Myoepithelial Cells: Their Origin and Function in Lacrimal Gland Morphogenesis, Homeostasis, and Repair

Abstract

Lacrimal gland (LG) is an exocrine tubuloacinar gland that secretes the aqueous layer of the tear film. LG epithelium is composed of ductal, acinar, and myoepithelial cells (MECs) bordering the basal lamina and separating the epithelial layer from the extracellular matrix. Mature MECs have contractile ability and morphologically resemble smooth muscle cells; however, they exhibit features typical for epithelial cells, such as the presence of specific cytokeratin filaments. Increasing evidence supports the assertion that myoepithelial cells (MECs) play key roles in the lacrimal gland development, homeostasis, and stabilizing the normal structure and polarity of LG secretory acini. MECs take part in the formation of extracellular matrix gland and participate in signal exchange between epithelium and stroma. MECs have a high level of plasticity and are able to differentiate into several cell lineages. Here, we provide a review on some of the MEC characteristics and their role in LG morphogenesis, maintenance, and repair.

Keywords: Branching; Epithelium; Fibroblast growth factor; Lacrimal gland; Mesenchyme; Morphogenesis; Myoepithelial cells; Progenitor cells; Regeneration; Smooth muscle actin; Stem.

Fig. 1

Lacrimal gland epithelial cell types. The LG epithelium (a) is composed of three major cell types: acinar (b), ductal (c), and myoepithelial (MECs) (d red) cells. Acinar cells synthesize and secrete proteins, water, and electrolytes. Ductal cells modify the secretory fluid by secreting electrolytes and water. Myoepithelial cells (MECs) produce basal membrane proteins and have contractile function

Fig. 2

Lacrimal gland myoepithelial cells. (a) Paraffin section of a mouse LG at postnatal day 60 (P60) stained with hematoxylin/eosin (H&E), demonstrating the acinar structure of the gland. MECs (white arrows) are hardly visible. (b) Paraffin section of a mouse LG at P60 stained with the antibody to SMA. Due to the large size of adult MECs, only part of cells can be seen (red) (nuclei are stained with DAPI). (c) Whole mount imaging of the mouse LG at P5. MECs (red) are located around differentiating acini, but not around the main duct (white arrow). Blood vessels (green) are stained with the CD31 antibody; the nuclei are stained with DAPI. (d) Whole mount preparation of a mouse LG at P60 demonstrating large MECs (red) with several long processes around the secretory acini. Epithelial cells are stained with the Panx1 antibody (green), nuclei are stained with DAPI. (e) Typical shapes of MECs in adult LGs as visualized with SMA expression. The cells have 4–7 long processes that may also be branched

Fig. 3

Lacrimal gland epithelial cell lineage(s). Illustration of the three main hypotheses in cell lineage hierarchy in the LG. (a) Hypothesis I: slow cycling LG stem cell produce a common progenitor that gives rise to all LG lineages, epithelial (acinar and ductal) and myoepithelial (MEC). Hypothesis II: The LG has lineage-restricted stem/progenitor cells that give rise to specific cell types within each lineage. (b) Hypothesis III: This hypothesis suggests that multipotent stem/progenitor cells exist in one of the LG cell lineages. Based on reported plasticity of MECs, MEC lineage may likely contain multipotent stem-like cells that can restore all epithelial lineages upon LG injury. Dashed arrows label unknown connections and straight arrows reported connections