Bioengineering the gut: future prospects of regenerative medicine

Key Points

  • The most common complications of surgical treatments for gastrointestinal disorders include stenosis or leakage; tissue engineering and regenerative medicine could reduce these complications

  • The gastrointestinal tract is complex in structure and function, which makes its regeneration challenging; however, a wide selection of cell sources and scaffolding materials are available

  • Alignment and innervation of the smooth muscle have important roles in mediating coordinated peristalsis and propulsion of luminal content; regeneration of the neuromuscular apparatus is of critical importance

  • The epithelial lining of the gastrointestinal tract has multiple roles in providing nutrition, innate immunity and protection; regeneration of a functional epithelium is essential for translational purposes

  • New stem cell strategies for in vitro modelling and in vivo therapies are emerging

  • Less is known about regeneration of the lymphatic system in the gastrointestinal tract and future studies must incorporate the lymphatics as part of the bioengineering process

Abstract

Functions of the gastrointestinal tract include motility, digestion and absorption of nutrients. These functions are mediated by several specialized cell types including smooth muscle cells, neurons, interstitial cells and epithelial cells. In gastrointestinal diseases, some of the cells become degenerated or fail to accomplish their normal functions. Surgical resection of the diseased segments of the gastrointestinal tract is considered the gold-standard treatment in many cases, but patients might have surgical complications and quality of life can remain low. Tissue engineering and regenerative medicine aim to restore, repair, or regenerate the function of the tissues. Gastrointestinal tissue engineering is a challenging process given the specific phenotype and alignment of each cell type that colonizes the tract — these properties are critical for proper functionality. In this Review, we summarize advances in the field of gastrointestinal tissue engineering and regenerative medicine. Although the findings are promising, additional studies and optimizations are needed for translational purposes.

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Figure 1: Cross-sectional microscopy image of a human small intestine stained with haematoxylin and eosin.
Figure 2: An overview of gastrointestinal tract tissue engineering and regenerative medicine approaches.
Figure 3: A bioengineered, intrinsically innervated smooth muscle construct.

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Acknowledgements

The work of the authors is supported by Army, Navy, NIH, Air Force, VA and Health Affairs to support the AFIRM II effort, under Award No. W81XWH-13-2-0052; GU 7 and NIH/NIDDK R01DK071614 and R42DK105593.

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K.N.B. and E.Z. researched data for article, contributed to discussion of content, wrote, reviewed and edited the manuscript before submission.

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Correspondence to Khalil N. Bitar.

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Bitar, K., Zakhem, E. Bioengineering the gut: future prospects of regenerative medicine. Nat Rev Gastroenterol Hepatol 13, 543–556 (2016). https://doi.org/10.1038/nrgastro.2016.124

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