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PLoS One. 2018 May 2;13(5):e0195315. doi: 10.1371/journal.pone.0195315. eCollection 2018.

Bioengineered intestinal muscularis complexes with long-term spontaneous and periodic contractions.

Author information

1
Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California Los Angeles, Los Angeles, California, United States of America.
2
Division of Pediatric Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California, United States of America.
3
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
4
Department of Pediatrics, Division of Gastroenterology and Nutrition, Mattel Children's Hospital and the David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America.
5
Department of Bioengineering, Stanford University, Stanford, California, United States of America.

Abstract

Although critical for studies of gut motility and intestinal regeneration, the in vitro culture of intestinal muscularis with peristaltic function remains a significant challenge. Periodic contractions of intestinal muscularis result from the coordinated activity of smooth muscle cells (SMC), the enteric nervous system (ENS), and interstitial cells of Cajal (ICC). Reproducing this activity requires the preservation of all these cells in one system. Here we report the first serum-free culture methodology that consistently maintains spontaneous and periodic contractions of murine and human intestinal muscularis cells for months. In this system, SMC expressed the mature marker myosin heavy chain, and multipolar/dipolar ICC, uniaxonal/multipolar neurons and glial cells were present. Furthermore, drugs affecting neural signals, ICC or SMC altered the contractions. Combining this method with scaffolds, contracting cell sheets were formed with organized architecture. With the addition of intestinal epithelial cells, this platform enabled up to 11 types of cells from mucosa, muscularis and serosa to coexist and epithelial cells were stretched by the contracting muscularis cells. The method constitutes a powerful tool for mechanistic studies of gut motility disorders and the functional regeneration of the engineered intestine.

PMID:
29718926
PMCID:
PMC5931477
DOI:
10.1371/journal.pone.0195315
[Indexed for MEDLINE]
Free PMC Article

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