Lymphatic Vascular Regeneration: The Next Step in Tissue Engineering

Abstract

The lymphatic system plays a crucial role in interstitial fluid drainage, lipid absorption, and immunological defense. Lymphatic dysfunction results in lymphedema, fluid accumulation, and swelling of soft tissues, as well as a potentially impaired immune response. Lymphedema significantly reduces quality of life of patients on a physical, mental, social, and economic basis. Current therapeutic approaches in treatment of lymphatic disease are limited. Over the last decades, great progress has been made in the development of therapeutic strategies to enhance vascular regeneration. These solutions to treat vascular disease may also be applicable in the treatment of lymphatic diseases. Comparison of the organogenic process and biological organization of the vascular and lymphatic systems and studies in the regulatory mechanisms involved in lymphangiogenesis and angiogenesis show many common features. In this study, we address the similarities between both transport systems, and focus in depth on the biology of lymphatic development. Based on the current advances in vascular regeneration, we propose different strategies for lymphatic tissue engineering that may be used for treatment of primary and secondary lymphedema.

Lymphatic Tissue Engineering and Regeneration

“…Lymphedema, characterized by chronic swelling of an extremity, results from local accumulation of interstitial fluid due to insufficient lymph drainage [4] and is one of the most prevalent lymphatic-dysfunction conditions [24]. Globally, up to 250 million people are affected by lymphedema with the most prevalent cause being the parasitic disease filariasis [33].…”

“…In developed countries, the most common cause of lymphedema is disruption of lymphatic pathways, typically from cancer treatments in the form of tumor removal or radiation. The swelling of soft tissues from lymphedema results in discomfort [24], lack of mobility, and other health complications, both disfiguring and disabling a patient due to excessive swelling, reduced mobility, and social stigma associated with the condition. A patient’s quality of life is significantly reduced on a physical, mental, social, and economic basis [34].…”

“…Chronic treatments, combined with superficial and transient improvements, places a large burden on the healthcare system and patients [140]. When taking into account a rising life expectancy and an increasingly sedentary lifestyle, the number of people affected by complications of the lymphatic system is going to increase in the future [24].…”

“…Unlike the circulatory system, the lymphatic system is a one-way drainage system that originates in tissues and organs, is funneled through a series of many small vessels emptying into fewer larger vessels, and empties into the circulatory system [5]. Continuous fluid flow between blood capillaries and tissues is achieved by lymphatic capillaries absorbing excessive fluids from the interstitial space which simultaneously provides nutrients to cells, eliminates waste products, and dissipates interstitial pressure buildup [24]. In the larger collecting lymphatics, valves assist in lymph propulsion and also prevent retrograde flow, ensuring a unidirectional propulsion of lymphatic fluids [4].…”

Minireview: Syndecans and their crucial roles during tissue regeneration

“…For example, FGF-2 stimulates fibroblast proliferation [73] and keratinocyte migration [74] in skin, while FGF-6 is increased and contributes to repair in injured skeletal muscle [75,76]. VEGF induces lymphatic vessel formation during bone and neuronal tissue regeneration [77].…”