Improving Transplant Equity by Bioengineering Organs for Transplants

May 01, 2023 - In a recent press release, CareDx Inc., based in Brisbane, CA, and Miromatrix Medical Inc., based in Eden Prairie, MN, announced a collaboration focused on researching bioengineered organs for human organ transplants. Tissue and organ bioengineering has been conceptualized for years, with many implications in improving transplant equity and addressing the shortage of organ donors. As researchers take steps closer to whole organ transplantation in humans, it is critical to understand the science behind bioengineering and how to minimize patient risk.

The collaboration between the two organizations is focused on improving the human transplantation process and using minimally invasive donor-derived cell-free DNA (dd-cfDNA) testing as a biomarker for allograft injury or organ rejection.

The aim is to decrease the burden of a transplant and the associated biopsies while gathering additional insight into the rejection and rejection prevention process.

Transplant Statistics

Throughout 2022, the United Network for Organ Transplants (UNOS) reported 42,888 transplants from 21,369 organ donors in the United States. Although it is essential to acknowledge all completed transplants, it is equally vital to recognize that hundreds of thousands of people are still on the transplant waiting list.

 “Organ transplantation is one of the largest unmet medical needs facing the world today. In the United States alone, over 42,000 transplants are performed annually, and over 113,000 people remain on the waitlist,” said Jeff Ross, PhD, CEO of Miromatrix, in an interview with LifeSciencesIntelligence.

The transplant process and matching system are complicated, involving multiple factors determining a patient’s position on the transplant list. Additionally, once a transplantable organ becomes available, providers must ensure that a certain number of match points coincide to minimize the risk of rejection.

Transplant Inequity

Despite a growing number of transplants each year, the equity gaps persist. Because of the scarcity of donor organs, patients must reach a certain financial threshold before being actively listed for donation. UNOS claims that these standards allow them to ensure patients follow postoperative care guidelines and minimize the probability of an organ being wasted. The natural consequence of this financial standard is that patients of lower socioeconomic status may be less likely to get a transplant.

Additional inequities based on race and gender have also been reported. For example, a study published in Transplantation notes that Black patients are 25% less likely to be considered for the transplant list than White patients.

“There's a whole process for a waiting list because transplantation is donor limited,” Robert Woodward, PhD, Senior Vice President, Research & Development, CareDx, told LifeSciencesIntelligence. “Across the board in all situations there would be more transplants if there was more donors”

Bioengineered Organs

Understanding the restraints on the transplant system by donor limitations, many researchers have hypothesized and begun investigating bioengineered organs and tissues as a potential alternative to deceased or living donors. Miromatrix uses organ tissues that may not have been used for transplantation for various reasons to create a scaffold of cells and eventually develop multiple organs from one organ’s tissue.

“Miromatrix Medical Inc. is a Minnesota-based biotechnology company bioengineering human organs to save and improve patients’ lives,” said Ross. “We utilize our patented perfusion decellularization and recellularization technology to first produce a non-cellular organ matrix with the native organ vasculature and architecture. Next, we recellularize the acellular matrix with human cells, creating a bioengineered human organ.”

The technology was first explored by Doris A. Taylor, PhD, and Harald Ott, MD, PhD, in a 2008 study published in Nature Medicine. In that study, the researchers explored regenerative medicine for heart transplants through perfused cadaveric rat hearts.

As a result of the study, the investigators could engineer, populate, and mature components of bioengineered hearts.

Animal Studies

In 2021, Miromatrix announced its first successful whole-organ transplant in a large animal model, marking the first-ever whole-animal organ transplantation. The study, published in Nature Communications Biology, was led by Scott Nyberg, MD, PhD, a surgery and biomedical engineering professor at the Mayo Clinic and head of its Liver Regeneration Program.

The investigators focused on liver transplantation, as a liver transplant is the only proven treatment for chronic and acute liver failure.

“Relevant to Miromatrix, roughly 95% of the waitlist is comprised of patients waiting for a kidney or liver, which is why our initial focus is on microkidney and microliver,” noted Ross.

The publication detailed the seeding and engraftment protocols for turning primary porcine hepatocytes into bioengineered livers (BEL) scaffolds. Researchers explanted pig organs from cadaver animals for future implantation.

They monitored five in vitro pig models, three of which had bioengineered liver implantation. The study validated their ability to use perfusion decellularization and recellularization processes to develop functional BELs capable of albumin production, ammonia detoxification, and urea synthesis.

Based on the results of this study and other promising in vivo data, Miromatrix hopes to progress toward clinical trials using tissue engineering and other bioengineering protocols to develop functional organs, including human livers and kidneys, for transplantation.

Improved Equity

Like most people working toward bioengineered organs, the teams involved in these studies hope to transform the transplant process, minimize wait times, and improve patient outcomes by closing equity gaps.

“By increasing the supply of organs available to patients, we envision a significant benefit to transplant equity. Additionally, the potential savings to the healthcare system are well documented and substantial,” said Ross. “For example, the American Journal of Transplantation has estimated that each kidney transplant could save the healthcare system over $1.5 million.”

The collaboration between the two organizations creates the possibility of bioengineering organs that are better quality or a better match for different patient populations. Instead of patients hoping their immune system does not reject the organ, providers can have a better idea of how a patient will respond and may be able to move away from traditional immunosuppression protocols.

This provides an additional step toward equity. Instead of patients being dependent on organ availability and having a partial organ match, they may be able to get the best match and ensure equitable outcomes regardless of donor availability.

“Things that increase supply always increase equity,” said Woodward. “There are other opportunities with bioengineered organs that can further increase equity.”

Monitoring Organ Rejection

Despite immunosuppressive protocols, Columbia Surgery notes that 10–12% of transplant recipients experience transplant rejection. While rejection can be acute or chronic and may not necessarily mean that a patient loses the organ, the process is very burdensome for patients and the healthcare system.

In the case of end-stage renal failure, a rejected organ may result in organ damage or return to dialysis, which can be a costly and strenuous treatment.

“CareDx is developing innovative donor-derived cell-free DNA (dd-cfDNA) testing services to non-invasively assess acute allograft rejection in Miromatrix’s pipeline of bioengineered human organs,” said Ross.

The technology provides a less invasive way to test for various outcomes in transplant patients. Among those outcomes is the risk of rejection. The blood test can provide indications of organ rejection or proper healing without a biopsy.

“Heart transplant patients joke that providers give them a new heart, and then they take it back one little piece at a time as they do the biopsies over the years. So, patients are happy to have noninvasive testing solutions,” added Woodward. With a minimally invasive tool, post-transplant care may be less burdensome.

Overall, bioengineered organs can revolutionize transplant care. Patients may have more equitable access to quality healthcare without a donor-limited transplant system. As the research progresses, the FDA, healthcare providers, and other scientists will continue to monitor the progress of transplant care.

Editor's Note: The first quote from Robert Woodward was revised for clarity on 05/01/2023.