Cell-Based Treatments to Fight Diseases with Luisa Iruela-Arispe, PhD 

Erin Spain, MS [00:00:10] This is Breakthroughs. A podcast from Northwestern University Feinberg School of Medicine. I'm Erin Spain, host of the show. Cell and Developmental Biology is a field that's integral to finding new therapies for a wide variety of diseases. Here at Feinberg, Dr. Lusia Iruela-Arispe, a vascular biologist, leads the Department of Cell and Developmental Biology as chair. She joins me today to talk about her research and the future of cell-based treatments for diseases. Welcome to the show.  

Luisa Iruela-Arispe, PhD [00:00:45] Hi, Erin. Thank you for having me.  

Erin Spain, MS [00:00:47] Well, tell me about cell biology and the ways that the field has grown in recent years to impact clinical practice and therapies for sick patients.  

Luisa Iruela-Arispe, PhD [00:00:57] Well, cell biology is an amazing discipline, is one that really encompasses or is part of many other issues like biochemistry, genetics, epigenetics. Everything is within cell biology. And so that's why I am so passionate about this particular area. And it has really grown tremendously, I think, in particular how it impacts cancer biology. If you think about all the chemotherapeutic drugs that we have today, they are mostly affecting sort of skeleton elements and the process of cell division in cancer cells. So it has been through understanding cell biology that we have made so many advancements, particularly in cancer, but not only exclusively in that area.  

Erin Spain, MS [00:01:41] Tell me about some of the human diseases that you're trying to improve through work in your lab.  

Luisa Iruela-Arispe, PhD [00:01:46] A laboratory is a vascular biology laboratory. I really very passionate about blood vessels. They are tubes that permeate our body, but in reality they impact both healing as well as they can accelerate or really make certain steps in disease progression worse. So by manipulating blood vessels, we can impact either the healing process or accelerate or even eliminate certain diseases. So it is really the route by which inflammatory cells, traffic. So everything they release to inflammation has to do with enabling inflammatory cells to leave the bloodstream and access the organs in general and affect disease. So by regulating that process, we can definitely control inflammation, but we can also control the trafficking of, let's say, cancer cells to prevent metastasis.   

Erin Spain, MS [00:02:40] How did you first become interested in blood vessels and studying the vascular system at this molecular level?  

Luisa Iruela-Arispe, PhD [00:02:46] I remember this vividly. I was a graduate student and I was hearing about the cell type endothelial cells, which are the cells that are present in all our blood vessels. They lined the inner side of all blood vessels, and this cells normally will just be responsible for transporting molecules and nutrients from the blood into our tissues and vice versa. So they act as a transporter, if you will, and they will allow cells to pass through. And one way to the other. But the neat thing is that they can also completely change and undergo a rapid process of proliferation to form new blood vessels. So they have this plasticity that is very unique to, I think, endothelial cells in which they can be fully differentiated or become as active as an embryonic cell just with a change of a dime just by having a growth factor activated them. I think that you can actually utilize them in obviously to form new vasculature and permeate new structures. So we are now in the area of regeneration, regeneration biology, and by creating new organs or organoids, we can replenish damaged tissue. We can definitely impact disease in a very positive way. But this organoids require vasculature. And so the other thing that you can do with the cells is you can enable them to integrate with other cell types, to permeate structures and provide nutrients and oxygen. So you can essentially 3D print them, you can manipulate them, and you can integrate them with other cell types to generate new tissues.  

Erin Spain, MS [00:04:28] That brings me to this idea of bioprinting. This is an emerging area of study which uses biological materials to create these tissue like structures that imitate natural tissue. How involved are you with this research right now?  

Luisa Iruela-Arispe, PhD [00:04:41] We definitely do plenty bioprinting. In fact, we have quite a few in the laboratory. So what we're doing is trying to integrate again, organoids brain organoids intestinal organoids and make them permeate a bowl with blood vessels so that they can grow. Expand. And better imitate, mimic normal organs. So that has been a fun project.   

Erin Spain, MS [00:05:05] You are able to work with so many different departments here at Feinberg and both on the clinical side and basic science. Tell me about some of these partnerships and some of the diseases that you're able to work on.  

Luisa Iruela-Arispe, PhD [00:05:16] There are several collaborations that we have going on. I mean, one with the Department of Pharmacology, Al George's Department. Being able to manipulate through pharmacological means, the function of any cell type is one of the basis of how to control disease in how to control health. So one of the areas that Al works a lot with is channels, ion channels, which control essentially flow of ions as well as a lot of properties of the cells in general. We have been collaborating with them very actively to understand how manipulation of those channels can actually improve vascular health. That's one example. We also collaborate with the problem neurology quite heavily. That has been also very interesting and fruitful and it takes us into the area of vascular dementia and how to improve the vascularization of the brain and what goes wrong when in cases of Alzheimer's and other situations that compromises the vasculature as well.  

Erin Spain, MS [00:06:17] Tell me about this idea of cell-based therapies. What is happening right now and how close are we to having more cell based therapies available to patients?   

Luisa Iruela-Arispe, PhD [00:06:26] The area that initiated this in a big way is hematology. So transplantation of bone marrow to replace bone marrow of patients that have mutations that lead to leukemia has been transformative. And this is something that for for blood is a lot easier because we have a way of delivering in these cells. Once we understood what was needed. They are professional. They know where to go and how to expand, and they're able to colonize in a way that substitutes disease for healthy bone marrow. So I think that we learn a lot from our process. And this idea now of how to use new cells to substitute for for all cells has taken over now because most cells are not circulating and they don't have the same properties of hematopoietic cells. It's become a little challenging and that's why the development of Organoids has been so interesting to biologists and developmental biologists and so biologists. And I think that that is going to be probably the future of regenerative medicine.   

Erin Spain, MS [00:07:37] Tell me about your recent article in Nature Cardiovascular Research. Your team discovered a new cell type that was not previously understood. Tell me about this exciting finding.   

Luisa Iruela-Arispe, PhD [00:07:48] So this is a new type of macrophage, which is professional, should say inflammatory, but also more like a cleaner, cell type that lives in the endothelium. So I mentioned to you, right, that the endothelium is this layer that is responsible for covering the inner surface of all the blood vessels. Normally that area only is comprised of endothelial cells, but we found through the study that was recently published that there's a new type of macrophage that is present in interwoven intertwines with this endothelial cells in areas of oscillatory flow. So let me take back this a little bit. So because some vessels are twisted and turn when blood goes through them, it creates turbulence and creates disturbed flow. So think again about pipes. And when pipes divide, what happens to the flow? It turns out in those areas of turbulent flow, there is accumulation of thrombin which results in clots. And so the function of this macrophage that we discover is to eliminate those clots. And that's very important because when we experimentally deleted them, when we remove them from these areas of turbulent flow, the vessels get clogged. So they get full of fibrin and they have intravascular thrombosis, which is obviously very problematic. That was a very exciting manuscript, an exciting paper, because it told us many things about the endothelium. And also it showed that we need to have this professional cells in areas of turbulent flow to avoid clause from being formed.  

Erin Spain, MS [00:09:31] Why is this finding so timely?  

Luisa Iruela-Arispe, PhD [00:09:33] Yeah, I mean, I think the reason why that was timely and so, so interesting is because of COVID. So there is this concept and this idea that one of the consequences of COVID 19 is to have problems with blood vessels, and that is why the long COVID is affecting so many systems. So this macrophages are affected, then intravascular thrombosis is a lot more frequent and. If you have intravascular thrombosis in small vessels in particular, you can have clogs and ischemia. So this is an ongoing investigation, obviously, and something that we are expanding significantly, but it can have very significant consequences to understanding disease and understanding how disturbance of one particular cell type can trigger consequences that are system wide.  

Erin Spain, MS [00:10:25] So what is the reaction been like from the scientific community to this finding?  

Luisa Iruela-Arispe, PhD [00:10:29] It was quite interesting. Obviously, the way that we perceive those reactions that right now is through Twitter is interesting to see. Right as essentially the pulse of what the impact of a discovery like this has been in. It was very active. We had a lot of very positive feedback. But it's a process and one discovery is discovered is only important if we communicate them to others and others walk them further. So this is going to be a process that I'm looking for, watching and continuing to participate, obviously.  

Erin Spain, MS [00:11:01] You also collaborated on an article in Nature with a former colleague of yours from UCLA that expands our understanding of how blood cells and endothelial cells cross-talk. Share those results with me.  

Luisa Iruela-Arispe, PhD [00:11:15] So as you mentioned, I'm a coauthor. You require the effort of multiple laboratories. And the senior author is my very dear friend, Hannah Mikkola. She is at Cell and Developmental Biology at UCLA. And what Hannah has been very interested in knowing is is how actually how to improve the generation of hematopoietic stem cells, in vitro. But for that, we needed to go in vivo. So as we learn and in fact, many years ago we published this hematopoietic cells come from endothelial cells, and so they bud off endothelial cells during development. So my contributions were to provide this understanding of endothelial cell biology and understand how they actually bud off from endothelial cells and learn the molecular intricacies of this crosstalk between endothelial cells and hematopoietic cells are bad enough. And what Hannah did is took this for and essentially she identified the key molecular drivers that can inform how we can better do this in vitro so that we can use in vitro systems to develop to form hematopoietic stem cells and use them for transplantation.  

Erin Spain, MS [00:12:29] This is sort of like step one. So what comes next?  

Luisa Iruela-Arispe, PhD [00:12:33] Yeah. So with this information that she just obtained in communicated to the community, she is now developing new systems, in vitro to do just that. So it is incredibly challenging because again, the beginning requires this cross-talk between two very different cell types and cell types that are at a different stage. Right, than what we normally use. So she needs to take them back to that time, that embryonic time take them back, meaning molecularly by disturbing them in vitro and recapitulate or mimic that genetic time, that differentiation time, so that we can actually provide benefits to millions of people that are affected by blood diseases or blood cancers or even perhaps even regeneration of blood.  

Erin Spain, MS [00:13:24] You actually took on your role as chair of the Department of Cell and Developmental Biology not too much before the pandemic started. But tell me about your role as chair and some of your goals for the department and what you've been able to accomplish so far.  

Luisa Iruela-Arispe, PhD [00:13:39] That's a big passion of mine. I mean, trying to shape a department like cell and developmental biology at Northwestern is a privilege. And I'm very, very excited about what the future awaits. So when I took on the department, you're absolutely right was like months before the pandemic. And so obviously a lot of our plans were curtailed by what followed. But nonetheless, the vision was articulated very clearly to all the members of the department, and it was shaped further by them as well. So I had the opportunity to discuss with them how I view the direction of the department in the next ten years and the pandemic. Allow us to have a more extensive conversation as to what are the directions and the path that we should go. And essentially we all agree that what we want is to build a department that is going to be the top department in the nation in the next 5 to 10 years. So the question is, where is the discipline going to be in 5 to 10 years? What are the challenges that we are going to encounter and where are we going as scientists in this area? So answering that question is kind of you need to have a little glass ball and understand where are the key directions. And I think that is. Very, very obvious that computer modeling quantification, math and integration with physics as well as biology is going to partake a very important role in the advancement and development of this discipline. So we want to hire people that can walk both walks. They feel comfortable with the idea of using modeling to develop hypotheses and then pass those hypotheses in what we call a wet lab in the laboratory with petri dishes and peppermints. So we want real biologists, but those that are also able to expand, understand  and if not embrace, like, for example, a dinosaur like myself. I'm not a computer scientist, but I definitely appreciate respect and I would love to collaborate with those who have those abilities to further our disciplines. So we are trying to identify raw talent that is able to embrace this vision and that hopefully has those elements already built in and incorporate them into the department. So I think that despite the pandemic, we have been able to actually move things forward in the same path as we intended originally.   

Erin Spain, MS [00:16:19] Thank you so much, Dr. Luisa Iruela-Arispe, for coming on the show, telling us about some of your recent discoveries and how you are leading your department. We really appreciate it.   

Luisa Iruela-Arispe, PhD [00:16:30] Thank you, Erin. I really appreciate it. Thank you.   

Erin Spain, MS [00:16:43] Thanks for listening and be sure to subscribe to this show on Apple Podcasts or wherever you listen to podcasts and rate and reviews. Also for medical professionals, this episode of Breakthroughs is available for CME Credit. Go to our Web site. Feinberg.Northwestern.edu and search CME.