Thursday, October 14, 2010

Stem Cells, Part 2

Stem Cell Differentiation

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.

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

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