Grants We Funded

Abstract

Project Summary: Increasing research on the lymphatic system has been provided us a better understanding of the underlying mechanism of lymphatic disorders. Advancements in the prevention and treatment of secondary lymphedema provided greater insight on monitorization and surgical manipulation of the lymphatic system. Additionally, there is evidence to show that lymphatic system is involved in the pathogenesis of various disease processes. However, despite its critical function in different organ systems, there is limited evidence regarding the presence and role of the lymphatic system within the peripheral nervous tissues. Peripheral nerve injuries can result from direct trauma, or iatrogenic injuries. Modalities promoting rapid recovery following nerve injury are an active area of research to improve overall outcomes, however the complex process of peripheral nerve regeneration is not yet completely understood. The current literature and scientific knowledge on the role of lymphatic system lack sufficient conception to target lymphatic system as a potential therapeutic in nerve regeneration. Therefore, there is a significant need to further understand the complex mechanisms involved in neural healing as well as identify new therapeutic targets and potential surgical measures to improve overall outcomes following nerve injury. Bringing a vascular supply following injury to the nerve promotes axonal regeneration and results in faster reinnervation. Since the role of the lymphatic system in nerve repair is unknown, the potential benefits of bringing a lymphatic tissue supply to the regenerating nerve is a topic of further study. Vascularized lymph node transfer has been shown to be effective in treating lymphedema. One of the key mediators in its effect is promotion of the lymphatic endothelial cells via the signal of vascular endothelial growth factor (VEGF), which is also a potent angiogenic factor for neural regeneration. Therefore, in this proposal, we aim to characterize the role of lymphatic system in neural recovery and identify whether transfer of a vascularized lymph node near a regenerating axon can promote axonal regeneration to a greater extent. Completion of our study will provide robust evidence for the presence of lymphatic system in the peripheral nerves and the role of lymphangiogenesis in recovery of nerve injuries. This will allow for development of novel therapeutics in nerve repair, such as lymph node transfer, to promote recovery following injury.

Impact Statement: Completion of our central goal will provide robust evidence for the presence of lymphatic system in the peripheral nerves and the role of lymphangiogenesis in recovery of peripheral nerve injuries. This will allow for development of novel therapeutics to facilitate lymphangiogenesis in peripheral nerve regeneration, such as lymph node transfer, to promote and hasten recovery following injury. Our approach is highly innovative because no investigatory considerations have been given to exploration of the role of lymphatic structures in peripheral nerve repair. The proposed model will serve as the initial testbed to explore novel approaches to improve a previously not explored aspect of neural recovery and can translate into a clinically applicable method.

Biography
Dr. Carolyn De La Cruz is a full-time faculty member at the University of Pittsburgh and specializes in tertiary reconstruction. She has had extensive post- graduate training spanning 10 years in research, general surgery and plastic surgery in Robert Wood Johnson and University of Miami. Following completion of her microsurgery fellowship at MD Anderson Cancer Center in 2004, she established the microsurgical breast reconstruction program at Magee-Women’s Hospital of UPMC. She performs all types of breast reconstruction including free flaps, implant-based reconstruction and fat grafting for women who have had mastectomies. For over a decade the microsurgical program has thrived at Magee Womens’ Hospital under her direction. Dr. De La Cruz’s mission is to give each patient specialized and individualized care. Subsequently, she started the multidisciplinary lymphedema program. She performs lymphatic surgery including LYMPHA, LVA and lymph node transplants for patients who suffer from lymphedema. In addition, she clinically uses ICG to diagnose patients with sub clinical lymphedema. This has been instrumental in understanding truncal lymphedema in breast cancer related lymphedema. She currently serves as the Director of Lymphatic Surgery at the University of Pittsburgh Medical Center. Dr. De La Cruz is active in training plastic surgery residents and has won teaching awards for her dedication. She is active in basic science and clinical research with numerous publications.