Stem Cells, Part 3

Diseases and conditions where stem cell treatment is promising or emerging. (See Wikipedia:Stem cell#Treatments). Bone marrow transplantation is, as of 2009, the only established use of stem cells. Image credit: Mikael Häggström. 

So we've explored embryonic versus somatic stem cells. We know the advantage of embryonic stem cells (tabla rasa cells, effectively) and of somatic cells (plentiful and unchallenged ethically but perhaps harder to work with). But what type of cell therapy are we talking about with stem cells? What can you do with them to fix people?

Well, you've already heard of one treatment that is proven with stem cells, even if you don't really think of it as being one: that of bone marrow transplants, which can be used to treat a huge variety of acquired and congenital diseases or disorders. But what are doctors and researchers planning to do with stem cells if the federal spending is finally freed to work with all kinds, embryonic and somatic?


I can tell you after days of researching this article that there is a huge amount of hype out there on stem cell therapy. People at centers all over the country talk about stem cell therapy as if it is already accepted, proven and fully vetted. In fact, it's not. 


Somatic stem cell therapy is much better understood at present and there are a number of promising indications for using somatic stem cell therapy to treat cancer patients, spinal cord patients and cardiac patients. But embryonic stem cell therapy is barely begun. In fact, the first clinical trial of an embryonic stem cell treatment started this week. And it's caused quite a lot of controversy, even among proponents of embryonic stem cell therapy.

"Without knowing more clinical detail, there's little that I can say," said Steve Goldman, chairman of the Department of Neurology at the University of Rochester in New York. "In more general terms... I remain concerned about the long-term safety of unpurified grafts of embryonic stem cell derivatives. Time will tell."

~ from The Washington Post 

Yes, in addition to the ethical controversy, there are still a number of concerns that need to be addressed scientifically about using stem cells. If these cells are always turned "on" for division, for instance, what will stop their rapid cell division and growth? Uncontrolled cell growth is usually called cancer. Or, leaving aside that unlikely outcome, what if reprogrammed cells just somehow lose their programming? What happens if a mesoderm stem cell differentiated into ectodermal tissue reverts back? All of these are questions that have been posed at various points in time, and not just in the lay literature opposed to stem cell research, as you can see from Dr. Goldman, above. Another worrisome factor has been contamination of the stem cell lines. This has actually been reported, and was cause for concern about the present stock of embryonic stem cell lines which scientists have been using for the past decade. In 2005, a group of researchers at UC San Diego and the Salk Institute in La Jolla reported in the journal Nature Medicine that they found solid evidence that human stem cells were contaminated with non-human sialic acid as a result of the culture media which was using non-human serum to sustain the cells. Subsequent work by Robert Lanza, et al. was published in The Lancet reporting a new embryonic cell line that was grown without serum feeding and therefore less likely to be contaminated. Yet the original group's finding draws attention to the fact that there is much that needs to be refined in the field of stem cell research. How that refinement will occur without federal research dollars may turn out to be very unfortunate for anyone who needs stem cell treatment. With only private sector funding of embryonic stem cell research and therapies, one can only imagine the simply exorbitant costs that these therapies will be have when they finally are offered. It will truly be medicine for the wealthy, no doubt.


The first clinical trial of embryonic stem cell treatment in human subjects was approved by the FDA in January 2009 for transplantation of differentiated neural cells called GRNOPC1, progenitor oligodendrocytes, into patients with spinal cord injuries. The study was on hold for more than a year because of microscopic cysts found in rat test subjects. That hold was lifted in July of this year. On Monday, October 11th, 2010 Geron Corporation announced that the first spinal cord patient was treated with the differentiated stem cells in Atlanta, at the the Shepherd Center. 


There is much argument about whether embryonic stem cell therapy is safe, is ethical and even whether it is likely to be effective. What is clear, however, is that if funding is not available to sufficiently research and test, even if in non-human subjects¹, that the likelihood of success on any level is poor. When contamination was reported in cell lines in 2005, within months Robert Lanza's group at the private firm American Cell Technology reported not just a potential way to grow cells without serum, but within a year, a way to extract the inner mass stem cells without destruction of an embryo. Research findings drove the science of stem cell technology forward.


If we don't publicly fund medical research in this country there will be two devastating outcomes: we will fall farther and farther behind the rest of the world, and we will end up with novel treatments that only the very wealthiest Americans will be able to afford.


Think of anyone you know who has any of the ailments in that figure above, who might potentially be treated by stem cell therapy. How much is too much to pay? 


So hopefully, when you next hear 'stem cell research' you'll ask what kind of stem cells and you'll ask whose research it is. Is it publicly funded and therefore yours, mine and ours? Or is it privately funded? And how about just saying "Yay! More research!"


Research and peer review drive science, and medicine, forward.


They are your very best hope for a healthy future.

¹ Readers should remember that the Dickey Wicker Amendment prohibits any embryonic stem cell research with embryos even from other organisms to be funded with federal dollars. Specifically:  For purposes of this section, the term "human embryo or embryos" includes any organism, not protected as a human subject under 45 CFR 46 (the Human Subject Protection regulations) . . . that is derived by fertilization, parthenogenesis, cloning, or any other means from one or more human gametes (sperm or egg) or human diploid cells (cells that have two sets of chromosomes, such as somatic cells).


© Bright Nepenthe, 2010

Stem Cells, Part 2

Stem Cell Differentiation

University of Kansas

Today's post is the most complex of the Stem Cell posts. The illustrations should break it down for the reader, so please stick with it. At the very least, it will give you a healthy respect for the inventiveness of scientists who are trying to develop stem cell therapies to cure all manner of diseases.

Yesterday we talked about embryonic stem cells. Because of their potential to be more versatile, embryonic stem cells have been more coveted for research. You may wonder how they are acquired. 

The most common means for acquisition of the inner mass of cells that yield pluripotent stem cells is to harvest them from unwanted embryos (morulas or blastocysts) that are left over after successful in vitro fertilization. Generally, couples can donate their no longer wanted/needed embryos for medical research. Of course, some of you may remember from my post back in August that some people think that choice shouldn't be left to the parents of these embryos... Even if the embryo is five days old and the size of the period at the end of this sentence, and is the result of tens of thousands of dollars of in vitro fertilization care and has 'parents,' some people believe it is unethical to harvest stems cells because clearly it will destroy the embryo.

So what were scientists doing during the Clinton/Bush years, when stem cell research was limited by the charming Dickey-Wicker amendment? (This amendment expressly forbad expenditure of federal research dollars on any program in which human embryos, or embryos in general, would be discarded, destroyed or subject to any injury or risk of cell death greater than that allowed on fetuses, which is pretty much nil...) When scientists could not gain access to embryonic stem cells, they tried to work with adult or somatic stem cells.

Somatic stem cells are so called because they originate from a developed body's tissues. That can be a child's body, or that of an adult. The differences are best illustrated in this handy image from Nature, the premier journal in the sciences:

Differences between embryonic and somatic stem cells.

Copyright 2006 Nature Publishing Group, O'Connor, T. P., & Crystal, R. G., Genetic medicines: Treatment strategies for hereditary disorders, Nature Reviews Genetics 7, 261–276

The problem with using somatic stem cells is that most of the time, tissue is well differentiated in a formed body (again, differentiation means the job of the cell line has already been determined. Liver cells are liver cells, nerve cells are nerve cells. So researchers have sought the chemical signals or hormones that would turn back the clock so to speak, and allow these dedicated cells to achieve undifferentiated growth again. Although, restriction of cell lines still is an issue. But clever ways around that problem involved using the placenta, fat tissue, bone marrow hemopoietic cells (cells that will develop into blood cells of all kinds) among others. A lot has to do with the origins of the cell type in the germ layer of the embryo.

Image attribution uncertain.

As shown above, the embryo has three different layers, called germ layers. They are the endoderm, the mesoderm and the ectoderm. Stem cells that originate from one layer can, by a process called transdifferentiation, develop into tissue of another layer. For instance, when we look at the fate of cells in the ectoderm, as shown above, we would be very surprised if we were to get ectoderm cells that could be differentiated into liver cells. That's in theory the job of endoderm cells. There is currently a serious debate about whether transdifferentiation, or essentially reprogramming of a stem cells's germ layer assignment,  can occur in humans. Even if you are capable of making stem cells transdifferentiate into other cell lines, who's to say that the reprogramming remains true? Along germ layer lines, though, we can see how for instance bone marrow stromal or mesenchymal stem cells be used to create blood and bone:

While this might be useful for a number of different disorders, it is not a solution for things like central nervous system dysfunction, cardiac disease or liver disease. Better results have been suggested, within the past few years, with the use of placental and umbilical cord stem cells or so called non-adult, postnatal stem cells. Many parents decide to bank the placenta and cord stem cells in case of future need and well developed stem cell therapies. Placental stem cells are pluripotent, just like the cells harvested from a blastocyst. Placental and cord stem cells might be capable of differentiation into a variety of useful cell lines, as shown below:

This diagram appears to have been based on the one below, from the University of Kansas Stem Cell Research Center. Remember that a blastocyst yields embryonic stem cells, however. The applications in the diagram above have NOT been clearly established.

The important thing to consider when using somatic stem cells is that you may have to work much harder, and the errors can be greater, in getting the cell differentiation you desire for your stem cell therapy. Pluripotent cells, either embryonic or postnatal placental and cord stem cells, offer the best guarantee. However it must be recognized that the placenta and umbilical cord are organs, that is that the tissue is inherently already largely differentiated. You can consider the situation like that with the bone marrow cells above.

Cell lines created from organs can have limitations that cells that have not yet even differentiated into germ layers (blastocyst embryonic stem cells) do NOT have. Blastocyst derived stem cells provide in all likelihood the best source for stem cell lines.

© Bright Nepenthe, 2010

Stem Cells, Part 1

Last week my stepmom sent me a link to a NY Times article on stem cell researchers who were fearing loss of their jobs, their entire life's work as researchers, because of the issues with funding of stem cell research in this country. I started, not once, not twice, but three times to write a post on the article but got so angry that I set it aside.

I started wondering whether many of you even know what stem cells are. So this for the rest of this week, I'm going to put up some posts with some basic information about stem cells, and stem cell research, closing on Friday with a discussion about the landmark announcement on Monday of this week of work on testing stem cell therapy for spinal cord injury patients and the use of mesenchymal stem cells in cardiac patients.

But first things first. What is a stem cell?

In order for a cell to be considered a stem cell, it has to have only two characteristics:

1. self-renewal or the capacity to undergo through cycles of undifferentiated cell division. (differentiation is just kind of like developing a particular function, so undifferentiated means the cell hasn't chosen what it's going to be when it grows up yet.) 

2. potency or the ability to then be differentiated into any specialized type of cell.

Potency, which has nothing to do with Viagra in this case, can be either totipotent (capable of differentiation into any type of cell, including into a fully functioning organism, e.g. "you can be whatever you want when you grow up, honey"), pluripotent (descended from totipotent cells and can differentiate into most types of cells but not all, "no sweetie, you can't be a pilot because your eyesight is really bad") or multipotent (already so differentiated that they can only further differentiate along the same line, "your degree in the sciences qualifies you for admission to the following science-related graduate programs..."). Unipotent cells already have a clear job or function.

This is all summed up visually here:

Image credit: Mike Jones

from Wikimedia Commons

Embryonic stem cells originate from the blastocyst.


A blastocyst is a clump of fertilized cells that has divided steadily for about five days after the sperm successfully hit and implanted in the egg or oocyte. Only a small subset of cells in the blastocyst yield pluripotent stem cells.

from Wikimedia Commons

Here are a couple of images of a human blastocyst from the University of Michigan Stem Cell Research Center:

This highly magnified human blastocyst (the early embryo) is about the same size as a period at the end of a printed sentence. _← (That period there is about the size...) Embryonic stem cells are created from the inner cell mass from leftover embryos at this stage after egg and sperm are mixed in a dish in a fertility clinic. Excess embryos used for research would never be used for fertility purposes, but are routinely discarded as medical waste. Photo credit: Gary Smith, PhD, University of Michigan. (text © University of Michigan Stem Cell Center.)

Magnified image of a human blastocyst. Green area is the inner cell mass, the cluster of cells along the inner wall of the blastocyst that provide the embryonic stem cells. The red cells are trophectoderm.  Photo credit: Gary Smith, PhD University of Michigan. (text © University of Michigan Stem Cell Center.)

Pregnancy is usually defined in weeks, not days, from the last menstrual cycle. 

Image Credit: David Rubens

from Wikimedia Commons

A blastocyst is not a fetus. 






© Bright Nepenthe, 2010

The Triumph of Life Over Reason... Oh, wait a minute...

Why it's enough to jar me from my reverie over the horrors faced by youth aged out of foster care. Thank you, JC!

A federal appellate court has just temporarily (one hopes) blocked Obama's much touted government funding for stem cell research. In the battle of the National Institutes of Health vs. Nightlight Christian Adoptions, the first round goes to... Nightlight! NCA is an organization that wants to make sure that every embryo has a loving permanent family. (No word on whether gays adopting embryos is cool with these people, but I'm-a kinda suspecting it's a no...) 

According to the NY Times the problem is the ever so charmingly named Dickey-Wicker Amendment, which prohibits the spending of federal money on the destruction of embryos. Because, why embryos are life and that would be like abortion or something. By the by, the NIH specifically requires that a couple donate embryos for this type of research voluntarily and were offered the options of donating their embryos to infertile couples. Some people wanted to donate their embryos for research. Because they wanted to HELP PEOPLE. (The already here ones) But that is not good enough. They may be your embryos, but they're really not YOURS.

Scientific Research That Could Save Many Lives

Pure, Unadulterated Evil

(Image Credit: Wikimedia Commons) 

"Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta. Pluripotent, The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta. Stem cell diagram illustrates a human fetus stem cell and possible uses on the circulatory, nervous, and immune systems." From here.

What is an embryonic stem cell, you ask? It is a collection of 50-150 cells in a blastocyst, which is an egg, four to five days past fertilization. The immortal stem cells we already have should, you'd think, be just a-plenty. But that would be your thought if you don't read that charming little journal Nature Medicine and didn't know about the fact that the present stock of human stem cells that are available for use were discovered, back in 2005, to have been contaminated with non-human DNA that expresses a sialic acid Neu5Gc, likely murine (from a mouse) in origin and to which many humans have antibodies. Thus making it a massively not-swell idea to use these presently available stem cells for human cell therapy. I don't know many people that would want some other species DNA to get into their brain during their Parkinson treatment. Or into their pancreas during their diabetes treatment, for instance. I am totally with them on that. Having been scarred for life by Richard Preston's The Cobra Event and Mira Grant's Feed, I'm really thinking that mixing species' DNA when seeking novel treatments is just not a plan.

Forgive my snide and irritated tone when I say that I am thoroughly disgusted at people seeking to bar research that would potentially cure many diseases in the young and old and in-between population of people already here, all while failing to think about promoting adoption of children who are already here.

LOOKING FOR A GOOD HOME

Image credit: Molecular Station

© Bright Nepenthe, 2010