Damage of a single organ accounts for the majority of human illnesses with liver disease affecting over 500 million people and accounting for over 2 million annual deaths worldwide

Award Details:

• Funding Agency: Advanced Research Projects Agency for Health (ARPA-H), National Institutes of Health
• Federal Grant Program: ARPA-H (CFDA 93.384)
• Prime Recipient: President and Fellows of Harvard College
• Award Amount: $17.815 million
• Award Date: September 26, 2025
• Completion Date: September 25, 2028
• Place of Performance: Massachusetts

Scope of Work:

Harvard College will develop the first off-the-shelf engineered liver tissue product to address the critical shortage of donor organs for liver transplant. The project applies next-generation technologies including induced pluripotent stem cell (iPSC) differentiation into all required liver cell types, immune engineering to prevent allogeneic cell rejection, bioreactor development for cell manufacturing and maturation, and biofabrication technologies to produce clinical-scale liver constructs. The ultimate deliverable is a Good Manufacturing Practice (GMP) manufactured biobank of universal liver tissues with demonstrated effectiveness in humanized mouse and pig models to support clinical trial advancement. The project culminates with a transplant-ready graft capable of metabolic offloading and supporting native liver recovery in patients with severe liver disease.

Sub-awardees and Supporting Work:

Three major collaborating institutions deliver specialized components: Columbia University will develop bioreactors for manufacturing and functional evaluation of liver cell populations and tissues in both Good Laboratory Practice (Phase I) and GMP (Phase II) configurations; MIT's Weiss laboratory will employ synthetic biology to genetically engineer iPSC lines and derive all liver cell types through iPSC and organoid differentiation; and the University of Colorado will fabricate hydrogel microparticles, develop suspension bath and digital light processing printing processes, and scale bioprinting methods to produce vascularized liver tissues suitable for preclinical and eventual therapeutic applications.

At this time the only curative therapy is orthotopic transplant of a donor liver. However due to the severe shortage of donor organs transplants are limited to only a fraction of the population who might benefit from liver replacement therapy largely due to the low availability and high cost and complex surgery and lifelong immunosuppression requirements. As such millions of patients are left without an accessible solution. The implant team aims to address this challenge by establishing the first off the shelf engineered product to address liver failure. The solution is built on several next generation technologies including tools to drive inducible pluripotent stem cell differentiation into all required cells of the liver and immune engineering to allow allogeneic cells to evade immune rejection and bioreactors to facilitate manufacturing and maturation of cells and engineered tissues at low cost and simple biofabrication technologies to build clinical scale constructs. Implant will generate a universal and transplant ready graft that cooperates with the native liver to maintain homeostasis and sometimes even leading to its recovery and regeneration through metabolic offloading and bringing hope to millions of patients for whom the current liver transplant paradigm fails. The project will culminate with a GMP manufactured biobank of cells and universal liver tissues with effectiveness demonstrated in humanized mice and humanized PIG models to support technology translation towards clinical trials. Beyond implant we expect the path to regulatory approval to progress through a narrow indication ultimately into serving the millions of patients with serious liver diseases. Overall this project aims to provide a solution that will revolutionize the treatment of liver disease and serving all populations many of whom are currently excluded from transplant.