Jason Buck Spence

US Patent:

20130137130, May 30, 2013

Filed:

May 6, 2011

Appl. No.:

13/695887

Inventors:

James M. Wells - Cincinnati OH, US
Jason R. Spence - Cincinnati OH, US
Aaron M. Zorn - Cincinnati OH, US
Noah F. Shroyer - Cincinnati OH, US

Assignee:

CHILDREN'S HOSPITAL MEDICAL CENTER - Cincinnati OH

International Classification:

C12N 5/071

US Classification:

435 29, 435377

Abstract:

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 al 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.

US Patent:

20200190478, Jun 18, 2020

Filed:

Oct 11, 2019

Appl. No.:

16/599620

Inventors:

- Cincinnati OH, US
Aaron M. Zorn - Cincinnati OH, US
Jason R. Spence - Ann Arbor MI, US
Noah F. Shroyer - Houston TX, US

International Classification:

C12N 5/071
C12N 5/077

Abstract:

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.

US Patent:

20170362573, Dec 21, 2017

Filed:

Jun 20, 2017

Appl. No.:

15/627588

Inventors:

- Cincinnati OH, US
Aaron M. Zorn - Cincinnati OH, US
Jason R. Spence - Ann Arbor MI, US
Noah F. Shroyer - Houston TX, US

International Classification:

C12N 5/071
C12N 5/077

Abstract:

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.