Showing posts with label cells and stem cells. Show all posts
Showing posts with label cells and stem cells. Show all posts

Friday, August 18, 2017

Classifying Cells and Cell Types

How do we describe the types of cells that comprise the human body? Pick any textbook of human biology and you'll find that cells are generally described as belonging to one of four types of tissue (nervous, muscle, connective, and epithelial) based on their broad function. At the next level of complexity, cells within a tissue are further described by their location and more specialized function (smooth muscle surrounding blood vessels; skeletal muscle attached to bones; cardiac muscle in the heart). Beyond these rather broad descriptions, many subtleties between cells are probably lost for lack of a way to measure or define them.

Some scientists think there may be a better way to identify and categorize cells. That's because what actually determines the differences between cells, both in terms of form and function, is the different proteins that they express. Those proteins are determined by the molecules of RNA that are present within the cell, which in turn are determined by which of the cell's genes are active. So to get a more refined measure of a cell's type and its true activity, it would make sense to measure not its shape, its location, or its broad function, but instead to determine which RNA molecules are present in the cell.

A group of enterprising scientists is attempting to do just that, according to an article in The New York Times. They've started with an organism (a type of worm) that has fewer than 1,000 cells. If all goes well, some day we may know a lot more about the incredible complexity of our various cells. And we may have to rethink how we classify cells and describe the relationships between them.

Saturday, July 1, 2017

A Skin Patch to Deliver the Flu Vaccine - An Update

Remember the skin patch (this blog, Mar 13, 2014) that was being developed to deliver vaccines without an injection? Back then, the patch had only been tested to see how well the dissolvable microneedles of the patch would be tolerated by patients. Last week the same researchers reported that it has now been tested with the flu vaccine.

In the latest study, healthy volunteers received the flu vaccine either by skin patch or by the usual syringe and needle, both administered by a health care worker. An additional group of volunteers were instructed to administer the skin patches themselves, to determine if self-administration was as effective as administration by a health care worker. The results were encouraging. Increases in antibody titers (a sign of immune system activation) were the same in both of the groups that used skin patches and the group that received an injection. Furthermore, the number of adverse reactions was similar in all groups. In other words, the skin patches seemed to deliver the vaccine safely and effectively, even when the patches were self-administered.

So are we done? Not quite. This was a Phase 1 study; a small number of volunteers was recruited to test the method's safety and potential effectiveness (in this case, potential effectiveness was assessed as an increase in antibody titer). A much larger study will be needed to see if the skin patch vaccine delivery method actually reduces the incidence of the flu. A much larger group of patients will be needed, since not everyone in a population gets the flu. This part of the study will probably take at least several more years.

Perhaps some day you'll be able to order a flu vaccine skin patch on the internet, have it delivered through the mail (or by a drone!), and administer it yourself. Today we're one step closer to that goal.

Thursday, September 1, 2016

New Guidelines for Human/Animal Stem Cell Research

The National Institutes of Health (NIH) is considering updating its guidelines for stem cell research. The proposed new guidelines would allow human pluripotent stem cells to be inserted into non-human vertebrate embryos under certain conditions. Federal funding for such research has been prohibited since 2009 to give NIH time to study the issues carefully.

It seems clear that the NIH wishes to avoid the accidental (or on-purpose) production of human/animal chimeras; animals that are too close to human in their physical, mental, or emotional traits. To avoid this possibility, NIH plans to review carefully any experiments in which the human cells are introduced before the gastrula stage in the embryo - when the three germ cell layers begin to develop. A special restriction is that human cells may not be introduced into primates before the blastocyst stage. Proposals will be reviewed by a special steering committee comprised of scientists, ethicists, and even animal welfare specialists. The committee may consider such things as where the human cells are likely to end up in the animal, as well as how the human cells might affect the animal's physical and behavioral traits.

Why do this type of research at all? Scientists argue that the chimeras produced in this way (perhaps rodents with some human cells or tissue types) would be useful for understanding some human diseases, as well as for drug testing on animal models. Perhaps one day it might be possible to produce human organs suitable for transplant in animals. But that day is a long way off.

What do you think? You have until Sept. 6 to submit your comments NIH.

Wednesday, July 9, 2014

The One-Dollar Microscope

A microscope that costs less than a dollar?  The Foldscope is made primarily of paper, plus a sapphire ball lens, a LED light source, and a small button battery.  It can be easily folded (assembled) into a working 2000-x microscope within minutes.  Although not as versatile as a microscope costing hundreds of dollars, the Foldscope is good enough that one can see individual cells in a sample, and even identify some bacteria and tropical diseases such as malaria and schistosomiasis.

The Foldscope was designed by scientists at Stanford University.   It is currently being tested by the first 10,000 persons who signed up to receive one.   From their many experiences, the volunteers will also help develop a crowd-sourced microscopy manual.  The goal of the scientists who developed the Foldscope was to create a simple cost-effective tool that could be used to stimulate curiosity in science and biology.  It may also have applications in global health.

You can’t buy a Foldscope just yet.  But at only a dollar apiece it may not be long before they are standard issue in most schools, and also in health clinics in poor countries.

Friday, April 4, 2014

Stem Cell Paper Challenged

Two months ago I reported on an exciting new finding (this blog Feb. 3, 2014) that a Japanese and American team of researchers had developed a simple way to produce pluripotent stem cells from adult cells.   The paper was hailed as a breakthrough of sorts.  If true, it suggested that deriving stem cells from embryos (always controversial) might no longer be necessary.

That finding is now in serious doubt, because other researchers have been unable to verify the data.   A blog site that is following attempts to duplicate the research says that most researchers no longer believe that the findings are real (search STAP cells).   The research institute where the Japanese researchers work is investigating.   So far the original paper has not been retracted, but that’s a distinct possibility.

How can we have any faith in scientific discoveries if the story changes month-to-month?  The answer is that science is not about having faith.   It’s about verifying and then verifying again, until we can have confidence, backed by reproducible data, in what we know.   It’s messy.  Sometimes the answer isn’t what we thought it was, but over time we get closer and closer to the truth, whatever it is.

As for pluripotent stem cells, it’s back to square one when it comes to creating them from adult cells, apparently. Embryos may yet be needed for awhile.

Monday, February 3, 2014

A New Way to Produce Fully Pluripotent Cells

Stem cells are undifferentiated cells that have the capacity to develop into many different types of adult cells. The best source of stem cells for research or medical treatment has always been stem cells harvested from very young embryos. The use of human embryos to harvest stem cells causes all sorts of ethical concern, of course, because human embryos must be sacrificed to harvest the cells. I doubt that anybody would actually prefer to harvest stem cells from embryos if there were another reliable source.

Some progress has been made in learning how to reprogram adult cells back into a “pluripotent” stage (capable of becoming multiple types of cells). Unfortunately, current techniques have not been able to produce pluripotent cells with virtually all of the properties of true stem cells.

Now, researchers in Japan and at Harvard University may have achieved a breakthrough of sorts. The researchers had been exploring ways to make adult cells revert to a pluripotent state closer to true embryonic stem cells. In a paper just published in Nature, the researchers exposed adult cells from mice to the stress of a solution with a high pH (a mildly acidic solution). Although many of the cells died, some of the ones that survived showed biochemical signs of having become pluripotent cells. More importantly, when the researchers injected these cells into embryonic mice, the cells grew and differentiated into virtually all types of adult cells, right along with the mice’s own cells.

It’s too soon to tell whether the technique would work with human cells. Nevertheless, the idea that exposing adult cells to a simple reproducible type of stress in the laboratory could cause them to revert to a pluripotent state very similar to embryonic stem cells is an exciting new concept. The day may yet come when human embryos are no longer needed as a source of stem cells. And that would definitely be a good thing.

Monday, May 20, 2013

Scientists Clone Human Cells

Using essentially the same techniques that resulted in the first cloned adult animal (Dolly the sheep), scientists at Oregon Health Sciences University have cloned human cells and coaxed them into developing into human embryos. Their intent was to be able to produce cloned cell lines from the embryos strictly for therapeutic purposes. The research is published online in the journal Cell. The researchers started with eight human eggs from a single human donor, and after enucleating the eggs, joined them with human skin cells. From these they obtained five blastocysts (early-stage embryos) and ultimately produced four cloned cell lines.

So far, human embryos produced by these techniques (known as somatic cell nuclear transfer) have not been allowed to develop into full-term human babies. The cloning of humans, of course, raises some serious ethical issues. Society will have to grapple with the issue soon, because it’s now clearly within the realm of possibility.

The basic idea behind reproductive cloning research is to be able to produce human tissues that are an exact match for the human patient from which the cloned cell was taken. Tissues produced these techniques could be used to produce skin for treating burns, or perhaps heart, or liver cells to repair a damaged organ, without fear of tissue rejection.

Do the potential medical benefits outweigh the ethical concerns associated with the creation and ultimately the sacrifice of human embryos? You decide.

Monday, January 23, 2012

Stem Cell Therapy Trial Halted


About a year and a half ago I reported on the first clinical trial of a therapy using stem cells (see "First Human Stem Cell Trial"). The trial, run by Geron Corporation, was designed to treat patients suffering from spinal cord injuries with neuronal cells grown from stem cells.
This past November Geron announced that it was cancelling the clinical trial and its entire stem cell research program. In a statement, the company said only that it will “discontinue further development” of its stem cell programs in order to focus on several promising new cancer drugs. According to Geron it was a decision based on the need to save money. By abandoning its stem cell research program, Geron will lay off 66 staff members and save about $25 million a year, according to a news article in Science.
Only four spinal cord injury patients were treated before the trial was terminated.. Preliminary results showed that their conditions did not improve after treatment.
Cancellation of the trial is certainly a setback for stem-cell-derived therapies, but it is not an outright disaster. At least one other clinical trial of a stem-cell-derived therapy, for macular degeneration, is already underway at a company called Advanced Cell Technology. And it’s still possible that another company will buy Geron’s stem cell program assets, which included work-in-progress on treatments for several other diseases.

Sunday, January 15, 2012

Stem Cell Fraud

The FBI has charged four men with illegally trafficking in stem cells, according to a report in a Charleston, S.C. newspaper. Apparently, one of the men convinced birth mothers at a clinic in Del Rio Texas to donate their placentas and umbilical cords to medical research. Instead, he allegedly sold the placentas and umbilical cords to a man posing as a doctor from a laboratory in Arizona, who shipped them to a third person, a faculty member at the Medical University of South Carolina. Stem cells were harvested in South Carolina and then shipped back to Texas, where a fourth person who operated a “biotherapy clinic” allegedly convinced terminally ill patients that the stem cells would be a miracle cure for diseases such as ALS, MS, Parkinson’s disease, and cancer. The patients traveled to Mexico for the stem cell injection procedures. The four men allegedly made more than $1.5 million from the scheme.

Stem cells are being used legitimately in human clinical trials, but those trials follow FDA guidelines that include government oversight and evidence of the patients’ informed consent. That was not the case here. According to an FBI spokesman, this was “a scheme whereby the suffering and hopes of victims in extreme medical need were used and manipulated for personal profit. The predatory and opportunistic nature of the crimes alleged in this indictment mirrors images from science fiction.”

We’ve all heard of the potential of stem cells, and we all hope that some day perhaps they will be a miracle cure for certain diseases. But the hard truth is that stem cell research and especially treatment of disease with stem cells is still in its infancy. No one should be experimenting on unsuspecting patients.

Tuesday, June 7, 2011

Setback for Induced Pluripotent Stem Cells

Ever heard of induced pluripotent stem cells (iPSCs)? They were supposed to be the answer to the politically-charged issue of the use of embryonic stem cells in research or disease treatment. The idea has always been that if fully differentiated somatic cells could somehow be induced to return to an undifferentiated state (i.e. become pluripotent stem cells), then they could replace embryonic stem cells altogether. In addition, since iPSCs could be derived from the patient for which they would be used, it was presumed that they would not induce an immune response in the patient.

That presumption now is in doubt. A recent paper reports that iPSCs derived from mouse cells cause an immune response when injected back into genetically identical mice, leading ultimately to rejection of the iPSCs.

Scientists generally were surprised by these findings, since iPSCs were not supposed to be immunogenic in genetically identical animals. But further analysis revealed that these iPSP’s may be over-expressing certain genes, leading to the production of proteins seen as foreign by the immune systems of the recipient mice. Whatever the reason, the finding casts doubt on the idea that iPSPs could replace embryonic stem cells any time soon.

Sunday, May 22, 2011

Stem cells for Joint Injuries

Stem cells are being used to treat some professional athletes with joint injuries, according to an article in the New York Times. In the still highly experimental procedure, stem cells harvested from the patient’s own bone marrow and fat are injected directly into the patient’s injured shoulder or elbow to try to speed up the repair process. New York Yankees pitcher Bartolo Colon had the procedure done in the Dominican Republic last year, and now he’s back in the Yankee’s starting line-up. Just a year ago his professional career appeared to be over; he sat out the entire 2010 season following elbow surgery.

Mr. Colon’s recovery is anecdotal evidence that the procedure may work. On the other hand, Mr. Colon’s recovery could have been an anomaly or may have been unrelated to the treatment. Clinical trials are now needed to determine whether the procedure would actually benefit most patients. It’s not against the law to try an experimental procedure such as this on patients who are willing to pay for it. But before the procedure is put into widespread general practice, it would be nice to know whether it truly is effective.

Reference: Kovaleski, Serge F. Pitcher's Treatment Draws Scrutiny. The New York Times online, May 11, 2011.

Wednesday, May 11, 2011

The “Telomere Test” for Aging

Telomeres are disposable non-coding regions of DNA at the tail end of each chromosome. Every time a cell divides and its chromosomes are replicated, a small piece of each telomere is removed. That’s because replication stops just short of the end of the original strand because of the need for a primer sequence on each developing new strand. This natural erosion of the telomeres is thought to play a key role in the aging process. Once the telomeres are worn away by repetitive cell divisions, according to at least one current theory of aging, the cell may begin to lose pieces of functional genes with each additional cell division. Eventually the loss of genes either causes the cell to stop dividing or the cell loses some of its normal function.

Now, two commercial companies (one in the U.S., one in Spain) are offering to measure the length of your telomeres - for a price, of course. According to a news report, the companies are promoting the idea that the length of your telomeres may be predictive of how fast you will age, and perhaps even predictive of your risk of developing chronic diseases. Long telomeres for your age? - you’re lucky, you may live a long life. Short telomeres? - perhaps you’d better change your lifestyle or begin looking at ways to reduce your risk of chronic diseases while there’s still time!

Pardon my skepticism, but it sounds a bit like having your fortune told. Spend your money if you wish, but don’t count on learning anything very meaningful just yet from measurements of your telomere’s lengths.

Monday, May 2, 2011

Stem Cell Research STILL Allowed (Barely)

A three-judge panel of the U.S. Court of Appeals ruled last week that government-funded researchers may use human stem cell lines derived from human embryos before a law apparently intended to ban such research went into effect. (For more on this issue, see blog posts dated Sept. 1 and 13, 2010). The panel ruled that because the language of the law banning research on cells derived from human embryos is written in the present tense, “it does not extend to past actions.”

Surely this will not be the end of it. It sounds like linguistic hair-splitting, even to me. Given that the 3-judge panel was split 2-1 on the issue, the ruling will probably be appealed to the entire Court of Appeals.

In the long run the only real solution may be for Congress to draft unambiguous legislation that makes it clear once and for all under what circumstances, if any, stem cells derived from human embryos may be used. And that will depend on whether either side in this issue can muster the necessary votes.

Stay tuned.

Monday, September 13, 2010

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.

Wednesday, September 1, 2010

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.

Sunday, August 1, 2010

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.

Friday, March 26, 2010

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.

Saturday, February 27, 2010

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.

Saturday, October 24, 2009

Infertility Patients Favor Stem Cell Research

Most couples that have had to resort to in vitro fertilization (IVF) techniques in order to have a child are in favor of stem cell research. When asked in a national survey what they might choose to do with their frozen embryos left over after they have successfully had a child, 60% reported that they were “somewhat likely” or “very likely” to donate them for stem cell research. In contrast, less than a quarter of the respondents planned to discard their frozen embryos, or expressed a desire to donate them to another couple.

Infertility patients are especially aware of the advances in science that have made it possible for them to have children. Perhaps they are just more grateful than most, but apparently most of them have resolved any internal moral dilemma over what to do with their leftover embryos. It is interesting, however, that most of them would rather donate their embryos to research than to know that their biological child was being raised by another couple.

Saturday, October 17, 2009

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.