Apical Cyst Theory: a Missing Link

Abstract

Introduction: The mechanism of the formation of apical cyst has been elusive. Several theories have long been proposed and discussed speculating how an apical cyst is developed and formed in the jaw bone resulting from endododontic infection. Two popular theories are the nutritional deficiency theory and the abscess theory. The nutritional deficiency theory assumes that the over proliferated epithelial cells will form a ball mass such that the cells in the center of the mass will be deprived of nutrition. The abscess theory postulates that when an abscess cavity is formed in connective tissue, epithelial cells proliferate and line the preexisting cavity because of their inherent tendency to cover exposed connective tissue surfaces. Based on the nature of epithelial cells and the epithelium, nutritional theory is a fairy tale, while abscess theory at best just indicates that abscess may be one of the factors that allows the stratified epithelium to form but not to explain a mechanism that makes the cyst to form.

The hypothesis: Apical cyst formation is the result of proliferation of resting epithelial cells, due to inflammation, to a sufficient number such that they are able to form a polarized and stratified epithelial lining against dead tissues or foreign materials. These stratified epithelial lining expands along the dead tissue or foreign materials and eventually wrap around them as a spherical sac, i.e. a cyst. The space in the sac is considered the external environment separating the internal (tissue) environment - the natural function of epithelium.

Evaluation of the hypothesis: This theory may be tested by introducing a biodegradable device able to slowly release epithelial cell mitogens in an in vivo environment implanted with epithelial cells next to a foreign object. This will allow the cells to continuously proliferate which may form a cystic sac wrapping around the foreign object.

Keywords: Abscess; Apical cyst; Embryonic stem cells; Endodontic infection; Epithelium; Induced pluripotent stem (iPS) cells; Neoplastic; Stem cells; Teratoma.

Figure. 1

Transwell system. Monolayer epithelial cells are grown to confluence in the insert-well and the cell culture medium level is adjusted such that the monolayer is at the liquid-air interface, allowing the stratification of the cells to occur. (A) Monolayer of oral epithelial cells on insert-well membrane became stratified after grown in liquid-air interface. Some epithelial cells migrated below the membrane and stayed monolayer because being in the liquid phase. (B) Monolayer of oral epithelial cells seeded onto the engineered submucosal tissue (gingival fibroblasts cast in collagen gel on the insert-well membrane) became stratified after grown in liquid-air interface. (A, B) histological analysis with hematoxylin and eosin staining.

Figure. 2

EB and teratoma formation. iPS cells derived from dental stem cells were allowed to form EBs in vitro (A–E) or teratoma in immunocompromised mice (F, G). (A) EB formation for 1week. (B, C) EB of 4.5 weeks. (D, E) Histological analysis of EB of 6 weeks. (F, G) Teratoma formation after 9 weeks in vivo. * indicates cystic space lined by epithelial-like cells. Scale bars: (A, D) 200 μm; (B, C) 500 μm; (E) 100 μm; (F, G) 400 μm. All animal procedures followed a protocol (protocol#AC-AAAB1141) approved by the Institutional Animal Care and Use Committee (IACUC) at the Columbia University (author's previous institute).