Stem Cell Research Continues (Temporarily)

In the long-standing battle between opponents and proponents of research involving stem cells derived from human embryos, last month a U.S. District judge issued a temporary injunction against the use of federal funds for such research (see this blog, Sept. 1). The injunction not only halted funding for future research projects that would have used stem cells derived from embryos, but also threw the funding for all current research projects into doubt. Researchers wondered whether their experimental animals would have to be euthanatized and their laboratory workers laid off.

To prevent that from happening, last week the U.S. Court of Appeals (the next step up the judicial ladder) issued a temporary injunction against the lower court’s ruling. The injunction will allow the National Institutes of Health to continue funding stem cell research temporarily, until an appeal is heard by the higher court. It also gives Congress time to act to change the law, but of course that depends on whether proponents of stem cell research can muster the votes to do so.

So now it’s in the hands of the U.S. Court of Appeals and Congress. Researchers, patient advocacy groups, and opponents of embryonic stem cell research will be watching closely. It’s time to lobby your congressman, if you have an opinion.

Injunction Against Human Stem Cell Research

In March of 2009 President Obama issued an executive order permitting the use of federal funds for research on stem cells lines derived previously from human embryos, arguing that the researchers had not destroyed the embryos themselves. The Obama executive order effectively overturned the ban of the Bush administration on the use of human embryonic stem cells for research. At the time, I reported in this blog that the Obama order might still face a legal challenge, based on a federal law called the Dickey-Wicker Amendment of 1999.

Last week it finally happened. As the result of a lawsuit filed by several Christian groups and two doctors opposed to human stem cell research, a U.S. District Court judge issued an injunction which blocks the National Institutes of Health (NIH) from implementing the Obama order. The judge argued that the Obama executive order clearly violates the language of the Dickey-Wicker Amendment, and even some supporters of the Omama order grudgingly agree. According to Harvard ethicist Louis Guenin, allowing research on cell lines merely derived from human embryonic stem cells would be like allowing research on dead bald eagles. It’s illegal to kill bald eagles, and therefore anyone doing research on bald eagles killed by someone else would be considered complicit in the crime.

If research on stem cells derived from human embryos is to continue, it appears that Congress will have to overturn the Dickey-Wicker Amendment. Whether there are sufficient votes in both houses of Congress to do so is anybody’s guess. In the meantime, funding for future projects is on hold. And while NIH’s interpretation is that currently-funded research projects can continue for now, not everyone seems to agree. We’ll have to see how this one shakes out. For starters, I’m sure we can expect the ruling to be appealed.

First Human Stem Cell Therapy Trial

The first clinical trial of a therapy based on human stem cells has received final approval from the Food and Drug Administration (FDA) and will get underway shortly, according to a press release from Geron Corporation, the company sponsoring the research. During the first phase of the trial, researchers will inject precursor cells to neural support cells called oligodendrocytes into the spinal cords of patients who have suffered recent spinal cord injuries and who have almost no chance of recovery of function otherwise. The hope is that the precursor cells will differentiate into mature oligodendrocytes (the cells that produce myelin) and that the myelin will form new sheaths around damaged nerves.

The trial was planned several years ago but held up by the FDA over concerns that the therapy could increase the risk of tumors forming in the spinal cord if the injected cells were not free of embryonic stem cells. The first phase of the trial is designed to test the safety of the procedure. It will be years before the technique becomes widely available for the repair of spinal cord injuries, even if it does eventually prove to be both safe and effective.

Stem cell researchers will be holding their breath. A failure in this first approved trial could set back the whole field of stem cell therapy research for years.

Re-creating Undifferentiated Cells

People who object to the use of embryonic stem cells (ES cells) for research or for therapeutic purposes continue to hope that induced pluripotent stem cells (iPS cells) might just be the answer. If adult cells could somehow be coaxed back (induced) into a state where they were once again capable of differentiating into all kinds of cells (i.e. were pluripotent), then embryonic stem cells just wouldn’t be needed any more.

Researchers announced several years ago that they had, in fact, found a way to create iPS cells. But are currently available iPS cells just as good as ES cells? In the first side-by-side comparisons of iPS and ES cells, two groups report that they are not. Both groups report that while iPS cells can differentiate into many cell types, they just are not very efficient at it, at least not yet.

The results are a disappointment, perhaps, but don’t count iPS cells out just yet. Scientists are still in the early stages of understanding how to create iPS cells in the first place. As the techniques improve, perhaps they’ll begin to look more and more like ES cells after all. And that would be a scientific advance welcomed by all.

New Stem Cell Guidelines

The National Institutes of Health (NIH) is about to change its definition of human embryonic stem cells (hESCs) in light of recent trends in stem cell research.

In March of 2009 President Barack Obama signed an executive order once again permitting the use of hESCs in research. According to the executive order, the NIH is charged with ensuring that NIH-funded research in which hESCs are used is ethically responsible, scientifically worthy, and conducted in accordance with applicable law. NIH does that by setting strict guidelines for what types of cells may be used and how they must be derived.

According to the current NIH guidelines, part of the definition of hESCs is that they are cells “derived from the inner cell mass of blastocyst stage human embryos”1. But the definition apparently had the unintended consequence of excluding some cell lines that were derived from even earlier, morula-stage cells (Review Figure 21.5 in Johnson’s Human Biology). The revised language will read, “derived from early stage human embryos, up to and including the blastocyst stage”, so that these more recent cell lines may be used in federally funded research projects.

The new guidelines do not change the rigorous ethical standards for deriving human cell lines. They just make more stem cell lines available to researchers.

1 Federal Register vol. 75, no. 35, Tuesday, Feb. 23, 2010, p. 8085-8086.

Stem Cell Therapy for Parkinson's?

Researchers in Europe are about to begin a long and expensive series of experiments to determine if transplantation of fetal brain cells into the brains of patients with Parkinson’s disease will improve the patients’ condition. The study is raising some eyebrows in scientific quarters. Two similar experiments carried out in the U.S. in the 1990s, admittedly when the techniques were less well developed, failed miserably.

If they get final approval to go ahead, the researchers will harvest fetal brain cells from 6-9-week-old human fetuses and then inject the cells into the brains of patients with Parkinson’s disease. Up to six fetuses will be needed to obtain the 8 million cells to be transplanted into each Parkinson’s patient, according to a news article in Science. The first patients will receive the injections in 2012 as part of a safety study. If all goes well, a double-blind trial complete with sham surgeries will be carried out to see if the procedure actually benefits patients.

Controversial? Yes. Worthwhile? You decide.

Obama Lifts Stem Cell Ban

Last week President Obama signed an executive order lifting the restrictions on stem cell research laid down by President Bush in 2001 (See the Current Issue in Human Biology 5th. ed., pp. 72-73). Most political analysts expect Congress to enact new legislation soon that will permit federal research dollars to again begin to flow for promising stem cell research projects.

President Obama’s executive order will permit federally funded researchers to use the hundreds of stem cell lines in existence today, as well as new stem cell lines created by private funding in the future. But there is still a prohibition in place, called the Dickey-Wicker Amendment of 1996, which prohibits federal funding for research “in which human embryos are created, destroyed, discarded, or knowingly subjected to risk of injury or death”. So while federally funded researchers will be able to use stem cell lines created by private funds (because they themselves did not destroy any embryos), they will still be prohibited from creating their own new cell lines from human embryos.

How long can the Dickey-Wicker Amendment can stand up in this new climate of stem cell research permissiveness? It's anybody’s guess. The debate continues…

Storing Umbilical Cord Blood

An article entitled “When Medicine Meets Marketing" (Newsweek Dec. 22, 2008, pp. 49-51) would be a good supplementary reading for when you cover the topic of blood in your human biology college course. The article describes how private blood storage companies are waging a fierce marketing campaign designed to convince young parents to bank their baby’s cord blood (for a hefty fee), just in case the stem cells in cord blood might be useful in the future. The scientific background for understanding the article is covered in Human Biology 5th ed., pp.154-155.

Based on what you have learned from the textbook and/or from the Newsweek article, are you more likely to; a) bank your baby's cord blood privately, b) donate your baby's cord blood to a public cord blood bank registry, or c) do neither? On what do you base your choice?

A Beating Heart is Created in the Laboratory

University of Minnesota researchers have succeeded in producing a beating rat heart in the laboratory. In their experiments, the researchers first removed all the heart cells from a dead rat heart by dissolving them away with a strong detergent, leaving just a scaffold of connective tissue and heart valves. Then they infused cells harvested from the heart of a newborn rat. Within two weeks a new beating heart developed.

The research marks a significant advance in our understanding of what it would take to grow human hearts. However, scientists caution that the ability to produce human hearts for implantation still may be decades away. First, it will have to be shown that the technique can be adapted to larger animals. And second, methods will have to be developed to create the hearts from stem cells rather than cells from a newborn. Obviously, no one would sacrifice a human newborn just to produce a new heart for an adult!

Nevertheless, this is an encouraging first step.

Stem Cell Breakthrough

In late November Dr. Shimya Yamanaka reported in Cell that he had produced human stem cells from adult human cells taken from the cheek of a middle-aged woman. On the same day, Dr. James Thomson reported in the online version of Science that he had achieved similar success with foreskin cells from newborns.

Scientists are hailing these two reports as a technical breakthrough in stem cell research. The key is that these two researchers derived their stem cells from older cells, NOT from embryonic cells. Stem cell research has always been highly controversial because most of the stem cells used in research come from human embryos (see the Current Issue in Human Biology 5th ed., pp. 72-73). But if human stem cells can be created from older cells without sacrificing human embryos, then the whole “sanctity-of-life” issue is off the table. An added benefit is that if a simple cheek cell can be used, then stem cells could be grown specifically for any patient, using cells taken from that patient.

It’s way too early to think of growing a new heart for a patient in heart failure from his/her own cells, though. Although these new findings show that we have reached a basic level of understanding of how to create stem cells, we don’t yet understand how to direct them into becoming the specific human organs or tissues we might need to treat disease. Many scientists, including Dr. Yamanaka and his colleagues, argue that it would be “a serious mistake” to move too quickly to end all embryonic stem cell research, based on these very first successes at creating stem cells from adult cells. They believe that embryonic stem cells are still likely to be necessary for decades to come.

Still, it’s encouraging to think that in our lifetimes, the controversy over stem cell research may just slowly disappear.

The Buzz on Bone and Fat

In Human Physiology 5th ed. (p. 104-105) I point out that bone growth, remodeling and repair are enhanced by weight-bearing exercise and can be stimulated by weak electrical currents. But I learned something new today - apparently it’s also known that that in several animal species including mice and sheep, just standing on a platform that vibrates at a low frequency (like a buzz) leads to bone growth. That’s interesting enough, but now scientist have demonstrated that when mice are placed on a vibrating platform for just 15 minutes a day they not only gain bone mass, they also have 27% less body fat. The work will be published in the Proceedings of the National Academy of Sciences Nov. 6, but it is already available online.

Huh? It sounds incredible - so incredible that it amazes even the scientists who did it. They caution that they don’t yet understand WHY the mice gain bone mass and have less body fat, but they have some hypotheses. One is that the low frequency vibrations may stimulate stem cells in bone to become bone cells instead of fat cells. Other scientists remain skeptical of this hypothesis, saying that perhaps the mice have less fat because they eat less or because they are doing more muscle work to maintain their posture on the platform. Certainly these are all good hypotheses that deserve to be tested.

According to a New York Times article published online on Oct. 30 (“Low Buzz May Give Mice Better Bones and Less Fat”, by Gina Kolata), a clinical trial is underway in elderly people to determine whether a buzzing platform will affect adult human bone density (and body fat) like it does in mice. Perhaps in a few years we’ll know, and a new therapy for osteoporosis will emerge.