Exploiting bone marrow microvascular structure for drug delivery and future therapies

The endothelium of bone marrow sinusoids regulates many important physiological functions. On the one hand, it serves as a gatekeeper controlling cellular traffic in and out of the marrow parenchyma, and on the other hand, the endothelium is capable of removing particulate material from the circulation by both intracellular and transcellular processes. Exploitation of these properties could provide a basis for the treatment of a number of bone marrow diseases and disorders. Thus, selective trapping of the circulatory pool of haemopoietic stem cells by marrow sinus endothelium has provided an effective form of correction of congenital marrow disorders and new approaches for gene therapy. Colloidal particles have been engineered to exhibit bone marrow-homing activity and may be of potential interest in diagnostic imaging and drug delivery. This article is concerned with understanding the mechanisms regulating particulate recognition from the blood by the medullary sinusoidal system of the bone marrow, the mode of transport of particulate matter from luminal to abluminal surfaces, and its ultimate fate within the marrow parenchyma.