Cell reprogramming in a predictable manner on the superhydrophobic microwell array chip

Reprogramming of somatic cells into the pluripotent state is stochastic and inefficient using the conventional culture plates. Novel micro-culture systems employing precisely controlled biophysical cues can improve the reprogramming efficiencies dramatically. Here we perform iPSC induction on our previously developed superhydrophobic microwell array chip (SMAR-chip) where cells undergo distinctive morphology change, switching from 2D monolayers to 3D clumps, and develop into bona fide colonies in more than 90% of the microwells. The PDMS substrate, together with the microwell structure and the superhydrophobic layer constitute a wellcontrolled microenvironment favorable for the morphogenesis and pluripotency induction. Investigation of the molecular roadmap demonstrates that the SMAR-chip promotes the transition from the initiation phase to the maturation phase and overcomes the roadblocks for reprogramming. In addition, the SMAR-chip also promotes the reprogramming of human cells, opening our method for translational applications. In summary, our study provides a novel platform for efficient cell reprogramming and emphasizes the advantages of employing the insoluble microenvironmental cues for the precise control of cell fate conversion.

Automated summary

Reprogramming somatic cells into pluripotent state using conventional culture plates is inefficient and stochastic. However, a novel micro-culture system called SMAR-chip, which utilizes precisely controlled biophysical cues, greatly improves the reprogramming efficiency. The study demonstrates that SMAR-chip promotes the transition from initiation phase to maturation phase and overcomes reprogramming roadblocks, showing potential for translational applications.