New Facility for Bioengineering Research Opens in Los Angeles

In a world eager to solve the problem of rejection in organ transplantation, a young American scientist developed a breakthrough test in 1964 that would help establish the compatibility of tissue types between organ donors and patients in need of transplants. Even though, today, efforts to meet organ transplant demand are shifting toward the field of bioengineering, as researchers search for ways to recreate complex organs with patient-derived cells, the legacy of that scientist, Paul Ichiro Terasaki, continues to inspire discoveries in transplant medicine through his philanthropic ventures.

The Terasaki Institute for Biomedical Innovation (TIBI), a nonprofit research organization established by Terasaki, professor emeritus of surgery at the David Geffen School of Medicine at the University of California Los Angeles (UCLA), will open the doors to a new facility in 2022. The newly-acquired addition will house interdisciplinary research in bioengineering, micro- and nanoscale technologies to enable transformative biomedical innovation as part of continuing research to solve the biggest problems related to organ transplantation and beyond.

Earlier this month, the Terasaki Institute announced the revamping of a building in the Woodland Hills area of the city of Los Angeles. Once home to the Weider Health and Fitness Center, created by bodybuilder and entrepreneur Joe Weider, the two-story building will be custom-designed to house the latest technology in cutting-edge research and will provide 50,000 square feet of floor space for up to 200 employees.

Located just 22 miles north of the original Terasaki Institute facilities in Westwood, the new space devoted to laboratory research will be designed to accommodate multiple teams of scientists, who will be developing bioengineered systems, devices, and other products with several biomedical applications. This new facility will be fully equipped to enable such technologies as tissue engineering and regeneration, biofabrication using 3D printing, nano- and micro-engineering, stem cell engineering, and the creation of human organs on chips.

When the new facility is inaugurated, with the renovation of the building set to begin in fall 2020, it will become the Terasaki Institute’s third research facility. In addition to the ample space and unique design features of the laboratory, the new facility will include in-house technology translation capabilities to be able to build prototypes and scale models of devices engineered by the institute. It will also be able to accommodate meetings, seminars, and conferences to further the education and exchange of ideas among its researchers and collaborators.

“I’m very excited about the addition of the new building to the Terasaki Institute. I believe that this addition will give us needed research space to bring together a number of leading scientists in our efforts to develop the next generation of biomedical innovations,” said Terasaki Institute’s new director and CEO, Ali Khademhosseini. “I’m particularly excited about furthering the great legacy of the Weider family and the building’s history in promoting health and fitness by focusing on individualized cures and diagnostics.”

Previously at Harvard Medical School, the Wyss Institute for Biologically Inspired Engineering, and most recently at UCLA Bioengineering, Khademhosseini has been an influential figure in pushing bioengineering forward. His research in regenerative medicine, tissue engineering, and micro- and nanotechnologies for the treatment of diseases has been related to advancements that allow reprogramming of adult cells to become progenitors, as well as editing genes. The bioengineer has also created a technique that uses a specially adapted 3D printer that could help advance the field of regenerative medicine by making it possible to 3D print complex artificial tissues on demand. He has also established the Khademhosseini Lab, an industry-leading tissue engineering lab that is co-sponsored by both MIT and Harvard and acts as a strategic partner to 3D bioprinting startup BioBots.

Ali Khademhosseini (Image: Ali Khademhosseini)

Stewart Han, president of the Terasaki Institute, has been working hard overseeing the planning and renovation of the new building: “It is exciting to be able to create a brand-new laboratory and research facility from the ground up, and it will greatly enhance our research capabilities when it’s completed. We also know that the new building will facilitate the future growth of our institute.

Founded in 2001, the Terasaki Institute was made possible through an endowment from the late Paul Terasaki, and it is expected to continue leveraging scientific advancements that enable an understanding of personalized medicine, from the macroscale of human tissues down to the microscale of genes, as well as to create technological solutions for some of the most pressing medical problems of our time.

Paul Terasaki in front of the Terasaki Life Sciences Building UCLA. (Image: Leslie Barton/UCLA)

“The board of the Terasaki Institute is very excited about the purchase of the new building in Woodland Hills, and we look forward to developing it into a world-class biomedical research center,” said board chair and diagnostic radiology specialist Keith Terasaki. “My father, the late Paul I. Terasaki, started the Terasaki Institute in hopes that it will make impactful discoveries in medical research. This new research facility will enable us to do so.”

To the field of transplant surgery, transplant pioneer Paul Terasaki enabled a broad understanding of organ transplant outcomes around the world. More than 70 years after his original discovery, patients still rely on organ donor transplants and the fundamentals of Terasaki’s laboratory developed tissue typing tests are still used today for the determination of transplant compatibility. Nonetheless, the Terasaki Institute envisions a world where personalized medicine is available to all. So, as the researchers at the institute continue to address the challenges that can finally advance the field of organ transplants from human donors to bioengineered artificial organs, they might bridge the gap between sickness and health. With one of the most productive 3D printing researchers as director, Khademhosseini, and a new facility to further explore biofabrication technology, we can expect to hear much more from the Terasaki Institute in years to come.

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Organovo: Bioprinting Could be the New Solution to Organ Transplantation

Remember when movies like The Island seemed like a scary yet foreseeable future? In 2005, the sci-fi thriller introduced a compound inhabited by clones used for organ harvesting, as well as surrogates for wealthy people in the outside world. Actually, 3D technology is proving that the future looks quite different, with tissue engineering taking center stage, anticipating a possible future where organ transplants will not be needed to survive. One of the most well-known tissue engineering companies is San Diego-based Organovo. It has been actively developing a line of human tissues for use in medical research and drug discovery for years.

The company, one of the first big players in bioprinting, was founded in 2007 by Keith Murphy and Gabor Forgacs with a focus on developing in vivo liver tissues to treat a range of rare, life-threatening diseases, for which there are few current treatment options other than organ transplantation. Organovo’s ultimate goal in developing their liver therapeutic tissue is to delay or reduce the need for a transplant. The firm is also trying to harness their foundational ability to characterize specialized human cells and to 3D bioprint functional tissues to create novel in vitro toxicology and liver disease modeling platforms.

According to Organovo, initially the new liver tissue will be ideal for treating chronic liver failure, a disease that attacks millions of people around the world. It could also be used for pediatric metabolic liver diseases. The implementation of the developed tissue could solve both conditions. The number of Americans affected by chronic liver failure is higher than previously estimated and affects 1.8% of the U.S. adult population – that’s over 4.5 million Americans. Furthermore, the global prevalence of liver disease accounts for approximately 2 million deaths per year, making liver transplantation the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates. It is no wonder Organovo is targeting the illness, and might also help reduce the high cost of living with chronic liver disease.

Research using Organovo’s bioprinters

In 2014, they announced successful printing of the liver tissue with the NovoGen MMX Bioprinter, that functioned as a real liver for at least 42 days, which the company later sold commercially as ExVive Liver Tissues for preclinical drug discovery testing. The in-house 3D printed tissue could change the way pharmaceutical companies develop, discover, and test new drugs before bringing them to market. Organovo later partnered with various universities around the world to attempt to 3D print fully functional human kidney tissues, as well as pharmaceutical and cosmetics giants, like L’Oreal to advance the development of synthetic skin tissue. Moreover, the company’s first bioprinted products are expected to make it to the U.S. Food and Drug Administration (FDA) in 2020 to begin clinical testing. Development of a healthy therapeutic liver tissue patch could treat a broad range of liver diseases, according to the company, claiming it’s objective will be to implant the patch to restore function or offset the deficiencies related to the condition.

Last year, Taylor J. Crouch, Organovo’s CEO said that “in each case, our objective in implanting a healthy tissue patch to restore function or offset the deficiency of a specific enzyme abnormality, with the ultimate goal of delaying or reducing the need for a transplant.” Since receiving the Orphan Designation (a special status given to a drug to treat a rare disease or condition) from the FDA in 2017 for 3D bioprinting therapeutic liver tissue treatment of alpha-1 antitrypsin (A1AT) deficiency, the company has been testing 3D printed human liver tissue in animals, laying human cells into a configuration that creates a tissue which is functional for human testing, and presented data on the performance of tissues in animal models for A1AT and hereditary tyrosinemia Type 1 (HTT1) at industry meetings over the past several months.

Presenting data that indicates therapeutic potential of bioprinted human liver ‘patches’ in a disease model

Samsara Sciences, a subsidiary of Organovo, commercializes human liver and kidney cells obtained by 3D printing for use in research applications since 2016. They transform donated tissue at the end of a birth-life-death cycle into millions of opportunities for learning. Through manipulation of DNA, RNA and human cells the company will, in the future, be able to create the tissues which repair damaged organs, boost the functions of organs or replace missing functions. But although Organovo’s spotlight is on liver therapeutic tissue, they are also pursuing multiple therapeutic indications including end-stage liver disease and a select group of inborn errors of metabolism (IEMs), which demand an urgent need for novel treatments due to the critical shortage of donor organs.

So, what makes Organovo special? For starters, the bioprinting firm was one of the most instrumental pieces in the development of 3D bioprinters able to develop liver and kidney tissue for drug discovery applications, and in 2010, they printed the first blood vessel. The key to their success lies in replicating native form and function, their 3D human tissues offer many advantages over standard cell-culture platforms due to the fact that three-dimensionality is achieved without dependence on integrated scaffolding or hydrogel components, that would not be found in native tissues, they have a tissue-like density with highly organized cellular features, such as intercellular tight junctions and microvascular networks.

Furthermore, additive manufacturing for medical applications will most likely be extremely lucrative, with a report suggesting that it could turn into a 2 billion dollar industry, bioprinting companies are racing to come out first. And with it’s ExVive artificial tissues in full force, it could become one of the leaders in the industry. Organovo’s revenues have already been climbing in the past three years, especially since their uptake of the tissue research is still going strong. Collaboration and grants brought in revenues over the past years, thanks to the company’s ongoing collaboration with Merck, one of the largest pharmaceutical companies in the world.

Congressman Scott Peters visiting Organovo lab to learn more about 3D bioprinting

They say that their goal is “to build living human tissues that are proven to function like native tissues, with reproducible 3D tissues that accurately represent human biology.” And while their current products revolve mostly around providing in vitro tissue models for drug testing, they are actively investing in developing artificial organs ready for transplant. The liver is the only organ in the body that can regenerate by replacing lost or injured tissue; however, if the liver fails, most people began a long waiting process, hoping to receive a full or part of the organ via transplant. Organovo is trying to cut the waiting time, helping millions on the way. Still, within five years of a liver transplant, 25 percent of patients on average have died and within 10 years, 35 to 40 percent die. That means the rejection rate is pretty high, so how will companies help the body accept the 3D generated tissue in the future?

That is one of the big challenges for the companies pushing the technology and the medical community. Perhaps, in the same way scientists are teaching the body to accept new organs, they can help it embrace it’s own ‘retouched’ cells. Although the company remains cautious and prudent about their research, there is no doubt that a great many people are awaiting news about 3D printed ‘organoids’ that could some day replace organ transplantation.