Clinically relevant animal models of lymphedema, near-infrared lymphatic imaging, and lymphatic microsurgery that enable non-invasive longitudinal quantification of lymphatic pump function.
In the pursuit of advancing lymphedema treatment, it is imperative to establish clinically relevant animal models and examination methods capable of quantifying lymphatic remodeling and function. However, current methodologies such as indocyanine green (ICG) near-infrared imaging fail to adequately quantify the functional characteristics of lymphatics. Moreover, the persistence of ICG dye adherence to LECs impedes longitudinal functional assessments. In addition, previous work imaging lymphatic function changes in rodent lymphedema models, have done so in animals where the swelling will reverse on its own given enough time. To address these limitations, we have developed non-invasive methods enabling frequent imaging of lymphatic vessels throughout the experimental timeline and applied this to rat lymph node dissection model with radiation which results in persistent irreversible swelling. The combination of imaging in the context of VLNT in an animal model of persistent disease, will provide the first ever direct evidence of functional regrowth of afferent lymphatics into the VLNT, answering the long-standing question of why this procedure works in many patients. In addition, it will enable the development and evaluation of therapeutic approaches to facilitate this process and improve VLNT efficacy in those patients who are currently nonresponsive to VLNT.
Contact: Shao-Yun Hsu
Novel biomaterial platforms to enhance functional collecting vessel lymphangiogenesis,
with translatable potential for promoting engraftment of VLNT into the host lymphatic
vasculature
We have previously engineered a PEG-based hydrogel designed to recapitulate the interstitial microenvironment to enhance the sprouting and growth of new lymphatic vessels. In addition to being able to fine-tune stiffness, binding sites for adhesion, and degradability, this hydrogel exhibits significant versatility in accommodating various proteins, such as Vascular Endothelial Growth Factor-C (VEGF-C), a crucial regulator of lymphangiogenesis. Therefore, our study aims to further optimize this hydrogel for lymphatic regeneration in the context of VLNT lymphedema therapy. Additionally, we have recently developed and patented a novel formulation of a lymphatic-targeting lipid nanoparticles (LNPs) for delivering mRNA to lymphatic endothelial cells
(LEC). Together, we will optimize these two novel and complementary biomaterial strategies to enhance lymphangiogenesis and lymphatic collecting vessel function in a clinically relevant animal model.
Contact: Shao-Yun Hsu