A Human Stem Cell-Derived Brain-Liver Chip for Assessing Blood-Brain-Barrier Permeation of Pharmaceutical Drugs.

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).

An Individual Patient's "Body" on Chips-How Organismoid Theory Can Translate Into Your Personal Precision Therapy Approach.

The first concepts for reproducing human systemic organismal biology were developed over 12 years ago. Such concepts, then called human- or body-on-a-chip, claimed that microphysiological systems would become the relevant technology platform emulating the physiology and morphology of human organisms at the smallest biologically acceptable scale and, therefore, would enable the selection of personalized therapies for any patient at unprecedented precision. Meanwhile, the first human organoids-stem cell-derived complex three-dimensional organ models that expand and self-organize -have proven that self-assembly of minute premature human organ-like structures is feasible, once the respective stimuli of ontogenesis are provided to human stem cells.

Supporting dataset of two integration-free induced pluripotent stem cell lines from related human donors.

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.

Generation of two additional integration-free iPSC lines from related human donors.

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.

Generation of four integration-free iPSC lines from related human donors.

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.

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

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.