Harvard University licenses kidney engineering

image: The teams of Jennifer Lewis and Ryuji Morizane previously discovered that culturing renal organoids under fluid flow causes endogenous endothelial progenitors to create more mature vascular networks that invade the entire organoid and interact with epithelial compartments. This discovery presents a critical step towards the future development of new approaches by Trestle to treat chronic kidney disease using 3D bioprinting and stem cell-based tissue engineering.
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Credit: Wyss Institute at Harvard University

(BOSTON/CAMBRIDGE, Mass.) – A newly launched startup builds on innovations developed over years at Harvard University’s Wyss Institute for Biologically Inspired Engineering, Harvard John A. Paulson School of Engineering & Applied Sciences (SEAS) and at Brigham and Women’s Hospital (Brigham) to engineer functional kidney tissue for kidney repair and replacement therapy.

Based in San Diego Biotherapeutic Trestle obtained a license, by Harvard Technology Development Office(OTD), to commercialize a suite of stem cell and 3D bioprinting-based renal regenerative medicine technologies developed at the Wyss Institute of Harvard, SEAS and Brigham. Founded in 2020, Trestle is led by Ben Shepherd, Ph.D. and Alice Chen, Ph.D., both of whom have extensive experience in commercial efforts focused on stem cell biology, tissue engineering, regenerative medicine and 3D bioprinting.

The lack of transplantable kidney tissue and whole organs is a huge challenge in the treatment of chronic and end-stage kidney disease. In 2021, in the United States alone, there were more than 550,000 patients on dialysis and 100,000 patients awaiting kidney transplants, but only about 20,000 transplants are performed each year, and almost 5,000 patients on waiting lists die each year without receiving a transplant. . Beyond kidney failure, there are more than 60 genetic diseases that directly or indirectly affect kidney function, many of which cannot be adequately treated with existing therapies.

The fundamental technology was developed by researchers at the laboratory of Jennifer LewisSc.D., who is a member of the Wyss Core Faculty, leading the Wyss Institute Organ Engineering Initiative, Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard SEAS and Affiliate Faculty Member of the Harvard Stem Cell Institute (HSCI). Lewis’ lab has collaborated with several clinicians, including Joseph Bonventre, MD, Ph.D., chief of the division of renal medicine and founding chief of the division of engineering in medicine at Brigham, and Ryuji MorizaneMD, Ph.D., who is now Assistant Professor at Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Affiliate Faculty at Harvard Stem Cell Institute, and Visiting Scholar at Wyss Institute.

“We are excited to integrate the biofabrication and stem cell biology technologies developed in the Lewis and Morizane labs into what we are building at Trestle. The Harvard, Wyss and Brigham teams have a proven track record in translational innovation, and we are excited to have the opportunity to continue their work for the benefit of patients,” said Shepherd, CEO of Trestle.

“More than a dozen members of my lab contributed to the tissue engineering innovations that created this technology platform,” Lewis said. “More recently, we have developed a new biofabrication method, known as sacrificial writing in functional fabric (SWIFT), which allows the manufacture of vascularized kidney tissue. I am delighted that Trestle is now embarking on translating this robust technology to meet the growing need for kidney tissue and organs.

Supported in part by Harvard OTD’s Physical Sciences & Engineering Acceleratorand later by the Wyss Institute’s Organ Engineering InitiativeLewis and his colleagues at Wyss and SEAS made seminal contributions in the field of multi-material 3D bioprinting. Using their technology platform, Lewis and collaborators created 3D kidney-on-a-chip models for drug screening and disease modeling and established foundational technology to rapidly generate large-scale vascularized kidney tissue. for repair and regeneration.

Key to the success of this approach was a collaboration between the Lewis Lab and Brigham researchers. Morizane, Bonventre and other clinicians had developed a method to generate kidney organoids from human pluripotent stem cells in vitro. These tissue constructs contained large numbers of well-organized nephrons, but lacked a vascular network that could be perfused with blood. This shortcoming was overcome by subjecting the organoids to fluid flow on bioengineered devices. In one collaborative effort Posted in Natural methodsjoint team succeeded in generating vascularized kidney organoids with enhanced nephron maturation in vitro.

“We were able to demonstrate for the first time more advanced renal architecture and functionality in human kidney organoids, which is important for creating tissue segments for use in drug testing and disease modeling and ultimately therapeutics. in vivo,” Morizane said. Lewis and Morizane are members of the Scientific Advisory Board of Trestle Biotherapeutics.

By combining these approaches with additional solutions for cell and tissue manufacturing, in-house expertise in kidney stem cell and organoid biology, and commercialization of 3D bioprinted human tissues, the Trestle team will work towards its goal. to create a new standard of care. option for patients with kidney failure through the development of bio-engineered kidney tissue capable of supporting vital kidney functions.

“Moving this visionary technology, developed by Jennifer Lewis, Ruji Morizane and their colleagues, to the world where it will contribute to the kidney repair and replacement therapies that patients so urgently need is a testament to the unique focus of Wyss Institute on advancing research and technology development that results in short-term positive impact. Now, with Trestle, we look forward to seeing this technology progress rapidly in the clinic,” said the founding director of Wyss Donald IngberMD, Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Children’s Hospital, and Professor of Bioengineering at Harvard John A. Paulson School of Engineering and Applied Sciences.

PRESS CONTACT

Wyss Institute for Biologically Inspired Engineering at Harvard University
Benjamin Boettner, [email protected], +1 617-432-8232

AVAILABLE MULTIMEDIA

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The Wyss Institute for Biologically Inspired Engineering at Harvard University (https://wyss.harvard.edu) uses design principles from nature to develop bio-inspired technologies that will transform medicine and create a more sustainable world. Wyss researchers develop innovative new solutions for healthcare, energy, architecture, robotics and manufacturing that translate into commercial products and therapies through collaborations with clinical investigators, corporate alliances and the formation of new startups. The Wyss Institute creates transformative technological breakthroughs by engaging in high-risk research and crossing disciplinary and institutional barriers, working as an alliance that includes the schools of medicine, engineering, arts and sciences, and design from Harvard, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Boston Children’s Hospital, Dana–Farber Cancer Institute, Massachusetts General Hospital, University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, Charité–Universitätsmedizin Berlin, University of Zürich and Massachusetts Institute of Technology.

Harvard Technology Development Office (OTD) promotes the public good by fostering innovation and translating new inventions made at Harvard University into products that are useful, available, and beneficial to society. Our integrated approach to technology development includes sponsored research and corporate alliances, intellectual property management, and technology commercialization through company formation and licensing. More than 90 startups have launched to commercialize Harvard technologies over the past 5 years, collectively raising over $4.5 billion in funding. To further bridge the development gap between academia and industry, Harvard OTD operates the Blavatnik Biomedical Accelerator and the Physical Sciences and Engineering Accelerator. For more information, please visit https://otd.harvard.edu.

Trestle Biotherapeutics, Inc. is a preclinical-stage company developing bioengineered therapies for patients with end-stage renal disease. Once implanted, these bioengineered stem cell-derived tissues will allow patients to stop dialysis, delay their need for transplants, and one day become organ replacements. Learn more about www.trestlebio.com.


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