Application of RM

With guest lectures from Dr. Will Eyestone and Dr. Michelle Theus this week, we moved deeper into content about potential applications of regenerative medicine. You had such good responses last week, so let’s keep in the same sweet spot for questions for students.

Were you surprised by anything you found out about this week? Any fun facts?

Are there any themes between the two presentations that are worth noting? Despite the different application, what themes in terms of approach or framing of problems that you might have seen?

How excited were you to learn that canines have naturally occurring hemophilia? (That was the surprise fact I’ll remember best.)

Looking forward to next week’s presentations on Medical Tourism!

8 comments:

  1. I enjoyed reading my colleagues’ responses last week and learning about all the different applications and thought processes that the previous presentations evoked. It’s fascinating to me that we can all hear the same lecture but key in to different points or take the same information and go in a different direction. That’s the fun of interdisciplinarity I suppose.

    Dr. Eyestone’s and Dr. Theus’ presentations both used a clinical example (hemophilia and spinal cord injury, respectively) to teach the various therapies that are available for treatment, which I thought was a smart approach to interest both the more scientist oriented of us and the more clinically minded. Both showed that there are multiple ways (cure vs. symptomatic treatment) and various levels are which a disease can be approached (cellular vs. genetic). And, often, we may need to combine approaches to reach the best therapy for a patient. I was pleasantly surprised to hear that the Miami project was using Schwann cells a potential therapy for spinal cord injury because it’s a smart move to use a similar cell from the patient’s own body to get around immune reaction. Now, if only it works…

  2. I was intrigued by Dr.Theus’s presentation. My research is mostly focused on tendon, and it is rare that I climb out my research bubble to look at different organs and how stem cells can help regenerate different organs. The challenges posed by the nervous system to regeneration make it a fascinating subject! We cannot simply harvest bone marrow from a patient and inject it into the brain. I was very interested to learn about the intelligent strategies and indirect methods scientists have invented to work around this problem. I actually wanted to know if schwann cells would be a better alternative to embryonic stem cells?, because even though the schwann cells are autologous, they sound very mature and decided in terms of lineage commitment, whereas the ESC’s are naive and definitely more potent. Also, would age be a factor here? So, in older patients with neural degenerative disorders, would ESC’s work better?

  3. I have a question.
    In the book, Deborah has asked twice, is it possible to use HeLa cells to clone her mother into her own egg, and thus give birth to a clone? Doctors say no, either because of the lack of scientific advancement, or ethics.
    My question, is it actually not possible at this day and age?

    I enjoyed both presentations, and the treatments sounded plausible, and not a part of science fiction. . Even today, you hear of scientists regrowing nerve cells, or 3D printing them.
    Dr. Eyestone’s did seem more far fetched, due to the video showing the DNA replacement, but scientists have proven that the method works. Just as nurses treat diseases by creating vaccines from dead, or weaker forms of the disease.

    I did have one more question.
    Scientists are fighting to recreate fully functioning organs, but have so far had several challenges, such as blood supply. We have found that the human body is not perfect, and some organs can be removed without side effects. Our organs are not perfect, and it is likely that at least one of your organs will fail during your life, or in the case of the heart, cause you to lose your life. Knowing these failures, why keep attempting to clone organs as they are, instead of recreating them in better ways? Dying of old age usually means that you have died of organ failure, so why not attempt to avoid that?

    1. Hi Jerry,

      I wanted to address your first question – is it possible to clone HeLa cells back in Henreitta Lacks, and the answer is no. HeLa cells are cancer cells, so they contain several mutations in the DNA that allow them to replicate an infinite number of times. This
      The technique used to clone Dolly (the sheep) has not really been discussed in this class. It’s called somatic cell nuclear transfer. Basically you replace the nucleus of an oocyte (or egg) with the nucleus from a “somatic” or permanent cell of an adult organism. The somatic cell’s nucleus has to submit to the oocyte factors until it essentially becomes a zygote and can develop normally into an embryo. From what I understand, this is much more complicated in humans that it is in any other species, but has not been well researched due to the ethical issues.

      In terms of your second question, I think the concept of creating functional organs is so complex that researchers and scientists are simply trying to stick to the basics and make what they know works before they try anything new. I do not think this class has painted organ creation in a proper light – it is extremely difficult and most of the people who are currently researching it are unsuccessful. There are a few clinical trials where scientists were “successful” in rebuilding organs, but really failed to achieve normal function due to immune reactions. To my knowledge, only the smaller organs have ever been successful enough to try in clinical trials because they are easier to perfuse.

  4. I really enjoyed thinking about the advancements that have been made in genetic medicine. In class we were talking about inserting genetic code for clotting factors that are not produced in hemophiliacs. Above Jerry talks about the ability for us to potentially use the knowledge and technologies developed to potentially strive toward or “re-create” a more “perfect” organism. This is not something out of a Sci-fi movie anymore; it could potentially be on the horizon. The issue is, we really don’t know how the genetic modification will perform long term. If we turn on production of clotting factors through insertion of a codon, then what happens if we need to turn it off? How much do we need to know so that we don’t mess up the biologic balance that has taken millions of years of evolution to develop?

    If the theme is to change the genome, at what point should we stop?

    As a veterinarian, I already knew about dog hemophilia. As stated on UPenn’s translational research page, companion animals can help us to combat the questions that we have about some human diseases. Not only do they suffer from some of the genetic diseases that we do, but they also share in our lifestyles. I think that as a group we need to have a discussion to find out what point or under what circumstances we are prepared to try out genetic treatments on other people or our best friends. We need to talk about what information we would want to have before giving it a go and what checks and balances we think we would need. We also need to think about when it is no longer fixing what is broke but when it is trying to enhance something that ain’t, and if that is feasible.

  5. I am impressed that the therapies today has come from the organ/condition level to the cell level, such as to repair DNA for hemophilia patients and to grow and promote axons to reconnect their targets for spinal cord injury we mentioned this week. I am not sure that I can answer Jerry’s question about why we build organs, instead of editing them to be better organs, but here I see a shift that at least in regenerative medicine, therapies go from the bigger, organ level to a much smaller, tiny cell level. This is not only the advancement of science or measurement tools, but also our horizon changes from visible organs to invisible cells. Thus, the question is not only about why we used to develop/transplant organs, instead of modifying them; it is an opening of a new therapy paradigm. Also, it is a new way to view and image bodies. We can see organs by our eyes, but now we rely more on microscopes or computing simulation than our eyes to see how our bodies work. This horizon shifting is the most important thing I learned for me this week.

  6. One theme of regenerative medicine that stood out to me this week was the need to combine multiple aspects of this field to develop effective treatments. Dr. Eyestone discussed cell-based therapies, which can involve stem cell treatments, gene therapy, or a combination of the two. I really enjoyed learning about the combination of stem cell therapy and gene therapy in current research—reprogramming the patient’s own cells to make induced stem cells, fixing a broken gene in those cells by gene therapy, and returning the cells to combine the promise of autologous stem cell therapy with gene therapy treatments. Dr. Theus’ lecture about regenerative medical treatments aimed at CNS repair also covered the need for consideration of multiple different issues to get a full picture of the problem. As we discussed in class, effective regeneration of CNS neurons requires more than just causing the neurons themselves to regenerate (although this alone is a significant hurdle). The environment around the neurons also must be changed (possibly by gene therapy or administration of growth factors) to favor growth in the injured area. Stem cells, gene therapy, or other regenerative treatments can be helpful alone, but these treatments are most promising when combined. Different sides of regenerative medical research need to work together to fulfill the promise of this field, and I appreciated this week’s glimpse into how that could work out in specific cases.

  7. I was particularly surprised at the idea that gene editing is considered relatively easy, and that the reason that human testing of the procedure is not done is more of a moral one than a technical one. Very seldom have scientists self-regulated themselves away from certain experiments, especially ones with such promise for people with genetic disorders. Granted, the complexity of genetic manipulation and the possibility of unintended consequences, combined with the moral pushback scientists know would occur from certain groups, makes a certain caution wrt this technology quite prudent. However, this voluntary eschewing (gesundheit) of a path of inquiry remains remarkable, but I wonder for how long it will hold.

    Scientists outside the United States may find themselves in a more accepting climate with respect to gene editing and human experimentation, and I’m not sure if we could get the toothpaste back in the tube, so to speak, once someone outside the US has started. The competitive nature of science and the belief that science done in the US is the best and most-safe/ethical/empirical might end up breaking that tacit agreement. One wonders what happens next.

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