Wednesday, January 10, 2007

Recent Happenings

There’s no way I can catch up on all the stories I missed over the last couple months (but I did get into law school!), so here are links to some of the ones I find more interesting, newest first (articles on money and politics are mostly not included, this is essentially just research):

1/10 BBC: British debate on hybrid cells (animal cells used as recipients of human DNA in cloning) taking place, research may be banned.

1/8: Press release from USC about stem cells causing cancer. An early, unrelated, story from CBC news discusses Canadian researchers’ findings that colon cancer is caused by cancer stem cells.

1/6 San Diego Tribune: Using stem cells to carry anti-cancer genes into the body. Similar story on press release 12/25 about neural stem cells.

12/22 UPI: Stem cells treat neuroblastomas in mice.

12/17 The Telegraph: Investigation into possible death of newborns in the Ukraine to obtain stem cells. (And people wonder why I am so firm on double-blind gov’t approved studies prior to treatment and wary of miracle cures from Kiev…)

12/15 AP (in The State): Researchers derive stem cells from unfertilized eggs. Related, more technical, article in The Scientist. Longer AP story on ABC News.

12/14 Press release: Mouse stem cells can help repair damaged brain tissue.

12/10 Boston Globe: Australia lifts ban on cloning.

12/10 Reuters: Scientists develop an “ink-jet” method of growing stem cells.

12/7 San Francisco Chronicle: Head of CIRM resigns for personal reasons, including age (69).

12/6 International Herald Tribune: Summary of laws about stem cell research around the world.

11/23 Boston Globe: Harvard researchers identify a cell that gives rise to all 3 kinds of heart tissue.

11/22 Reuters: Advanced Cell Technology clarifies its use of frozen embryos in a new technique for creating stem cells.

11/17 CNN: Iranian advances in stem cell research.

11/12 BBC: Stem cells from bone marrow help repair insulin-producing pancreatic cells. See also this related article.

11/9 The Independent: Stem cell transplantation repairs eyes in mice. Related story by Washington Post stem cell writer Rick Weiss in the Seattle Times.

11/9 CBS: Researchers develop potential lung cancer vaccine from mouse stem cells.

10/31 The Daily Record: Scientist in the UK grow miniature liver from umbilical stem cells.

10/23 The Age: Stem cells may cause brain tumors.

Other news includes using stem cells to regenerate teeth in pigs, a discovery that breast cancer stem cells may be resistant to radiation treatment, the possibility of using fat-derived stem cells in breast reconstruction, a stem cell heart trial in Britain, stem cell injections ease muscular dystrophy in dogs, heart damage repaired in pigs with stem cells, regrowth of neural stem cells in mice, additional risk of cancer after receiving allogeneic stem cell transplants, and heart valves grown from amniotic stem cells.

Well, that list by no means covers everything, but it should provide a decent swath of what’s been happening in the stem cell world.

Amniotic Fluid a Source of Effective Stem Cells?

Amniotic Fluid a Source of Effective Stem Cells?

A reader rightfully took me to task for not reporting on this—as it happens, I was on vacation when the news broke. I am now back from several days of skiing and making an effort to find out what happened in the world while I was on the mountaintop… You have probably already heard by now that scientists at Wake Forest University and colleagues from Harvard have been able to grow new tissue from stem cells obtained from amniotic fluid. The press release begins:

Scientists have discovered a new source of stems cells and have used them to create muscle, bone, fat, blood vessel, nerve and liver cells in the laboratory. The first report showing the isolation of broad potential stem cells from the amniotic fluid that surrounds developing embryos was published in Nature Biotechnology.

Needless to say, this is being hyped as an alternative to embryonic stem cell research. And perhaps it could be. According to the release,

Atala said a bank with 100,000 specimens theoretically could supply 99 percent of the U.S. population with perfect genetic matches for transplantation. There are more than 4 million live births each year in the United States. In addition to being easily obtainable, the AFS cells can be grown in large quantities because they typically double every 36 hours. They also do not require guidance from other cells (termed “feeders”) and they do not produce tumors, which can occur with certain other types of stem cells. The scientists noted that specialized cells generated from the AFS cells included all three classes of cells found in the developing embryo - termed ectoderm, mesoderm, and endoderm. In their high degree of flexibility and growth potential, the AFS cells resemble human embryonic stem cells, which are believed capable of generating every type of adult cell. “The full range of cells that AFS cells can give rise to remains to be determined,” said Atala. “So far, we’ve been successful with every cell type we’ve attempted to produce from these stem cells. The AFS cells can also produce mature cells that meet tests of function, which suggests their therapeutic value.”

This is obviously highly important research.

However, before jumping up and down with excitement or calling this a resolution to the stem cell dilemma (the Vatican has endorsed these new kinds of stem cells), there is still a lot that needs to happen. It took seven years of research for the researchers to get to this point (which, incidentally, gives an example of why people should not call embryonic stem cell research a dead end only nine years after the first human embryonic stem cell was isolated), and laboratory conditions are not the human body. Successful animal and human trials will have to take place for several years before any therapies can be approved by the FDA, so people in need of immediate help will not have this resource. It will be fabulous if this works, especially if the problems of rejection and tumor growth have been overcome, and I hope that trials can be expedited, but it’s not a proven therapy yet. One important issue to watch further is the long-term effects; do the cells survive and reproduce continuously, for example, or does the effect diminish after several months? Will they be effective in extremely rare genetic disorders or will an exact genetic match (e.g. cloning) be required in these cases? Another issue will be delivery of cells to the affected area—can these cells migrate or will they need to be injected into a specific location? None of these are insurmountable issues by any means—but they are areas where we don’t yet have answers and need more research. Procedures for collection of amniotic fluid will also have to be established—consent, timing, storage, etc.

Besides possibly offering an eventual solution to the dilemma of embryonic stem cell usage, it seems to me that this study probably has some other really important information for cell biology research in general—what is the controlling mechanism that enables them to act without guidance from other cells? What proteins are turning on or off what genes? Has the culture medium been significant? How do the cells interact with scaffolding devices used in tissue engineering? Do they interact with their niches in the way that some cells in the body seem to?

So, although I don’t think this is a wonder-cure yet, I hope the research continues and expands—both for therapies and for scientific knowledge.

Stem Cells in the New Year

Stem Cells in the New Year

Well, 2006 has gone, and we have a new Congress. Stem cells are back on the political agenda now that Democrats control the House (and the Senate—maybe—depending on Tim Johnson’s recovery from stroke). Reuters reports that leaders of both parts of Congress intend to put forth the same bill that Bush vetoed last year; they predict it will again pass easily and that there may even be enough votes to over-ride a veto. AP reports on the same thing, but with a focus on the new research showing that stem cells obtained from amniotic fluid (see separate post on this) may be effective—according to an article in the Houston Chronicle (among may others), Congressional leaders are not embracing this research as a replacement for embryonic stem cell research right now, but it may present an additional argument on the side of people who are opposed to hESC research. However, the Boston Globe reports that the researcher who worked with the amniotic stem cells is telling Congress that his work is not a substitute for hESC research, and that appears to be the line stem-cell supporters will be following in Congress.

Wednesday, November 08, 2006

Election Day Tidings

Oh what a beautiful morning:

A good day for stem cell research supporters in several key elections:

First, the ballot initiative in Missouri:
St. Louis Post-Dispatch--here are the raw numbers.

Constitutional Amendment #2 Constitutional
amendment to allow any stem cell research that federal law
allows

98% of precincts
simple majority

1,057,930 Yes
1,012,164 No
Passing
Updated: 11/8/2006 6:48:01 AM
And here's a story:

Stem cell proposal wins, AP says
By Matt Franck
ST. LOUIS
POST-DISPATCH
11/08/2006

A Missouri ballot measure to protect embryonic stem cell research won slim voter approval Tuesday, narrowly surviving an opposition campaign that for weeks had eroded the measure’s popularity, according to the Associated Press, which called the measure shortly before 2:30 a.m. Wednesday.

In other state news, in Wisconsin, Jim Doyle has retained the governorship, and in Michigan Jennifer Granholm has also kept her post. Stem cell research has been a campaign issue in both states.

Tuesday, October 17, 2006

Lou Gehrig’s Disease Progress?

A press release from Johns Hopkins reports that rats bred to have amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, had delayed onset and prolonged life when human stem cells were transplanted into their spinal cords. Onset was delayed by an average of 7 days and lifespan extended by 9 days. One of the things the research demonstrates is that the new cells were not themselves subject to the degeneration the surrounding cells suffered. Many of the cells developed into nerve cells and grew nerve endings to connect with other cells.

The next step in the research is to try grafting the cells along the length of the spinal cord; in this first study, the grafts only affected muscles and nerves below the waist and not those responsible for breathing. If the transplanted cells can be shown to have a significant effect in maintaining normal breathing, that would be a very important step forward. The study is also useful as a model of how stem cells change when transplanted. Human clinical studies are still far away.

There are more detailed articles on the study on Reuters, the Independent, and the BBC, among others.

Lawsuit Against Stem Cell Transplant Program

Lawsuit Against Stem Cell Transplant Program

A hospital, blood center, cancer center, and other institutions in Kansas City have been sued by a group of former patients and family members of deceased patients regarding stem cell transplants performed in the late 1990’s. The suit alleges that the various institutions were negligent in reviewing stem cell quality. The patients were apparently [I’m reading between the lines of the article here] given stem cell transplants as part of their treatment for cancer. About 25 % of the 40 people who received treatment died within a few months, and half were dead after two years. These are much higher mortality rates than those usually associated with stem cell transplants. The case is up for trial next March. Unsurprisingly, the defendants affirm the quality of their program.

Obviously there are a number of questions here the answers to which will probably only come out in court. Certainly the number of deaths raises concerns, but there could be many other factors: how were the patients selected for the program? How advanced was their cancer? What kind of cancer did they have? Were they told this was experimental and did they give informed consent to the risks? In at least one possible universe, the people who received the treatment may have been among those most likely to die from other causes. I’m only speculating here, and can certainly speculate the other way as well: Maybe someone in the lab cut corners, or perhaps the equipment was contaminated. The line between genuine error and negligence can be very blurry at times, and it’s quite possible that several things, any one of which alone would not have been problematic, combined to become deadly. If it goes to a jury, it will be interesting to see what happens. (I’m expecting pre-trial 11th hour settlements myself….)

Friday, October 06, 2006

Research Update

Research Update

Well, I had no intent to write this infrequently but time sure slips away. I spent a lot of time studying for the LSAT (took it last week), which means that I got behind in all my work, and so it goes. So here are some very short synopses of research developments over the last few weeks.

Researchers at the University of Missouri have been able to derive five different types of cells from adult stem cells in pig blood, bone, blood vessel and nerve cells. The adult cells gave no indication of tumor formation. The technique involved isolating the stem cells and exposing them to different chemicals. The study also made use of a fluorescent gene marker to track the cells as they developed when they were re-inserted into a pig’s body. Press Release. In another study, researchers at Northwestern University were able to make a new cell from human blood stem cells: human megakaryocytes (bone marrow cells that produce blood platelets that are responsible for blood clotting) derived from adult hematopoietic stem cells were, for the first time, reprogrammed into neutrophil-like cells similar to the white blood cells that are responsible for fighting infections.” Press Release.

The small heart stem cell trial taking place in Australia is showing success. Researchers said that patient have had improvement ranging from 10-60% in their heart functioning. The stem cells were separated from the patients’ blood and reinjected. Very short article on ABC. There were similar studies in Europe with different results, according to Forbes: a German team showed that patients who received the injections had 5.5% increase in function, compared to 3% for those who did not, and that they suffered fewer second heart attacks. Another German study had similar results. Both are notably less than what the Australians are claiming. Further, a Norwegian trial of 100 patients did not give any evidence of improvement. Researchers quoted said that research must go on, but this is not a therapy yet. See also the Mercury News.

Researchers have used human embryonic stem cells to slow vision loss in rats with a disease similar to of macular degeneration; the stem cells took the place of failing retinal cells, and the rats that received the stem cells had twice the visual acuity of the control group 40 days later. 18 different stem cell lines, including the federally approved ones and private ones, were used, with identical effects. This is good news for rats—it is less certain if this would work in people, since macular degeneration is a uniquely human disease. Washington Post.

The Batten Disease trial is about to get started, with one patient receiving treatment and the others receiving it thirty days later if there are no safety issues. This is a rare but horrible disease which slowly deprives children of motor function, speech, sight, communicative ability, and then they die. I really hope this works. Forbes.

You’ve probably already heard about this one, but researchers have been able to obtain stem cells from non-viable human embryos. Press release. This has of course not solved any ethical controversy—how do you know an embryo is dead? And even if it is, do you want to get cells from it? The chance of abnormality or genetic mutation is probably higher in an embryo that does not sustain itself. Seems to me that this might be useful for studying specific diseases but does not offer much that is not otherwise available. Houston Chronicle (Washington Post story).

Canadian researchers have used a monoclonal antibody developed in France to halt or cure acute myeloid leukemia in mice. The drug blocks a particular protein on the surface of a cancerous stem cell, thus preventing the cell from moving around and achoring itself anywhere in the body. Nowhere to settle, no more cancer cells to spawn. The researchers estimate it is at least 5-10 years before a trial could even be considered in humans. CBC. One should remember that the drug that caused the nearly fatal reaction in six British men last spring was also a monoclonal antibody.

Researchers at the Universities of Connecticut and of Pittsburgh have successfully cloned mice from a differentiated cell, using a type of specialized white blood cell called a granulocyte:

Surprisingly, the granulocytes were the most efficient donor cells for nuclear transfer among the different lineage cells, with 35 to 39 percent becoming a blastocyst, an early embryo consisting of about 100 to 150 cells, compared to 11 percent for the progenitor cells and only 4 percent for the stem cells. Only the granulocytes were able to produce two live cloned pups, although both died within a few hours of birth. As a control, the researchers performed nuclear transfer using embryonic stem cells; 49 percent developed to the blastocyst stage and 18 cloned pups were born.

Prior attempts to used different types of regular cells in cloning have failed. Any resulting blastocyst from a mature cell has had to be combined with a fertilized embryo. (Is any embryo unfertilized?) This research implies that the animal clones that have succeeded may be due to adult cells in the tissue environment. This is a pretty significant development, and obviously a lot more research is needed. It does confirm that the standard nuclear transfer procedure from ESCs is still more successful than any alternatives. The fact that the two mice that were cloned to birth died almost immediately suggests that something in the cloning process from regular cells is inhospitable to mammals. Press release. There has been a lot of media play on this one—the BBC has a decent article.

Researchers at the Howard Hughes Medical Institute have found an off-switch for skin stem cells; turning on the transcription factor gene Tcf3 blocked the differentiation of all three types of mature cells that a skin stem cell can develop into. The primary use for this knowledge will probably be in research, since it has been hard to keep stem cells from differentiating.

Possible bad news for breast cancer victims; researchers at the University of Southern California have found that almost all tumor cells in the bone marrow of women who have breast cancer are stem cells. This suggests that the likelihood of metastasis for women who have differentiated breast cancer—tumors in the bone marrow, not just the breast tissue—lasts longer than previously thought, perhaps for the rest of a lifetime. A lot more research still has to be done, and I expect will with this kind of finding.

Finally, this is not research, but it is important—the WARF will not collect royalties on any stem cell research done (by universities or non-profits) with its cells in the state of Wisconsin. Because of the way the WARF works, that’s a pretty strong incentive. Companies that relocate will also be eligible for grant money from the state. Governor Jim Doyle is working hard to make the state a desirable place for stem cell researchers. Milwaukee Business Journal. And the US Patent and Trademark Office has decided to review the WARF patents. This is no big surprise—they review about 90% of the patents requested. The executive director of a patent foundation said that 70% of the reviewed patents are revoked or modified. Mercury News (AP Wire).

And there you have it. I don’t see any particular theme to this research except that so much is still unknown.

Thursday, September 14, 2006

Wisconsin and others

Wow, it’s amazing how much time disappears when your kid comes home 2 1/2 hours earlier from school…

Anyway, just a little bit of interesting information related to WARF, the Wisconsin foundation connected with the University of Wisconsin Madison that handles the business side of stem cells. According to an article in Wisconsin Technology today, a review of the stem cell patents is expected after a legal challenge filed in July by a California group. The US Patent office will announce whether or not it will review next month. WARF expects a review and expects that the review will uphold the patent.

Also, the WiCell part of WARF has made an agreement with ACT in Alameda to distribute cells from the new so-called “ethical” stem cell lines. This could be interesting if ACT gets money from the CIRM, because of the profit sharing goals for the CIRM. It makes sense from a logistical stance for ACT to partner with WiCell, as WiCell already houses the national stem cell bank and distributes many other stem cell lines, both federally-approved and not, so researchers can get their material from a single source. But who collects any profit could be a legal knot.

It will also be interesting to see how much research gets done on these new stem cells, given all the negatives that have been voiced by scientists. Will there be sufficient interest in doing research for it to be worth it to produce them? With only two samples so far, there’s not much to work on comparatively.

Way Back When

Lost in the mists of my vanished time was a press release on EurekAlert saying that Harvard researchers have discovered a compound that increases the natural production of one’s own stem cells in the brain (at least, if one is a mouse). The research on the LTB4 compound also showed that when stem cells are stimulated to proliferate by the LTB4 compound, the cells have more LTB4 receptors. I presume this would make them more likely to proliferate further themselves when they are exposed to this molecule.

And in another story, European researchers have found out that when the cellular pathway known as “Wingless” is overactive—essentially, stuck in the on position—in hematopoietic stem cells, bizarre things happen—some cells disappeared, some occurred too frequently, some were unable to produce B or T cells or to develop into new kinds of cells. The key appears to be a protein called beta catenin, which kept the pathway open. This may be a clue as to what goes wrong in blood cancers.

And, in research you may have already heard about, three different papers on the aging of stem cells were published last week showing that a gene called Ink4a is key to the process by which stem cells shut themselves down. The suggestion is that this keeps them from accumulating and passing on mutations which could eventually lead to cancer. The gene was already known to be a tumor suppressor gene, but when scientists knocked it out in mice, the mice stem cells continued to repopulate. However, the mice developed cancer. While trading a short lifespan for a cancer-filled longer one doesn’t seem like a great deal, the research could give important directions to go in for cancer research and medicine.

Friday, September 08, 2006

I have been swamped

Summer ended and my work kicked into high gear again. Not a whole lot has happened in the last week and a half, so you haven't missed much--continued discussion of the Lanza method for taking one cell from an embryo continues, with people on both sides of the issues saying he overstated the research--embryos were actually destroyed in his work, and a number did not survive the procedure.

There have been a couple of significant changes in my life that are limiting my time for this blog quite a bit--my son started a new school, and he is home a lot more and wanting to spend time with me. I have also decided to acquire another degree and start law school next year, so I am trying to take time to read a lot of basic legal material to really familiarize myself with concepts and language so they don't hit me like a steam engine when I start. So I am going to keep this blog going, but on a much reduced scale--I'll probably only update on actual research at this point, and that may be done erratically. There are a couple things that happened that I will post on after I've had time to digest them...

Wednesday, August 30, 2006

Here and There—treatments and techniques

Here and There—treatments and techniques

There’s been another warning in Britain about stem cell clinics out of the country that treat patients for multiple sclerosis and “cosmetic skin techniques.” The Scotsman reported that three experts—the head of the national stem cell bank, the head of the MS Society, and the chief executive of the Medical Research Council—wrote a letter reiterating cautions about these clinics. While the experts welcome research into stem cell treatments, the research should be done under strict scientific standards. The clinics in the Netherlands have not offered any research (controlled double-blind study, for example) substantiating the claims that stem cells can help MS. There are anecdotal reports of the expensive treatment working; as far as I know, none of these people have been followed up with over a period of years to see what the long-term effects, either good or bad, might be.

Coincidentally, the BBC published a recent story about a 5 year old girl with Batten’s Disease who is undergoing stem cell treatment in China. The article does not report the additional info that Batten’s Disease is invariably fatal, often with paralysis and blindness first, and that there is an approved clinical study in the US. With this disease, I do believe that the patients have nothing to lose.

There’s still a lot of huff and blow about the new stem cell technique. Christopher Scott Thomas, from the Stanford Center for Bioethics, has an opinion piece published in the San Francisco Chronicle today that does a nice job of stating the problems with Lanza’s research. Like many researchers, he believes that all lines of research need to be studied because no one knows what will work for what disease—for example, maybe adult stem cells work well for hearts, embryonic stem cells for neurodegenerative disease, and the Lanza type cells for immune system issues. We simply don’t know enough yet to rule out any reasonable line of research.

And speaking of new lines of research, scientists in Australia have succeeded in getting stem cells from plants to grow into an entire new plant. The Age reports that two plant biologists say that if the genetic control mechanisms in plant stem cells can be identified, then that might provide clues to how it works in animals and people. While being able to direct a stem cell to grow an entire or partial new plant is a big achievement, and certainly has no ethical issues in itself, plants have the ability to greater or lesser extents to regenerate already. That may be a big difference! The article also does not say if there is any difference between types of plants used and their relative success; for example, does a wild plant have stem cells that are less likely to be reprogrammed that those from a cultivated nearly-related species? It’s an interesting field of research, but there’s still an immense amount to find out about how helpful this is to working with humans, and it’s no substitute for embryonic stem cell research.

Monday, August 28, 2006

Check-in

Check-in

No research news today, and not much on any other fronts either—the new, “ethical” method of creating ESCs is still receiving a lot of coverage, although the headlines are no longer so uniformly glowing: the fact that this does not necessarily resolve issues is starting to be discussed. The Washington Post had a story about the journal in which the results were published (Nature) re-issuing its press release after receiving a message from a Catholic bishop. Another story, in the Seattle Times (from multiple sources), described some of the negative reaction from both scientists and conservatives.

Otherwise the other “big” story (Reuters and elsewhere) is one about English soccer players storing stem cells against future injury. There are 5 players known to have done this. They froze stem cells from the cord blood of their newborn infants, hoping that that the stem cells can be used later in repairing cartilage or ligament damage. One hopes they were planning to have the children anyway.