University of Michigan

Cincinnati Children's Hospital Medical Center

Georgia Tech Research Corporation

Jason R Spence

James Macormack Wells

Noah F Shroyer

Aaron M Zorn

Alyssa Miller

Andres Jose Garcia

Miguel Quiros

Briana Dye

Emily Holloway

Ricardo Cruz-Acuna

Asma Nusrat

The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal 'organoids' were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage. In conclusion, PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development, homeostasis and disease.

Methods and systems for converting precursor cells into intestinal tissues through directed differentiation

The invention disclosed herein generally relates to methods and systems for converting stem cells into specific tissue(s) or organ(s) through directed differentiation. In particular, the invention disclosed herein relates to methods and systems for promoting vascularized human intestinal organoid tissue having an intestine-specific EC transcriptional signature from hindgut spheroid tissue produced in vitro from the described methods.

Compositions and methods for obtaining vascularized human intestinal organoid tissue, and related uses thereof

The invention disclosed herein generally relates to methods and systems for growing, expanding and/or obtaining 3-dimensional lung-like epithelium comprising cells having SOX9 protein activity and SOX2+ protein activity. In particular, the invention disclosed herein relates to methods and systems for growing human cells having SOX9 protein activity and SOX2+ protein activity in vitro, and for promoting pluripotent stem cell derived ventral-anterior foregut spheroid tissue into 3-dimensional lung-like epithelium comprising cells having SOX9 protein activity and SOX2+ protein activity.

Compositions and methods for obtaining 3-dimensional lung-like epithelium and related uses thereof

The invention disclosed herein generally relates to methods and systems for converting stem cells into specific tissue(s) or cells through directed differentiation. In particular, the invention disclosed herein relates to methods and systems for promoting functional basal-like cells from pluripotent stem cell-derived lung bud tip progenitor organoid tissue through activation of SMAD signaling via activation of TGF&#x3b2;1 (and/or the TGF&#x3b2; signaling pathway) and BMP4 (and/or the BMP signaling pathway).

Compositions and methods for obtaining functional basal-like cells

Disclosed herein are synthetic hydrogel useful for the generation, storage and administration of cellular structures such as spheroids and organoids.

Synthetic hydrogel carriers for cellular structures, generation of organoids, and treatment of tissue injury

The invention disclosed herein generally relates to methods and systems for converting stem cells into specific tissue(s) or organ(s) through directed differentiation. In particular, the invention disclosed herein relates to methods and systems for promoting definitive endoderm formation from pluripotent stem cells. The invention disclosed herein further relates to methods and systems for promoting ventral-anterior foregut spheroid tissue formation, 3-dimensional lung tissue formation, and lung organoid tissue formation produced in vitro from the described methods.

Growing community of inventors

Ann Arbor, MI, United States of America

Jason R Spence