All right. Well, what a valiant effort by Shannon. Shannon, I want to thank you for doing this series. It's really wonderful and it's exciting to see the great response that it's had. And thank you so much, Laura, for your help as well. And thank you for everyone, for your patience as we work through these. I don't know if everyone heard, but I actually, my computer died this morning, just died out of nowhere. So I'm working on a brand new computer that's giving me some trouble, probably not the least of which because I'm in Paris currently. So I bought a French computer and I don't think it plays well with me. But so I want to actually, if you want to go ahead and move to the first slide, the next slide. I want to start with this image. Go back one. I want to start with this image, which I don't know if anybody in the group has read the book, The Medici Effect by Franz Johansen. It's a it's a very cool book that kind of talks about innovation. Benjamin, I see you. You've read the book. It talks about innovation and it really seeks to ask the question, you know, where do breakthroughs come from and how can we cultivate them? And so in this book, this this image, Franz Johansen talks about this image, which is actually an advertisement that was made by HSBC Bank some years ago now. And as you can see, we have the same image three times. So depending on where you're coming from, your reaction to this image can be very different. A huge favor. Quinta. Oh. One second. Did you say. Sorry, is it is it still working? My screen just froze. Can everyone still see that? Are you flying blind? Actually, we need to go back one. There we go. Okay. Okay, so the idea here is that, you know, depending on your background and your own experiences and your personal perspective, the way you see something can be very different. Now, HSBC Bank uses as a means to say that they have knowledge of cultures from around the world. So that makes them very well equipped to do business internationally. But what Franz, you know, really highlighted is another message that this advertisement really gives. And that there's a lot of value in seeing things from a slightly different angle. So I like this image because I think it speaks very nicely to exactly what we're trying to do in regenerative rehabilitation. So if you move to the next slide, Kuntho, here we have kind of the schematic of what regenerative rehabilitation really represents. And so regenerative rehabilitation is this intersection of the two fields, regenerative medicine and rehabilitative medicine. So rehabilitative medicine, of course, this is a field that we are all very well familiar with. But regenerative medicine is the topic that I think Shannon is doing such a great job through this series of really kind of bringing more and more to light in the context of rehabilitation. And so this is one definition of regenerative medicine. And that is the process of creating living, functional tissues to repair, replace tissue or organ function that has been lost due to age, disease, damage or congenital defects. And the idea here is that when we bring these two fields together, then it's really at this intersection that we have the potential to optimize independence and participation of individuals with disabilities. So I don't need to make a case for rehabilitation, but next slide, why regenerative medicine might be an interesting question. So in this, it's probably worthwhile to take just a moment to step back into how the field really started. So we'll start with some examples of some gaps in medical practice that scientists began to notice and then want to address. First example, in the next slide, we can take joint replacements. So we know that joint replacements do very well overall. Success rates for first time joint replacements are on the order of 80 to 90%. However, what we know is that if an individual has a joint replacement too early in life, when they're too young, then it's very likely they'll have to have a second joint replacement. And in those cases, the joint replacements do not do nearly as well. So the question is, can we do better? Likewise, another example is the context of organ replacements and organ transplants. Here again, I was actually very surprised. My colleagues who was a transplant surgeon really was speaking of the tremendous success of these organ transplants. That's greater than 90% on average. And as you can see, organ transplants now are being performed for a wide array of indications. However, though the success rates are very high, in the next graph, we can see that there's a major problem with this approach. Because, do you mind advancing to the next slide, Kunthal? There you go. Because what we see is that, well, when the individual has the organ available to them, unfortunately, there's this massive shortage of organs available in the first place. And so this is a disconnect. This is an old graph. You can see it only goes to 2013. But I wasn't able to find one that so beautifully, I think, illustrated this trajectory and this disconnect between the need, that is, this gray line, and how this need for organ transplants steadily increases over time. And that's a trend we've continued to see since 2013. Whereas the number of donors has remained relatively flat. So here again, the question is, can we do better? So regenerative medicine scientists, in the next slide, then actually took a different perspective. And they turned to biology for inspiration. And here in the next, we see that in regenerative medicine, a lot of the field of regenerative medicine was very much inspired by this recognition that there are a number of different species that have this remarkable capacity to regenerate after an amputation. So very severe amputations, as you can see here from between zero, day zero to 35, in this case, a cricket, we get a really nice restoration of the original structure and function of the regenerated limb. And so the question is, can we really tap into some of that regenerative potential and then try and harness it and thereby enhance regenerative potential of our patients? In the next slide. So these are just some regenerative medicine statistics that you may have heard in some of the other talks. But I think it's really a testament to the expansion, the rapid expansion of the field. And again, this trajectory of growth in the field of regenerative medicine, I think, is really an indication that we'll start to see more and more of these technologies in the clinic by our patients. So in the next slide. I just wanted to share then a couple examples of really, I think, beautiful success stories in the context of regenerative medicine. So, for example, stem cell therapies for the treatment of blood disorders. Actually, this is an indication that has been around for over 50 years. And in many cases, it really is the gold standard for treatment of blood diseases. And I think, you know, this is bone marrow transplantation is something that's not very new to us at all. But this example on the right, that is stem cell transplantation for the treatment of corneal injuries. I think that perhaps is a little less known. And this is a paper that came out in the New England Journal of Medicine back in 2010. But the field has continued to enjoy continuous progress into applications into medical practice. In this paper, what they demonstrated is that harvesting stem cells from an intact region of the eye could then be transplanted into a damaged cornea. And as you can see, they saw really remarkable restoration of corneal function after stem cell transplantation. In fact, the success rates were on the order of 75 percent and higher. What I love about this paper is that they actually followed patients for up to 10 years. And what they found was that those individuals who were successful within the first year, again, that was about 75 percent success rate, those individuals remained successful throughout the 10 years follow up. And so particularly in Europe now, stem cell therapies for the treatment of similar types of corneal injuries are being more and more widely used. Next slide. However, there are a number of indications of regenerative medicine technologies where regenerative medicine may make an impact. But we've encountered persistent barriers to clinical translation. So, for example, in the context of bone regeneration or skeletal muscle regeneration, we just haven't seen success such that we would be able to more effectively use these in the clinic in a really regular manner. So a major advance in the field of regenerative medicine, in the next slide, is the recognition that many of these tissues are highly sensitive to extrinsic forces, whether that be extrinsic tensile forces, shear forces, even electrical stimuli, and that these extrinsic forces have a potent capacity to really dictate stem cell function and thereby tissue regenerative capacity. And so this has really been a marriage of bioengineering together with regenerative medicine. So as to kind of dictate stem cell function in the hopes of making the therapeutic applications more viable. Next slide. So this is one of my favorite examples of, you know, using this extrinsic forces and trying to tap into these, the potential of these extrinsic forces to maximize functional outcomes. This is a paper that was published some time ago now out of George Chris' laboratory when he was at Wake Forest. And so essentially what they do is they start with kind of a framework for building a tissue in a culture dish. And so here they start with a decellularized scaffold that you can see in the upper left hand corner. So this is completely, all cells have been removed and all we have is the remaining structure. Then once they have the overall structure that they want to create, then they seed it with cells, in this case, muscle stem cells. The muscle stem cells, when given the appropriate growth factors, will then fuse and create muscle fibers. And these muscle fibers then form almost a mini muscle in the culture dish. Now, this is interesting because in regenerative medicine and tissue engineering, they're really looking at the application, the transplantation of these muscle in a dish to be able to transplant and enhance skeletal muscle regeneration after injury and severe defects. But what they found in this paper is that when they just took this muscle and they transplanted it into, in this case, it was an animal, a rat model of severe muscle injury. What they found was that the muscle integrated in, structurally it looked OK, but functionally it did nothing. The investigators then decided to add extrinsic mechanical stimuli, then recognizing the potential of the stimuli to induce a more functional response of the tissues. So essentially what these bioreactors do is they just kind of tensile strain the muscle tissue cyclically over time and over a period of many days. Here, what they found was sort of preconditioning or exercising this muscle tissue in the dish prior to transplantation significantly enhanced the capacity of this transplanted tissue to incorporate into that host tissue in a very functionally meaningful way. Next slide. So the recognition of extrinsic forces typically performed in bioreactors and in a culture dish, as I just showed, has increasingly drawn attention to the clinical specialization, our clinical specialization, that really focuses on the application of mechanical forces, electrical forces, range of motion and various modalities to be able to integrate together with these regenerative medicine technologies and tissue engineering approaches. Next slide. So with that, then, I'd like to share some of the research from our laboratory that is focused on evaluating regenerative rehabilitation approaches, specifically in the context of skeletal muscle. So my laboratory is interested in skeletal muscle stem cells and skeletal muscle regeneration in the context of severe injuries and aging, for example. In the next slide, I have a very, just in case it's been a while that everyone has reviewed the regenerative cascade of skeletal muscle, I thought I would give a brief overview. Incidentally, what you see here, this signature is my daughter. She made this schematic for me because I had very particular points that I wanted to be able to highlight that I didn't find in any publications. But so essentially we start here with a single myofiber just as an illustration. And what you can see here in pink is a myofiber, which is multinucleated, and it's surrounded by this extracellular matrix and in this black scaffolding surrounding the muscle fiber. We have a small percentage of normally quiescent muscle stem cells. And so these muscle stem cells make up about two to three percent of the total myonuclear content. And what we see with injury, if you click forward, is that we get a progressive degradation of the myofiber. And you can continue to click through here, Kunthal. So as we get the degradation of the myofiber, what we see is this normally quiescent population of muscle stem cells will enter into a phase of proliferative expansion. And this is really to amplify the stem cell numbers that are able to participate in that regenerative cascade. Critically, what we see is that these muscle stem cells will align within the framework of that remaining extracellular vesicles or extracellular matrix. And so the extracellular matrix remains essentially intact when the injury is not too severe. And so this framework then guides the muscle stem cells such that they can enter in and they align. They almost form a train and then ultimately they will fuse together and form a new muscle fiber. Again, very nicely recapitulating the original structure and function of the tissue before it was damaged. But as I mentioned, this is really the cascade that happens when the muscle injury is not too severe. In the context of very severe injuries, as you can imagine, it's not only the myofiber that is lost, but also we get a critical loss of muscle stem cells. And so there aren't sufficient number of stem cells available to be able to participate in that regenerative cascade. And so this has really led investigators to then ask the question as to whether we can transplant stem cells to then boost that endogenous regenerative capacity of the tissue. Next slide. And so this has been something that has been investigated for some time now, looking at stem cell transplantation into acutely injured tissue, including skeletal muscle. Unfortunately, what we've seen is actually the onset of, again, persistent barriers that have impeded our progress in these applications. And if you click forward. So what we see, not only in the context of skeletal muscle, but in many different injured musculoskeletal tissues where we've attempted stem cell transplantation, what we see is that there's actually a poor survival of the muscle stem cells. And in fact, it's been reported by some that up to 90% of the donor stem cells will actually die within 24 to 48 hours after transplantation. Of the stem cells that do remain, we see that oftentimes there's a poor migration. So, for example, if you can envision injecting stem cells locally into the site of a muscle injury, what we see all too often is that those stem cells reside at that injury site and don't really move throughout the tissue to participate in regeneration. And then finally, we see that a large proportion of the stem cells that are transplanted in actually form, rather than the desired muscle tissue, form scar tissue at that injury site. Now this maybe isn't so surprising because in the context of a very severe injury, there are a lot of signals from that tissue that are kind of triggering even the endogenous stem cells to form scar tissue with the goal of trying to minimize the extent of injury and further damage. So at the end of the day, if you click forward once, it's not surprising that we actually see a pretty modest improvement in function using these stem cell therapeutics for the treatment of skeletal muscle injury. Next slide. So that's really where this regenerative rehabilitation paradigm comes in. Our idea is, can we dictate the behavior of those donor stem cells, even following transplantation, so that we can direct them to kind of behave in the manner that we intend them to? That is, functionally incorporate into that host tissue. And so this is the paradigm that we proposed a few years ago now, kind of showing the sequence of this regenerative rehabilitation paradigm. And that is that we start with a transplantation of stem cells or tissue engineering device into the host tissue. But then soon after that, we apply in vivo stimulation. Again, whether that be in the context of electrical stimulation, mechanical stimulation, or thermal stimulation. And ultimately, our goal is towards enhanced functional outcomes for our patients. Next slide. Okay, so implementing this regenerative rehabilitation paradigm, we designed a study where we wanted to evaluate stem cell transplantation following an acute and severe muscle injury. In this case, we used a contusion injury. And we wanted to evaluate the potential of a regenerative rehabilitation paradigm to enhance outcomes. Here for the severe contusion injury, what we did is we have the muscle anesthetized, and we actually drop a stainless steel ball through an impactor onto the tibialis anterior muscle. And so this creates a severe contusion injury throughout the muscle belly. One day after injury, then we locally inject stem cells from a donor source. And then after that, we randomize our animals into one of two groups. If you click through. So we have our sedentary control groups here on the left, where we just stem cell transplantation, put the animals back in their cages, and hope for the best. Versus this one, where we actually started the animals on a treadmill running protocol one day after transplantation. We started the animals slow because, of course, they had this very severe contusion injury. And then we gradually progressed them up to their tolerance. At the end of the protocol, after five weeks, these animals were running one hour a day on a 10% incline. So a pretty rigorous exercise protocol. Next slide. And so this is what we saw. The first thing we wanted to take a look at is how did our stem cells do, our donor stem cells. And so we engineered our cells to express this LAX-Z reporter. And so all of our donor nuclei show up in blue. It's very easy for us then to go through and just simply quantify the number of new blue nuclei across our groups. When we looked at eight days, actually, we saw that there was really no difference between the two groups. Whether that be stem cells or stem cells that had received the animals that had also received the treadmill running. And so this suggested to us that there really wasn't that much of a difference in the survival of our donor stem cells. However, at five weeks, what we saw was a significant increase in the number of donor cells available. And it was encouraging to see that the large portion of those donor nuclei were really within the muscle fibers. So suggesting that these donor cells had really contributed to muscle regeneration. Next slide. We also took a look at migration. As I mentioned, migration is an important barrier in these stem cell therapies. And so what we saw was with the animals that had received stem cell transplantation, plus or minus treadmill running, at eight days, most of the cells, as expected, were at that injection site. Even after five weeks, what we saw was that in the absence of treadmill running, most of the donor cells were at that injection site. However, in the presence of treadmill running, what we saw was our donor nuclei were really nicely spread out, really throughout the whole muscle belly, suggesting that the treadmill running protocol had enhanced the migration of our donor stem cells. Next slide. But, you know, that's in the context of a severe muscle injury where much of the extracellular matrix that I mentioned to be so fundamental is largely intact. When you have a case such as volumetric muscle loss, however, there's such a critical size defect that not only is there a significant loss in the number of stem cells available for that regenerative cascade, but there's also a critical loss of muscle structure. So in the next slide, just going back to that schematic, in these cases of very severe volumetric muscle loss injuries, what we see, next slide, is that the extracellular matrix is also lost. And so the stem cells then lose any type of orientation that they may have to be able to form those new muscle fibers. And so even if we give additional stem cells, donor stem cells, to that injury site, they really won't be able to have any kind of guidance to know how to develop a lineup and form those functional muscle fibers. And so a different approach here is needed. And that is a tissue engineering approach. So I wanted to share this paper. This came out in 2016 out of Tom Rando's laboratory at Stanford University. And so this is really an engineered muscle fiber approach, together with a stem cell seeding delivery. And specifically, they're looking at this tissue engineering approach for the treatment of volumetric muscle loss. So what you can see here on top in these scanning electron micrographs is a native fiber. And so you can see the muscle fiber in the back with the stem cells that are kind of along the periphery of the muscle fiber. And so what they did is they actually engineered artificial muscle fibers. And I think the beautiful part of this study is that they really engineered the muscle fibers to very closely mimic the structure and biochemical composition of the native fiber. And so the stiffness properties of this engineered matrix looked very close to what we would see in a native fiber. And then they seeded these engineered muscle fibers with donor muscle stem cells. Next slide. So then what they did is they transplanted these engineered muscle fibers together with the muscle stem cells into an animal model of volumetric muscle loss. And then they wanted to evaluate function. They evaluated function using two different ways. Ex vivo, they essentially remove the entire muscle and they perform electrical field stimulation of the muscle to be able to directly evaluate the capacity of the muscle fibers, both donor together with the newly derived muscle fibers from the tissue engineering device and look at the contractile capacity of the muscle fibers themselves. And here what you can see is they saw an improvement in the capacity of the muscle fibers to contract, suggesting again that those donor muscle fibers were indeed functional. However, when they did this other means of evaluating functional outcomes, this in vivo paradigm, essentially what they did is they leave the muscle in its native orientation within the animal, and then they stimulate the nerve to be able to see how much of a contraction they're getting. Here you can see they really saw no functional benefit. There was no difference between the muscles that had received the tissue engineering device plus muscle stem cells versus the sham surgery controls, even though they saw beautiful muscle fibers at that transplantation site. And so they thought that perhaps this was really an indication of a lack of innervation. And so one way to promote innervation then was it is through the application again of extrinsic mechanical stimuli. And so in the next slide, that's what they decided to do. So they did this implantation of the engineered muscle fibers plus muscle stem cells. And then shortly after they subjected the animals to a treadmill running protocol, very similar to as we had done. And here what they found in the next slide is that combining the two, so looking at the tissue engineering device plus exercise, led to a significantly increased functional capacity, again, using this in vivo functional testing approach. And this increased force producing capacity was consistent with an enhanced innervation of that treated tissue. Next slide. And so just to kind of speak a little bit to the clinical and translational relevance of this work, you know, what I've shown you so far have been mostly animal studies, all animal studies and cellular studies. We're starting to see more and more of these regenerative rehabilitation paradigms in the clinic. And I was very fortunate to start working with Dr. Steven Badalak and Peter Rubin on this DOD funded clinical trial that's looking at a tissue engineering approach, again, for the treatment of people with very severe muscle injuries. Next slide. And so I just wanna kind of walk you through the study a little bit and kind of, this is actually a study that we just started. Again, we started recruitment. And so we were funded for an initial phase and we found some outcomes that they're presented here in these two papers. I won't go into what we saw too much for the sake of time, but we learned a lot from those initial studies. And so we're currently recruiting subjects again. This is just to kind of demonstrate what the procedure looks like. And so we have the individuals come in with a volumetric muscle loss, and here you can see implantation of the scaffold device. Next slide. And then one day after implantation, a very, very aggressive by most regenerative medicine, musculoskeletal applications, I would say, we start the individuals on a rehab program. And we essentially started them on activities according to their own tolerance. So what we've learned from this study so far and what we're applying into the second phase of the DOD trial is that we're really starting to get a better sense of who's a good candidate. So for example, one of the things that we learned is that those individuals who seem to show the best functional outcomes are those individuals who had remaining muscle, viable muscle tissue at that site, much like the picture I just showed to you, where there's healthy muscle, they cut away the scar tissue, implant the scaffold. That healthy muscle at that injury site seems to be very important, most likely because those endogenous stem cells will go and participate in the regenerative cascade. On the other hand, we did have some individuals to participate in this trial who had anterior compartment syndrome. And so essentially all of the muscle was debrided away. In those individuals, what we saw was a much, much more modest effect of the scaffold device. Again, I think just because of the lack of healthy tissue and lack of stem cells to kind of boost that regenerative and restorative response. Next slide. So those are some directions that we're going in the context of skeletal muscle. And I would say that regenerative rehabilitation in general really started with a very musculoskeletal focus because it's easy to envision why muscle and bone and tendons and ligaments could benefit from mechanical stimuli. But I would say that in recent years, we've started to see more and more applications of regenerative rehabilitation in the context of neurological disorders. And one of the areas that we've seen some advances that I think are pretty encouraging are in the context of cell therapies for the treatment of stroke. Next slide. And so this is a query that I did. This is so just accessed recently. As you can see, I went to clinicaltrials.gov just to get a sense of how many stem cell trials are currently at different stages of recruitment on the website. And as you can see, there are a total of 94 studies when I use the Boolean search terms, stem cell and stroke. And so these are various types of stem cell therapies for the treatment of stroke. And this is actually increasing at a pretty good pace. I know that five clinical trials were added just within the last several months. So in the next slide, I think recognizing this encouraging pace of advancement for stem cell therapies in the treatment of stroke. Savitz et al, they convened, many investigators who are working in this space convened to be able to talk about kind of what are key considerations when thinking about cellular therapeutics for the treatment of stroke. And so they had many things. This was a paper that they published as a result of the conversation and the discussions of their meeting. And some of the key points is similar to what we're thinking about in the context of skeletal muscle. They're really trying to understand who is the best patient to receive these types of cellular therapies, at what stage after the infarct, acutely versus chronic, you know, what are the dosing? I think these are all really important questions that they've been trying to address even in preclinical studies. But if you click through, it was really encouraging to see that a major part of their discussion really focused on this recognition that there is a need to consider rehabilitation as a variable that must be addressed when looking at these stem cell therapies for stroke. And that is because of course, rehabilitation is fundamental in recovery for patients with stroke. And so it's really important to understand how might rehabilitation and the cellular therapy be interacting either for good or for bad. And so that really is what inspired Mike Moto at the University of Pittsburgh to evaluate using a preclinical model, whether a regenerative rehabilitation approach is capable of enhancing stroke outcomes. In the next slide, we have the study schematic. And so just very briefly to kind of give an outline of what the study looked like, essentially they had rats that they induced a stroke through an occlusion paradigm. And then of those stroke animals, they actually randomized them to either control with no extra intervention, stroke plus physical therapy. In this case, it was a treadmill running again, stroke plus cellular therapy. And in the last group, there was a combination of cell therapy and physical therapy. And of course they compared that to uninjured control rats. Next slide. So for the sake of time, again, I wanted just to give a brief overview of some of the findings. And in fact, it was interesting. This study was very comprehensive in terms of the number of outcome variables that they looked at ranging from, at the tissue level, trying to evaluate the number of stem cells, their differentiation, very similar to what we did in muscle, all the way through functional outcomes. And yet there was this consistent theme, regardless of the outcome that they evaluated, there was this consistent theme in terms of what they saw. And I'm illustrating that here, just with this one variable, in this case, sensory motor functional recovery. So the way that they test this in the rats is after stroke, they put a tape on the animal's paw, and they essentially measure the time that it takes for the animal to recognize there's a tape and try and remove it. And so, as you can imagine, a quicker time to recognize that tape signifies a better outcome. And here, what they saw was that when compared to stroke alone, cell transplantation improved sensory motor functional recovery. Exercise, not surprisingly, also improved recovery. And then when they look at the combined approach, what they saw was it was a little bit better, but was really only a sub-additive effect. That is, we're not seeing even the addition of cells plus exercise. And so somehow there is an extent of attenuation of one of the effects of either cells or exercise or maybe each are being attenuated. So clearly there's a lot of room for improvement. And what we'd really like to see is a synergistic effect where a combination of exercise and cells really amplifies the benefit way beyond what we see with either intervention in isolation. One of the things, and I've been collaborating with Mike Moto and one of the discussions that have really come out is that we think that this may be really reflective of the fact that a treadmill running protocol does not contain any type of task specificity. And of course, in rehabilitation, neurologic rehabilitation, we know that task specificity is really key for enhancing and maximizing functional outcomes. And so a major question is, would outcomes be improved if we more closely mimicked rehabilitation protocols as we use in the clinic? Next step or next slide. So I think that's where doctors, David Rankinsmeyer and Sunil Gandhi at the University of California Irvine come in because they're building this robotic rehabilitator. And essentially, as you can see, the idea here is to really have the animal do more functional tasks as a means of rehabilitation. And this device that they're building, I think is beautiful because they can actually modify the device such that the animal has to pull the lever a certain number of times before it gets its liquid reward. They can adjust the tension of the lever so that the animal needs to pull harder or lighter, again, to get that reward. And so there's a lot of things that they're looking, a lot of variables that they can manipulate, again, really trying to mimic a more clinically relevant rehabilitation paradigm. And so this is cool. And I know that Dr. Rankinsmeyer is currently having, he's doing some work looking at this robotic rehabilitator and looking at stem cell transplantation plus the rehabilitation to see if it might enhance outcomes in the context of spinal cord injury. Next slide. So that kind of brings us, I think, full circle. I've shared some examples of this regenerative rehabilitation paradigm, kind of where we've started with ex vivo stimulation, the potential of bioreactors to enhance the functional outcomes of the tissues that we're generating in the laboratory. And then more of this clinically relevant paradigm of combining cellular therapeutics or tissue engineering approaches with rehabilitation modalities and paradigms. Again, with this ultimate goal of enhancing functional outcomes for our patients. Next slide. So with that, for anyone that is interested, we're really excited about what will be our ninth annual symposium on regenerative rehabilitation. It'll be held on November 4th through 6th in Austin, Texas. Fingers crossed that we will be able to have it in person as we are planning. I wanted to mention, actually, if you click forward one more time, Quintal, I wanted to highlight that we have lots of travel awards available to attend our symposia. We're really trying to encourage junior investigators, but also individuals who might be interested, who haven't really had too much exposure with regenerative rehabilitation, but may have some curiosity about it, may even be wondering about how it might apply to clinical protocols, where we offer these travel awards to support people to be able to join us and hear what I think is really great and exciting and cutting-edge science. Next slide. So no matter when I present or what I present, I always need to take a moment to thank my wonderful lab. Quintal, I don't think you're in any of these pictures. We needed an updated picture with you as well, Quintal. But it's really just such a wonderful group of individuals that they make this science really fun and interesting, and just a great bunch to work with every day. And next slide. And of course, I wanna thank the support. So these regenerative rehabilitation efforts are supported by the NIH. We have the Alliance for Regenerative Rehabilitation Research and Training, which serves to support educational efforts and also new and budding research in the field through pilot grants. We have a number of different institutions that are a part of ART, so really broad in scope. I know we have individuals from all over the country. We are geographically diverse with this idea that we wanna be able to be easily accessible to the most people possible. And finally then, I want to thank you for your attention and your patience as we tried to get these slides up and running. Thank you so much. Thank you, Quintal, for helping with your... Does anybody have any questions? I know we're already a little bit past, but of course, you're welcome to email me or anyone else. Yes, Brooks. That talk was awesome. Thanks a lot for staying on and everyone for figuring that out. The one thing that came to my mind that is consistent with the stem cell site migration and the nonspecific exercise modality that seem to have these effects is improvements in vascularization. So I don't know if in any of these animal or even clinical models now that scar tissue's gone and healthy skeletal muscles at the surface to receive those stem cells, if vascular quality is something that you've looked at that could explain some of this. That is such a great question or comment, Brooks. Thank you for raising that because in fact, it's such a cool area, I think. And I do know of some people who are really interested in that in looking at how the vascular network is important for... And the response of exercise, for example, in promoting vascularity and how that might enhance outcomes. And for example, in the context of skeletal muscle, that's really exciting because what we see is that muscle stem cells are juxtaposed very closely with the capillaries. And they've shown that with exercise muscle, more capillaries are associated with more stem cells. We, in our work, we did look, and for the sake of time, I didn't present it, but for example, the treadmill work, we did demonstrate that that treadmill running significantly enhanced vascularity of the muscles following stem cell transplantation. And that engraftment actually was significantly correlated with vascularity of the tissue. So I think it's a great... At this point, we've only done associations. We haven't really done targeted methods to try and really understand the mechanisms behind those interactions. But I think it's a great thought. Awesome, thanks. Victor. Hi, I'm Victor Brigham, a third year medical student at Cincinnati. I just wanted to ask if maybe, I don't know if you could talk about what, like when this goes to people, like what kind of team is in, professors that's involved in doing this? Because I saw on some of your slides that, you know, like in some injuries, you got to like open up the legs, maybe a surgeon's involved, there's physical therapy. So what kind of team is involved, will be involved in this? Oh, you know, so I do have a slide that I sometimes use that shows a team because I think it's, for example, the Department of Defense Clinical Trial that I've been participating in. It's cool for that reason in terms of the multidisciplinary group. So as we have an individual, for example, that we think might be eligible for this study, the individuals who are involved include the surgeon, as you said, who is evaluating whether it's technically feasible to implant this scaffold in. We have radiologists who, you know, are trying to look at what might be the best position and localization of the scaffold once it's in. We have, of course, then the rehabilitation therapists. And the idea here is the rehab is, the rehab input I think is critical from the very initial start of deciding whether a patient is going to be a good candidate because it's the rehab perspective that really says, you know, if we can restore muscle function at this site, will that actually lead to, you know, better physical functioning? And so we do those kind of very comprehensive assessments. And so, you know, it is a very broad team. Of course, then we have the regenerative medicine scientists who are the ones who are developing the scaffold or, you know, the stem cell therapy in the first place. So it's been a cool kind of experience seeing this multidisciplinary team coming together, each adding their own different perspectives to say, you know, who is the best candidate and then taking that all the way through to the final stages of assessment evaluation. I guess we'll take one more. Marcos? Did you have a question, Marcos? Looks like your hand is raised. Okay. Well, thank you again. I so appreciate everyone's patience. And next time I'll be getting the PowerPoints from all our presenters before. But I definitely appreciate all the learning you've provided us today. So thank you again. Thank you, everyone. Dr. Ambrosio, can you hear me? Oh, yes. I'm back. I'm sorry. Terrific presentation, Dr. Ambrosio. So I have one question. I tend to work with extracorporeal shockwave therapy. Do you think that there is a role of extracorporeal shockwave therapy in such modalities like assimilating those transplants and stem cells based on the patient's medical history? And if so, how does that work? So, you know, I don't know much about it, but I definitely have seen some combinations of cellular therapies with shockwave therapy. And, you know, it seems as if there's, I can actually, maybe Marcos, if you give me your email, I know that there's a paper that looks specifically at how to do that. And I'm not sure if you've seen it, but I think there's a paper that looks specifically I know that there's a paper that looks specifically at the combination of the two. So I can look for that paper and I can send it to you. Oh, for sure. It's ready in the chat. Is it in the chat? Yeah. Thank you. Okay, great. Let's see. It didn't come through. Ah, okay. Now I got it. Okay, Marcos, I'll send you an email then with that. Thanks everyone.

regenerative rehabilitation

regenerative medicine

rehabilitative medicine

stem cell therapies

functional outcomes

skeletal muscle injuries

stroke

multidisciplinary