Stem Cell Research Progress Blog

2007-01-10T15:50:00.000-08:00

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?

2007-01-10T13:26:00.000-08:00

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

2007-01-10T13:21:00.000-08:00

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.

Election Day Tidings

2006-11-08T08:37:00.000-08:00

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.

Lou Gehrig’s Disease Progress?

2006-10-17T09:43:00.000-07:00

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

2006-10-17T09:42:00.000-07:00

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….)

Research Update

2006-10-06T12:33:00.000-07:00

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.

Wisconsin and others

2006-09-14T14:32:00.000-07:00

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.

I have been swamped

2006-09-08T12:26:00.000-07:00

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...

Here and There—treatments and techniques

2006-08-30T14:41:00.000-07:00

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.

Check-in

2006-08-28T11:14:00.000-07:00

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.

Stem Cell Circuitry

2006-08-25T16:25:00.000-07:00

Stem Cell Circuitry

A fairly detailed press release from the Howard Hughes Medical Institute reports that researchers there have created a mathematical model of hematopoietic stem cells which helps explain how they become white blood cells. The researchers studied stem cells called myeloid progenitors, which can turn into either macrophages or neutrophil cells (vividly described as garbage disposals and vultures, respectively), and express genes for both. By looking at this “circuitry” and how the myeloid cells developed, the scientists found that increased concentration of one transcription factor normally found in macrophages turned off the signals which would direct the cell to develop into a neutrophil. Both macrophages and nuetrophils expressed low levels of this protein (PU.1); it was increasing the concentration that made a difference. They also identified a repressor gene in the neutrophil cells which shuts off the regulatory genes needed to become a macrophage.

The researchers then used the presence of the PU.1 and of the repressor gene to develop a mathematical model of the regulatory network of the stem cells. The amount of one of the two genes countering each other decreases as the other genes is increased. Theoretically this could be used to predict what a cell would become. I don’t entirely understand why having a mathematical model is more useful than looking at the genes in the standard biological ways, unless it enables more precise predictions or allows work to be done extensively on the computer before trying to duplicate the results in the lab. I would expect that there have to be certain constants for some genes and not for others, and I don’t have any guess as to whether proportionality is sustained. One of the keys seems to be that the transcription factors are operating in a binary fashion: if A is on, B must be off; if B is on, A must be off. It may be that this model provides a paradigm that can be manipulated with more control than other kinds of experiments. At any rate, it’s interesting.

Wnt Crucial to Pancreas and Liver Development

2006-08-25T11:38:00.000-07:00

Wnt Crucial to Pancreas and Liver Development

I reported a while ago (Ribbit! 5/11/06) on research being done at the University of Edinburgh on the African clawed frog. Now, according to a story on Scientist Live, the researchers have shown that in frogs the anterior endoderm, from which the liver, pancreas, intestinal lining, and other organs develop, is formed by a cascade action leading to production of the Wnt protein. Research on mouse embryonic stem cells suggests that the same action may exist in mammals and that Wnt may be useful in directing embryonic stem cells to differentiate into anterior endoderm cells. Another related finding is that turning off the Nodal protein is also important to the development of the anterior endoderm, and the researchers are trying to use Wnt to turn off the Nodal protein in mouse ESCs.

New Research on Mesenchymal Stem Cells’ Plasticity

2006-08-25T11:16:00.000-07:00

New Research on Mesenchymal Stem Cells’ Plasticity

Researchers at the University of Pennsylvania have found out that the environment surrounding mesenchymal stem cells is highly determinative of how the cells will differentiate. The press release says, “According to the researchers, soft microenvironments that mimic the brain guide the cells toward becoming neurons, stiffer microenvironments that mimic muscle guide the cells toward becoming muscle cells and comparatively rigid microenvironments guide the cells toward becoming bone.” Cells have structures called the skeleton and use chemical signals as we use muscles to move; the stem cells can therefore “feel” how hard they are pressing against their surrounding environment. This triggers particular chemical signals telling them how to differentiate.

Because the cells are in part triggered to differentiate through their physical environment, changes to the environment might cause the cells to fail to differentiate even if the chemical conditions are right. The example given in the press release is that of heart damage, where scar tissue prevents the cells from differentiating into heart muscle tissue.

The researchers hope that this work can be used to create stem-cell specific environments in the lab so that appropriate cells could be transplanted. Possibilities of this were shown by the fact that the cells reacted differently to different firmness in the gel culture medium.

I wonder if there are similar conditions for the growth of embryonic stem cells. On the face of it it seems like their earliest signals would have to be entirely chemical, since there is no variance in the environment, but perhaps as the embryo develops physical environments become significant to the fetal stem cells.

Stem Cells Without Damaging Embryos?

2006-08-23T13:17:00.000-07:00

Stem Cells Without Damaging Embryos?

Last fall the biotech company ACT (Advanced Cell Technology) published research showing that it was possible to remove one cell from a developing mouse embryo and use it to originate a line of embryonic stem cells. (See blog posts from 10/17/05 and 10/18/05 for more info and links.) Now ACT had done this with human cells. Unsurprisingly, this is being hailed by some as a way to create embryonic stem cells without destroying embryos.

Before I get into the science of it, I have one crucial question: if the embryos are allowed to develop, who is going to take care of the resulting child? If the embryos are destroyed as they are now, then there’s no difference—so for this to be a major change in the ethics debate, the embryo has to fully gestate to infancy. The ideal scenario is that the new cells are extracted from embryos already destined for implantation via IVF; the parents get their baby, the scientists get their cells, everyone’s happy-- but extremely strict ethical guidelines and standards will need to be followed so that the parents are not pressured to allow this research to be done, and the issue of compensation will have to be thoroughly explored. The situations that could develop without these are terrifying: Are researchers going to have to hook up with adoption agencies? Who is going to donate her womb, and will she be paid? It seems to me far more unethical to cause an embryo to develop without having a parent waiting for it than it does to destroy a blastocyst. While I would like to believe the situation will always be aboveboard, there have to be fundamental protections in place.

OK, cautionary note aside, here’s what some of the media are saying about this technique. The BBC summarizes the technique nicely: “Using spare human IVF embryos, the researchers removed single cells from them, employing the same procedure used for pre-implantation genetic diagnosis (PGD), a technique that has been used in IVF so cells can be removed from the embryo and tested for genetic disorders.” In other words, the extraction is not a new technology; it is the successful creation of ESCs from the extracted cells that is the news. The researchers used 16 embryos and were successful in creating 2 lines. A thorough article in the San Jose Mercury News expands on the technique: the PGD testing—which has its own ethical issues—involves removing a cell and allowing it to divide. One of the resultant cells is then tested for genetic defects and mutations. The other resultant cell would be the one that could be used in research. An AP story in the Houston Chronicle is also instructive as to possible consequences of and objections to this technology, and gives a decent scientific grounding.

Issues that are being raised are the quality of the stem cell lines obtained—obviously this is not known yet, but it will have to be established before scientists see these as a reasonable alternative. There’s the issue as to whether the genetic testing can cause any damage to the embryo/child—no defects have been observed thus far in 1000 cases of the testing—but it’s still disrupting natural development, and the effects, if any, over a life-time are not known. There is also the question of whether the separated cell itself has viability; if it does, then we’re back at square 1 of the debate. And then there’s the legal issue—would these cells be exempt from the federal funding restrictions or still bound by them because they are derived from an embryo?

In other words, just because this can be done does not mean it is a solution to the embryo-destruction question, and it is problematic in other ways too. Certainly this seems like something that has potential, but don’t count on it to become the new scientific method for ESC research any time soon.

Recent Happenings

2006-08-21T14:15:00.000-07:00

Well, I’ve been delinquent. Part of it is that my DSL has been giving me fits and I am in fact switching to a different provider this week, and part of it is that there really hasn’t been much happening. Lots of sound and fury about stem cell research in general still, but very little concrete action. No new good research. A few things are of interest in the human affairs side of it:

In the “whatever happened to…” category, Hwang Woo-suk is back in a lab doing animal research. He lost his license to work with human cells, but can still carry on with animals, provided that he does it at his own expense. No more funding for him! His reputation is so shot that he is widely expected never to publish again, so I don’t know what he’ll do with the outcomes of his research. Apparently he is doing work with organ regeneration in pigs. Read all about it on The Hindu and in Chosun Ilbo.

Other news has to do with funding for stem cell research in Illinois. This has been somewhat controversial, as $10 million was shifted by the governor from a line item for “scientific research” in the budget specifically to stem cell research without legislative approval. Now, some of the grant money is being distributed. The Belleville News-Democrat reported last week that the first $5 million in grant money has been disbursed; the 7 researchers are located at the University of Illinois College of Medicine in Peoria, Southern Illinois University, and both the Chicago and Champaign-Urbana campuses of the U of Illinois. The newspaper of SIU, The Southern, also has a story, most of which focuses on the issue regarding the source of the funds. I have to say that, while I am glad the research is going ahead, it does seem like it was somewhat of an underhanded way to do it and I don’t think these decisions should be made by executive fiat. I don’t completely absolve the Legislature—they could have asked what “scientific research” meant and refused to approve it that generally—but I don’t think Gov. Blagojevich is setting a good precedent for a reasoned discussion of the issues.

Cool News on Brain Cells

2006-08-17T12:56:00.000-07:00

Cool News on Brain Cells

Researchers at the University of Florida have used mature human brain cells to generate new brain tissue in mice. The press release reports that the researchers acquired the stem cells from the brains of epilepsy patients who had undergone surgery; the tissue came from a part of the brain not normally associated with stem cells.

The cells were cultured in a dish and given appropriate growth factors, at which point they differentiated into progenitor cells and could be coaxed into neurons. Further, when the researchers put cells that had not been cultured with the growth factors into mouse brains, the cells created new neurons. Of great significance is that the scientists were able to produce millions of cells from a single cell—the director of the institute where the research was conducted said, “This is a completely new source of human brain cells that can potentially be used to fight Parkinson's disease, Alzheimer's disease, stroke and a host of other brain disorders. It would probably only take months to get enough material for a human transplant operation.”

There are several theories as to how this occurred. Researchers think it is possible that there are stem cells in the grey matter that start dividing under certain conditions; another theory is that when the normal cells are removed from their environment, they revert back to a more primitive stage.

This is pretty exciting, given that the brain is the area of the human body that we know doesn’t continue producing new cells through someone’s life. Obviously mice have pretty different brains from humans, and there may be something in their body chemistry which humans lack that produced this result—perhaps the cells express a particular protein that binds to mouse stem cells and stimulates them to produce, or turns off something that keeps them regulated. Humans might not have that particular receptor. But, of course, they might, and when you can start building neurons in a dish and keep them alive in an animal, you’ve got something very important.

I’m assuming that there is nothing fundamentally different in these brain cells between a person who has epilepsy and a person who does not, that the epilepsy surgery created an opportunity to harvest cells but is otherwise entirely irrelevant. But that might at least be confirmed. I’d also like to see if, with the right growth factors, these cells could become multi-potent or can only produce neurons, and if those growth factors have similar results on cells taken from other parts of the body, whether stem cells or normal ones. I’d also like to know what sort of cancer risk the mice had, what kinds of mutations occurred and at what rate, and so on. But there’s tremendous possibility in this.

Start lining up to donate parts of your brain!

Brain Cancer and Stem Cells

2006-08-15T15:10:00.000-07:00

Brain Cancer and Stem Cells

Researchers at Preston Robert Tisch Brain Tumor Center at Duke University have identified stem-cell like glioma cells that expressed the growth factor VEGF generate the production of blood vessels that keep cancer cells alive and growing. This production of blood vessels is called angiogenesis.

The press release reports that the researchers identified the stem-cell like cells in tumors by use of known antibody markers. They then compared them to other tumor cells and found that these cells expressed more VEGF and formed more tumors with more blood vessels. When the VEGF activity was blocked with an antibody, the new blood vessel formation stopped and so did the tumor growth.

This research is not a way to cure brain cancer, but it does suggest that turning off the VEGF expression in the cancer stem cells could at least stop the progression of the disease. If it was combined with chemotherapy that killed the other cells, it might lead to a long-term remission.

It has been fairly well established at this point that a number of different kinds of cancers have cells with stem-cell like properties that may be causing the growth of the tumor cells and that are resistant to traditional chemotherapy because it targets cells based on their rate of division; the stem cells do not divide at the same rate the other tumor cells do. A lot of research has been done to identify these cells, but less has been successfully done so far to figure out what to do with them once found. Being able to inhibit key growth factors seems like a very important component of treatment.

The relationship between cancer and stem cells still consists of a large number of unknowns. Whether by synchronicity with this study or by design, UCSF Today published an article yesterday about cancer stem cells in general—take a peek if you are interested. There is also a cool stem cell photo and some links.

Retina Research

2006-08-15T14:48:00.000-07:00

Retina Research

Scientists at the University of Washington have successfully used human embryonic stem cells to treat diseased portions of the retina in mice, according to an article in the Seattle Times. The research was done with one of the federally approved lines. Stem cells derived from mice have previously been shown to have an effect upon retinal damage, but this is reported to be the first time human ESCs have done so. The MIT Technology Review also has a story on the subject.

The major challenge of the research was finding the right combination of growth factors. The scientists used growth factors that contribute to the development of the head in humans and mice, and also used a growth factor that contributes to a large eye size in frogs. With this combination of growth factors, the cells developed into retinal progenitor cells about twice as fast as they would in utero. The new cells replaced damaged rods, cones, and amacrine cells in the retina. Being able to create cells that developed into photoreceptors is a significant step forward in treating eye disease with stem cells, as it has been very difficult to reliably get stem cells to differentiate into the right kind and number of eye cells.

The researchers hope that this might lead to a treatment for human retinal diseases, such as macular degeneration, within two years. (It would be used for degenerative diseases and not—at least so far—as a treatment for blindness caused by other factors.) They are watching for the results of a California biotech company (ACT in Alameda) that is using the same ESC line as they did in similar research. ACT hopes to start human trials by the end of next year.

The next step will be to transplant the stem cells into blind animals and to see if the blindness can be reversed. Treatments of the eye with stem cells are really important, not only because vision is such a key sense to people, but also because they may provide information about how to treat the degeneration of other kinds of neural tissue. Since the retina is essentially an extension of the nerves in the brain, what works for the retina might work for brain or spinal degeneration.

In a somewhat related story, the Glasgow Daily Record reported that a young Scotsman is going to have umbilical-cord derived stem cell treatment to try to cure a rare degenerative disease of the eye called Lebers. The stem cells will be injected into his arm and his temples. The procedure will take place at a clinic in Rotterdam which has claimed success with using umbilical stem cells to treat multiple sclerosis. Most neurologists do not believe the MS treatment actually works, so it will be interesting to see if there is a success in the treatment for the nerve damage this man has sustained.

Australian Update

2006-08-15T14:14:00.000-07:00

Australian Update

The Sydney Morning Herald reported that John Howard will allow a conscience vote on expanding stem cell research, and that he was “surprised this morning by the depth of feeling within his party room…” He has been under pressure for a while to allow a conscience vote on the subject since the Lockhart report that was issued earlier this year recommended reducing the restrictions on embryonic stem cell researach.

There is still an issue as to in what form a bill will be brought to the floor of Parliament; one senator plans to introduce a private bill but under normal parliamentary procedure, it would need to be agreed to by the government for a vote to proceed. However, it appears that there are a number of voices calling for a free vote, and that Howard is hearing them.

Australia currently allows embryonic stem cell research on leftover IVF embryos. The new rules would permit therapeutic cloning. Another, very similar story was carried in The Age; it quoted one senator who is opposed to therapeutic cloning as saying that there should still be a debate on it.

Blog Future

2006-08-13T11:23:00.000-07:00

Blog Future

Well, I’ve been doing this blog for nearly a year, and it’s time to check in and see if it is worth continuing. The subject matter is still interesting to me, and I think I’m doing a pretty good job at reporting on research developments and providing a single source of this information for interested people, but there are a couple issues that may get in the way of continuing it past the end of August.

One is money (which also equals time). It costs $$ to keep this going, in the form of the technical services (domain name and hosting, etc.), publicity (for example, listing the blog in Internet directories or Google ads for it), and of course there’s my time. I have decided to apply to law school for next fall, in part to study issues such as the stem cell patents, and I want to do as much prepartory work as I can for the first year so that my family life does not get shafted.

There’s also the issue of traffic (which is part of what leads to the issue of money). There are a number of regular readers out there, but it’s not a huge number, and it’s not really increasing. Is it worth it to keep this going when there aren’t actually a large number of people who benefit from it?

Given these issues, it’s important to see what support is available from readers, in the form of a small donation and letting friends and colleagues know about it and adding links to it where appropriate (with reciprocal linking if desired, of course). If readers can make donations totaling $1000 by the end of the month, it can keep going for a while— otherwise, it’s been a fun ride but time to move on.

Another Use for Stem Cell Transplants

2006-08-13T11:14:00.000-07:00

Another Use for Stem Cell Transplants

Stem cell transplants are well known as a procedure after chemotherapy to help restore a drug-ravaged immune system, but that is not the only situation in which an infusion of stem cells into the blood can help. A few days ago the North Carolina Wilmington Star ran an article about the use of stem cells as a treatment for systemic scleroderma. The disease involves an overproduction of collagen, thereby causing the skin and internal organs to harden and become immobile. The article is mostly about the disease and various treatments that are being tried, one of which is stem cell transplants. While they have shown promise, they are still considered experimental and thus are unlikely to be covered by insurance, putting them out of reach for many patients.

I’m not surprised that stem cells might be effective against this disease, since it is an autoimmune disorder and stem cells appear to be highly effective against lupus, another autoimmune disease. Since the article did not focus on the treatment, there was no reporting of how many clinical studies have been done, what results have been, and so on. The NIH Clinical Trials site (clinicaltrials.gov) showed 4 current clinical studies recruiting when I search “scleroderma stem cells,” so try that if you are interested in finding out a little bit more.

Odds and Ends

2006-08-10T10:10:00.000-07:00

Odds and Ends

The stem cell initiative got on the November ballot in Missouri; the initiative petition has been certified…. The Chief Scientist of Australia has criticized John Howard as too conservative on the stem cell issue….Harry Reid told some of his Nevada constituents not to give up hope on stem cell funding….The Los Angeles Times had a fairly extensive story on the issue of duplicate lab facilities and the problems researcher are having interpreting exactly where federal dollars can go….The governor of Maine, John Baldaccci, issued a statement calling for expanded funding for stem cell research….

As is fairly evident from the above, stem cell research’s social and political effects are still much more prominent in the new than research about what is actually going on. I did some searching of clinical trials, only to find that almost all are still recruiting so there are no results to report yet—the Patel trials on hearts that began a year ago in Pittsburgh are still seeking people, for example.

So I went to the EurekAlert website, where scientific press releases are posted, and found two on stem cells, both to appear in the journal Cell. In the first, researchers at Rockefeller University have identified progenitor cells in the sebaceous glands. They also found that a gene known as Blimp1 appears to control how many progenitor cells there can be in any given gland. The researchers don’t know how this works yet, but they do think it is useful information in the study of how stem cells are regulated in the body. The second is key enough that I am reporting on it separately (see post titled “Mouse Pluripotency from Adult Cells”).

Mouse Pluripotency from Adult Cells

2006-08-10T10:09:00.000-07:00

Mouse Pluripotency from Adult Cells

A press release about a study to appear in the journal Cell reports that researchers from several different Japanese institutes have derived pluripotent stem cells with embryonic stem-cell like properties from fibroblasts, which are structural fibers in connective tissue. The researchers selected 24genes which had previously been found to play a role in early embryos and embryonic stem cell identity, and found that 4 of them (Oct3/4, Sox2, c-Myc, and Klf4) could induce pluripotency in fibroblast cells from embryo and adult mice. The researchers call these cells “induced Pluripotent stem cells,” or iPS. They also found that when the new cells were injected under the skins of mice, a number of different kinds of tumors with characteristics of the three main “germ” tissues in mammals. When the iPS were injected into mouse blastocysts, they aided in the development of the mouse embryos.

There are still a lot of unknowns: are the cells truly pluripotent, or do they have some limits on their development that have not yet been identified? What is the risk of abnormal development, mutation, or cancer with these cells? Do human cells use the same proteins? Can cells other than fibroblasts be induced into pluripotency with some or all of these factors? Nevertheless, I think this is an important finding and one that needs to be pursued aggressively.

I also want to point to this as an example of how embryonic stem cell research has results—without the information about embryo and embryonic stem cell development, the researchers would not have been able to limit their investigations to 24 genes. It is certainly the case that adult stem cells have more therapeutic uses than embryonic stem cells right now, but the research that is done on the embryonic stem cells contributes important knowledge to what adult stem cells do.

Stem Cells Regenerate in the Mouse Inner Ear

2006-08-08T10:47:00.000-07:00

Stem Cells Regenerate in the Mouse Inner Ear

CBS reported last night that scientist at Stanford have been able to use stem cells to regenerate the tiny hairs in the inner ear that are a key part of hearing. (The hairs transmit the sound signals to the nerves.) The work was done by injecting the stem cells into mouse embryos; it has yet to be done on live mice. The story, being for TV and therefore almost devoid of any real information, did not say what kind of stem cells were used. It is also belated; the San Francisco Chronicle had a story on the subject back in January, and Stanford itself, reporting in May 2005 that the scientist was coming, also spoke to the fact that pluripotent cells had been identified in ears.

The sad thing is reading the comments—people are asking desperately if they or a family member would be eligible for this treatment, or how to find out about it. If it hasn’t even happened in live mice, there is certainly no clinical study in humans going on right now. I believe that CBS has a responsibility to have stated this clearly in the story—this is indeed what I would call an example of media hype. People are not always good at understanding what information their source is giving them—I sometimes get comments to this blog asking me similar questions even when I have identified the state of the research and who is doing it—but precisely because this happens the media have a responsibility to be clear that a therapy is not imminent. People should always discuss a study with their physician, not with a journalist, even if it is a journalist who brings it to their attention. The Chronicle story quotes the researcher as saying it might take 10,000 mice and 10 years, which is the kind of info that the public needs.

Don’t get your science news from TV, folks! Print is better by far.