In a landmark development, scientists at the Institute for Bioengineering of Catalonia (IBEC), in collaboration with the Biomedical Research Institute of A Coruña (INIBIC) and numerous international partners, have achieved a major milestone in regenerative medicine.

Their innovative approach enables the scalable production of human kidney organoids that can be integrated with porcine kidneys using ex vivo machine perfusion technology, a step that brings kidney organoid transplantation closer to clinical reality.

This pioneering research, recently published in Nature Biomedical Engineering, represents a decade-long journey to bridge laboratory innovation and clinical transplantation, paving the way for personalized and regenerative therapies.

What are human kidney organoids?

Human kidney organoids are miniature, three-dimensional structures derived from pluripotent stem cells that replicate many essential elements of kidney architecture and function. While they are not full organs, they serve as powerful tools for studying kidney development, drug screening, and disease modeling, and could one day be used to regenerate or repair damaged renal tissue.

Until now, scalability and consistency have been the biggest challenges in translating kidney organoid research into clinical use.

Scalable, cost-efficient production method

The research team, led by Dr. Núria Montserrat -- now serving as Catalonia’s Minister of Research and Universities -- developed a robust, systematic protocol that allows for the mass production of thousands of kidney organoids.

Using advanced microaggregation techniques combined with precise genetic engineering tools, they achieved uniform organoid generation in a controlled laboratory setting. This method also eliminates the dependence on complex or costly reagents, significantly reducing research costs and production time.

Integration into living porcine kidneys

A key innovation of the study was the integration of human kidney organoids into living pig kidneys maintained on normothermic machine perfusion devices—machines used in transplantation to preserve organs ex vivo by supplying oxygenated blood at body temperature.

Through this technology, the scientists successfully implanted organoids into porcine kidneys, observing their survival, integration, and functional stability for 24 to 48 hours both ex vivo and in vivo within the same animal model.

Monitoring function and immune compatibility

Machine perfusion allowed continuous monitoring of vital physiological parameters such as renal filtration and tissue oxygenation, providing real-time insights into viability and immune response.

Remarkably, the human organoids remained viable without triggering notable immune reactions or signs of cytotoxicity. The porcine kidneys maintained functional integrity, demonstrating the potential compatibility of cross-species organoid transplantation under carefully controlled conditions.

Toward organ regeneration before transplantation

The breakthrough opens the door to preconditioning donor kidneys with human stem-cell-derived organoids to repair or enhance organ function before transplantation.

Such a capability could improve transplant outcomes, reduce waiting times for patients, and address global organ shortages. The study’s translational potential was reinforced through partnerships with key clinical and research organizations, including Spain’s National Transplant Organisation and several leading biomedical centres.

This methodological advance addresses one of regenerative medicine’s toughest challenges: producing large quantities of standardized organoids.

By combining microaggregation and gene-editing technologies, the team optimized cell differentiation to yield kidney-specific cell types, including renal tubules and podocytes, vital for normal kidney function.

Immunofluorescence imaging confirmed the organoids’ structural and functional integrity, showing expression of critical markers such as LTL, WT1, PODXL, and DAPI -- hallmarks of sophisticated kidney-like architecture.

Leap toward precision and personalised medicine

The combination of high-throughput organoid generation and real-time ex vivo perfusion represents a quantum leap in tissue engineering.

This approach allows rapid testing of patient-derived cells for personalized drug screening or tailored therapies for kidney disease, marking a new era in precision nephrology. The scalability and reproducibility of the system set a new benchmark for clinical translation in bioengineering.

The research underscores the importance of interdisciplinary collaboration, with teams from Europe and the United States uniting experts in bioengineering, immunology, transplant surgery, and stem cell biology.

Partnerships with medical technology companies specializing in perfusion devices further highlight the synergy between academic research and industry innovation—a model crucial for advancing regenerative medicine.

Next frontier: functional maturation and human trials

Looking ahead, the team aims to extend organoid survival post-transplantation and promote full functional maturation within xenogeneic models.

Their long-term goal is to advance toward human clinical trials, exploring immune modulation, vascular integration, and long-term stability. The combination of regenerative engineering and machine perfusion could redefine the future of organ transplantation and transform global healthcare.