Highly parallel production of designer organoids by mosaic patterning of progenitors.

Autor: Porter CM; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Bioengineering Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Soft and Living Matter, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Precision Engineering for Health (CPE4H), University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Qian GC; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Bioengineering Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA., Grindel SH; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Bioengineering Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Soft and Living Matter, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Precision Engineering for Health (CPE4H), University of Pennsylvania, Philadelphia, PA 19104, USA; Materials Research Science and Engineering Center (MRSEC), University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Hughes AJ; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Bioengineering Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Soft and Living Matter, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Precision Engineering for Health (CPE4H), University of Pennsylvania, Philadelphia, PA 19104, USA; Materials Research Science and Engineering Center (MRSEC), University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: ajhughes@seas.upenn.edu.
Jazyk: angličtina
Zdroj: Cell systems [Cell Syst] 2024 Jul 17; Vol. 15 (7), pp. 649-661.e9. Date of Electronic Publication: 2024 Jul 08.
DOI: 10.1016/j.cels.2024.06.004
Abstrakt: Organoids derived from human stem cells are a promising approach for disease modeling, regenerative medicine, and fundamental research. However, organoid variability and limited control over morphological outcomes remain as challenges. One open question is the extent to which engineering control over culture conditions can guide organoids to specific compositions. Here, we extend a DNA "velcro" cell patterning approach, precisely controlling the number and ratio of human induced pluripotent stem cell-derived progenitors contributing to nephron progenitor (NP) organoids and mosaic NP/ureteric bud (UB) tip cell organoids within arrays of microwells. We demonstrate long-term control over organoid size and morphology, decoupled from geometric constraints. We then show emergent trends in organoid tissue proportions that depend on initial progenitor cell composition. These include higher nephron and stromal cell representation in mosaic NP/UB organoids vs. NP-only organoids and a "goldilocks" initial cell ratio in mosaic organoids that optimizes the formation of proximal tubule structures.
Competing Interests: Declaration of interests The authors declare no competing interests.
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Databáze: MEDLINE