Where did the name EVATAR come from?
Avatars are representations of people in a digital or virtual world. And just like Eve is typically thought to be the mother of all humans, EVATAR is the mother of all microhumans.
What do you mean by tissue constructs and how is this different?
Instead of looking at one particular cell type, we are able to look at the many different types of interacting cells in each tissue, by using 3D tissue models, recapitulating human physiology.
What size are the tissues?
Approximately 1-3mm on a 6.5mm trans well insert.
Is EVATAR made from stem cells?
Not currently. We use primary human cells, however we are working to develop stem cell integration in the future.
Why are these tissues removed from women?
We obtain tissue from women undergoing hysterctomies for benign conditions, such as uterine fibroids.
Could an egg implant or could an embryo develop in this system?
No, that is not the purpose of this system.
What do we still not know about reproductive health that this system could address?
There are a number of issues this system could be used to address. Here are just a few: recurrent pregnancy loss, luteal phase insufficiency, contraceptivedevelopment, ovarian cancer, uterine cancer, cervical cancer, or infection.
What has been most difficult technical hurdle?
When building a system like this from scratch, there are a number of technical hurdles to overcome in the beginning. We maintained a constant dialogue between biologists and engineers to determine the right amount of fluid, the right flow rate. There was a lot of iteration before we finally had a system that could last 28 days and support each of the five tissues.
What about some of the aspects not incorporated, like immune cells?
While we don’t necessarily have immune cells in the system, epithelial cells do have innate immune properties, such as secreting antimicrobial peptides, and cytokines, and we are able to monitor that in our system.
How did you get to a 28 day culture period and why has this not previously been possible?
3D cultures have previously not lasted 28 days because the cells aren’t able to get all the nutrients and oxygen they would get in the body. Additionally, in static cultures, the cells/tissues are living in their metabolic waste. In humans, the kidney normally removes metabolic waste, which we previously weren’t able to do in tissue culture. The circuitry in our system allows us to remove metabolic waste, allowing long term culture.
Why did you use mouse tissue for the ovary and human tissue for the other organs?
Ovaries never come out of young women, nor should they, unless there is a potential for sterilization due to cancer treatments. In hysterectomies, the ovaries are typically left in the woman, because the hormones are so important for many different tissues, such as the heart, brain and bones. Mice have the exact same hormones – estradiol and progesterone have exactly the same structure in both mice and humans. Similar to how we are able to engineer a mouse-like cycle during in vitro fertilization by inducing polyovulatory cycles, we are able to do the opposite in this case and induce the human cycle in the mouse ovary.
What are potential future tissues that could be included?
In the future, we could include a number of tissues, such as: bone, cartilage, cardiac tissue, islets, adrenal gland, hippocampus, adipose tissue, and more. We are also currently working on a male version of this system that contains testis and prostate tissue.
Read the Nature Communications research article
Evatar was funded entirely by the National Institutes of Health
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