The human splenic microcirculation is entirely open as shown by 3D models in virtual reality.

The human spleen is equipped with an organ-specific microcirculation. The initial part of the venous circulation is formed by spleen-specific large microvessels, the sinuses. Sinuses eventually fuse to form venules and veins. For more than 170 years there have been debates, whether splenic red pulp capillaries join sinuses, i.e., whether the microcirculation is closed or open-or even simultaneously closed and open. We have now solved this question by three-dimensional reconstruction of a limited number of immunostained serial sections of red and white pulp areas, which were visualized in virtual reality. Splenic capillaries have special end structures exhibiting multiple small diverging endothelial cell processes, which always keep a certain distance to the walls of sinuses. Only very few capillary ends were difficult to diagnose. Positive identification of these end structures permits to conclude that the human splenic microcirculation is entirely open. This is also true for the perifollicular capillary network and for capillaries close to red pulp venules. Follicles are supplied by a relatively dense open perifollicular capillary net, which is primarily, but not exclusively, fed by sheathed and few non-sheathed capillaries from the surrounding red pulp network.

Exploring human splenic red pulp vasculature in virtual reality: details of sheathed capillaries and the open capillary network.

We reconstructed serial sections of a representative adult human spleen to clarify the unknown arrangement of the splenic microvasculature, such as terminal arterioles, sheathed capillaries, the red pulp capillary network and venules. The resulting 3D model was evaluated in virtual reality (VR). Capillary sheaths often occurred after the second or third branching of a terminal arteriole and covered its capillary side or end branches. The sheaths started directly after the final smooth muscle cells of the arteriole and consisted of cuboidal CD271++ stromal sheath cells surrounded and infiltrated by B lymphocytes and macrophages. Some sheaths covered up to four sequential capillary bifurcations thus forming bizarre elongated structures. Each sheath had a unique form. Apart from symmetric dichotomous branchings inside the sheath, sheathed capillaries also gave off side branches, which crossed the sheath and freely ended at its surface. These side branches are likely to distribute materials from the incoming blood to sheath-associated B lymphocytes and macrophages and thus represent the first location for recognition of blood-borne antigens in the spleen. A few non-sheathed bypasses from terminal arterioles to the red pulp capillary network also exist. Red pulp venules are primarily supplied by sinuses, but they also exhibit a few connections to the capillary network. Thus, the human splenic red pulp harbors a primarily open microcirculation with a very minor closed part.