KidneyX Innovation Accelerator Interview 2

Kidney News interviewed Jeff Ross, PhD, CEO of Miromatrix Medical, about the company’s work to bioengineer new kidney grafts consisting of human cells grown in pig extracellular matrix scaffolds. Ross presented the work, “Building New Kidneys,” at the inaugural KidneyX Summit in Washington, DC, on April 29, 2019.

KN: Why build new kidneys, and why now?

Dr. Ross The numbers are truly eye-opening—more than 700,000 Americans are living with kidney failure that requires dialysis or transplantation. Unfortunately, less than half of the patients who start dialysis will survive five years, while those fortunate to receive a kidney transplant have a more than 90% survival rate. Our mission is to dramatically reduce the number of patients on dialysis, as well as save millions of lives by eliminating the kidney transplant waiting list.

KN: Please briefly describe your KidneyX 2019 award-winning entry, “Building New Kidneys.”

Dr. Ross Our unique perfusion decellularization process essentially washes out the cells from a discarded pig kidney, leaving all the vasculature or blood vessels and microstructures that define the kidney’s structure intact. Our groundbreaking technology then introduces human vascular and kidney cells into the decellularized kidney matrix, under defined culture conditions, ultimately recellularizing it. The first step in the process is the introduction of vascular (endothelial) cells to revascularize the kidney matrix and demonstrate that it can be implanted and sustain long-term perfusion. This was our award-winning entry demonstrating we achieved a critical milestone because without an intact and functional vasculature, there is no way to bioengineer a whole kidney. We are now focused on introducing the functional kidney cells to next demonstrate renal function of the recellularized kidney, with our ultimate goal to develop fully functional transplantable kidneys.

KN: You note that the Miromatrix products MIROMESH (soft tissue reinforcement) and MIRODERM (advanced wound care) have been implanted into thousands of patients. How does your approach to building new kidney grafts build on these products?

Dr. Ross Through MIROMESH and MIRODERM, we’ve been able to demonstrate the vast potential of decellularized porcine matrix. These products are derived from pig livers. Using the same process of perfusion decellularization, we remove all the liver cells while still leaving the overall liver matrix intact, including the vasculature. The decellularized livers are then made into MIROMESH and MIRODERM. So far, thousands of patients have been implanted with our material with no reported adverse reactions related to immunological responses. The data helps derisk our approach and provides the initial data to support starting with a pig matrix as a safe approach.

In addition, we recently completed and published our prospective multicenter clinical study evaluating MIROMESH for laparoscopic paraesophageal hernia repair. The two-year follow-up study published in The American Journal of Surgery shows GERD patients who underwent laparoscopic paraesophageal hernia repair using MIROMESH saw improved long-term patient outcomes, with no reinterventions, and a 10% two-year radiographic recurrent rate. In the meantime, doctors tested our MIRODERM product against many of our leading competitors in the biological wound matrix field in a case series and published the results in WOUNDS. The study demonstrated that our product was able to close at least half of the most difficult diabetic foot ulcers where other treatments failed. We’re not only giving those patients new hope, but we’re also showing that pig organs can be decellularized, leaving behind all the organ’s natural design and architecture.

KN: The kidney is much more complex than these two applications. How can you be sure the kidney product will succeed?

Dr. Ross As you noted, there is a large difference between a decellularized matrix and a fully recellularized functional matrix/organ. While our commercial products have laid the initial foundation, the work we presented at KidneyX demonstrates our ability to revascularize the whole kidney with human endothelial cells and achieve sustained perfusion, which is a large step forward for regenerative medicine and tissue engineering. We have started seeding the revascularized kidney grafts with functional kidney cells, and we are seeing exciting results that continue to encourage us that we will succeed.

KN: One questioner noted there are approximately 32 cell types in the kidney and asked about the certainty of their roles being preserved once they become part of 3D architecture that’s very precise. How would you respond?

Dr. Ross It was a great question and certainly one that is critical given the native architecture and function of the kidney. What we have seen in our development process is the natural homing of the seeded cells to their native microenvironment. We believe this is being driven by the kidney matrix, and the process of perfusion decellularization preserves the intact matrix and associated proteins, providing a repeatable process. We have seen this response both in the homing of seeded cells and cases of functional plasticity in both the kidney and liver.

KN: You stated that Miromatrix is aiming for in vivo functionality by 2020 and that the product could be in humans by 2022. Given the need for trials and regulatory approvals, are these dates realistic?

Dr. Ross The common response when people see our approach and data is, “Wow, that is amazing technology, but it will be 30 years before we see it in the clinic.” My response is, “We are a lot closer than you think!” Through our commercial products, initial revascularization, and now focus on achieving in vivo functionality in a large animal model by the end of 2020, we believe our goal of initiating human clinical studies as early as 2022 is a realistic goal. There is still a lot to be done, so it could move some depending on the exact regulatory pathway and data, but we are making great progress, and the future is much closer.

June 2019 (Vol. 11, Number 6)