Daring AM: Stanford’s $26.3M Venture to Bioprint and Implant a Human Heart into a Pig

Stanford University, fueled by a $26.3 million federal contract, is gearing up to bioprint a human heart and implant it into a pig. The researchers behind this effort have already begun bioprinting soft biocompatible materials with living cells meticulously patterned into a predetermined architecture to create cardiac tissue. However, Mark Skylar-Scott, team leader and Assistant Professor of Bioengineering, says they must refine the process at least a thousand times to understand how to keep these tissues alive and need a pipeline capable of handling trillions of cells. He also points out that to support this massive endeavor, they are working on new 3D printing hardware to manufacture human tissues larger, faster, and with higher resolution.

“This is going to be an enormous generational challenge, so we better get started,” explains Skylar-Scott, specializing in bioprinting. “Our goal is to manufacture human tissues at therapeutic scale, bridging the gap between cells on a dish and organs on a living patient.”

Heart’s blueprint

Focusing on developing new 3D printing technologies is just the tip of the iceberg for Skylar-Scott. The expert believes that researchers will need decades of work to produce functional 3D printed organs and to advance stem cell and developmental biology. Skylar-Scott remarks that this is “a monumental task,” mainly because a human heart contains over 10 billion cells from more than two dozen cell types, all precisely arranged in a 3D pattern to form a functional, beating organ. The sheer scale of the challenge means that “perfection will come through repetition.”

Furthermore, the heart presents a unique challenge with its intricate chambers, valves, and vessels. Spearheaded by Skylar-Scott, the researchers aim to conquer this complexity. Their method involves using automated bioreactors to produce vast amounts of heart cells. From cells that beat in rhythm, creating the heartbeat, to cells that form blood vessels ensuring the heart gets its supply of oxygen and nutrients – they’re producing them all.

Mark Skylar-Scott. Image courtesy of Stanford University.

After refining their techniques and learning the nuances of heart design, the team plans to produce a functioning, viable heart that will be transplanted into a pig. With anatomical and physiological similarities to humans, pigs have long been considered suitable models for various medical research areas. These include cardiovascular studies, transplantation studies, and more. For instance, the size and function of a pig’s heart are quite similar to that of a human’s, making them particularly valuable in cardiovascular research. Additionally, pigs share a high degree of genetic similarity with humans, which further justifies their use in such studies.

While using pigs as test subjects is common in medical research during the preclinical phase, the larger context surrounding these practices is worth noting. There’s growing optimism in the scientific community that innovations like bioprinting could eventually diminish the reliance on animal models. It must be said that the dichotomy between the potential to reduce animal testing through advanced technologies and the present-day dependence on animal models has been a topic of discussion in the scientific community for years. Organizations like the Wyss Institute for Biologically Inspired Engineering at Harvard University are at the forefront of alternatives to animal testing, such as organs-on-chips technology. Though still nascent, bioprinting presents potential alternatives to traditional animal testing. However, the technology’s current limitations likely influenced Stanford’s decision to proceed with a pig for this particular endeavor.

“We will use these vast numbers of cells to practice, practice, practice, and learn all the design rules of the heart and optimize viability and function at the whole-heart scale for eventual implantation into a pig,” sums up Skylar-Scott.

To prevent rejection, the bioprinted human heart will be transplanted into a pig with severe congenital immunodeficiency. However, the team’s approach uses patient-specific stem cells that may not require immunosuppression when transplanted into that patient.

“Your own heart, made out of your own cells; that is the dream,” adds the researcher. But he’s also cautious. While the aspirations are high, Skylar-Scott believes the full realization of this dream, especially for humans, might still be decades away. However, projects like this are vital in moving closer to that reality.

A 3D bioprinter in the Skylar-Scott lab prints a sample of heart tissue in 2022. Image courtesy of Andrew Broadhead/Stanford University

Life’s matrix

To support this massive endeavor, the team not only plans on building new 3D printing technology but has already begun collaborations with surgeons at the Stanford School of Medicine. Their expertise is crucial to guide the bioprinting process, say the researchers, ensuring the tissues are suitably robust for implantation. After all, bioprinting a heart isn’t just a task for bioengineers. It requires expertise from various fields: cardiology to understand heart functions, materials science to decide on the best bioinks, biochemistry for cell production, and many more. Fortunately, Stanford has all these experts nearby.

Moreover, what propels this project forward is a game-changing $26.3 million federal contract via the Advanced Research Projects Agency for Health (ARPA-H), a US Department of Health and Human Services (HSS) agency. It is part of ARPA-H’s Open Broad Agency Announcement (Open BAA). This landmark initiative responds to the Biden-Harris Administration’s vision to tackle the acute shortage of organ transplants through on-demand 3D tissue printing.

With over 100,000 US citizens languishing on waitlists for vital organs like hearts and kidneys, the HSS has signaled its intent to revolutionize the field with this hefty investment. Alarmingly, over 6,000 lose their lives annually due to inaccessibility to compatible organs. On top of this, millions require tissues like corneas, skin, and cartilage for grafts and transplants, which could be life-altering.

Organ odyssey

To address this, ARPA-H launched the Health Enabling Advancements through Regenerative Tissue Printing (HEART) project. Stanford University is at the heart of this mission. The research team must enhance cell purity, upscale 3D bioprinting speed, and pioneer computation modeling and tissue maturation techniques.

As ARPA-H Program Manager Paul Sheehan explains, “The HEART Project has set the ambitious goal of 3D-printing a working human heart in one hour. The project represents exactly the kind of challenging and impactful topics ARPA-H is looking to support. Multiple technology advances will be necessary for this project’s success, a success that could dramatically improve the lives of patients who would otherwise be on transplant wait lists.”

With $305.4 million in funding, Open BAA aims to support groundbreaking health research and technological innovations. Open BAA began accepting abstracts in March 2023 and is open until March 2024. Aside from Stanford’s HEART project, Open BAA has also awarded $104 million to Harvard Medical School to defeat antibiotic resistance, $37 million to Thymmune Therapeutics to help restore immune and endocrine function, $49.5 million to Georgia Institute of Technology to aid in multi-cancer early detection, $19.9 million to the University of Missouri for cancer immunotherapy, $45 million to Rice University to create a device designed to trigger the immune system against tumors, and $24 million to Emory University to program immune cell functions to cure disease.

While crafting a 3D printed, working human heart in just an hour, as Sheehan suggests, might sound like a colossal aspiration today, it remains a long-term ambition. One that many other researchers in this niche subsegment share. Stanford’s ambitious project pushes boundaries and paves the way for innovations that could redefine life as we know it. The research team believes there is immense potential in bioprinting, and this project offers a tantalizing glimpse into a future where solutions are tailored, addressing the root cause of health issues. Although the road ahead is long and filled with hurdles, the journey is worth watching.