Innovations in Space-Grown Human Tissue Boosted by ACS Award

Implanted liver cells developed in the Tissue Orb

Tammy T. Chang, MD, PhD, FACS, isn’t simply reaching for the stars by conducting research aboard the International Space Station; she’s hoping to revolutionize the future of liver transplantation by growing tissue in microgravity.

A past recipient of the George H. A. Clowes Jr., MD, FACS Memorial Research Career Development Award, Dr. Chang intends to use the condition of weightlessness within low Earth orbit (approximately 1,200 miles above the Earth’s surface) to engineer the self-assembly of human liver tissues in order to provide an alternative to traditional liver transplants.

“It was extremely gratifying to learn that I was a recipient of the Clowes Award in 2016,” said Dr. Chang, a professor of surgery at the University of California, San Francisco (UCSF), and director of the Chang Laboratory for Liver Tissue Engineering, which is a basic and translational research lab dedicated to liver tissue engineering. “As a researcher, it is very validating to learn that your peers have recognized the importance and significance of your work and collectively decided to support it.”

Dr. Chang performs an open total colectomy on a patient with medically refractory colonic pseudo-obstruction on the acute care surgery service.

The clinical problem that Dr. Chang and her team are working to address is centered around the fact that while transplantation is a very effective treatment for patients with liver dysfunction or severe liver disease, there are not enough donor organs available to treat every patient.

Although a record number of liver transplants (12,344) were performed in the US in 2025, which was an uptick of 8% from the previous year, more than 9,000 Americans currently are on the liver transplant waiting list, a number that continues to grow daily.^1,2

Investigators at the Chang Lab are focusing on the liver beyond the demonstrated clinical need for more available organs: namely, the liver’s significant capability to regenerate in response to injury and metabolic demand.

“The main and long-term goal of the lab is to develop a tissue-based therapy developed from stem cells that can take on liver function and then be implanted into patients as a tissue replacement treatment. This is the work that the Clowes Award has supported,” Dr. Chang explained.

Dr. Chang was recruited to UCSF as a faculty member in 2011, the same year she launched the laboratory.

“The Clowes Award came at a time when I was starting to transition professionally and really grow my lab. The value of the Clowes is that it’s a long-term award—5 years. This long-term structure provides the necessary stability for strategic planning and extended research horizons,” she said.

During the Clowes Award period, Dr. Chang received additional funding from the National Institutes of Health in the form of an R01. Her project, “The Role of Matrix Rigidity and Hepatocyte Mechanotransduction in Fibrotic Liver Disease” investigated how the stiffening liver extracellular matrix influences hepatocyte dysfunction.³

Dr. Chang also received grants from two federal funders of research in 2018 to study the effects of microgravity on biological systems—the NASA Space Biology Program and the National Science Foundation (NSF) in collaboration with the Center for the Advancement of Science in Space.

“The College and the ACS Foundation have been there from the beginning to support my research to conduct liver tissue engineering in space,” added Dr. Chang, referring to the ACS Resident Research Scholarship (2006–2008) that supported 2 years of full-time research between her third and fourth years of general surgery residency training at UCSF.

Dr. Chang stands in front of the vehicle assembly building at the Kennedy Space Center, where rockets and space vehicles are assembled vertically for launch.

“That early funding helped propel my career trajectory and enabled me to seek grant funding from NASA and NSF. The path to success for obtaining grants begins with receiving one grant, which then leads to additional success with obtaining other grants,” revealed Dr. Chang. “The fact that I could put on my biosketch or my CV that I had received support from the ACS at this level indicates to the people reviewing my grants that I’ve already received recognition and approval from my professional society, and that says a lot.”

Beyond the financial boost, this type of validation helps reinforce an investigator’s reputation for excellence.

“The fact that the ACS Foundation and the College support surgeons conducting research really facilitates surgeons in obtaining broader research support from the medical research community, not just because of the financial sponsorship, but because it represents an endorsement from your peers and members of your society,” she said.

Gravity of the Situation

While it is possible to simulate microgravity in an Earth-bound laboratory using rotating bioreactors, Dr. Chang and colleagues suggest that liver organoids sustained in actual microgravity have the potential to become larger and could even grow blood vessels. In other words, something that can be accomplished up there cannot happen down here.

The Chang Laboratory’s research focuses on the differentiation of induced pluripotent stem cells in microgravity. Developed from normal adult human cells, these initial cells are reprogrammed to act like embryonic stem cells, according to Dr. Chang.

Dr. Chang examines liver organoids within the Tissue Orb under a microscope.

These stem cells are, in turn, built into liver tissues in microgravity that function like a smaller, simpler liver.⁴ Unlike Earth-bound tissue engineering methods that “rely on exogenous matrices or culture plates, microgravity allows cells to float freely and organize naturally, resulting in more physiologically accurate tissues.”⁴

“We have found that if you place these cells in a suspension culture with very low-shear stress, similar to weightlessness in space or microgravity, the cells will self-organize and self-assemble and—compared to conditions that are gravity-restricted or grown in conditions under Earth’s gravity—these cells become better liver cells and function better compared to other methods,” she said.

The cornerstone of this experiment is a bespoke bioreactor known as the “Tissue Orb.”

“My lab designed the Tissue Orb, which is patented by our university as an idealized bioreactor that would facilitate and promote tissue self-assembly and self-organization,” explained Dr. Chang. “This bioreactor will be flown to the International Space Station to test our hypothesis. Hopefully, this will be done this fall. Currently, we are in the midst of what’s called a ‘payload verification test’ where we are charged with demonstrating that the hardware is working and that it is possible to get results on the ground as a trial run. And if we get positive results there, we may be approved to fly in mid-October.”

Advancing novel tissue engineering in space could represent a life-changing future for liver patients on Earth. This progress starts with one, notable “glimmer” of space-based tissue growth.

“I think the hardest part is getting that first signal, that first positive spark that demonstrates this is possible. And a lot must happen and has to go right in order to do that,” said Dr. Chang. “We’ve achieved some of those signals in the lab. Now, to achieve that signal in space has been challenging. It has taken us years to build a concept, build the hardware, and collaborate with the International Space Station National Lab and implementation partners to get what is necessary up into orbit.”

Dr. Chang said that if they obtain strong, rigorous data showing their hypothesis is possible, then they are well on their way to overcoming the scientific challenges in creating these liver tissues that could stand in for whole liver organ transplants.

“While there might be scientific, technical, and regulatory issues to solve, we are pushing forward with the work. I think our most near-term application from what we’re developing is in children with inborn errors of metabolism. These are hereditary metabolic diseases that affect liver function. And we have been talking to patients and patients’ families, and they don’t want to wait. They want something to resolve what’s happening now. So, the onus is on us to develop something as efficiently and as safely as possible.”

In order to facilitate the safe return of engineered tissues to Earth, Dr. Chang’s lab also is developing state-of-the-art cryopreservation technology involving isochoric supercooling, a preservation method that maintains tissues below freezing without damaging them. “Our goal is to bring functional tissues generated in the unique environment of space back to Earth in a viable state, where they can be used for a range of biomedical applications, including disease modeling, drug testing, and ultimately, therapeutic implantation,” Dr. Chang explained.

In an article published in 2023, Dr. Chang and colleagues described an organ preservation model that sustained supercooling in pig liver tissue for 24 to 48 hours without ice nucleation, though conclusive evidence that the preserved organs can be successfully transplanted is still pending.⁵

Four Tissue Orbs were installed into spaceflight hardware.

Translating Bedside Impact into Research Purpose

For many surgeons, the most inspiring moments in practice are not born from clinical success alone, but from the human connections formed along the way. Dr. Chang described how the lived experience of treating individual patients has become a powerful driver of her research.

“I’ve been a general surgeon with a primary clinical practice in acute care surgery for the last 15 years,” she said. “As surgeons, we are privileged to connect with a patient who is at a critical point in their life—and that connection is powerful. That human connection from clinical experience motivates the research aspect of my work, although it is a longer road. What you do every day in the lab, analyzing the data and so on, may not have that direct patient impact, but the research that we are pursuing has the goal of greater impact for larger populations of people.”

Balancing the dual role of the surgeon-researcher requires more than time management; it necessitates robust institutional support.

Dr. Chang and her research team run through experimental procedures in preparation for launching liver organoids into space.

“Patient care comes first, and that’s clear in my mind. So, when I am on call on clinical service, that is what I’m doing. My team in my lab knows that, and that’s how I guide my time,” explained Dr. Chang. “But when I am off clinical duty, I’m also working with a team of colleagues and other attending surgeons that allows me to focus on advancing research in the lab, training the person who needs to be trained in the lab, writing manuscripts and grants, and helping develop new ideas that are going to push the work forward.”

Surgeons occupy a vantage point that few others in medicine can share—a reality that helps motivate surgeons who have one foot firmly planted on the patient side and the other in research.

“Surgeons have such a unique perspective on human disease that other physicians or clinicians may not have access to because we actually see the disease process and anatomy, and we know the techniques and approaches that can be used to manipulate that anatomy,” Dr. Chang said. “Having that unique perspective gives surgeons involved in research valuable insight into what questions should be asked and the range of possibilities.”

To learn about the basic requirements and obligations associated with the Clowes Award, visit facs.org/clowes. For more information about the ACS Foundation, the programs it supports, and how to contribute, check out facs.org/foundation.