI) is caused by dominant mutations in the type I collagen genes. In principle, the skeletal abnormalities of OI could be treated by transplantation of patient-specific, bone-forming cells that no longer express the mutant gene. Here, we develop this approach by isolating mesenchymal cells from OI patients, inactivating their mutant collagen genes by adeno-associated virus (AAV)-mediated gene targeting, and deriving induced pluripotent stem cells (iPSCs) that were expanded and differentiated into mesenchymal stem cells (iMSCs). Gene-targeted iMSCs produced normal collagen and formed bone in vivo, but were less senescent and proliferated more than bone-derived MSCs. To generate iPSCs that would be more appropriate for clinical use, the reprogramming and selectable marker transgenes were removed by Cre recombinase. These results demonstrate that the combination of gene targeting and iPSC derivation can be used to produce potentially therapeutic cells from patients with genetic disease.

University of Michigan

Researchers are on the path to using both gene therapy and induced pluriopotent stem cell technology (iPSC) together to create a possible treatment for sickle cell anemia.  Sickle cell is a recessive genetic disorder that is cause by a single base mutation in the gene for hemoglobin.  This single base mutation changes the shape of the hemoglobin molecule which causes red blood cells to collapse into a sickle shape.  These sickle shaped red blood cells clog blood vessels causing pain, infections, organ damage and death.

Using a patient's own stem cells, researchers at Johns Hopkins have corrected the genetic alteration that causes sickle cell disease (SCD), a painful, disabling inherited blood disorder that affects mostly African-Americans. The corrected stem cells were coaxed into immature red blood cells in a test tube that then turned on a normal version of the gene....

Using one adult patient at The Johns Hopkins Hospital as their first case, the researchers first isolated the patient's bone marrow cells. After generating induced pluripotent stem (iPS) cells - adult cells that have been reprogrammed to behave like embryonic stem cells - from the bone marrow cells, they put one normal copy of the hemoglobin gene in place of the defective one using genetic engineering techniques. The beauty of iPS cells is that we can grow a lot of them and then coax them into becoming cells of any kind, including red blood cells," Cheng said.

In their process, his team converted the corrected iPS cells into immature red blood cells by giving them growth factors. Further testing showed that the normal hemoglobin gene was turned on properly in these cells, although at less than half of normal levels. "We think these immature red blood cells still behave like embryonic cells and as a result are unable to turn on high enough levels of the adult hemoglobin gene," explains Cheng. "We next have to learn how to properly convert these cells into mature red blood cells."

At least that is what The Scientist is calling them.  Induced pluripotent stem cells (iPSC) are adult cells that have been reprogrammed back to a pluripotent state.  A pluripotent cell is simply a cell can become most or all of the 200 cell types of the body.  iPSCs behave like embryonic stem cells, which are naturally pluripotent, but iPSCs do not require the destruction of an embryo. They are the perfect alternative to therapeutic cloning or somatic cell nuclear transfer (SCNT).  SCNT creates a cloned embryo that would be destroyed for the pluripotent stem cells inside.  Many scientists have called SCNT "the most promising" way to make pluripotent stem cells because it would create embryonic stem cells that are a genetic match to a patient.  The problem with SCNT is that to make pluripotent stem cells that are a genetic match, human eggs are needed and a cloned embryo is created and destroyed.  Induced pluripotent stem cells also creates pluripotent stem cells that are a genetic match to a patient because the reprogrammed adult cell is from the patient.  But iPSCs technology does not require eggs or cloned embryos to do it.

In fact, the idea of reprogramming an adult cell back to a pluripotent state is credited to Japanese scientist who wanted another way to get patient-specific pluripotent stem cells without creating and destroying embryos.  Dr. Shinya Yamanaka, stated in the New York Times:

“When I saw the embryo, I suddenly realized there was such a small difference between it and my daughters,  I thought, we can’t keep destroying embryos for our research. There must be another way.”

"If human embryonic stem cell research does not make you at least a little bit uncomfortable, you have not thought about it enough."

And now iPSCs are coming into their own proving that ethics and science make good partners.  Researchers are finding that iPSCs are great for creating models of disease.  Previously, scientists would have to create a mouse or other animal that exhibited the symptoms of a human disease that they were interested in studying.  Now they can take a skin cell from a person with a disease, reprogram that cell back to a pluripotent state, and then differentiate them into cells of interest whether they be neurons or fat cells.  iPSCs can continue to grow in culture and be frozen giving researchers a nearly limitless supply of diseased cells to work on.  This is especially useful in brain disorders because isolating neurons from the brain of a patient is dangerous. 

For all of these reasons and more, The Scientist, calls iPSCs the "new supermodel" for understanding human disease:

Move over mice. Human induced pluripotent stem (iPS) cells are making strides to become the next best thing in translational research—disease-specific human cells grown in a dish. Using a variety of approaches, researchers have generated stem cells from mature adult cells of disease-afflicted patients and subsequently differentiated them into the various tissue types involved in the disease.

“The idea is that you can have a pluripotent stem cell line from a patient that already contains all the genetic background of the disease,” says Gustavo Mostoslavsky, a stem cell researcher at the Boston University School of Medicine. Now that the generation of iPS cells is “routine,” he adds, scientists can use the method to generate in vitro disease models, from which they can learn about molecular causes, as well as potential preventions and treatments.

The strategy is proving particularly valuable for neurodegenerative diseases, in which it is not easy to safely and ethically extract affected cells of the brain. Instead, researchers can remove more accessible cells, such as those of the skin, regress them into a pluripotent state, and then re-differentiate them into neurons. Furthermore, iPS cells can be expanded in culture and/or frozen for years, providing an unlimited supply of cells from a single patient that can be used to create any cell types needed for the study of a particular disease, now or in the future.

Among the diseases that are being modeled with iPS cells are amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Parkinson's and Rett Syndrome.  I am particularly excited about the Rett Syndrome model because I spent years sequencing the MECP2 gene of little girls looking for the mutations that cause Rett Syndrome. 

And iPSC technology can be used to create models for many other diseases as well.  Dr. Yamanaka envisioned iPSC technology as an alternative to creating and destroying human embryos for research.  It is because he recognized the value of life in its earliest stages that induced pluripotent stem cells were born and now are revolutionizing the way we study human disease.

Induced pluripotent stem cells (iPS cells) are adult cells that have been reprogrammed back to an embryonic-like (pluripotent) state without creating or destroying embryos.  Prolifers have been pointing to iPS cells since they were created as an alternative to destroying embryos for embryonic stem cells.  Unlike embryonic stem cells that come from an embryo that is genetically different, iPS cells would be better for transplant because they would already be a genetic match to the patient. iPS cells are also an alternative to cloning embryos for stem cells.  The only reason to clone an embryo to harvest stem cells would be to get embryonic stem cells that are a genetic match to the patient.  iPS technology achieves the same result as cloning without any eggs and without cloning and destroying human embryos.

First the good news on iPS cells.  Researchers at Johns Hopkins have found that iPS derived liver cells behave just as well as liver cells derived from embryonic stem cells and other adult stem cells in a mouse model.  From Genetic Engineering and Biotechnology News:

Researchers have demonstrated that mature and immature liver cells generated from induced pluripotent stem cells (iPSCs) derived from multiple adult cell types are as effective as both embryonic stem cell (ESC)-derived hepatocytes and primary human hepatocytes at engrafting and functioning in the livers of experimental mice. The Johns Hopkins University School of Medicine team that carried out the studies say iPSC-derived cells were equivalent to the ESC-derived cells and primary hepatocytes in terms of their capacity to regenerate damaged livers and with respect to the levels of human-specific liver proteins they secreted into the animals’ bloodstreams.

But another study has some bad news.  IPS cells are created by reprogramming an adult cell back to an embryonic state.  Researchers at UC San Diego have found that the reprogramming of the cells caused rejection in the immune system of the mice they studied even though the iPS cells were genetically identical.  From the New York Times:

In an unexpected setback to efforts to harness a promising new type of stem cell to treat diseases, researchers reported on Friday that tissues made from those stem cells might be rejected by a patient’s immune system — even though the tissues would be derived from that very same patient.

The research involved so-called induced pluripotent stem cells, or iPS cells, which can be made from skin cells and which appear to have the characteristics of embryonic stem cells. That means they can theoretically be turned into nerve, heart, liver or other types of cells and transplanted to repair damaged organs.

The initial creation of human iPS cells in 2007 electrified scientists because the cells seemed to have two big advantages over embryonic stem cells. They were not controversial, because their creation did not entail the destruction of human embryos. And since the stem cells could be made from a particular patient’s skin cells, they could be used to make tissues that presumably would not be rejected by that patient’s immune system.

But that latter assumption was never really tested, until now. When Yang Xu, a biologist at the University of California, San Diego, and colleagues did so, they found that iPS cells made from mouse skin cells were nonetheless rejected by genetically identical mice.

Of course the BAD news about iPS cells made the New York Times and the GOOD news was left to the technical media outlet that has less readers.  That observation aside, this is not great news not because the iPS cells were rejected so much as it will be a rallying cry for those who want to continue destroying existing IVF embryos for stem cells and for those who want to clone and destroy new embryos.  They will argue that this rejection problem is a reason to push embryo destructive avenues again.

This is a ridiculous notion.  If genetically identical stem cells were rejected just because of some reprogramming, certainly embryonic stem cells from a totally different organism will also be rejected and even more so.  Robert Lanza, cloner extraordinaire, from Advanced Cell Technology is already saying that this opens the need for SCNT or cloning again.  This is also nonsense because SCNT does not really create genetically identical embryos.  Because SCNT uses eggs, there is DNA leftover from the woman who donated the eggs.  And if genetically identical iPS cells were rejected just because of some reprogramming, certainly cloned embryonic stem cells that have DNA leftover from the woman who supplied the egg will have a greater chance of being rejected as well.

Scientists have discovered that fat cells are easier to make into induced pluripotent stem cells (iPS cells) than skin cells.  IPS cells are adult cells that have been programmed to act like embryonic stem cells by inducing pluripotency, or the ability to become most or all of the 200 cell types in the body.  From NatureNews:

Fat cells and pigment-producing skin cells can be reprogrammed into stem cells much faster and more efficiently than the skin cells that are usually used — suggesting large bellies and little black moles could provide much-needed material for deriving patient-specific stem cells....

The Stanford researchers used liposuction to extract a couple litres of fat from the bellies of four overweight individuals aged 40 to 65. They then treated the tissue to remove all the gooey, globular fat, leaving behind a collection of fat tissue stem cells. Unlike standard techniques, which require about a month to culture skin biopsies to populations large enough for the reprogramming process, the fat tissue was ready to go after two days of pretreatment.

What's more, the cellular reprogramming took only two more weeks and was 20-times more efficient than when converting fibroblasts using the same technique. "We basically shave off six to eight weeks compared to what the other guys are doing with fibroblasts," says Wu, who is now working to find safer ways to reprogram fat without using viruses.

Please! Stanford researchers: Where can I sign up to donate!?  I've got 10 to 15 lbs of fat that can be put to much better use than making my bottom not fit into my favorite jeans. 

Now that I think of it, I've got a dozen or so moles that you can have too.  Call me!

Chinese researchers have announced that they have created induced pluripotent stem cells and have used them to produce living mice.  From USA Today:

The paper writes that two teams of Chinese researchers succeeded in "inducing cells from connective tissue in mice to revert back to their embryonic state and producing living mice from them."

I had to scratch my head at this because of the nature of iPS cells.  Induced pluripotent stem cells are cells that are reprogrammed to an embryonic state by introducing genes into the cell or by growing them in a certain medium.  These cells are, as the name suggests, pluripotent, which means that they can become all of the roughly 200 cell types in the body. 

So why did this announcement confuse me?  Because pluripotent cells are not whole organisms.  They lack the ability to become placenta tissue and therefore are not on their own a complete organism.  They are just cells.  Only a totipotent cell has the ability to become all of the cells in the body plus placenta.  A zygote, the product of conception, or the product of somatic cell nuclear transfer (better known as cloning) is totipotent.

The Church does not object to research on pluripotent cells because they are just cells not organisms, so to date the Church has not come out against iPS cells.  The Church DOES object to creating and destroying human organisms to obtain pluripotent stem cells for research.  Which is why the Church opposes embryonic stem cell research and cloning because they create and or destroy human organisms for research.

But if induced pluripotent stem cells can by themselves give rise to mice, then should the Church oppose iPS cells as well?  Does the act of inducing pluripotency give rise to a new organism?  It would seem on the surface that it does, but let us dig a little deeper.  From the LA Times:

The technique that the two teams of Chinese researchers used is called tetraploid complementation. When researchers first started studying iPS cells, they would assess their properties by injecting them into a blastocyst, a very early embryo. What they found in those studies was that the iPS cells and the host embryo's cells would contribute to the resulting animal, producing a chimera - a mosaic of genetically different cells.

More recently, researchers have fused the cells of the host blastocyst so that each cell contains double the number of chromosomes, making them tetraploid. When that is done, the host cells can form only the placental tissues; all the animal's tissues must come from the injected iPS cells.

What you need to take home in this scientific jargon is that the iPS cells alone did not give rise to the new mice.  They were fused with an existing blastocyst (a 5 to 7 day old embryo) that provided the ability to make a placenta.

Some have likened iPS cells to somatic cell nuclear transfer or cloning:

Dr. Robert Lanza, chief scientific officer at Advanced Cell Technology Inc. in Worcester, Mass., who was also not involved in the studies, cautioned that the results "revive many of the same ethical issues as reproductive cloning." Although generating fetuses with iPS techniques is technically different from cloning, the bottom line is the same -- the generation of an organism that is genetically identical to the source of the donor cells.

I think this is wrong.  Creating iPS cells is not the same thing as cloning.  As shown above, creating iPS cells alone does not create a new organism.  The iPS cells were fused with an altered embryo to give rise to the mice in the study.  Somatic cell nuclear transfer or cloning, on the other hand, does create a whole organism that is capable of growing into a fetus, infant, etc., on its own.  (This has been shown in all of the various species that have been cloned using somatic cell nuclear transfer.)  There is a scientific, and more importantly, MORAL difference that cannot be lost in this story.

In light of this further knowledge on the way in which these mice were generated, I believe we as Catholics can still support induced pluripotent stem cell research as an alternative to cloning and destroying embryos to obtain pluripotent stem cells.

iPSCs are a great discovery.  One that pro-lifers everywhere have hailed as the reason that we no longer need to destroy embryos for research.  While I am all for practical arguments against embryo-destructive research, I know it is a mistake to rely solely on practical arguments in opposing research on human embryos.  First and foremost we must oppose embryo-destructive research because it is WRONG.  We are setting a dangerous precedent by allowing science to perform research on our fellow humans, no matter how young they are, and no matter how well-intentioned the goal.

I have said that we abandon the embryo at our own peril.  Which means if we allow the embryo, a member of the human species, to be gutted for harvestable biological material, then all of a sudden other members of our species begin to look like that as well.  The "they are going to die anyway" argument is particularly insidious because it sounds so reasonable.  But the slippery slope is treacherous.  Death row inmates are going to die anyway, why not put their organs to good use like the Chinese?  What about those in a persistent vegetative state?  Why not use the organs from aborted fetuses?  They are going to die anyway right?  That is the suggestion of a stem cell scientist in Britain.

Do I think it is any coincidence that while we are cannibalizing the youngest of our species for parts, some lawmakers are suggesting commuting sentences for prisoners who consent to be live organ donors?  Or that the AMA wants to look at paying people for their organs?  Or that it is being proposed that your organ donor sticker on your driver's license supersede any other advanced medical directive or instructions you may have in place?

And finally I get to the point of this post.  I knew that while iPSCs hold great promise, and may be a suitable alternative to destroying embryos to get pluripotent stem cells, they would never be an exact substitute for embryonic stem cells.  From Science Daily:

UCLA researchers have found that embryonic stem cells and skin cells reprogrammed into embryonic-like cells have inherent molecular differences, demonstrating for the first time that the two cell types are clearly distinguishable from one another.

The data from the study suggest that embryonic stem cells and the reprogrammed cells, known as induced pluripotent stem (iPS) cells, have overlapping but still distinct gene expression signatures. The differing signatures were evident regardless of where the cell lines were generated, the methods by which they were derived or the species from which they were isolated, said Bill Lowry, a researcher with the Broad Stem Cell Research Center and a study author.

“We need to keep in mind that iPS cells are not perfectly similar to embryonic stem cells,” said Lowry, an assistant professor of molecular, cell and developmental biology. “We’re not sure what this means with regard to the biology of pluripotent stem cells. At this point our analyses comprise just an observation. It could be biologically irrelevant, or it could be manifested as an advantage or a disadvantage.”

So iPSCs are not exactly like embryonic stem cells.  That is probably in their favor for clinical applications.  But this means that we cannot use the argument that now that we have iPSCs that embryonic stem cell research is no longer necessary.  They make a suitable alternative but will not be an exact substitute.  Another reason that we must be vocal that the reason to stop destroying human embryos for research is first and foremost because it is morally wrong.

A new technique of making artificial stem cells has been made safer, according to a scientific team from the Scripps Research Institute and other academic centers.

The cells, called Induced Pluripotent Stem cells, are made from fully differentiated adult cells, regressed back into an embryonic like state....

The Scripps-led team found a way of producing these act-alike cells in a way that makes them more suitable for human therapy....

...previous methods of making these act-alike embryonic stem cells have used dangerous methods of genetic modification, giving the cells a propensity to turn cancerous....

The new research describes a way of chemically modifying the cells to make them regress without genetic modification.

In previous experiments, genes were inserted into the cells that made transformational proteins, causing them to regress to an embryoniclike state.

In the new study, the researchers bathed the cells in these proteins to cause the regression.

Now I want to point out some very important lines in this story:

1.  These act-alike embryonic stem cells, discovered a few years ago, don't carry the ethical difficulties of real embryonic stem cells, taken from days-old embryos.

2.  These cells are very common and can be removed without harm to the donor, providing a nearly limitless supply.

3.  The cells may also act as disease models to test drugs for effectiveness and for toxicity.

4.  Tests of these cells found them to act just like real embryonic stem cells, including their ability to turn into different cell types, such as beating heart cells, muscle cells, neurons and pancreatic cells.

No ethical issues...limitless supply...can be used in disease models...and they act like real ESCs!  Tell me again why we are still throwing millions of tax-payer dollars at stem cell lines created by ripping open our fellow human organisms?

As of now, there are two ways that scientist are looking to achieve this.  Therapeutic cloning is the first.  Therapeutic cloning would create a cloned embryo that would be a "genetic match" to the patient and then that cloned embryo would be destroyed for the embryonic stem cells inside.   Unfortunately, this approach has all kinds of problems.  First and foremost, it would create and destroy human life which is never justified even if the outcome is a proposed good.  Secondly, this approach would require a multitude of human eggs which would put young women at risk of exploitation.  Egg donation is an involved process that in some cases can cause infertility and, in rare cases, death.  Thirdly, the cloned embryo would not truly be a genetic match to the patient because there would be DNA leftover from the woman who donated the egg.  Finally, this approach opens the door to reproductive cloning, or cloning to produce children, which nearly everyone finds repugnant.

Induced pluripotent stem cells (iPS cells) are considered the alternative to cloning for embryonic-like stem cells. In this approach, scientist take a cell from the patient and "reprogram" it back to an embryonic-like state.  These cells would be a genetic match to the patient and they appear to behave just like their embryonic brothers.  No eggs, no embryos, no cloning, no creation or destruction of human life.  Genetically matched pluripotent stem cells without all of the ethical issues.

In the past, this approach had one real problem.  To "reprogram" the cell, researchers had to insert four genes into the DNA of the cell with viruses.  Some of these viruses have been known to cause cancer and inserting and leaving genes in the genetic material of a cell that would be used for therapeutic reasons is never a good idea. 

This week researchers have announced that they have overcome this problem.  They used a system that inserts the four genes needed to reprogram the cell and then removes them.  From the Washington Post:

In the new work, Nagy and his colleagues in Toronto and at the University of Edinburgh in Scotland instead used a sequence of DNA known as a transposon, which can insert itself into the genetic machinery of a cell. In this case, the researchers used a transposon called "piggyBac" to carry four genes that can transform mouse and human embryonic skin cells into iPS cells. After the conversion took place, the researchers removed the added DNA from the transformed cells using a specific enzyme.

"PiggyBac carries the four genes into the cells and reprograms the cells into stem cells. After they have reprogrammed the cells, they are no longer required, and in fact they are dangerous," Nagy said. "After they do their job they can be removed seamlessly, with no trace left behind. The ability for seamless removal opens up a huge possibility."

This breakthrough naturally begs the question: Can we stop destroying human embryos for their biological material now?  Some scientists say that research into both iPS and embryonic stem cells is needed to see which will be better for treatment.  But I say, why create and/or destroy human life when there are promising alternatives that do not?  Why take more of the limited taxpayer dollars and divert them from iPS research to research on embryos, cloned or otherwise, when the ethics is such a huge issue?:

"Stem cell research that requires destroying embryos is going the way of the Model T," Richard M. Doerflinger of the U.S. Conference of Catholic Bishops said. "No administration that values science and medical progress over politics will want to divert funds now toward that increasingly obsolete and needlessly divisive approach."

I truly believe that the research into iPS cells would not be advancing at such an accelerated rate if there was not such a huge outcry all over the world against using human embryos for research.  This moral outrage was called all kinds of ugly names.  Those of us who expressed it were labeled religious fanatics with no compassion for the sick.   I believe, in the end, it will be this unpopular moral argument against using human embryos for research that will be tipping point toward a better and more ethically sound treatment.

The problem with iPS cells was that to induce pluripotency (the flexibility to become many different types of cells) researchers had to use retroviruses that would insert transforming genes into genetic material of the cell. These retroviruses have been known to cause cancer.

Last week scientists announced that they induced pluripotency with adenoviruses, which are considered to be harmless because they do not insert the transforming genes into the DNA of the adult cell. From the Washinton Post:

Scientists last year shook up the scientific and political landscape by discovering how to manipulate the genes of adult cells to convert them into the equivalent of embryonic cells -- entities dubbed "induced pluripotent stem cells," or iPS cells -- which could then be transformed into any type of cell in the body. Subsequent work has found that the cells can alleviate symptoms of Parkinson's disease and sickle cell anemia in mice.

But the first iPS cells were created by ferrying four genes into the DNA of adult cells using retroviruses, which can cause cancer in animals. There was also concern because the viruses integrated their genes into the cells' DNA. In the new work, Hochedlinger and his colleagues used a different type of virus, known as an adenovirus, to carry the same four transformative genes into the DNA of mouse skin and liver cells. The adenovirus does not integrate its genes into a cell's DNA and therefore is believed to be harmless.

"The adenovirus will infect the cells but then will clear themselves from the cells. After a few cell divisions there are no traces of the virus in the cell," Hochedlinger said. "You can't tell the virus was ever there."

As with iPS cells produced using retroviruses, tests showed that the new cells were indistinguishable from embryonic stem cells and could be transformed into any type of tissue, including lung, brain, heart and muscle; unlike the retrovirus-engineered cells, they do not produce cancerous tumors.

"What our experiment shows is you can do this without an integrating virus. You do not need integration of the DNA into the genome to produce iPS cells," Hochedlinger said.

Embryonic stem cells are not even close to adult stem cells in trials and treatment for disease. But anytime that fact is brought into the open, ESC supporters say that ESC research is vital to understanding how a disease progresses and for use in drug discovery. The idea is to make or take embryos with certain diseases then rip them open, harvest the pluripotent stem cells inside and then use those stem cells for research into disease progression and new pharmacological treatments.

I have read repeatedly that using human embryos in this way is not only important but necessary. Not so much. Researchers have created 10 pluripotent stem cell lines with diseases ranging from Parkinsons to diabetes. These lines did not come from embryos, but from patient cells that have been reprogramed or "induced" back to pluripotency. They call these iPS cell lines. From Cell:

Tissue culture of immortal cell strains from diseased patients is an invaluable resource for medical research but is largely limited to tumor cell lines or transformed derivatives of native tissues. Here we describe the generation of induced pluripotent stem (iPS) cells from patients with a variety of genetic diseases with either Mendelian or complex inheritance; these diseases include adenosine deaminase deficiency-related severe combined immunodeficiency (ADA-SCID), Shwachman-Bodian-Diamond syndrome (SBDS), Gaucher disease (GD) type III, Duchenne (DMD) and Becker muscular dystrophy (BMD), Parkinson disease (PD), Huntington disease (HD), juvenile-onset, type 1 diabetes mellitus (JDM), Down syndrome (DS)/trisomy 21, and the carrier state of Lesch-Nyhan syndrome. Such disease-specific stem cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation in vitro, thereby enabling disease investigation and drug development.

These iPS lines are now going to be used for research into these diseases. The ethical alternatives keep on coming.

Stem cells are supposed to cure everything, if you buy into the media frenzy. First we were told that embryonic stem cells were the best. But because of Bush's very right but very unpopular stance on funding ESC and cloning research, scientists have been looking for alternatives. Induced pluripotent stem cells, or iPS, came from looking at alternatives to riping open existing embryos or cloning new ones to obtain pluripotent stem cells. iPS cells are adult stem cells that have been "reprogrammed" back to a pluripotent or "embryonic" state.

Scientists at Harvard have used nuclear reprogramming technology to take normal pancreatic cells, not stem cells, and program them to produce insulin. From the LA Times:

Harvard study may ultimately shift treatment options away from stem cells for a variety of diseases.

Injecting a cocktail of proteins directly into the bodies of diabetic mice, researchers have converted normal pancreas cells into insulin-producing cells -- a genetic transformation that could pave the way for treating intractable diseases and injuries using a patient's own supply of healthy tissue.

The Harvard University scientists activated a trio of dormant genes that commanded the cells to transform themselves, much as a person might upload a new operating system onto a computer to change a PC into a Mac.

Within 10 days, the pancreas cells ceased their normal function -- making gut enzymes to digest food -- and instead produced insulin to regulate blood sugar, according to a study published online Wednesday in the journal Nature.

Doug Melton, co-director of the Harvard Stem Cell Institute and the study's senior author, said the same approach could be used to generate motor neurons for patients with amyotrophic lateral sclerosis, to make cardiac muscle cells for heart attack victims or to create other crucial cells that can repair damage wrought by a range of illnesses.

"We were able to flip the cell from one state into another," Melton said, adding that the approach should be useful in treating disorders in "any case where there's a cell type missing and there are neighboring cells that are still healthy."

This is really great news for diabetics. And as the headline suggests, this announcement may shift the focus away from embryonic stem cell research and even stem cell research altogether.

This made me wonder how the pro-cloning-embro-destructive research crowd are reacting to this development. I needed to look no farther than a press release from the California Institute of Regenerative Medicine or CIRM. In case some of you are not familiar with CIRM, it is the regulatory body that oversees the $3 billion dollars of California taxpayer money that is earmarked for cloning and embryonic stem cell research. Californians were told that if they funded cloning and embryonic stem cell research, cures would come. And even during a state budget crisis, Californians bought it.

This press release is more about how CIRM is still relevant, than it is about the amazing work of these Harvard scientists:

CIRM applauds the creativity and value in the research reported and shares the excitement in the promise it might hold. However, it emphatically refutes assertions by opponents of embryonic stem cell research that this new study proves embryonic stem cell research is not necessary. In fact, the Harvard study poignantly points out the value of embryonic stem cell research.

This maybe true, but this seems like a super desperate attempt to make sure everyone still believes that embryonic stem cell research is still king. Case in point, this section describing the limitations of nuclear reprogramming:

The research reported in Nature is a major advance but it has significant limitations. It can be considered a type of gene therapy and has many of the same limitations and concerns that have been identified in the field of gene therapy. The genes that reprogrammed the cells were carried into the cells by adenoviruses, which have caused severe immune reactions and triggered cancers in gene therapy. The mice in this study were immune compromised mice, so that complication was not seen in this model, but to-date has proven difficult to overcome in humans.

Huh, last I checked, immune response and tumor formation were "significant limitations" to embryonic stem cell research as well. Funny how that is not mentioned. I love the last paragraph which basically screams "we are still important and by-gum people still love us":

CIRM was established in early 2005 with the passage of Proposition 71, the California Stem Cell Research and Cures Act. The statewide ballot measure, which provided $3 billion in funding for stem cell research at California universities and research institutions, was overwhelmingly approved by voters, and called for the establishment of an entity to make grants and provide loans for stem cell research, research facilities, and other vital research opportunities. To date, the CIRM governing board has approved 229 research and facility grants totaling more than $614 million, making CIRM the largest source of funding for human embryonic stem cell research in the world.

I think I am finally rested enough from working and trying to raise a family that I can approach my computer to blog. (I just had to clean the house top to bottom first!)

A lot of people have been asking me about the ethics of induced pluripotent stem cells or iPSCs. These are cells that have been taken from an adult and reprogrammed into becoming more like an embryonic stem cell which are considered pluripotent. In case you forgot what pluripotent means, a pluripotent stem cell can become all of the tissue types in the body, EXCEPT placenta. (This is important as you will see later.)

Do No Harm has a great Fact Sheet on iPSCs and how they compare to their more hyped embryonic brothers. It is a good read to keep you up to date.

I think an important addition is the claim that inducing an adult cell to become pluripotent may create an embryo and therefore defeats the purpose of the procedure. THis is not the case. A zygote, (a single celled embryo) is totipotent which means it can become all of the tissue types of the body AND also placenta. It is a complete organism. Which means that if impanted in a uterus, it has the chance to grow into an infant. Therapeutic cloning by SCNT creates a totipotent cell, or a zygote which is allowed to grow to the 200 cell stage where pluripotent stem cells are available. This organism would then destroyed for its inner stem cell mass.

Any induced pluripotent cell is NOT totipotent. It is not a complete organism. It is just a cell. This is an important distinction to make and keep clear.