Kidney organoid systems for studies of immune-mediated kidney diseases: challenges and opportunities

Abstract

Acute and chronic kidney diseases are major contributors to morbidity and mortality in the global population. Many nephropathies are considered to be immune-mediated with dysregulated immune responses playing an important role in the pathogenesis. At present, targeted approaches for many kidney diseases are still lacking, as the underlying mechanisms remain insufficiently understood. With the recent development of organoids—a three-dimensional, multicellular culture system, which recapitulates important aspects of human tissues—new opportunities to investigate interactions between renal cells and immune cells in the pathogenesis of kidney diseases arise. To date, kidney organoid systems, which reflect the structure and closer resemble critical aspects of the organ, have been established. Here, we highlight the recent advances in the development of kidney organoid models, including pluripotent stem cell-derived kidney organoids and primary epithelial cell-based tubuloids. The employment and further required advances of current organoid models are discussed to investigate the role of the immune system in renal tissue development, regeneration, and inflammation to identify targets for the development of novel therapeutic approaches of immune-mediated kidney diseases.

Modeling oxidative injury response in human kidney organoids

“…Kidney organoids are immature and are more closely related to embryonic kidney epithelium and interstitium [ 78 ]. In addition, longer-term injury studies are currently not feasible, as organoids lack a blood supply, filtration, or tubular flow, and are lacking an immune system, which may not allow modeling of some of the molecular and cellular responses seen in injured adult kidneys [ 79 ]. However, organoids still have the potential to be useful for studying the efficacy and safety of potential therapeutics, as they provide the advantage of multiple cell types and structures over standard 2D culture systems [ 80 ].…”

Immunotherapeutic approaches for systemic lupus erythematosus: early overview and future potential

“…There is no ideal animal model for evaluating fully humanized antibody efficacy in SLE. Despite challenges in creating appropriate models for biologics, organoids derived from tissue-specific progenitor cells of SLE patients, such as kidney and skin tissue, show promise for understanding SLE mechanisms [ 77 , 106 ]. Likewise, upcoming technologies like organs-on-chip, artificial intelligence (AI) advancements, and CRISPR-Cas9 genome editing will greatly influence our understanding of SLE’s causes, biomarker identification, and the progress of diagnosis and treatment.…”

Generation of chimeric kidneys using progenitor cell replacement: Oshima Award Address 2021

“…In addition, improvements in comprehensive analysis techniques such as single-cell ribonucleic acid sequencing have allowed for detailed analysis of renal development, and significant progress has been made in differentiation induction techniques that mimic the developmental process from pluripotent stem cells to cells of kidney lineage. Organoid technology, which combines multiple cell types and utilizes their self-organizing ability to create tissue-like cell populations, is aimed at in vitro organ regeneration only, and it is the mainstream of current kidney regeneration methods [ 4 , 5 ]. Decellularization technology, which uses organs from which cells have been removed as a scaffold for cell differentiation, and kidney-on-a-chip technology, which uses artificial chips on which cells are seeded, are also technologies that were greatly influenced by the discovery of iPS cells (Fig.…”