Mini organs, big impact: How organoids are revolutionizing infection research

00:00:00: Heart, brain, lungs, tiny little.

00:00:10: There is movement, nerve impulses are transmitted, blood vessels form, cells divide and differentiate.

00:00:18: Organoids start to come to life.

00:00:22: What might sound like science fiction has long been a reality in research.

00:00:27: All clusters of cells in a petri dish, grown from stem cells, have some of the various functions of real organs.

00:00:35: And you can do a lot of research with them.

00:00:38: For example, how organs function, how they form and what happens to them when they come into contact with a pathogen.

00:00:46: This is what Dr. Kristin Metzdorf does at the HZi.

00:00:49: Together with Professor Josef Penninger, she heads the Innovative Organoid Research Group.

00:00:55: Here, many organs are cultivated and in some cases genetically modified.

00:01:00: The aim is to investigate how they react to pathogens and what damage the pathogens cause in various tissues

00:01:07: and how the organoids then repair themselves or change permanently.

00:01:12: They can also be used to research drugs such as vaccines.

00:01:16: How this works, how we all can benefit from organoid research, this you can listen to in our new episode of In Fact.

00:01:25: Hello from the HZi Library.

00:01:31: I'm sitting here with Dr. Kristin Metzdorf.

00:01:35: Hi, Kristin.

00:01:35: Hi.

00:01:36: Organoid research actually sounds like science fiction to me, but is it really like simple, complete organs,

00:01:46: but just in miniature? How big are they? And since when is it even possible to grow them?

00:01:52: It might indeed sound like science fiction when scientists create complex life forms in the lab.

00:02:00: But however, it's like this, that organoids are not complete mini organs,

00:02:04: but they are rather 3D dimensional cell structures that mimic certain organ structures.

00:02:11: The whole term of organoid changed over the years.

00:02:18: It appeared in 1940, the first time where it was really referring to tissue mass or tumors that were isolated,

00:02:27: and later it came to these 3D structures that organoid referred to.

00:02:33: The most promising change in organoid research and how we now interpret organoids like they are

00:02:44: was in 2009 where it was possible to isolate stem cells from the colon.

00:02:53: And even in lab, it was possible that these structures appeared again.

00:03:03: So you had really miniature colon organoids that were mimicking the function.

00:03:10: And then since 2014, more and more cell culture protocols appeared for different organ-like

00:03:17: structures. And due to the different organoids, we have differences in their size.

00:03:25: So when we are talking about, for instance, heart organoids, we are still talking about micrometers

00:03:31: with the 400 micrometers of the heart organoid. It's rather as big as the one of a fruit fly.

00:03:40: But when we talk about brain organoids that we are growing in the lab, they are the size of the

00:03:47: whole fly. So with 1 to 2 millimeters, you can really see them by eye.

00:03:52: And is it possible with all organs or which organoids are you able to grow on your lab?

00:03:57: And how do you do it?

00:03:59: It's not possible to create organoids for all organs and with the same precision and also the

00:04:04: functionality, because the whole human system is very complex. And when you are thinking about how

00:04:10: also the organs take over specific functions, like the colon, for example, you have the small

00:04:24: intestine, you have the colon, and it has different function where the food comes from,

00:04:30: actually. And you can only always take a part of this whole system and mimic it in culture.

00:04:37: And yeah, this gives you, how we are doing it is that we have the stem cells. So these

00:04:47: delts are, or they still have all the information they need to grow in different cell types.

00:04:53: And we feed them with growth factors. So we push them in a specific direction to grow

00:05:00: certain structures. And depending on the structures that we actually need,

00:05:05: we put the growth factors. And in the end, we have, for instance, a colon organoid or brain

00:05:12: organoid or a little heart.

00:05:13: You do not do this by your own. You have a robot, yeah?

00:05:20: Yes.

00:05:20: Kind of this.

00:05:21: We have a cell culture robot. So on our lab, this cell culture process is automated. And

00:05:26: we call this cell culture robot Molly. Molly is taking good care of the organoids. So she's

00:05:32: feeding them. And also there's a microscope integrated. So she also tells us when the

00:05:39: structure is not correct and ask if she needs to feed again, for instance.

00:05:45: And what do you examine, actually, in the organoids? Which infectious diseases do they

00:05:51: help you with your research?

00:05:53: So what we find very exciting is that we can look at electrical activities from the

00:05:58: organoid. So in a simplified manner, we can write EKGs for heart organoids. And in this

00:06:06: case, the electrodes are not attached to the patients, but the organoid is placed on a little

00:06:12: chip where the electrons are implemented. And all the time when the heart is beating,

00:06:19: we can measure this electric activity. And in terms of infection, this is really nice to see

00:06:27: how the structure behaves. So when we infect it with SARS-CoV-2, then we can see how long

00:06:34: our changes are appearing. Are they even changes appearing? And when is the heartbeat coming back,

00:06:41: for instance, to normal? And the same you can also do, of course, with brain because

00:06:46: neurons are also communicating by electrical signals. And this also brings me to the

00:06:54: infections that we can do because each organ has, of course, certain pathogens that are

00:06:59: most likely to infect this organ. And therefore, we are more concentrating on different kind of

00:07:07: pathogens. The HZi has an BSL3 laboratory. So we have the possibility to also work with

00:07:15: pathogens that are for the risk assessment in the BSL3 lab, like the Mpox virus or SARS-CoV-2,

00:07:22: or even bacteria like mycobacterium tuberculosis. Very interesting. And your department has

00:07:30: not been at the edge that I thought very, very long. How long did it take until you were able

00:07:35: to grow the first real organoids? So the cultivation of organoids is very individual and also

00:07:41: demanding. So therefore, the most important thing is always the know-how.

00:07:48: And we were very lucky to recruit some people that have all the know-how we actually needed.

00:07:56: And it takes some time for organoids to grow.

00:08:01: So for gut or heart organoid after 30 days, it's ready for infarction.

00:08:07: When we think about brain, for instance, it takes almost two to three months until we can use it.

00:08:12: And therefore it took some time and our forced organoids we were able to provide to our collaboration partners in August last year.

00:08:22: Why are they so important for research?

00:08:25: What advantages do they have over other model systems such as animals, for example, or cell cultures?

00:08:34: So first of all, these organoids consist of different cell types.

00:08:37: And they are building 3D structures, so they are in very close proximity to each other.

00:08:44: That means they have different signaling pathways activated and metabolic activities that you can measure.

00:08:53: And therefore it's more from the physiological relevance more important.

00:09:00: We are also able to grow organoids from patient material, which makes it very beneficial for individualized medicine and to have some translational research that comes with these patient material.

00:09:14: And also when we talk about the organoids coming from human cells, it of course also has the potential to reduce animal experiments.

00:09:24: We cannot take out of our, or they still lack actually the immune system and the whole complexity.

00:09:35: So it also represents a very early stage of the maturation of these organs.

00:09:42: Yeah, can you imagine?

00:09:44: And do other research groups at the age that I or even other research institutions also work with your organoids?

00:09:52: Yes, also the groups at HCI are increasingly relying on organoid research.

00:09:59: And we have within the HCI multiple collaboration that are also very attractive for us because all this research group here has their specialties.

00:10:11: This means they exactly know what they need.

00:10:14: They know which cell types, which pathways, which receptor needs to be within the organoid that the infection could even happen.

00:10:24: And you are also able to send organoids.

00:10:29: So you can certain cell types, you can freeze down and send them to collaboration partners, for instance.

00:10:35: Or just like the heart organoids ship them as they are.

00:10:40: You just cover them and put them on the way for another research project.

00:10:45: And when you look into the future, what is your vision?

00:10:48: What do you want to achieve with this research platform?

00:10:53: And yeah, what insights do you hope to gain with this?

00:10:58: The organoid platform is only one part of our department and it was funded by the Federal Ministry of Research.

00:11:07: And of course, it's meant to provide an innovative organoid platform for infection research.

00:11:16: And we would like to utilize the organoids for many research projects, also to other groups, to learn from their specialty and include it in our organoids.

00:11:27: So that we can make them more complex, more relevant for research.

00:11:35: And in the end, develop better systems to be faster in preventing pandemics, for instance.

00:11:44: Organoid research here at the HCI is headed by Josef Penninger.

00:11:49: He is also managing director and heads research groups in Austria and Canada.

00:11:56: How much does he contribute here and how often can you exchange your ideas or results with him?

00:12:06: So the vision behind the project came with Josef to the HCI.

00:12:11: And alongside with a lot of other sub-projects that all are aiming for researching the resilience mechanism of microbes and humans.

00:12:21: And this organoid platform is overall one of the visions we want to implement for the whole HCI.

00:12:29: And he brings the expertise, he brings the network also from the international side that is even needed for developing these kind of platforms.

00:12:39: And his other departments in Canada and in Vienna, they both contributed a lot in organoid research over the past years.

00:12:48: And we have regular lab meetings where we of course have the exchange, also the scientific exchange, where to go with the organoid research, of course.

00:13:01: And now when you look into the further future, what is your long term goal?

00:13:07: Where would you like to go with the organoid research and your department and especially you as a person, as a researcher?

00:13:17: What do you want to achieve?

00:13:19: We aim to really provide complex organoids that are getting better and better in their structure to solve infection problems.

00:13:31: And for this we need to understand the host-pathogen interaction.

00:13:36: And I think the organoids, especially with activity measurements, for instance, are a very good tool to do so.

00:13:43: And I hope we find a lot of new therapeutic treatments.

00:13:49: And especially when it comes to situations like pandemics, that we can fast find already solutions to prevent it.

00:13:59: Last question. How did you actually come to organoid research?

00:14:03: I'm a trained neurobiologist.

00:14:05: So I looked a lot for signaling between neurons and during the pandemic I went to infection research.

00:14:18: And the organoids now give me the chance to look at both things.

00:14:24: So look at cells and their communication and how they behave under infections.

00:14:29: And of course, Joseph gave me the chance to be part of his vision and I just took it.

00:14:37: So I think when I hear you talking about it, it's something that really drives you and how much time from the day or from the week do you spend at the lab or here for your research?

00:14:56: I really like research and I also consider it as my hobby.

00:15:01: So I'm always very interested in the results and when they are coming up.

00:15:07: And yes, of course, social life is also part of my life.

00:15:13: And maybe a little bit of sleep.

00:15:16: Thank you for your time and for the interesting information.

00:15:19: Thanks a lot for having me.

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