A newly launched startup is constructing upon improvements developed over a number of years on the Wyss Institute for Biologically Impressed Engineering at Harvard College, Harvard John A. Paulson Faculty of Engineering & Utilized Sciences (SEAS), and Brigham and Ladies’s Hospital (Brigham) to engineer useful kidney tissue for renal restore and alternative remedy.
Jennifer Lewis’ and Ryuji Morizane’s groups discovered beforehand that culturing kidney organoids underneath fluid movement causes endogenous endothelial progenitors to create extra mature vascular networks which pervade the entire organoid and work together with epithelial compartments. This discovering presents a vital advance towards the long run growth of latest approaches by Trestle to deal with persistent kidney illness utilizing 3D bioprinting and stem cell-based tissue engineering. Credit score: Wyss Institute at Harvard College
San Diego-based Trestle Biotherapeutics has been granted a license, by Harvard’s Workplace of Know-how Improvement (OTD), to commercialize a collection of stem cell- and 3D bioprinting-based kidney regenerative drugs applied sciences developed at Harvard’s Wyss Institute, SEAS, and Brigham. Based in 2020, Trestle is led by Ben Shepherd, Ph.D. and Alice Chen, Ph.D., each with deep expertise in industrial efforts targeted in stem cell biology, tissue engineering, regenerative drugs, and 3D bioprinting.
The dearth of transplantable kidney tissues and complete organs is a gigantic problem within the therapy of persistent and end-stage kidney illness. As of 2021, within the U.S. alone, there are greater than 550,000 dialysis-dependent sufferers and 100,000 sufferers ready for kidney transplants, but solely about 20,000 transplants are carried out annually, with almost 5,000 sufferers on ready lists dying annually with out receiving a transplant. Past kidney failure, there are greater than 60 genetic ailments that instantly or not directly have an effect on renal operate, a lot of which can’t be appropriately handled with present therapeutics.
The foundational know-how was pioneered by researchers within the lab of Jennifer Lewis, Sc.D., who’s a Wyss Core School member, main the Wyss Institute’s Organ Engineering Initiative, the Hansjörg Wyss Professor of Biologically Impressed Engineering at Harvard SEAS, and a Affiliated School member of the Harvard Stem Cell Institute (HSCI). Lewis’ lab has collaborated with a number of clinicians, together with Joseph Bonventre, M.D., Ph.D., Chief of the Division of Renal Drugs and Founding Chief of the Engineering in Drugs Division on the Brigham, and Ryuji Morizane, M.D., Ph.D., who’s now an Assistant Professor on the Massachusetts Normal Hospital (MGH) and Harvard Medical Faculty (HMS), an Affiliated School member at Harvard Stem Cell Institute, and a Visiting Scholar on the Wyss Institute.
We’re very excited to convey the biofabrication and stem cell biology applied sciences developed within the Lewis and Morizane labs into what we’re constructing at Trestle. The groups at Harvard, Wyss, and the Brigham have a famend monitor file in translational innovation, and we’re thrilled with the chance to hold their work ahead for sufferers’ profit.”
Shepherd, CEO, Trestle
“Greater than a dozen members of my lab contributed to the improvements in tissue engineering which have created this know-how platform,” stated Lewis. “Most not too long ago, we developed a brand new biomanufacturing methodology, generally known as sacrificial writing in useful tissue (SWIFT), that permits the fabrication of vascularized kidney tissues. I’m happy that Trestle has now launched to translate this sturdy know-how to handle the rising want for kidney tissues and organs.”
Supported partly by Harvard OTD’s Bodily Sciences & Engineering Accelerator, and later by the Wyss Institute’s Organ Engineering Initiative, Lewis and her colleagues on the Wyss and SEAS made seminal contributions to the sector of multimaterial 3D bioprinting. Utilizing their platform know-how, Lewis and her collaborators have created 3D kidney-on-chip fashions for drug screening and illness modeling and have established foundational know-how for quickly producing vascularized kidney tissue at scale for restore and regeneration.
Central to the success of this strategy was a collaboration between the Lewis Lab and researchers on the Brigham. Morizane, Bonventre, and different clinicians had developed a way for producing kidney organoids from human pluripotent stem cells in vitro. These tissue constructs contained giant numbers of well-organized nephrons, however lacked a vascular community that may very well be perfused with blood. This deficiency was overcome by subjecting the organoids to the movement of fluids on bioengineered gadgets. In a collaborative effort revealed in Nature Strategies, the joint crew succeeded in producing vascularized kidney organoids with enhanced nephron maturation in vitro.
“We had been capable of reveal for the primary time a extra superior kidney structure and performance in human kidney organoids, which is vital for creating tissue segments to be used in drug testing and illness modeling and, finally, in vivo therapeutics,” stated Morizane. Lewis and Morizane are members of Trestle Biotherapeutics’ scientific advisory board.
By combining these approaches with further options for cell and tissue manufacturing, inner experience in stem cell and kidney organoid biology, and the commercialization of 3D bioprinted human tissues, the crew at Trestle will work in direction of its aim of making a brand new standard-of-care choice for sufferers with kidney failure by way of the event of bioengineered kidney tissue with the flexibility to imagine very important kidney features.
“The transfer of this visionary know-how, developed by Jennifer Lewis, Ruji Morizane, and their colleagues, out into the world the place it’ll contribute to kidney restore and alternative therapies that sufferers so urgently want is a testomony to the Wyss Institute’s distinctive give attention to advancing analysis and know-how growth that lead to constructive close to time period impression. Now with Trestle, we stay up for seeing this know-how quickly advance to the clinic,” stated Wyss Founding Director Donald Ingber, M.D., Ph.D., who can be the Judah Folkman Professor of Vascular Biology at HMS and Boston Kids’s Hospital, and Professor of Bioengineering on the Harvard John A. Paulson Faculty of Engineering and Utilized Sciences.
