Research Award Recipients

Matrix directed differentiation of bioprinted kidney organoids to promote maturation and vascularization

Co-applicant(s): Keekyoung Kim

Lay Abstract

Background: Studying kidney diseases in the lab has always been challenging. Conventional two-dimensional (2D) cell cultures do not recapitulate the full structure or function of a real kidney. Over the past decade, organoid technology, voted Nature Method’s Method of the year in 2017, has revolutionized the study of organ development and modelling diseases. We and others can now grow three-dimensional (3D) miniature versions of kidneys, called kidney organoids, from stem cells. These mini-kidneys can form some of the key parts of real kidneys, including structures called nephrons, which help filter blood. However, one major problem remains: these kidney organoids do not have blood vessels, which are essential to deliver nutrients and oxygen—just like in the body.

Purpose: To create a more realistic and functional mini-kidney, we are supplementing the organoids with growth factors and blood vessel cells that provide the support needed for better tissue development and improved blood vessel networks. We aim to develop a mini-kidney model that better mimics the real organ, so it can be used to study kidney diseases, test potential therapies, and ultimately support future work in regenerating kidneys.

Method: We will use new bioengineering techniques to help grow and connect blood vessels inside the kidney organoids. This involves:

1. Adding special growth factors and blood cells to kidney organoids to promote blood vessel formation.

2. 3D bioprinting of mini-kidneys in a supportive hydrogel called GelMA to help everything hold together and grow properly into structures that better resemble real kidneys. Anticipated outcome: We expect that by improving the environment in which these mini-kidneys grow, we will be able to make them more mature and more similar to real kidneys. This would make them much more useful for studying kidney diseases and testing potential treatments.

Patient engagement: Stem cells can be made from individuals with various diseases. This current proposal will establish better model systems to study kidney diseases and to develop miniature kidneys f:or therapeutic testing and regenerative medicine applications. Patients interested in growing their own mini kidneys will be recruited in the next phase for disease modelling and therapeutic testing in the future.

Relevance to Patients/Communities: Our research group is one of the few in the world with the expertise and team capable of bioengineering 3D kidney organoids using advanced protocols. Our work will advance our understanding of kidney development and aid in the goal of rebuilding a kidney.

Conclusion: For people with chronic kidney disease, new treatment options are urgently needed. By creating more realistic mini-kidneys that include blood vessels, we are taking an important step toward better disease models, more accurate drug testing, and potentially growing kidneys from a patient’s own cells in the future.