A rhino heart beats again… many years after his death

 Stem cells are amazing! They have the potential to become any cell type in the body. We all start as stem cells in the early days of development, but as we grow, most of our cells lose that ability.

Recent advances in stem cell research have changed that fact. In 2006 Shinya Yamanaka identified a method to turn skin cells back into stem cells and the field of induced pluripotent stem cell (iPSC) research began. Now this field is one of the fastest growing areas of research. iPSCs can be used for disease modeling, drug testing, regenerative medicine and research in many fields. Here at the Institute for Conservation Research we are planning to using stem cells to try to save endangered species. 

In the Frozen Zoo® we have skin cells from twelve northern white rhinos, including “Angalifu” and “Nola” (pictured above) who lived here at the Safari Park. With these skin cells we are making iPSCs in the hopes that one day these cells can be "convinced" to become eggs and sperm and used to make embryos, which we would then transfer to southern white rhinos as surrogates.

You may wonder how we “convince” these cells to become anything? Well, it’s not easy. Picture a roadmap with iPSCs as point “A” and gametes as point “B”. We know where we want to end up, but we don’t really know all of the turns and roads to take that will get us to the end result. We call this process of turning stem cells into other cell types differentiation.

Rhinos are a non-model species, meaning we don’t have as much information about differentiation as you would if you were working on mice and humans. We need to take information from these organisms and see if we can apply it to rhinos, hoping that many of these maps are the same across species. 

Cardiomyocytes, or heart muscle cells, are one cell type that are regularly made in mice and humans for research. We thought that might be a good starting point in rhinos and ordered a commercially available human kit to test. Now, would the rhino cells act just like the human cells the kit was made for? Or would it take longer since rhinos have a much longer developmental timeline? Or maybe it wouldn’t work at all? We could only try it and find out.

Trial and error is the heart of all research and that’s what makes it so exciting and fun!

My colleague, Tom Nguyen, and I started the test. We grew iPSCs from Angalifu and followed the directions. The protocol would take at least eight days - let the waiting begin! We needed to change the media or “feed” for the cells every other day, using three different types of media throughout the process to make cardiomyocytes, at least in humans.

We waited and watched the cells change their shape. Was that really how they were supposed to look? There wasn’t anyone to ask since only a few people in the world have ever seen rhino iPSCs, much less cardiomyocytes. 

It was my turn to feed the cells after about a week of following the protocol.

We had had a busy day and it was late when I made it into the lab. I changed the media, realizing that I had accidentally changed a couple of them that didn’t need to. Oh well, I hoped it wouldn’t matter, or maybe it would even make the cells happier, but it could also have the opposite affect and kill the cells. Trial and error, we would learn something no matter what.

It’s very tedious, meticulous work to take care of cells and you have to be careful and sterile in everything you do. If you are tired or having a bad day, it is very easy to make a mistake that could lead to bacteria contamination in your cells.  

The next morning Tom came to me, very seriously asking if I had looked at the cells yet. My heart sank. Had my mistake killed some of the cells? Or had I been so tired that I had contaminated the cells?

Tom smiled at my concern and told me no, they aren’t contaminated, but they were beating.

Beating heart cells in a dish from a northern white rhino!

We practically danced in the hallway. Here was our proof of principle that at least some of the pathways (or maps) were conserved across species. And maybe, just maybe the pathways to make gametes will be the same too.

Stay tuned to find out. Until then, I will forever remember the day I first saw rhino cardiomyocytes beating in a dish. Angalifu is indeed still living on in the Frozen Zoo® and I have seen his beating heart cells in our lab.

Comments

Awesome!

This is awesome, great work! I am a PhD student at San Diego State and I work with human/murine cardiac stem cells and cardiomyocytes. I know the feeling of seeing the cells beating in culture, so exciting!! Keep it up :)

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