Stem cell therapy is probably one of the most promising medical advancements this century. Yet, the politically charged embryonic stem cell issue has stymied research. But there is good news for your future!

Every day you hear or see something about a new stem cell therapy for this or that. However, because of the controversy concerning the source of stem cells for use in research or treatment one must usually leave the country in order to participate in this potentially life changing treatment.  And a host of stem cell therapy clinics all over the world are ready to accommodate you, even Kiev.^1,2

The good news is advancements in the use of adult stem cells, also known as somatic cells has changed the playing field. Unfortunately once one starts reading about stem cells, we’ll refer to them as SCs from now, one can easily go into information overload with the different terms like totipotent, unipotent, induced stem cells and so on. So, before you run off to Romania or whatever, here's what's going on in this emerging but highly controversial field.^3,4

But first some basic biology.

Humans have 46 chromosomes. Creationists believe that it all happened at the same time, more or less whereas at some point, most evolutionists theorize, and it's just a theory, that some sort of "fusion event" happened to some unsuspecting 48 chromosome chimpanzee ancestor and the first hominid, human-like mammal began its history on earth.  That was allegedly 3 million years ago and we still have, for the most part, the same genes. And just look where it's gone from there. It's amazing that we can now trace any person's 46 chromosome ancestry back to Africa with a little saliva and $290. 

This is a photograph of what could have been any person's first Stem Cell.  A human egg cell just fertilized by a sperm.

Remember each sperm and each egg has 23 chromosomes each, giving us our customary 46 chromosomes total. This just-made SC is also referred to as a Zygote.  A zygote doesn't last long. 

Once the first cell division happens the zygote is officially an embryo. This zygote like all other SCs, has one, the ability to replicate unchanged, and two, the ability or potency, when signalled, to differentiate into more specialized cells. Both cells of this earliest two-celled embryo are identical twins and identical to the original zygote.^5,6

This is a photograph of what could have been any person's first Stem Cell.  A human egg cell just fertilized by a sperm.

All of the cells so far, the zygote and the embryos are known not only as SCs but totipotent SCs.  So they can propagate unchanged and when signaled properly they can differentiate into virtually any cell type.  They can also, most importantly, differentiate into the cells needed to nurture the pregnancy—the placenta and related structures, if signaled to do so.

Cell division continues and the last totipotent SCs are seen when the state of development known as the morula is reached.  The inside of the morula has about 16 SCs.  These are still totipotent, if taken and transplanted to a receptive uterus, an entire human organism can be made. These are the last naturally occurring totipotent SCs.  Every person never has more than about 16 totipotent SCs. 

This is a morula, the embryo with about 32 cells total.  About 5 days after conception.  To clone, you have to have totipotent DNA.  Or else the placenta, cord, etc. won't form to nurture the pregnancy.

From here these totipotent SCs will differentiate into what are known as pluripotent SCs.  The pluripotent SCs can still propagate themselves unchanged, or given the proper signals they can differentiate into any body cell type except those of the placenta and related structures. 

There are three paths these early pluripotent cells can take and they correspond to what biologists have classified as the three layers of the embryo.  The ectoderm, which will form the skin and the elements of the nervous system, the mesoderm, which forms blood, bone and some urogenital structures, and endoderm, forming the intestinal tract and lungs, among other things. Pluripotent cells can transform into any body cell type and in doing so an entire adult human organism can be formed.

Once the pluripotent cells start to differentiate, they give rise to the next step down the cascade of SC types, the multipotent ones.  They populate little niches of potency where they are also known as precursor cells.  An example would be the blood precursor cell which can give rise to different blood cell types, or a neural precursor cell which can give rise to neurons or the structures that keep neurons insulated or situated properly. 

Finally, at the end of SC differentiation are the unipotent cells, such as the liver precursor cells. The liver SCs are an example of how versatile the SCs are. The liver precursors can regenerate an entire organ from as little as 25% of the original organ. This is how one liver donor can benefit multiple recipients.

Besides the potencies of SCs; totipotency, pluripotency, multipotency, and unipotency, other classifications use different characteristics. There are embryonic SCs which include the totipotent ones that can create an entire organism and there are somatic SCs, the ones that populate the organism once it is formed. The somatic SCs repair and replace damaged cells of the body, like bone, heart muscle, nerve cells, intestinal lining. With the ability to replace and repair, the potential for treatment options was obvious.

That's the story of naturally occurring original SCs that have kept the human organism reproducing since that first precursor hominid got its first complement of 46 chromosomes. 

Now, a brief timeline history of Stem Cell science

The Russian histologist Alexander Maksimov, is generally given credit for discovering, around the turn of the 19th century, a particular bone marrow cell that seemed to reproduce itself time and time again, without differentiating.  He decided to call it a SC.  The idea of giving marrow by mouth for people with bone marrow disease soon followed and of course failed miserably.  Actually, giving marrow broth for broken bones is a centuries old "cure" used by indigenous people in various locations.

The first recognized use of SCs was in 1956 to a leukemia patient who went into complete remission. It was performed by Dr. E. Donnall Thomas, one of the first marrow transplant specialists. Thirty-five years later he won the Nobel Prize in Medicine.

Dr. E. Donnall Thomas, Nobel Laureate, age 90.

In the late 50's there was a disastrous nuclear accident at one of France's nuclear plants and in desperation, physicians transfused marrow from healthy donors with limited success.  Shortly after, Jean Dausset identified antigens that determined a particular individual's ability to reject foreign tissues. He called them Human Leukocyte Antigens, or HLAs.  The term is still used in transplant medicine today.  Until he perfected his system, the only marrow transplants were between identical twins.  These were the first successful SC transplants and used unrefined marrow.   By 1973 the first marrow transplant  was done between two unrelated individuals using the HLA system.  It was successful, well, after 7 attempts. 

In the 60's and 70's neuron SCs and more types of marrow SCs were discovered as well as hematopoietic SCs in umbilical cord blood.  In 1968 a successful marrow transplant treated a severe immune disorder known as Severe Combined Immune Deficiency. In 1981 totipotent embryonic SCs were isolated from blastospheres, the 32 cell embryos and in 1997 leukemia is shown to originate from a hematopoietic SC, the first proof of the long suspected theory that leukemia was basically a genetic defect. 1998 was the year that SCs were finally cultured successfully by James Thompson at the University of Wisconsin.

The pace picks up from here.  In 2001 the first embryonic SCs were cloned and propagated. After George Bush banned funding for other than existing SC lines, the discovery is made that SCs can be made by reprogramming somatic cells, like skin or blood. 

These engineered cells were called Induced Pluripotent SCs or iPSCs. One of their first uses was a government funded clinical trial for treatment of Multiple Myeloma, bone marrow tumors.  It was largely successful. Practical applications were put to the test when among other experiments, rats with transected spinal cords regenerated the nerves after injection of neuron SCs. The 'French Medicine Baby', noted above, is nonetheless part of, for better or worse, the result of an increasing understanding of SC biology.

The Politics

The reliance on embryo harvesting has been minimized by the development of induction techniques for somatic cells. However, despite all the advances, SC research continues to be politically sensitive and explosive. The controversial use of in vitro fertilization and harvesting "acceptable" eggs for implant is an emotional issue for those who believe life begins as soon as the egg is fertilized, or sooner.⁷

And it isn't regulated in many countries. In fact, in the U.S. there is no federal law regarding the legality of embryo harvesting but currently 13 states ban cloning. However, there is federal law regarding the funding of stem cell research. In 1973 the U.S. Congress voted to put a moratorium on funding for embryo research.  In 1988 a National Institute of Health advisory panel  voted overwhelmingly to lift the ban and Congress acted on the recommendation. But President George Bush vetoed the bill.

George H. W. Bush

President Clinton lifted the ban but changed his mind in a year after he noted quite a vocal response from, among others, pro-life political groups.  He later allowed research on cells harvested from spontaneously aborted fetuses in 2000. 

George W. Bush, out of moral concern, allowed research only on the 26 existing cell lines.  Later it was learned that 16 of them were obtained unethically without proper documentation or consent. 

President Obama lifted the ban in March 2009. Shortly therafter a federal court instituted an injunction, but as of May 2011 federal funding is back on the table.

Here's just a small sampling of what's happening with SC research and therapeutics.

One of the big breakthroughs in SC research was the development of SC induction where induced pluripotent SCs, the iPSCs, could be made by sending certain signals inside the cell to turn on certain genes. As a result, the dependence on the politically sensitive embryonic sources was obviated. This was a major hurdle which took ten years of research.

Either by transcriptors, the signalers, or by inserting genes, the potential for treating so many of our illnesses is myriad. Cancer, birth defects, heart disease, all the degenerative neuron illnesses like ALS and MS. We can dare to imagine cell based cures. The specific factors or transcriptors have even been identified and have names like Nanog and Oct4.

Totipotent cells, for instance, can be directed through the various stages of differentiation to actually make functional heart or brain cells. Or the multipotent cells of the nervous system can be signaled to produce the insulation for the spinal cord cells that allow for transmission of electrical signals from the brain. Before this era of therapeutic biology began, it was believed that neuron cells could not regenerate. The big, unsuspected discovery was that somatic adult neuron SCs are hard to find, but harvestable, and reprogrammable.

The technique of transdifferentiation is used when, for instance, a multipotent hematopoietic SC is de-differentiated into one of the pluripotent SCs, then re-differentiated into, say, a neural multipotent SC. One tissue cell type, say an unipotent bone marrow stromal cell that makes the fibers that hold the other cells in place, may be reprogrammed or restarted as a SC that produces white cells. Of interest even viruses themselves carry signals into the cell and induce it to de-differentiate or transcriptors, the messengers, signal the cell from the outside.

Akin to the term de-differentiation is that of undifferentiated known to cancer doctors as the hallmark of the disease they treat. Cancer has always been known to be the result of loss of regulation of cell growth and division. And actual cancer SCs have been isolated and cultured. Now it's hoped that cancer treatment could consist of signaling the cancer cells to actually turn off. However, there seems to be resistance in some cases and recurrences indicating that there are alternate or redundant pathways for making cancer cells.

But the hunt for the magic bullets against cancer continues with this new cell based technology. Isn't an advance in our ages-long battle with cancer overdue? One use of SCs is to coax embryonic SCs into behaving like vaccines and inducing immune responses with specific antigens against cancer cells. There are several promising studies in this area. Actually, there are over a thousand cancer trials going on world-wide, SCs are involved in quite a few, but that's a topic for another article.

Use of a patient's own SCs avoids virtually all of the rejection issues of standard transplants. It's all in the signals. The donor shortage that has plagued transplant medicine for years could be eased, if not eliminated, by the use of replacement cells for heart disease, Alzheimer's disease, burns, and end stage lung disease. The most commonly transplanted organ is the kidney. Instead of a major operation it's foreseeable that replacement of the specialized filtering cells could be injected and instructed to repair. Cell based therapy would take the "repair cells" to the organ so they could replace or repair.

It's hard to keep up with everything. Specialized cell replacement, for heart muscle tissue, or pancreas glucose regulating cells are currently in animal testing phase. Heart patches have been made that seem to replace damaged heart tissue, make it beat in concert with the rest of the heart, and even grow new blood vessels. Specialized cell cloning and implantation is being tested for lung transplant patients, including those with cystic fibrosis. 

Other SCs seem to replace the retinal cells lost in Macular Degeneration, retinitis pigmentosa or congenital blindness. SCs are being tested for their ability to repair neurons damaged by multiple sclerosis or Parkinsonism. SCs teased into being multipotent neural SCs are replacing and repairing neurons damaged by stroke. And in one of the most exciting applications, a few patients paralyzed by trauma are receiving specially grown neural cells that will reinstitute the nerve cells of the spine so they can feel their arms and legs and walk again. The animal trials have had spectacular results.  

A bump in the road

Recently described and obviously important is the fact a virus that can signal de-differentiation can also cause cancers of its own.  They represent an area of concern to cellular researchers and the problem is under active investigation.Specifically,  a type of tumor known as a teratoma probably comes from some sort of primordial pluripotent cell formed by a de-differentiation of somatic cells.  These tumors have tissues from all three layers of the primitive embryo.  Surgeons have been taking these unusual tumors out for years and finding teeth, hair, and other strange things.  Now we know probably know the origin of these tumors.

What about Stem Cell Banks?

Do it!  If reading this article does nothing else it should convince you to "bank" your child's embryonic SCs.  Not necessarily the totipotent ones, which is probably not possible now.  But certainly any of the pluripotent SCs, especially those from umbilical cord blood.  Although the ability to induce cells to various types and levels of potency is growing rapidly, there's probably never going to be a better source of undifferentiated tissue than a person's own undifferentiated SCs. It costs about $2000 to startup, and $125 a year to keep them in the freezer bank.

Also available soon, is the use of the 3rd molar pulp tissue as a source of pluripotent cells, if samples are taken before the "wisdom teeth" erupt through the gum.  Though the patient might not be very willing, the potential benefits are myriad.

And what about the offshore clinics?

There are now about 300 of them popping up around the world.  Their growth has been explosive according to investigators.  I culled the list for a representative few and I was unable to get any of them to divulge to me any basis in science for their treatments, other than their loose theory  that SCs work because they're SCs.  And they wouldn't give me any credentialing information about their doctors that made any sense.^8,9

The development of signalers and transcriptors is not addressed by these clinics and we know for a fact that simply isolating various types of SCs and injecting them into the body just does not work over the long term. The unsuspecting patient can pay up to $20,000 per cancer treatment, for instance, and it's sad to see more families made destitute by cancer and the other chronic debilitating illnesses.

Ethical, science based, practical applications, for the most part, are limited to clinical trials. As of this publication date, there are only a few Food and Drug Administration approved SC treatments. And currently all for blood disorders like leukemia and thallassemia. But there's undoubtedly more on the way. Sometimes the best and safest, though not foolproof, shortcut is to get involved in an existing clinical trial.¹⁰

And let's not forget SC Ethics

We have reached our next milestone in the development of knowledge and technology and ability to change, manipulate, and use the biology of the cell:  The actual engineering of our life's stuff, DNA.  From that first cell's ability to divide and replicate in some corner of our world's oceans many years ago, to the first 46 chromosomed homonids, to today where we are developing the technology to repair, replace, and even reproduce organs.

There was so much going on in the world at the time it went unnoticed by many, but there was a news story in late January 2011 about the exciting, yet controversial "French Medicine Baby" whose embryo was engineered to specifically have certain genes so its stem cells and DNA could be used to treat two of its older siblings after its own birth. Both older siblings had a hereditary condition known as Thallasemia. The 'French Medicine Baby' story will hopefully end happily.  Its SCs will be used for treatment of its Thallessemia afflicted siblings.¹¹

But what about the other embryos?  The ones that carried the undesirable gene?  What are the ethics for that? Clearly we need more direction from somewhere regarding issues like embryo creation and destruction and use of harvested embryos for therapeutic cloning.

Actually, the French weren't the first to use embryo therapy! The first generally recognized use was in Minnesota in 2002 for a six-year-old girl with a condition known as Falconi's anemia. Falconi's anemia is a disastrous, often fatal, recessively inherited disease where the patient's marrow cells do not repair themselves.  There seems to be no precursor or repair cells in these patients. People, usually children, die slowly over a few years from complications of anemia, leukemia, and bone tumors.¹²

Embryologists fertilized several of the patient's mother's eggs, tested them all for the anemia gene, kept the unaffected ones, should have been about a fourth of them all, and implanted one.  After the birth of the normal infant, at age one month, its hematopoietic stem cells were transplanted to the marrow of the Falconi affected patient who showed reversal of her illness in a few weeks and remains in remission, now after three years, without further treatment. Of interest, the authors of the study acknowledge their own personal issues with the ethics of Therapy Embryos. 

The Latest Politics

In France, as well as the United States there is no federal law governing the creation or destruction of embryos.  However, quite a few states ban it, and federal budgets yearly prohibit funding of research that involves creation or destruction of embryos.  But there are also no federal laws applicable to private concerns and there is no ban for the federal funding  of 'adult stem cell' research.

President Obama in early 2009 reversed the Bush policy on stem cell research by lifting the ban on federal  funding for embryonic stem cell research.  However, a  U.S. District Court judge in August of 2010 after hearing testimony from 'adult SC' researchers who argued that lifting the ban would limit funds for adult SC research and an adoption group who argued that there would be less embryos and therefore less adoptions, issued an injunction against the use of federal funds. This was eventually overturned and progress on SC research continues.

The Bottom Line

Policy on such a vital area for human progress against our diseases, with their suffering, should not be determined by which judge political and religious groups seek out and choose.  We, as a society, need to make decisions with the advice of knowledgeable experts in the field of law, medicine, religion, and ethics.

And, we all need to study more and develop a knowledgeable, informed position for the issues that we face in this fascinating, promising era of Cell-based therapies.  But, above all, we need to accept the fact that a new age in medicine has arrived and we need to embrace and support it while at the same time developing our own responsible, well-informed, position on the ethics and morals involved with it.

Well, that may be more than you wanted to know about SCs.  Hopefully now you'll understand the news coming out of this field and be able to make intelligent decisions about the therapies that are coming or are already here.  By the way, the first cloned animal was not Dolly the sheep, but actually a tadpole in 1952. It didn't get a lot of press at the time.

Published May 2, 2011, updated July 3, 2012

 References

1. Hill E, When will stem cell therapy be a reality?  BBC News, April 1, 2009
2. A Closer Look at Stem Cell Treatment? The International Society for Stem Cell Research
3. Adult Stem Cell Research Foundation
4. Cell Therapy Foundation
5. Human Development, HHMI, YouTube.com, April 17, 2007
6. Embryo, Wikipedia
7. Krausen K, Religion on Politics on Science, Science Watch, Skeptical Inquirer, March/April 2011
8. Stem Cell Fraud, a 60 Minutes Investigation, CBS News, January 8, 2012
9. Open Letter to Address Stem Cell Treatment Proliferation, International Cellular Medicine Society, April 10, 2010
10. Clinical Trials Stem Cells, National Institutes of Health, ClinicalTrails.gov
11. Mariotti A, France's first 'saviour sibling' stirs ethical debate about biotechnology, France 24, International News, 9/02/2011 
12. Raya A, Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells, Nature 460, 53-59 2 July 2009

Senior Correspondent Jones practiced emergency medicine in Southern California for 30 years and now writes for HealthWorldNet.com. He has also published several scientific papers as well as his novel A Murder in West Covina, Chronicle of the Finch-Tregoff case.