Why Miromatrix Medical believe the turning point to solving organ shortage is in sight

Medical Plastics News editor Laura Hughes spoke with Jeff Ross, CEO of Miromatrix Medical to learn more about the fully implantable human organs Miromatrix is creating, and why the organisation believes that the turning point to solving organ shortage is in sight.

Could you tell me about the fully implantable human organs you are creating?

At Miromatrix, our mission is to eliminate the organ transplant waiting list.

The idea is to take a pig organ that was going to be discarded and perfusion decellularise it. The word decellularise means to remove all of the cells from the organ. This is achieved by cannulating the organ and perfusing a mild detergent through it, essentially washing the cells out. This will leave you with a perfect scaffold or matrix that still contains the key architecture.

By starting with an existing organ, the method essentially preserves the blue print of an organ. After the pig cells are removed, we infuse the organ matrix with human cells in order to be able to create and reanimate that organ.

What sort of materials do you use for these implants?

Ultimately, our bioengineered organs will be comprised of a decellularised whole organ matrix derived from a pig and then recellularised with human cells. 

We are focused on ensuring the functioning of these implants. Therefore, currently we are infusing cells in to our liver construct and demonstrating the functionality of those. Later these cells will go in to longer-term implants to hopefully demonstrate that we can recover an animal. Our goal is to remove the animal’s native organ, replace it with our bioengineered organ, and have the animal survive. Once we achieve that, our next step will be human clinical studies.

How does this technology differ to what is currently available?

This technology came out of the University of Minnesota, and their whole concept was focused on looking at how to advance regenerative medicine.

Prior to their research, the idea of using a biologic and natural extracellular matrix wasn’t new. Previous technologies relied on immersion decellularisation, where they would take tissues and put them in to a solution. The decellularisation solution would essentially need to diffuse in, dissolve the cellular material, then diffuse back out.

By this method, there was no way to decellularise complex tissues. This meant that you could do thin tissues, but the technology wasn’t suitable for whole organs.

Perfusion decellularisation means instead of working from the outside in, we’re able to work from the inside out. We use that native vasculature to perfuse a solution in and through the whole organ or tissue to remove all the cellular material; this enables the decellularisation of complex tissues including whole organs.

What are some of the main challenges that you have faced during this process?

One of the first challenges was the ability to source the organ from any donor, for instance from a pig or from a human source.

The natural thought would be to use human organs; however, the challenges with this are that you still have the issue of cadaveric organ sourcing and additionally, the organs that you can source are often damaged and/or diseased. We’ve learned that if the matrix is damaged or diseased, it then gets conferred on to the cells resulting in an inconsistent product.

Therefore, a pig source would be perfect, especially with the medical device history of pig bowels and other tissues being successfully placed back in to humans.

We then had to answer the key question about whether the scaffold would be immunogenic since we were decellularising the whole liver and placing it back inside the body. Instead of tackling the issue with a fully recellularised liver, we chose to start with a decellularised liver in order to derisk the ultimate approach.  

After careful research, sourcing pig livers and decellurarising those, we launched two products called Miromesh and Miroderm.

We have positive data for thousands of patients who have been implanted with these products, and we have recently finished two prospective clinical trials on them. Most importantly, there has been no reported immune related issues with the implantation of Miromesh and Miroderm.

We therefore believe that we have really been able to derisk our approach and demonstrate the ability to utilise a pig source, which allows us to have perfect quality control and utilise something that was in most areas being discarded.

Our next big hurdle was one that has really plagued tissue engineering in general – how to revascularise the tissue.

Tissue engineering was really good at demonstrating that you could take cells and the matrix and put them both together to create sheets of tissue. The challenge was however, that these sheets were really thin and translucent, meaning that although in theory it works it may not be clinically relevant.

For more complex diseases we need a thicker tissue, and the only way to get this is by having a vasculature which allows for the delivery of nutrients to those cells and the ability to take waste away.

So now that we have derisked the matrix, the next step was to place endothelial cells (specifically human endothelial cells) back in to the liver matrix. The goal was to determine if we could revascularise or essential repave the vascular channels inside the decellularised organ.

Right now, we are preparing to publish the results we believe demonstrate that we were successful and that we can revascularise the organ, place it back in to a large animal, and get sustained perfusion.

When do you expect this to be rolled out within patients?

We are currently sourcing human livers and getting ready to source human kidneys that were deemed unsuitable for transplant. This means that although the organs are classed as high quality, they are not transplant candidates.

In order to make them transplant viable, we’re isolating out human cells and seeding them on to our decellularised organ matrix. Our end goal is to have a completely human recelluarised organ whether that’s a liver, a kidney a lung, or a heart for transplantation.

We think that we are really making great progress by taking down those initial barriers and demonstrating early signs functionality. Based on our progress, we are targeting as early as 2021 for our first human clinical studies.

A lot of people say, “this stuff is really cool, maybe my kids are going to see it.” I then tell them, “we are a lot closer than that.” Cell therapies are advancing at a rapid pace.

We still have to take down hurdles such as obtaining agency approval, but we believe we are making good progress.

Your goal is to eliminate the organ transplant waiting list, do you really believe this is something that is achievable?

Absolutely, but in steps.

Today, we’re focused on solving the urgent need of bridging the gap that exists between those who need life-saving organs and the shortage of them. That’s why our first product will be isolating primary cells for organs that were unsuitable for transplant.

Long term, the holy grail of what we are really working on is that secondary generation product. Some day we hope to isolate cells from a patient and create an organ specifically bioengineered just for them. This would mean that they would no longer require immunosuppression. If we can achieve that goal, we can eliminate the organ transplant waiting list.

Miromatrix will be presenting their technology at the BIO International Convention in Philadelphia in June, following its Pipelines of Promise award.