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

自体诱导性多能干细胞衍生的四器官芯片

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作者:Anja Patricia Ramme, Leopold Koenig, Tobias Hasenberg, Christine Schwenk, Corinna Magauer, Daniel Faust, Alexandra K Lorenz, Anna-Catharina Krebs, Christopher Drewell, Kerstin Schirrmann, Alexandra Vladetic, Grace-Chiaen Lin, Stephan Pabinger, Winfried Neuhaus, Frederic Bois, Roland Lauster, Uwe Mar

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.

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