In Pursuit of the Parietal Cell – An Evolution of Scientific Methodology and Techniques

Abstract

The stomach has unique embryologic and anatomic properties, making the study of the parietal cell technically challenging. Numerous individuals have devoted decades of research to unraveling the pathophysiological basis of this cell type. Here, we perform a scoping review of novel in vitro and in vivo methodology pertaining to the parietal cell. First, we evaluate early in vitro methods of parietal cell analysis. This section focuses on three major techniques: gastric gland isolation, parietal cell isolation, and parietal cell culture. We also discuss parietal cell physiology and pathophysiology. Second, we discuss more contemporary efforts involving confocal microscopy and gastric organoids, a new technique that holds much promise in unveiling the temporalspatial dynamics of the cell. Finally, we will discuss findings from our laboratory where we identified an active gastric vacuolar H + -ATPase as a putative mechanism for refractory GERD. Overall, this review aims to highlight the major milestones in understanding an elusive yet important cell. Though in no way comprehensive, we hope to provide a birds-eye view to the study of this unique cell type in the gastrointestinal tract.

Human Gastric Multi-Regional Assembloids Favour Functional Parietal Maturation and Allow Modelling of Antral Foveolar Hyperplasia

“…In particular, spontaneously emerging parietal cells have never been reported, to date, in human primary organoids in expansion medium 15 , but only seen transiently in hPSCs 10,14 . Literature reports an overall difficulty in their identification in primary murine models as well 12 , but there are examples of murine-derived fundic organoids presenting parietal cells 13 . Therefore, we designed a system to allow the self-aggregation of human gastric organoids in more complex multi-regional structures, defined as assembloids, where cells can reach maturity and functionality (Fig.…”

“…One of the major limitations of primary gastric models is related to the absence of more complex cell interactions, which render simple organoids an incomplete tool for modelling the organ of origin 11 . For instance, functional acid-producing parietal cells present in gastric tissue biopsies are poorly represented in murine primary gastric epithelial organoids 12 . On the other hand, examples of murine-derived fundic organoids presenting parietal cells have been reported 13 .…”

Neuroendocrine mechanism of gastric acid secretion: Historical perspectives and recent developments in physiology and pharmacology

“…Once the major effectors of acid secretion were uncovered, studies by John G. Forte (1934–2012) and George Sachs (1935–2019), in particular, interrogated the intracellular mechanisms that regulate acid secretion including the structure of parietal cells, 21,22 the physiology and cell biology of parietal cells, 23,24 the physiology of proton pump functions, 25,26 and the location and function of ion pumps that are essential to support acid secretion 27 (Figure 1). For timely reviews see References 23,28,29.…”

“…Parietal cells are also under endocrine (e.g., gly-gastrin), paracrine (histamine, somatostatin) and neural control (acetylcholine released from vagal nerve-chAT + neuron) via the muscarinic acetylcholine receptor subtype 3 (M 3 ) receptor. G cells are under neural control (acetylcholine on M 3 R and galanin on Gal1 receptor) and paracrine control (somatostatin on SSTR particular, interrogated the intracellular mechanisms that regulate acid secretion including the structure of parietal cells, 21,22 the physiology and cell biology of parietal cells, 23,24 the physiology of proton pump functions, 25,26 and the location and function of ion pumps that are essential to support acid secretion 27 (Figure 1). For timely reviews see References 23,28,29.…”