Pericytes, the mural cells of the microcirculation, are part of the mouse and human islet microenvironment [5; 11; 29; 30]. Pericytes are complex cells [31]. The unambiguous distinction of pericytes from other perivascular cells requires inspecting their basement membrane at the ultrastructural level [32]. However, pericytes can be identified in tissue sections using antibodies against pericyte surface markers, such as neuron-glial antigen 2 (NG2) and platelet-derived growth factor receptor-beta (PDGFRb). Pericytes have a typical bump-on-a-log morphology: a cell body with a prominent nucleus and cytoplasmic processes on the surface of capillaries [31; 33] (Figures 1H and I). Following this classification, we have previously reported that mouse and human islet capillaries are covered with pericytes and estimated an average pericyte : endothelial cell ratio of 1:3 – 1:2 for mouse and human islets [11]. Pericytes interact closely with islet endothelial cells and are present on straight parts of islet capillaries as well as at capillary branch points (Figure 1A). Interestingly, pericyte density in islets is higher than in the surrounding exocrine tissue (Figure 1A; [30]). Pericytes in mouse and human islets also express PDGFRb, although expression of this receptor is not limited to pericytes in human islets [10].
Pericytes in mouse islets have contractile properties [11]. To determine if pericytes in human islets also help regulating islet capillary diameter, we examined in more detail pericytic expression of a-smooth muscle actin (aSMA). aSMA is expressed by cells of smooth muscle cell lineages, allowing us to visualize arterioles that feed into pancreatic islets (Figures 1B and 1C). In most human islets only one feeding arteriole would be seen, in line with previous findings [34]. aSMA positive cells are also present within the human and mouse islet parenchyma (Figures 1C and 1D). The density of aSMA immunostaining inside human islets is higher than what is found in mouse islets (Figure 1E), as previously reported [35]. Around 50% of the aSMA positive immunostaining colocalizes with NG2 (Figures 1C, 1D and 1F). This fraction tends to decrease with donor age (data not shown). Importantly, around 60% of the NG2 positive cell population expresses aSMA (Figures 1C, 1D and 1G; [11]). In human islets, a subset of these double positive cells are found tightly wrapping the capillary end of the feeding arteriole (Figure 1C and 1H). These pericytes have a different morphology than those found in the islet parenchyma. Indeed, it is known that pericyte morphology depends on their location in the capillary bed: more circumferential cytoplasmic processes at the arteriole end, more longitudinal processes in the middle, and a stellate morphology towards the venule end of the capillary bed [33]. Given the circumferential morphology of their cytoplasmic processes and the fact that they are associated with an arteriole instead of a capillary (vessel diameter of 8-10 µm), this type of islet pericytes resembles more a transitional state towards smooth muscle cells. Therefore, in this study, we named them “SMC” pericytes, while pericytes in the human islet parenchyma and covering capillaries are referred to as human islet pericytes (Figure 1H). In mouse islets, the morphology of pericytes (and of blood vessels, see Figure 2C) is more homogenous and, thus, we refer to them all as mouse islet pericytes (Figure 1I). To summarize, a significant number of mouse and human islet pericytes expresses aSMA, as previously reported for pericytes in the central nervous system [11; 36]. These data indicate that pericytes in human and mouse islets may participate in blood flow regulation but in human islets they are more heterogenous in terms of morphology and contractile protein expression.