Stem Cells, The Blood Brain Barrier, and the Future

In the article, "Snorting Stem Cells", we reviewed earlier this week, we learned that there was a significant effort in 2009 towards developing a method for delivering stem cells to the brain, notably through "snorting" (for lack of better word). However, as interesting and hopeful as the article was, it failed to address some important questions that were brought up during discussion, such as: "What happens when the blood brain barrier, something designed to keep self and foreign particles, is made more permeable in order to retain a greater proportion of stem cells post-snorting?" And: "What happens once the stem cells reach the brain? Stem cells themselves have no therapeutic ability unless induced to differentiate and mature into potentially beneficial cells, so how do we get them to differentiate?" Obviously, I don't have the answers to these questions, but the purpose of this blog is to facilitate discussion, so let's start with a general overview on the blood brain barrier and stem cell function.

Discovered over 100 years ago by one Paul Ehrlich, the blood brain barrier serves to protect the brain from foreign (antigens, toxins) and self particles (leukocytes, macrophages) in the blood. Ehrlich found that upon administering different dyes through the blood, all major organs would stain, with the exception of the brain. Thus, the idea of a blood brain barrier existing was born. Today, we know that the barrier is primarily mediated by tight junctions and astrocytes. The tight junctions of the barrier are found in capillary endothelial cells, and serve to selectively limit the diffusion of non neural molecules. The astrocytes maintain the barrier through release of certain chemical messengers, and maintain the brain water uptake through aquaporin-4 water channels. Most importantly, however, was the discovery that molecules could make it across the blood brain barrier if they were lipid soluble enough, thus allowing for transport by diffusion. In fact, this is how many psychoactive drugs enter the brain.

Remarkably distinctive from other cells, are stem cells. Characterized by their ability to divide into virtually any cell our body needs, stem cells are pluripotent and non-specialized. There are two types of stem cells currently known: embryonic and adult stem cells. Both retain the basic function of stem cells described above, with greatest difference in location and specificity of division. Embryonic stem cells possess the ability to divide into the three primary germ line layers: the ectoderm, mesoderm and endoderm, which in turn divide into the cells that our body is comprised of. Adult stem cells are more rare and limited in their ability to divide-- they are usually found in more tissue/organ specific areas and can only divide into cells respective to their location. For example, hepatic stem cells will only be able to develop into other hepatic cells.

So how does this all relate to the questions posed in class? Well if you remember, in the article they stated that an enzyme was given to increase the permeability of the blood brain barrier. We decided that this was dangerous, since we don't know what else could make it in. Considering that the amount of stem cells that made it into the brain was such a meager amount (500/300,000) to begin with, a 3 fold increase claimed by increasing barrier permeability can be considered negligible. Furthermore, when taking into account the rapid division ability of stem cells, only a small amount would be localized in the brain to induce a larger, therapeutic effect. Also, since the blood brain barrier allows molecules in by diffusion based on their liposolubility, an interesting path for future research could be along the lines of trying to increase the lipid solubility of stem cells. Secondly, the question of how the adult stem cells would differentiate once in the brain could be answered upon inspection of stem cell behavior. As stated above, adult stem cells usually divide into cells in the organ in which they are found. So by snorting stem cells and allowing them to enter the brain, one might be able to trust that they divide into brain cells, right?  Well, for individuals who have damaged brain tissue from incidences such as stroke, the snorted stem cells could act as a repair mechanism in which new neural tissue could be regenerated in areas that the stem cells were localized.

Ultimately, this is just all food for thought. It can't be denied that stem cell/blood brain barrier research is still in its infancy and has vast reservoirs of untapped knowledge to be found.

Sources:

"Blood Brain Barrier and Cerebral Metabolism." Blood Brain Barrier and Cerebral Metabolism. UT Texas Medical School, n.d. Web. 30 Sept. 2014.

"Frequently Asked Questions." Stem Cell Basics: Introduction [Stem Cell Information]. National Institute of Health, n.d. Web. 29 Sept. 2014.

Morrison, Deanne. "Snorting Stem Cells." : UMNews : University of Minnesota. N.p., n.d. Web. 01 Oct. 2014.