Autologous induced pluripotent stem cell-derived four-organ-chip

Abstract

Microphysiological systems play a pivotal role in progressing toward a global paradigm shift in drug development. Here, we designed a four-organ-chip interconnecting miniaturized human intestine, liver, brain and kidney equivalents. All four organ models were predifferentiated from induced pluripotent stem cells from the same healthy donor and integrated into the microphysiological system. The coculture of the four autologous tissue models in one common medium deprived of tissue specific growth factors was successful over 14-days. Although there were no added growth factors present in the coculture medium, the intestine, liver and neuronal model maintained defined marker expression. Only the renal model was overgrown by coexisting cells and did not further differentiate. This model platform will pave the way for autologous coculture cross-Talk assays, disease induction and subsequent drug testing.Lay abstract Models of four human organs-intestine, liver, brain, kidney-were cultivated in a micro-bioreactor, called microphysiological system. The organ models were placed in distinct compartments of the bioreactor which were connected by a microfluidic network. This fluidic circulation enabled a cross-Talk between the four organ models similar to the human blood circulation connecting the organs in the human body. The organ models were engineered from induced pluripotent stem cells derived of a single donor. Therewith, all organ models shared the same genetic background. This might allow for a more accurate and patient specific testing of drugs in future.