Significant advancements in the field of preclinical in vitro blood-brain barrier (BBB) models have been achieved in recent years, by developing monolayer-based culture systems towards complex multi-cellular assays. The coupling of those models with other relevant organoid systems to integrate the investigation of blood-brain barrier permeation in the larger picture of drug distribution and metabolization is still missing. Here, we report for the first time the combination of a human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier model with a cortical brain and a liver spheroid model from the same donor in a closed microfluidic system (MPS). The two model compounds atenolol and propranolol were used to measure permeation at the blood–brain barrier and to assess metabolization. Both substances showed an in vivo-like permeation behavior and were metabolized in vitro. Therefore, the novel multi-organ system enabled not only the measurement of parent compound concentrations but also of metabolite distribution at the blood-brain barrier.

Integration-free induced pluripotent stem cells from related human donors' exhibit great potential to the ongoing development of organ models. Blood cells from two different human donors were isolated, purified and reprogrammed into induced pluripotent stem cells. These induced pluripotent stem cell lines were characterized precisely for pluripotency markers (with the PluriTest and flow cytometry analysis) and their differentiation capacities into meso-, ecto- and endoderm. The induced pluripotent stem cell lines are available for commercial use and are therefore of high interest for many groups working in stem cell research. A normal karyotype of the induced pluripotent stem cells was proven with the KaryoStat assay. In total 6 human donors that belong to one family donated blood for induced pluripotent stem cell reprogramming. In this "Data in Brief" publication, we show the dataset for the two male iPSC lines HUMIMIC TISSUi006-A (StemUse106) and TISSUi007-A (StemUse107). The main characterisation was recently published by Ramme et al. in Stem Cell Research [1]. All iPSC lines were also examined negative for any mycoplasma or bacteria contamination.

The integration-free iPSC lines TISSUi006-A and TISSUi007-A were generated by reprogramming blood cells with episomal vectors. The male human donors belong to a Caucasian family in which four additional family members donated and iPSC lines were generated. All iPSC lines within this family are approved for commercial use by donor consent. Those iPSC lines offer the opportunity to study the influence of affiliation within one family. In future, more iPSCs lines of many more family members can be created to understand the effects of relatives with different ages on the reprogramming into iPSCs and differentiation into specific cell types.

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.

Four integration-free iPSC lines were generated by reprogramming peripheral blood mononuclear cells with episomal vectors. All four human donors (two male and two female donors) belong to one Caucasian family within three different generations with the age between 19-82 years. Additionally, all iPSC lines are approved for commercial use by donor consent. Those iPSC lines offer the opportunity to study the influence of affiliation within one family. In future, more iPSCs lines of many more family members can be created to understand the effects of relatives with different ages on the reprogramming into iPSCs and differentiation into specific cell types.

Stem cell-derived cortical neurospheres are of great interest in basic neurobiology research and drug research. Cultivation in controlled, stirred-tank bioreactors can improve the homogeneity of neural spheroid cultures and allows culture scale-up. We used a DASbox Mini Bioreactor System for the generation of human induced pluripotent stem cell (hiPSC) spheroids and subsequent neural differentiation. Results from three independent bioprocesses demonstrate the reproducibility of the neural differentiation protocol. In a single DASbox Mini Bioreactor, we obtained 2 x 108 cells, demonstrating the potential of stirred-tank bioreactors for the generation of high numbers of iPSCderived neurospheres.

Microphysiological systems are fundamental for progressing towards a global paradigm shift in drug development through the generation of patient-on-a-chip models. An increasing number of single- and multi-organ systems have been adopted by the pharmaceutical and cosmetic industries for predictive substance testing. These models run on heterogeneous tissues and cell types from different donors. However, a patient is an individual. Therefore, patient-on-a-chip systems need to be built from tissues from one autologous source. Individual on-chip organ differentiation from a single induced pluripotent stem cell source could provide a solution to this challenge. We designed a four-organ chip based on human physiology. It enables the interconnection of 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 cross talk led to further differentiation over a 14-day cultivation period under pulsatile blood flow conditions in one common medium deprived of growth factors. This model platform will pave the way for disease induction and subsequent drug testing.