Epithelial machines of morphogenesis and their potential application in organ assembly and tissue engineering

Abstract

Sheets of embryonic epithelial cells coordinate their efforts to create diverse tissue structures such as pits, grooves, tubes, and capsules that lead to organ formation. Such cells can use a number of cell behaviors including contractility, proliferation, and directed movement to create these structures. By contrast, tissue engineers and researchers in regenerative medicine seeking to produce organs for repair or replacement therapy can combine cells with synthetic polymeric scaffolds. Tissue engineers try to achieve these goals by shaping scaffold geometry in such a way that cells embedded within these scaffold self-assemble to form a tissue, for instance aligning to synthetic fibers, and assembling native extracellular matrix to form the desired tissue-like structure. Although self-assembly is a dominant process that guides tissue assembly both within the embryo and within artificial tissue constructs, we know little about these critical processes. Here, we compare and contrast strategies of tissue assembly used by embryos to those used by engineers during epithelial morphogenesis and highlight opportunities for future applications of developmental biology in the field of tissue engineering.

Figure 1. Apical contraction and epithelial morphogenesis

Epithelial bending shapes the vegetal plate during invagination in the Sea Urchin late mesenchyme blastula (A). Lytechinus pictus embryo stained with phalloidin. Finite element models demonstrate that the vegetal plate of the late mesenchymeblastula (B) can invaginate after gel swelling (C), apical-basal shortening (D), or apical contraction (E). F) The neural groove in Xenopus laevis displays apically localized F-actin and (G) b-catenin showing both structural proteins are apically localized in the superficial layer. H) Apically contracting cells (red apices) within an otherwise resting epithelium. (A–E) are modified from (Davidson et al. 1995; Davidson et al. 1999).

Figure 2. Cell attachment and penetration in porous scaffolds

Cells are added to porous biomaterial scaffolds (A) and allowed to attach to the biomaterial surface (B). With time, cells attach and penetrate the porous structure (C) and eventually populate the entire scaffold and deposit their own extracellular matrix (D). Cells attach and align to the porous fibres of the biomaterial scaffold (E) via integrins and move using their actin cytoskeleton (F).

Figure 3. Origami and engineering of 3D tissues

A sheet of paper, with a single fold along the red dotted line can be made into a structure with 2 planes (A) or other 3D shapes (B, C, D). A simple paper sheet in origami is compared with 1-dimensional epithelial sheet (E). If the cells (in E) contract at their apical ends, a 3D structure can be generated (F). If few cells (with red circles in G) in a large epithelial sheet contract at apical or basal ends (H), a trough or a crest could be created, which when replicated at multiple locations make intricate architectural forms(I).