For the first time, they manage to generate kidney organoids with a complex vascular system

These are asembloids, micrometric organoids formed by the union of kidney organoids with 3D vascular organoids. These small cell culture systems are useful for disease modeling and drug screening.

The study in which this advance was achieved was led by the Institute of Bioengineering of Catalonia (IBEC).

The study authors have described a new approach to produce mini-kidneys in the laboratory that replicate a complex vasculature, similar in some characteristics to that of human kidneys. These “asembloids” are created by joining 3D kidney organoids with endothelial organoids.

Organoids are three-dimensional structures grown in vitro that mimic organ functions and are a promising tool for disease modeling and drug screening. However, these small organs often lack nervous, immune, or vascular systems due to the complexity of such systems.

Reproducing in the laboratory the complex vascularization system of the kidneys, a highly irrigated tissue, has been a challenge for scientists for more than a decade. Now, this new study has allowed us to find an approach that had not been tested before:

“We have assembled kidney organoids with vascular organoids. To successfully carry out this process, it is essential to identify the ideal moment to join them, taking into account the moment of development of each of the organoids,” explains Núria Montserrat Pulido, ICREA research professor, principal investigator at IBEC and leader of the study. “When these two types of organoids are together, they begin an interaction process in just three hours. The result of this procedure is truly spectacular,” she highlights.

These findings not only provide valuable information on the development of renal organoids, but also lay the foundation for designing new vascularization procedures for these organoids. This could have applications in organoid transplants in clinical settings and in research on vascular dysfunctions in human diseases.

“We need to have this vascular system in our organoids if we want to model systemic pathologies that affect the kidney through the bloodstream, such as an autoimmune disease or diabetes, for example. We also believe that the approach we have used in this study could also be applied to other organoid models,” explains Elena Garreta Bahima, researcher in the Montserrat group at the IBEC and first author of the study.

The next step, says Montserrat, will be to introduce these vascularized organoids into a microfluidic chip to be able to carry out even more specialized studies in order to mimic conditions that occur in complex diseases as well as allow vascular connection with other organoids, such as cardiac organoids, a work that Today they are being developed in the laboratory at IBEC.

Kidney asembloid. (Photo: IBEC)

Print with cells

The research team had already seen in previous studies that the kidney organoids they generated contained a vascular component: endothelium cells, which are what end up giving rise to blood vessels. Using kidney tissue of porcine or human origin, they created a biocompatible hydrogel, which could be used as an ink for 3D printing.

With this basis, they decided to simplify the system to make it more accessible and economical. Among all the proteins that make up the hydrogel, they selected collagen I, one of the most abundant proteins in the extracellular matrix of kidney tissue, and generated a biocompatible gel with which they validated their experimental results.

This work represents a significant milestone in the field of emerging and advanced therapies, one of IBEC’s main research areas. These therapies are innovative medical treatments that use cutting-edge technologies to address complex diseases and disorders.

The study has also brought together researchers from other centers that are part of the National Platform of Biomodels and Biobanks of the Carlos III Health Institute (PISCIII-BB) in Spain, highlighting the importance of network collaboration for defining solutions. in biomedicine based on bioengineering. This Platform, coordinated by Núria Montserrat, deputy director of clinical translation initiatives at IBEC, provides high-level scientific and technological services by integrating and coordinating the activities of all its units in response to the needs of the National Health System, in addition, it manages more of 500,000 biological samples and related clinical data.

In addition to IBEC, the Hospital Clínic of Barcelona, ​​the Center for Applied Medical Research (CIMA) of the University of Navarra, the Biomedical Research Institute of A Coruña (INIBIC), the Leartiker technology center (Basque Country), and the Gregorio Marañón General University Hospital (Madrid), in Spain.

The study is titled “Natural Hydrogels Support Kidney Organoid Generation and Promote In Vitro Angiogenesis.” And it has been published in the academic journal Advanced Materials. (Source: IBEC)