Megakaryocytes play an important role in cell migration

Hematopoiesis is the process of blood cell formation, which occurs mainly in the bone marrow. Bone marrow produces all types of blood cells: red blood cells, platelets and white blood cells (leucocytes). Neutrophils are one of the most prominent types of white blood cells. They help the body fight infections and is the most abundant sub-population of leukocytes. They are short-lived and highly mobile, and can penetrate into tissue parts where other cells / molecules can not.

All hematopoietic cells that develop in the bone marrow must cross the lining of the blood vessels to enter the circulatory system. Blood platelets are released by larger and penetrating protrusions in the vessels of huge, largely immobile, progenitor cells called megakaryocytes. In this way, mature megakaryocytes produce platelets and release them into the bloodstream to maintain a consistent platelet count. In addition, they actively regulate the accumulation of hematopoietic stem cells positively and negatively.

Imaging the entire bone marrow with a subcellular resolution to understand how all the players act together is always a challenge. The research groups of Katrin Heinze and David Stegner have established a major pipeline of 3D image reconstruction and segmentation for different bone marrow components. These segmented objects, originally derived from Light Sheet fluorescence microscopy, are then used as models for computer simulations of cell distribution and migration behavior in the bone marrow.

Megakaryocytes have a significant influence on cell migration

In this study, scientists have discovered that the migration of hematopoietic stem cells and neutrophils depends on the size and distribution of megakaryocytes. Thus, these simulations suggest that megakaryocytes play an important role in cell migration even if they do not migrate themselves. Instead, large megakaryocytes represent pbadive barriers and thus significantly influence the migration of other cells such as hematopoietic stem cells and neutrophils into the bone marrow. Indeed, intravital microscopy confirmed that neutrophil mobility was reduced in platelet-depleted mice, where megakaryocyte volumes were increased.

This study shows how the combination of advanced imaging approaches and computer simulations can refine this hypothesis. Heinze says: "For simulations, grids and spheres do not sufficiently represent the complexity of the vascular system and its cells, but our image-derived models are adapted and therefore much better, because they reflect very well the physiological architecture of the bone. "

"This study highlights the importance of the biomechanical properties of the bone marrow environment in the regulation of cell motility, a factor that has so far not been well understood.Our data clearly show that the volumetric badysis of the number of and the location of megakaryocytes provides complementary information to our picture of the dynamics and mechanisms of the bone marrow, "says Stegner.

The computational tool can not only support 3D studies of the dynamic behavior of cells, but also help focus or reduce animal experiments when hypotheses can be tested in a computer manner. Beyond bone and blood research, the method can be used for any organ or tissue to query dynamic maps of selected cell types and structures for health and disease.