Miromatrix will present its latest transplantable liver milestone at The Liver Meeting® hosted by the American Association for the Study of Liver Diseases (AASLD) on October 20-24 in Washington, D.C. Building on the company’s successful liver re-endothelialization efforts, Miromatrix has advanced its ability to demonstrate functional liver vasculature by maintaining long-term vascular patency of its engineered liver grafts in a porcine model.
A poster describing these advancements entitled “Towards Long-Term Vascular Patency of Tissue Engineered Liver Grafts: a Large Animal Study” will be presented at the conference on October 20th (Poster #712). Twenty-seven porcine liver grafts were seeded with endothelial cells cultured in bioreactors, 20 of which were evaluated in vitro to determine important factors that predict in vivo vascular patency. Grafts with higher glucose consumption rate (GCR) had evidence of better endothelial coverage (p=0.012) and correlated significantly with graft flow (r=0.83, p<0.01). Three grafts had radiological evidence of vascular patency via advanced CT imaging until complete graft thrombosis 7 to 10 days after transplantation. Grafts with longer vascular patency had higher flow rates immediately after transplantation (p=0.028). Immune studies using pig serum suggested that graft thrombosis at day 7-10 was likely attributable to development of cytotoxic antibodies and acute humoral rejection. It was concluded that GCR is an excellent marker of endothelial coverage and subsequent portal blood flow in engineered liver grafts. The 7 to 10 days of vascular patency achieved in humanized revascularized liver grafts transplanted in pigs (without heparinization) provides the required foundation for engineering functional liver grafts. This is the first such study to demonstrate long-term patency of a clinically relevant liver graft in vivo, setting the stage for longer term implants with completely recellularized liver grafts.
Additionally, Dr. Mohammed Shaheen from the world-renowned Mayo Clinic in Rochester, MN will make an oral presentation entitled “Impact of Xeno-Compatibility on Outcomes of Bioengineered Humanized Liver Grafts” at the meeting on October 22nd (Parallel 20: Organ Preservation and Cell Transplantation, 4:45-6:15pm EDT). The presentation will focus on the xeno-compatibility of Miromatrix’ bioengineered liver grafts revascularized with HUVECs in a porcine model of auxiliary liver transplantation and successful in vivo reperfusion as measured by CT imaging. Highlights include the characterization of porcine sera and related cytotoxicity to HUVECs with mean cell death of 83.2±14.4%. There are high levels of anti-HUVEC IgM in naïve pig serum as deactivation of IgM by heat and dithiothreitol significantly reduced cell death to 22.2±11.8% and 6.15± 4.4%, respectively (p<0.01). The cytotoxicity profile of pig sera to HUVEC cells rose further after transplantation (95.7 ± 3.4%) at day 7, and remained high even after IgM deactivation (85 ± 8.9%, p< 0.01) suggesting the appearance of new anti-HUVEC IgG. The relative contribution of IgG and IgM to cytotoxicity in day 7 samples increased by ~35% and ~460% (p=0.047), respectively, compared to baseline and corresponded with the loss of perfusion to the implanted liver grafts. Blood group incompatibility between pigs and HUVECs had no measurable contribution to the level of cytotoxicity. It was concluded that pigs harbor naturally occurring anti-human antibodies targeted against HUVECs. In addition, an adaptive immune response ensues within 7 days after exposure to our HUVEC-derived bioengineered liver grafts. Immunosuppression studies to delay the buildup of antibodies to the human endothelial cells are ongoing with promising results, providing the appropriate preclinical model to evaluate a fully recellularized liver graft.
“The work being presented at The Liver Meeting® represents a significant achievement in our mission to bioengineer transplantable organs,” says Jeff Ross, Ph.D., CEO of Miromatrix. “We’re excited to demonstrate our ability to revascularize decellularized, whole grafts with human endothelial cells and to achieve long-term continuous perfusion within the host. This demonstration of functional vasculature sets the stage for our upcoming preclinical trial later this year and gets us one step closer to our goal of creating lifesaving organs.”
The Liver Meeting® is the premier Annual Meeting in the science and practice of hepatology, including the latest findings on new drugs, novel treatments, and the results from pilot and multicenter studies. For conference details, visit aasld.org/events-professional-development/liver-meeting.
Miromatrix Medical Inc. is a Minnesota-based biotechnology company on a mission to save and drastically improve countless lives by eliminating the organ transplant waiting list. Through their proprietary perfusion decellularization and recellularization technology, the company is creating fully implantable human organs including livers, kidneys and heart products, as well as liver-derived biological products such as MIROMESH® (soft tissue reinforcement) and MIRODERM® (advanced wound care). Miromatrix’ perfusion decellularization and recellularization technology is protected by a series of issued patents and pending patent applications in all major markets worldwide. Miromatrix’ collaborators include The Mayo Clinic, Texas Heart Institute and Mount Sinai Hospital.
Jeff Ross, Ph.D.