by Taylor Petruccelli
I came across this topic in research for another class. Hopefully it will spark some interest in our blog…
Brian Vastag of Science News reported in mid March of this year about a neurologist and his team that implanted stem cells in diseased mice to initiate the growth of various types of brain cells. These newly produced brain cell types were recorded to extend the lifespan of each originally diseased mouse by seventy percent. The neurologist was Evan Y. Snyder, a leading figure in stem cell research, especially such pertaining to the Central Nervous System. Currently employed under staff at Harvard Medical School as Assistant Professor of Neurology, Snyder completed this study and experiment over ten years ago at the Burnham Institute for Medical Research in La Jolla, California. The study entailed developing murine stem cells that would be used to propagate neurons and support cells, called astroglia and oligodendrocytes, aimed to repair and protect the brains of the mice. The mice in the experiment were infected with Sandhoff disease which is characterized by an insufficient amount of the enzyme hexosaminidase (hex). Hex aids in lipid metabolism which helps eliminate excess lipids, or fats, from the brain. Without this important enzyme these damaging lipids amass, often in children, leading to death before age ten. Sandhoff disease and around fifty other diseases, such as Tay-Sachs, are all based around this inability of the brain to rid abundant lipids. Thus, Snyder implanted stem cells at birth that would eventually reproduce daughter cells competent in restoring enzyme production. He therefore achieved in creating an embryonic stem cell that when implanted around neural cells was capable of becoming a specialized cell, in this case one to produce hex. Snyder remarked that “The implanted cells knew exactly how to repair the brain,” a comment he followed with: “Even the dumbest stem cell is smarter than the smartest neurobiologist” (Vastag, 2007).
Snyder’s study opened up possibilities to also develop a human counterpart of the murine neural stem cell (NSC). It was discovered that stem cells from human fetal brains and human embryos, along with that from the mouse brain, were proficient in curing or neutralizing the harmful effects of the murine Sandhoff disease. This understanding brought Snyder and other neurologist back on board. Correspondingly, through a strategic advancement of experimental steps, Snyder and his team mirrored the process of propagating multipotent murine NSCs with that of a human equivalent, in order to achieve similar results in creating engraftable human neural stem cells capable of curing an array of diseases and genetic defects (Vastag, 2007; Flax, 1998).
In their basic form, neural stem cells are primordial, undesignated cells employed to reproduce a variety of highly specified cells of the Central Nervous System (CNS). NSCs sustain three main abilities or uses. First, they are postulated to evolve into cells for multiple regions of the CNS, predominantly including neurons, astroglia, and oligodendrocytes. Second, NSCs are meant to propagate, or reproduce, new NSCs with equivalent potential, otherwise called self-renewing. Lastly, they have to present a therapeutically benefit to the CNS, whether through populating or degenerating a specified region. The realization that murine neural cells with stem cell attributes, created in vitro, could effectively adjust to, in this case, a mouse’s brain after implantation, sparked the interest of neurologists to discover the relevant medicinal values of NSCs. It is hoped to uncover the abilities to cure genetic defects, injuries to the CNS, congenial or acquired brain deficiencies, among many other health issues (Flax, 1998).
How neural stem cells work is to first be isolated from the embryonic source. In the mouse experiment the neural cells with stem cell properties were isolated from the murine CNS of an adult. Then the individual NSC is reproduced in vitro through multiple techniques, all of which are efficient and safe. After full cultures of NSCs are propagated, they are implanted into specific germinal zones during growth periods to encourage reproduction during the normal natural developmental stages. With abundant plasticity, ability to adapt and mold, these cells relocate themselves and begin to differentiate in a suitable means for increasingly specialized cells of the CNS. Due to the success this process has undergone in rodent experiments, its potential in the human counterpart has been long awaited (Flax, 1998).
To read further in depth on Snyder and his team’s experiments you can find his article (see references) on nature.com. However I gained access to it through the Vassar Library using Scopus (no link), so to read it you will have to look it up (sorry).
Although Snyder accredits the success to the stem cell rather than any neurobiologist, he himself discovered something remarkable and unprecedented. Rather than trying to create specialized cells physically, he allowed science to take over with natural creation. It seems the paradox between creating a single specialized cell from the start or allowing a cell to differentiate and migrate on its own follows a seemingly unscientific adage: “You bring a man a fish, you feed him for a day, but if you teach a man to fish, you feed him for a lifetime.”
Flax, J. D., Aurora, S., Yang, C., Simonin, C., Wills, A. M., Billinghurst, L. L., et al. (1998).
Engraftable human neural stem cells respond to developmental cues, replace neurons, and
express foreign genes. Nature Biotechnology, 16(11), 1033-1039.
Vastag, B. (2007). Brain fix. Science news, 171(11; 11), 163-163.