Saturday, March 7, 2009

A Bright New Day for Stem Cell Research – Undoing Bad Policy

The “Breaking News” alert came to my phone last night: on Monday, President Obama is planning to sign an executive order reversing the restrictions on embryonic stem cell research put in place by President Bush in 2001. This comes as a surprise to no one, as Obama made it clear that he was opposed to these restrictions throughout the 2008 presidential campaign.

The occasion of this reversal of federal policy seems to be a good time to talk a bit about stem cells. The President’s decision is sure to provoke intense debate, and this debate can only be healthy if it is based on fact, not emotion.

Let’s start with the basics. What is a stem cell?

Photo Credit

As I discussed in a prior post, a stem cell is a primitive cell that is capable of generating more “daughter” cells with more specific function as well as making more copies of themselves. Every organ and tissue in your body contains stem cells. As the most mature cells die, they are replaced by cells derived from these “organ stem cells,” which also continuously replenish themselves. Stem cells such as these are often referred to as “adult stem cells” because they are found in adult humans. There are also “umbilical cord stem cells” which are found in the blood in the umbilical cords of newborn babies and many oncologists believe that there are “cancer stem cells” that drive the growth and spread (“metastasis”) of tumors.

Photo Credit

The controversial cells are called “embryonic stem cells” because they are derived not from adults but from human embryos. In the process of obtaining embryonic stem cells, the embryo is destroyed.

Photo Credit

Why all the excitement about stem cells? Because stem cells are so primitive, and their job in the body is to produce cells with a more specific function, it is believed that stem cells can be coaxed into producing virtually any other tissue type. This means that the therapeutic implications of stem cell biology are limitless.

Doctors could grow new organs to replace defective ones, and if they used the patient’s own stem cells, there would be no need to take medicines to prevent rejection. Diabetics could get a new pancreas that works instead of injecting themselves with insulin. Patients with spinal cord injuries could walk again.

So why the controversy?

Arguments about the ethics of stem cell research arise from questions about the source of the stem cells. Although “adult” stem cells can be obtained from an adult person, who can give informed consent for the procedure and who will (most likely) not be harmed by the procedure, embryonic stem cells require the destruction of an embryo. Those who believe an embryo is a human life entitled to the same protections as a child or adult argue that this amounts to murder and believe that it is unethical to murder an embryo to help treat disease in an adult.

Opponents of embryonic stem cell research believe that adult stem cells provide appropriate material for study and should be the sole focus of stem cell research.

Do they have a valid point? Maybe, but maybe not. So-called “adult stem cells” are not as primitive as embryonic stem cells. They already have some characteristics of the organ from which they are derived (liver, kidney, bone marrow…). So to make them turn into a different tissue is more complicated and more difficult. These “adult stem cells” have to first lose the characteristics of the tissue they came from and then gain the characteristics of the tissue they are being turned into. So far, doctors have been unable to accomplish this task on a large scale. Embryonic stem cells, because they are the most primitive stem cells available, should be easier to turn into the tissue of choice.

Since 2001, federally funded scientists have been forbidden to work with embryonic stem cells that were not already in existence. This has significantly limited progress in developing stem cell-based therapies. Despite this, the ban has not been all bad. As with all clouds, there was a silver lining. The limitations imposed by President Bush forced scientists to be creative. One novel source of stem cells that may not have been developed otherwise, is called “induced pluripotent stem cells,” abbreviated iPS. These are cells that do not start as stem cells but are manipulated in the lab to act like stem cells. Many scientists are as excited about the potential of iPS as they are about other stem cell types.

Clearly this is a very complex topic, and I have oversimplified a lot. The bottom line is that I am excited that the order President Obama is signing will not only open the door to new stem cell research, but may also signal a new era in science policy – an era where scientific decisions are made based on science, rather than on ideology.

Related Posts:
The Stem Cell Thing
Stem Cells, or “A Rose By Any Other Name…”
Cancer Stem Cells and Familial Cancer Risk for Breast Cancer


Haimson said...

Great breakdown of the issue. I love to hear your take on some of the possibilities for stem cell therapies in the near future.

Arps said...

Wow! That sounds good. Definitely the use of embryonic stem cells will help more than the adult variety. & this leaves us in the hope that an answer to a lot of illnesses lies in the future.

Anonymous said...

There's one important point that you left out, David. The embryos used are donated - they would have otherwise been destroyed. If someone wants to claim one of the destroyed embryos is equivalent to a human being, he or she should explain why the death of that embryo, which was inevitable, shouldn't come to some good for our society. It's parallel to harvesting organs from dying people, though I know we wait for brain death. Actually, that's a great analogy because the embryos used don't have brains.

Anonymous said...

My son is a biomedical engineering student and does adult stem cell research during the summer. Great strides are being made in transforming adult stem cells into practically any kind of cell. Embryonic cells no longer have a monopoly on this capacity. In fact, I think adult stem cells have the most exciting potential. We will one day grow our own replacement parts, and because the cells are our own, we will not need anti-rejection drugs. Embryonic cells have risks, development of teratomas, e.g. Ultimately, I hope the success of adult stem cell research will render embryonic research unnecessary, eliminating the ethical issue. Karen

Anonymous said...

Over 100 years ago, a Russian histologist suggested stem cells be applied for scientific research. They are the human body’s equivalent of a generator, as they can renew, regenerate, and replicate under the right conditions.

The apex of cellular therapy and regenerative/reparative medicine has been reborn after an 8 year moratorium that basically halted federal funding for stem cell research with most states in the U.S.

Now the NIH can award grants to scientists involved with biomedical research involving stem cell therapy through the CMS to each state in the U.S.

While never banned, stem cell research had limited funding during this time. And this was unfortunate, because there are several likely uses of stem cells.

These uses include the replacement of tissues in the human body, as well as repairing cell types that are defective. Also, stem cells can deliver genetic therapies that are needed in certain patients.

ESCs are totiplotent if obtained from the morula which is a pre-blastocyst stage. Normally, the stem cells are acquired from the blastocyst itself. From this source, the stem cells can be any cell in the human body except for the placenta, and are pluripotent.

Embryonic stem cells are obtained from a 4 day old embryo called a blastocyst, and are pluripotent from this source. The blastocyst contains about 100 cells, and is not suitable at this stage for implantation into the uterine wall.

The inner core of the blastocyst has about 20 cells, and this is where stem cells are obtained.

These cells are unspecialized cells that can be developed or morphed into the over 200 cells available in the human body through differentiation, as ESCs are undifferentiated by nature.

As such, they can become any human cell, as long as they are prevented from clumping or crowding together when explanted into cultures as they are propagated. After stem cells are cultured, they are moved to what are called stem lines.

Until recently, ESCs were believed to be most beneficial instead of the adult stem cell alternative (ASC), as these stem cells are limited to application to the tissue the stem cells were obtained from only. However ASCs (somatic stem cells) now can be coerced into differentiation through plasticity (trans-differentiation). This likely will reduce if not eliminate those opposed to stem cell therapy because of moral and ethical reasons related to the utilization of ESCs.

Thanks to molecular biology, four transcription factors control the transfer of genetic information from DNA to RNAS to regulate gene expression. So ASCs can have the same beneficial qualities as ESCs.

In the past, viral vectors and exotic genes interfered with the purity of ASCs. Now ASCs are re-programmed using plasmids instead of viruses and oncogenes that can become detrimental for the patient treated.

So now, ASCs can safely become induced pluripotent cells with the same potential as ESCs. As a result, the ASCs are free of genetic artifacts that potentially can interfere with transgene sequences.

They are capable of, and are able to renew and reproduce with minimal effort, stem cells, under the right laboratory conditions.

Human blood can be reproduced with stem cells under the right conditions, it has been shown by researchers.

SCT can also be used to investigate disease states for better treatment options.

Disease-specific stem cell lines, which are those cells that are pluripotent and are created with the same genetic errors of certain diseases, are studied for this reason.

So there clearly is a huge potential for stem cell-based therapies. The first FDA approved clinical trial occurred early in 2009. This human trial will involve evaluating primarily the safety of ESCs designed to be used as treatment for spinal cord injury patients. The trial was submitted by Geron Corp.

Pfizer, the largest drug company, has implemented stem cell research, as they are an asset to drug discovery by creating within the organization a regenerative medicine unit. Other large pharma companies are implemented similar research protocols for the same reasons.

Geron Corp. in California is the world’s leading esc developer, and financed researchers at Univ. of Wisconsin, who isolated the first human esc in 1998.

Stem cell therapy potentially can cure multiple sclerosis, among other disases and those with damaged human tissue. The therapy prevents the advancement of disease, as well as reverses the neurological dysfunctions associated with MS. Patients are injected with their own stem cells obtained from their bone marrow, which are called haemopoietic stem cells.

These particular stem cells are the origin of all blood cells. Further large clinical trials are needed to support these results. Studies have shown between 70 and 80 percent of MS patients who received stem cell therapy did not relapse afterwards.

Allogenic, or donor transplants, have a risk of graft versus host disease. Autologous, which is the patient’s own stem cells, are preferable and most beneficial. Similar results from this autologous bone marrow transplant cellular therapy are seen with Chron’s disease as well.

During the procedure, the immune system is reset so it is not in an autoimmune state where it attacks the human body. The process lasts about 2 months, and consists of 6phases:

1. Initial chemo
2. Release of stem cells
3. Acquisition of stem cells
4. Cells are then frozen until ready for transplant
5. Second chemo to reduce leukocytes
6. Autologous stem-cell transplant. Immune system is reset.

Positive results from stem cell therapy are seen usually within a month, and patients can request another treatment about 6 months after the first treatment presently. This stem cell paradigm of therapy addresses the etiology of a disease state, instead of focusing on the symptoms only. As such, this is the practice of regenerative medicine with the implementation of SCT.

Some believe ethical restraints are needed regarding the use of ESCs for therapeutic reasons. Yet they improve the quality of life of those with devastating diseases which involves suffering without any relief.

So stem cell therapy and research may be the most right and ethical thing to do for such patients. Not only is the tremedous suffering relieved with those possessed with devistating diseases, their functional ability is restored for those who receive stem cell therapy.

Embryos are acquired from fertility clinics (IVFs) that have thousands routinely stored and are abnormally fertilized. This means that they could never go on to become a human, and would be destroyed otherwise.

Ironically, one could argue it is inappropriate to discard what may be valuable and ethical for others, potentially.

Most couples with frozen embryos would gladly give them to such research, surveys have concluded.

These embryos are believed by many to not be morally equivalent to human life, but only have the potential for life. And they are used for therapeutic cloning, known as somatic cell nuclear transfer, and not reproductive cloning.

Ten states have banned this cloning out of ignorance, it seems. Bioethic principles, which are beneficience, or physician-centered decisions, as well as non-maleficence, which is first do no harm, are not corrupted.

Furthermore, autonomy, which is the patient’s right to determine their health, and justice or fairness remain intact.

Stem cells should be utilized for those terminally ill as well, many believe. Many are seeking stem cell therapy overseas due to retrictions that exist in the U.S. presently. The United Kingdom is believed to be the leader in stem cell research presently.

Dan Abshear

Faith said...

Stem Cell research is fascinating. Our cousin is going through a trial at NIH right now- we are hoping to get great results from it....just at the beginning of the process, so, it will be a while. Thanks for the explanations, David- it really helped!