PhD Student Leiden University Medical Centre, Netherlands
Abstract: The crosstalk between heart and kidney is crucial for maintaining organ homeostasis. Both organs have vital functions in the human body and reciprocally influence each other’s behavior: acute or chronic damage in one organ often leads to dysfunction of the other. A dual-organ on-chip model to study the cardiorenal axis was previously described, but analysis of their reciprocal interactions in vitro has not been carried out.
We combined human induced pluripotent stem cell-derived kidney and cardiac organoids (kOs and cMTs, respectively) in a co-culture setup. The kO and cMT models were first examined separately for proper structure formation and maturation. kOs were subjected to damage by nephrotoxic compounds for 72 hours which affected glomerular and tubular structures. Injury in kOs was evaluated as viability, functionality and gene expression. Within 24 hours, kidney damage was morphologically with changes of nephron structures. Damaged kOs were then co-cultured with cMTs for another 72 hours. This was indirectly detrimental to cMTs, evidenced by decreased viability and altered contraction.
Our work suggests that kO and cMT co-culture could capture dual-organ crosstalk. It also highlights the importance of multi-organ systems in disease modeling by providing (patho)physiologically relevant representation of organ interactions. By analyzing the interaction between heart and kidney in this human system, our work advances organoid-based disease modeling and offers new insights into the mechanisms underlying dialogue in organ dysfunction that affect both organs.
Funding Source: This work is supported by the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW, supported by the Novo Nordisk Foundation grant [NNF21CC0073729]).
