Modeling the Lymphatics

In this issue of Lymphatic Research and Biology, we feature two prospective investigations that attempt to model aspects of the lymphatic system.

In the first of these, Jafarnejad and colleagues ¹ have used a computational modeling approach to assess lymph flow and fluid exchange with blood vessels in lymph nodes. As they indicate, computational modeling has been used extensively to afford insights into the physiologic and immunologic function of biological tissues. Prior techniques, when applied to the lymph node, have been useful for the investigation of cellular interactions but have not adequately addressed the transport of lymph or the fluid exchange in the node. The authors' computational flow model was developed from the murine popliteal lymph nodes to identify the key characteristics of the system. The data derived from the model indicates that the preponderant fraction of lymph flow occurs through a peripheral path through the subcapsular and medullary sinuses, with sequestration of deeper paracortical flow by parenchymal blood vessels. Fluid absorption is driven chiefly by differential oncotic pressure between lymph and blood. The conclusion of this groundbreaking work is that the lymph node microenvironment, coupled with changes in inflow/outflow conditions, can dramatically alter the distribution of lymph, cytokines, antigen, and cells within the node, thereby representing a set of variables that can directly influence the immune response.

Kumasaka and colleagues have pursued an alternate approach to the modeling of the lymphatics system, ² in this case addressing the perplexing lymphatic pathology of lymphangioleiomyomatosis (LAM). In their investigation, they have attempted to model the disease by the culture of cells derived from LAM cell clusters. These are unique microstructures commonly found in LAM-associated chylous effusions, representing aggregates of LAM cells surrounded by lymphatic endothelium.

The investigators isolated LAM cell clusters from LAM-associated chylous effusion and embedded them in three-dimensional culture gels. They observed morphological changes over time through serial evaluation. They observed differing tendencies toward tube formation based upon the relative position to one another of the inherent lymphatic endothelial cells. They were also able to demonstrate treatment effects related to the administration doxycycline or recombinant human VEGF receptor-3. These fascinating preliminary observations suggest that this approach holds promise for future investigation of this puzzling and elusive lymphatic disease.