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  • Review Article
  • Published:

The extracellular matrix of the gastrointestinal tract: a regenerative medicine platform

Nature Reviews Gastroenterology & Hepatology volume 14, pages 540–552 (2017)Cite this article

Subjects

Key Points

  • The extracellular matrix (ECM) is an ideal therapeutic substrate for functional remodelling of damaged gastrointestinal (GI) tissue, owing to its composition and roles in tissue development, wound repair and homeostasis

  • Components of the host response have been associated with ECM-induced site-appropriate constructive and functional tissue remodelling, including angiogenesis, innervation, stem cell recruitment, antimicrobial activity and modulation of the innate immune response

  • The GI tract presents distinct challenges for regenerative medicine, such as its requirement for motility and nutrient absorption, its diverse pH conditions and its tissue-specific 3D ultrastructure

  • ECM bioscaffolds comprise structural and functional molecules that are secreted by resident cells, and ECM bioscaffolds have been prepared from the decellularization of tissues from the oesophagus, small intestine, stomach and colon

  • Despite the challenges imposed by the GI tract, the use of ECM bioscaffolds for the reconstruction and regeneration of GI tissues has shown promise in preclinical and early clinical studies

  • Several studies have highlighted the potential benefits of using tissue-specific ECM bioscaffolds to facilitate the constructive and functional regeneration of tissues of the GI tract

Abstract

The synthesis and secretion of components that constitute the extracellular matrix (ECM) by resident cell types occur at the earliest stages of embryonic development, and continue throughout life in both healthy and diseased physiological states. The ECM consists of a complex mixture of insoluble and soluble functional components that are arranged in a tissue-specific 3D ultrastructure, and it regulates numerous biological processes, including angiogenesis, innervation and stem cell differentiation. Owing to its composition and influence on embryonic development, as well as cellular and organ homeostasis, the ECM is an ideal therapeutic substrate for the repair of damaged or diseased tissues. Biologic scaffold materials that are composed of ECM have been used in various surgical and tissue-engineering applications. The gastrointestinal (GI) tract presents distinct challenges, such as diverse pH conditions and the requirement for motility and nutrient absorption. Despite these challenges, the use of homologous and heterologous ECM bioscaffolds for the focal or segmental reconstruction and regeneration of GI tissue has shown promise in early preclinical and clinical studies. This Review discusses the importance of tissue-specific ECM bioscaffolds and highlights the major advances that have been made in regenerative medicine strategies for the reconstruction of functional GI tissues.

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Figure 1: Overview of extracellular matrix bioscaffold decellularization and preparation.
Figure 2: The biologically active molecular components of extracellular matrix bioscaffolds.
Figure 3: The origins, regions and layers of the major segments of the gastrointestinal tract.
Figure 4: Use of extracellular matrix bioscaffolds in gastrointestinal tissue repair and regeneration.
Figure 5: Conceptual workflow for proteomic analysis of extracellular matrix proteins.

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Authors and Affiliations

  1. McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, 15219–3110, Pennsylvania, USA

    George S. Hussey & Stephen F. Badylak

  2. Department of Surgery, School of Medicine, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, 15213, Pennsylvania, USA

    George S. Hussey & Stephen F. Badylak

  3. Department of Materials, Imperial College London, Royal School of Mines, Prince Consort Road, South Kensington, London, SW7 2AZ, UK

    Timothy J. Keane

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PowerPoint slides

Glossary

Decellularization

A process used in tissue engineering to remove cells from a tissue or an organ, without affecting the extracellular matrix of the original tissue.

Stricture

Narrowing of a tube or channel.

Xenogeneic

Tissues or cells belonging to individuals of different species.

Allogeneic

Tissues or cells from the same species that are genetically dissimilar and immunologically incompatible.

Anorectal fistulas

Small tracts that develop between the end of the bowel and the skin near the anus.

Anastomosis

A cross-connection between adjacent channels of the body.

Matricryptic peptides

Hidden peptide residues in collagen molecules that are released after the degradation of the parent molecule.

Caustic oesophagitis

Injury to the oesophagus due to the ingestion of a strong alkali or acid.

Barrett oesophagus

A condition in which the cells of the oesophagus grow abnormally.

Oesophageal stenosis

An abnormal narrowing of the oesophagus.

Oesophageal dilatation

Stretching or widening of the oesophagus.

Oesophagoplasty

Plastic surgery for the repair or reconstruction of the oesophagus.

Diverticula

A protrusion of a hollow (or a fluid-filled) structure in the body.

Oesophageal transection

The removal of the lower end of the oesophagus with end-to-end anastomosis.

Ileostomy

A surgical procedure in which a piece of the ileum is diverted to an opening in the abdominal wall.

Celiotomy

A surgical procedure that involves a large incision through the abdominal wall to gain access to the abdominal cavity.

Onlay mesh repair

Use of a mesh material placed over a defect to repair an incision.

Matrisome

The ensemble of extracellular matrix (ECM) and ECM-associated proteins.

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Hussey, G., Keane, T. & Badylak, S. The extracellular matrix of the gastrointestinal tract: a regenerative medicine platform. Nat Rev Gastroenterol Hepatol 14, 540–552 (2017). https://doi.org/10.1038/nrgastro.2017.76

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