lymph-angiogenesis

Everything is connected....

Last year I wrote on how gentle stretching promotes healing by influencing immune elements present in the tissues as injuries resolve, and a 2002 paper by Swartz and Boardman (1) details how mechanical forces in the interstitium are a vital to the formation of new lymph vessels.

This is my Mum after a bad fall which we treated daily with MLD beginning on Day 2. Information from both papers help to explain how MLD can have such a positive effect on injured tissue simply by creating gentle circular movements in the skin.

The interstitial-lymphatic interface as a continuum

Swartz and Boardman (1) offer a fascinating observation that functional lymph vessels act as a mechanical extension of the interstitium, and that certain mechanical stimuli in the extracellular matrix (ECM) are what initiate and organise the growth of new lymph vessels.

This is different to the commonly held view that lymph-angiogenesis occurs primarily in response to the same molecules which initiate new blood vessel growth. Now, it seems that hypothesis is wrong.

Fluid movement is crucial to growth and maintenance of lymph vessels

During lymph-angiogenesis, lymphatic endothelial cell migration and organisation happens in the direction of flow through the interstitium. That is, new lymph vessels grow upstream along channels created by mechanical stresses on the ECM fibres.

Likewise, a constant flow of lymph through the collector vessels is required for proper valve formation and maintenance. If lymph flow drops too low vessels degrade and atrophy.

Mechanical stress forces are crucial to lymph formation

The anchoring filaments form a responsive connection between the endothelial basement membrane and the fibres of the ECM, and this makes the vessel highly sensitive to mechanical stresses in the interstitium.

Fluctuations in fluid pressure stretch the fibres of the ECM which recoil and generate small oscillations in pressure, effectively creating a tissue pump which facilitates movement of the pre-lymph along the pre-lymphatic channel.

Constant lymphatic pumping in the lymph collector vessels also exert pressure forces into the ECM drawing fluid along the pre lymphatic channels. The overlapping valves of the endothelium prevent reflux back towards the interstitium and allow the initial lymph vessel to be emptied.

Ultimately, tissue mechanics determine the development and maintenance of new lymph vessels and the formation of lymph at the interstitial-lymphatic interface. Any interruption at this interface has consequences for both the tissue and vessels portions of the continuum. Lymph will not be formed and fluid will not drain from the tissues.

Mechanical stress forces are crucial to tissue healing and health

This view of the interstitial-lymphatic interface as a continuum responding primarily to mechanical forces, supports our use of MLD to promote tissue health and stimulate lymph-angiogenesis after acute injury, including surgery of any kind.

We know that gentle stretching forces in healing tissue increase resolvins which are immune molecules essential in the later stages of tissue healing. Now we can add mechanical forces as a factor in the growth of new lymph vessels as well.

1. Swartz, M. A. and K. C. Boardman Jr (2002). "The role of interstitial stress in lymphatic function and lymphangiogenesis." Annals of the New York Academy of Sciences 979(1): 197-210. https://nyaspubs.onlinelibrary.wiley.com/doi/full/10.1111/j.1749-6632.2002.tb04880.x

Abstract: The management and control of tissue fluid balance depends on the highly regulated orchestration of various interstitial factors. In particular, lymphatic function, lymphatic biology, and development (lymphangiogenesis), and the extracellular matrix all contribute to interstitial fluid balance. In light of the dynamic interdependence of these factors, our lab has been working towards establishing a mechanical‐molecular picture of the process of lymph angiogenesis—that is, bridging the physiological context of lymph angiogenesis with its molecular regulation by studying the coordination of mechanical forces, ECM development, lymphatic biology, and lymphatic capillary organization and development. Our working hypothesis is that the physiological driving force for lymph angiogenesis is the need for organized interstitial fluid flow. This paper will outline the rationale and background for such an approach and highlight some of the recently published findings of our lab and others that support this concept.