Gorr, 6:00 R10 USING STEM CELLS TO FACILITATE NERVE REGENERATION Emma McBride (elm123@pitt.edu) Electrospun nanofibrous scaffolds, the second type, are “fine polymer nanofibrous meshes” with “a high surface area to volume ratio” [2]; researchers have found that a diameter of 283 nanometers of the nanofibers most effectively promotes the growth of the neural stem cells which are placed on the scaffolding [1]. “Contact guidance” is another property of nanofibrous scaffolds which aids the outgrowth and elongation of new nerves [1]. Clearly there are advantages and disadvantages of each type: hydrogels are easily injected into the brain tissue but they do not help direct the growing nerves, which electrospun nanofibrous scaffolds do. Therefore, the best scaffold would be a combination of hydrogels and nanofibrous. Although miniscule protein scaffolds may seem trivial, they are crucial in terms of today’s concern over regenerative medicine. INTRODUCTION: OVERCOMING BRAIN DISEASE WITH SCAFFOLDING AND STEM CELLS I believe that everyone is entitled to a maximum state of well-being and that the role of those in the medical field is to help people achieve this. The most heartbreaking and uncontrollable diseases often occur in the brain which is where scientists and engineers should focus their research. One such way that this can be achieved is in tissue engineered brain tissues. One of the breakthroughs in regenerative medicine is the use of neural stem cells on a protein scaffold to promote the growth of new, healthy brain tissues. Although some risks are associated with the use of stem cells, I believe the overall benefits of patient-derived stem cells are more important. Parkinson’s disease is an example of a disease positively affected by this approach. The engineering codes of ethics provide support for the claim that neural stem cells will be beneficial in the medical field. In order for people to realize this, however, we need to educate our engineering students on the application of ethics to engineering issues. Sowing Stem Cells as Seeds Stem cells are the “seeds” that grow on the architecture laid out by the scaffolding. By definition, “stem cells (SCs) are characterized by self-renewability, that is the ability not only to divide themselves rapidly and continuously, but also to create new SCs and progenitors more differentiated than the mother cells” [3]. Unlike embryonic stem cells, adult stem cells do not have the ability to differentiate into any type of tissue because they are already partially committed to a certain type, and they are “often defined by the organ in which they reside” [2]. We are most interested in using adult neural stem cells, “a kind of specific primitive nerve cell, [which] exist in the nervous system” [4]. Neural stem cells are multipotent which means they “are capable of yielding a more restricted subset of cell lineages” [3], including neurons and glia [2]. This ability of stem cells to differentiate into the cells and tissues that we need is one of their many benefits. STRUCTURE AND GROWTH: APPLYING TISSUE ENGINEERING PRINCIPALS IN THE BRAIN The technologies relevant to this discussion are tissue engineered scaffolding and neural stem cells. The protein scaffold acts as a support for the stem cells to grow on. The Most Effective Scaffolding Tissue engineers mimic the cell’s natural support, the extracellular matrix, by creating protein scaffolds. As stated in the book Tissue Engineering by Fon et al., “The fundamental role of scaffolds is to ensure cell survival, and to enable controlled proliferation and differentiation” [1]. Currently, the two major types of scaffolding in use are hydrogel and electrospun nanofibrous scaffolds. Hydrogels are long polymer chains whose macroporous structure allows for a “high nutrient and waste exchange” [2]. Because hydrogels have similar properties to the soft tissue of the brain [2], the structure conforms to the shape of the injury site where it is injected [1]. The best attribute of hydrogels is the pore size, the optimal size being 30 micrometers, because it “promotes the healing of biomaterial implants by suppressing the effects of the [foreign body response]” [1]. BENEFITS OUTWEIGH RISKS Tissue engineered scaffolding has numerous benefits and no risks. The hydrogel and electrospun nanofibrous scaffolding techniques allow for axon regeneration which is not normally present in adult nervous systems [1]. Scaffolds offer physical and chemical support to the growing stem cells. Similarly to the extracellular matrix, tissue engineered scaffolds encourage “neurite outgrowth” by “anchoring cells and promoting axonal growth” [2]. The scaffolds also provide nutrients and growth factors, stimulating the stem cells to differentiate and grow. University of Pittsburgh, Swanson School of Engineering 10/30/12 1 Emma McBride for Parkinson’s disease makes the effort of researching neural stem cells worth it. Stem cells, specifically neural stem cells, have advantages as well. According to research, neural stem cells “can not only carry out self-division growth, but also differentiate into nerve cells and neuroglial cells” [4]. They have the ability to form new nerves, which has many medical applications. From the perspective of the operating room, there is minimal damage to the patient and “no immunologic rejection” [4]. However certain risks come with using stem cells in general. One of these is that “self-renewal and plasticity are properties which also characterize cancer cells” [3]. Although some fear that if we lost control over the stem cells, tumors would form, but there is only a small chance of this warning coming true. Also, as with all transplants, certain stem cells, such as embryonic, have the risk of inducing Graft Versus Host Disease, “an enhanced inflammatory/immune response … against an environment perceived as a foreign one” [3]. We can avoid this disease though by using patient-derived neural stem cells. Because these stem cells are from the patient’s own body, the immune system does not identify them as foreign. If we use neural stem cells in medical applications, the risks are negligible when compared to the benefits. PERSONAL BELIEFS Several times when I was younger, I heard the myth that most humans only use a small percentage of their brains, and that a few “special people” had the ability to tap into the rest of the brain. While I know now that this is not true, I am still fascinated by the power and capabilities of the human brain. Last year I read a book about a property of the brain called plasticity. The brain’s ability to adapt and repair itself is amazing, and scientists should fully take advantage of this property by helping the brain fix itself. When the brain deteriorates as a result of disease, so much of its power and potential is lost. If scientists initiated the process of plasticity with stem cells and scaffolding, the brain would have the ability to restore its own functions. I believe that everyone has the right to their health, and scientists and biomedical engineers should not stop exploring all possibilities until the cure is one hundred percent effective. We need to make it our priority to find the best cure. For Parkinson’s disease, this might be using stem cells to regrow dopaminergic nerves, so this approach should be researched thoroughly. Although these are the personal morals that I follow, there are national codes of ethics that all engineers must abide by. RESTORING NERVE CONTROL DAMAGED BY PARKINSON’S DISEASE We can apply neural stem cells and scaffolding to revert the damage done by Parkinson’s disease. Parkinson’s affects 1% of adults over 60 with “the loss of a distinct cell type (e.g., dopaminergic neurons) and degeneration of highly defined neural pathways” [5], [1]. This depletion of dopamine results in the loss of control of movement, including rigidity and tremors [1]. Because today’s medicines cannot “[revert] the course of the disease, and they cannot restore the loss of function incurred,” the current “drug treatment strategies only provide limited relief of motor symptoms, and the beneficial effects often wear off after approximately 5 years” [1]. Therefore this is not a long term solution. According to an article on dopamine neurons, “cellreplacement therapies may provide the most promising curative treatment for [Parkinson’s disease]” [5]. The neural stem cells, with the aid of tissue engineered scaffolding, would differentiate into the dopamine neurons. There is a likely possibility of restoring the physical and mental facilities affected by the disease “if cells can be placed in the brain to produce suitable, controlled levels of dopamine release” [5]. The hydrogel scaffolding provides a supportive environment for the stem cells to grow [1]. In current practice the transplantation of the stem cells is not at the site of cell loss, so normal circuitry cannot be recovered [2]; therefore in the future we should focus on getting closer to the site of cell loss in order to revert as much damage caused by the disease as possible. The possibility of finding the cure CODES OF ETHICS: ARE THEY APPLICABLE? National Society of Professional Engineers Code of Ethics While the National Society of Professional Engineers (NSPE) Code of Ethics is generally useful to engineering companies, they do not apply to this discussion on adult neural stem cells. It is mostly related to the business side of engineering that companies have to deal with. The canons regarding business matters are useful in company situations but not in research applications such as stem cells. For example, canon number four states “Engineers shall act for each employer or client as faithful agents or trustees” [6]. The parts of this canon detail financial obligations that engineers must follow such as not accepting compensation from outside companies or more than one company at a time [6]. Basically, engineers are not allowed to deceive their employers or clients, which is true to all other professions as well. Furthermore, canon four of the Professional Obligations discusses the handling of confidential information in business affairs, and discourages disclosing information gained at one company to another [6]. There are also general guidelines provided for in this code of ethics. Canon two states that “Engineers shall perform services only in the areas of their competence” [6]. 2 Emma McBride According to an article on this issue, “codes [of ethics] can offer guidance and a common understanding of a commitment to ethics that can uphold a professional image. However, codes cannot substitute either for individual capabilities in solving ethical dilemmas or substitute for ethics education” [8]. One way that we can teach ethics individually to engineering students is through assignments such as this one, which encourage students to research the ethical policies of a field they are interested in. I believe that these writing assignments have been useful because they guide us towards making a decision about what kind of engineer we want to be. These assignments model the papers that we will have to write as engineers, as well as guiding us to explore current engineering issues and ethics. I think that freshmen engineering students should continue to write these types of assignments. We can apply this rule to Biomedical Engineering because there are so many specializations available, such as tissue engineering or building prosthetic limbs or developing pacemakers, and engineers should not work in an area other than their specific one. While these guidelines are useful, they do not impact my position that engineers should focus their research on neural stem cells. The only canon that directly applies to this discussion of neural stem cells is canon number one which states that “Engineers shall hold paramount the safety, health, and welfare of the public” [6]. This canon is the fundamental point of the Biomedical Engineering Society Code of Ethics and is further explained there. Biomedical Engineering Society Code of Ethics The more specific rules described in the Biomedical Engineering Society Code of Ethics reinforce my position that neural stem cells should be used to research cures for brain diseases. These codes are more applicable than the NSPE codes in a discussion on medical research. Firstly, the guidelines for conducting research outline appropriate conduct. The first canon declares that researchers must respect the rights of their subjects by following ethical and moral responsibilities [7]. This is crucial to the discussion of testing neural stem cells as a possible cure for Parkinson’s disease because before it is an official treatment, there must be many trial groups. These volunteers have rights to safety and health which must be respected. The section on health care obligations also addresses the rights of patients. Canon one especially deals with the rights to confidentiality and privacy [7]. The second rule states that engineers shall “consider the broader consequences of their work in regard to cost, availability, and delivery of health care” [7]. This is applicable to the topic of researching new treatments because it is expensive to investigate and difficult to find funding. Engineers need to consider the effectiveness and practicalities of breakthroughs in medicine. I believe that it will take much effort to perfect a treatment involving adult neural stem cells but that in the end, the benefits of finding the best cure to Parkinson’s will outweigh the cost of exploring this field. Finally, the rule on training obligations for biomedical engineers maintains that engineers “honor the responsibility not only to train biomedical engineering students in proper professional conduct in performing research and publishing results, but also to model such conduct before them” [7]. CONCLUSION: OUR DUTY TO THE HUMAN RACE With all the technology available to scientists and engineers, we have a duty to the rest of the world to find a solution to the diseases that plague our society. An example of such a disease is Parkinson’s, for which there are various ineffective drug treatments. We should not stop at just alleviating symptoms; we should find a way to truly restore all the original abilities that were damaged. Neural stem cells have the potential to be this solution. This line of thinking abides by the code of ethics’ canon about the welfare of the public because a cure for Parkinson’s would improve their health. The best way to inform the public about these ethical rights is by educating engineering students. Then they will be able to make decisions about engineering issues such as whether or not to use neural stem cells in a possible treatment for Parkinson’s disease. Although there are some risks and public objection, the benefits of neural stem cells and the possibility to cure previously incurable diseases cannot be ignored. REFERENCES [1] D. Fon, D.R. Nisbet, J.S. Forsythe, G.A. Thouas, W. Shen. (2011). “Tissue Engineering of Organs: Brain Tissues.” Tissue Engineering. (Online Textbook). http://www.springerlink.com/content/w481529730833nh4/fu lltext.pdf [2] A. L. Rodriguez, C. L. Parish, D. R. Nisbet. (2012). “The Potential of Stem Cells and Tissue Engineered Scaffolds for Repair of the Central Nervous System.” Stem Cells and Cancer Stem Cells, Volume 4. (Online Textbook). http://www.springerlink.com/content/p046167436022650/fu lltext.pdf?MUD=MP [3] D. Lodi, T. Iannitti, B. Palmieri. (2011). “Stem cells in clinical practice: applications and warnings.” Journal of Experimental & Clinical Cancer Research. (Online Article). INCORPORATING ETHICS IN EDUCATION One crucial aspect of training biomedical engineers is integrating engineering ethics into education, but it is difficult to teach morals and values to individuals. 3 Emma McBride DOI: 10.1186/1756-9966-30-9 [4] B. Guo, M. Dong. (2009). “Application of neural stem cells in tissue-engineered artificial nerve.” Sage Journals. (Online Article). DOI: 10.1016/j.otohns.2008.10.039 [5] R. Fricker-Gates, M. Gates. (2010). “Stem cell-derived dopamine neurons for brain repair in Parkinson’s disease.” Regenerative Medicine. (Online Article). DOI: 10.2217/rme.10.3 [6] National Society of Professional Engineers Code of Ethics. http://www.nspe.org/Ethics/CodeofEthics/index.html [7] Biomedical Engineering Society Code of Ethics. http://www.bmes.org/aws/BMES/pt/sd/news_article/52746/_ self/layout_details/false [8] J. Li, S. Fu. (2012). “A Systematic Approach to Engineering Ethics Education.” Science and Engineering Ethics. (Online Article). DOI: 10.1007/s11948-010-9249-8 ACKNOWLEDGMENTS I would like to thank Barbara Edelman for answering my questions about my topic and for clarifying the instructions. I would also like to thank Writing Center consultant Grace Noble for reading over my paper and giving useful comments. 4