Molecular Mechanisms and Targeted Therapy of Lymphedema and Lipedema
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".
Deadline for manuscript submissions: 31 August 2025 | Viewed by 296
Special Issue Editors
Interests: lymphangiogenesis; inflammatory regulation; immune responses; fibrosis; secondary lymphedema; T cells; lymphatic trafficking
Special Issues, Collections and Topics in MDPI journals
Special Issue Information
Dear Colleagues,
Lymphedema (LE) is a chronic, debilitating condition causing swelling, pain, and infection risk, affecting millions worldwide, especially cancer survivors. It is often underdiagnosed, and current treatments are limited. More research is needed to understand its molecular drivers and develop effective therapies. Significant progress has been made in the past decade in LE research, leading to our understanding of the role of chronic inflammation in driving the pathology. Both innate and adaptive immune responses are found to be involved and especially Th2-differentiated CD4+ T cells have been found to be the major cause of lymphatic dysfunction and fibrosis. Preclinical models directly targeting the CD4+ T cells, Th2 cytokines, TGF-b signaling (fibrosis) and Leukotriene B4 signaling showed promising results that need to be escalated to the clinical level.
In addition, surgical interventions like lymph node transplantation and lymph venous bypass offer potential for reversing lymphedema pathology. These procedures emphasize the need for advanced pre-surgical lymphatic imaging, innovative surgical techniques, and improved methods for evaluating surgical outcomes.
Lipedema (LD) is a chronic adipose tissue disorder primarily affecting women, characterized by a disproportionate and symmetrical accumulation of painful fat, often in the lower extremities, resistant to diet and exercise. The known molecular mechanisms underlying lipedema are genetic predispositions, hormonal influences, abnormal adipogenesis, pathological angiogenesis, impaired lymphatic function leading to excessive interstitial fluid, extracellular matrix remodeling and fibrosis, and immune cell infiltration, especially M2 polarized macrophages, which may contribute to adipose tissue accumulation. These cellular and molecular aberrations contribute to the characteristic painful and nodular subcutaneous fat and the unique inflammatory profile seen in lipedema.
Targeted therapies for lipedema are currently limited due to the incomplete understanding of its underlying mechanisms. Existing treatments are largely palliative rather than directly addressing the root causes. Conservative strategies include complex decongestive therapy (CDT) involving manual lymphatic drainage, compression garments, and exercise. Liposuction is often used to remove the abnormal fat deposits and has shown significant improvement in quality of life for many patients. Pharmacological approaches, such as the potential of drugs like tirzepatide, which exhibits anti-inflammatory, anti-fibrotic, and thermogenic properties, to target key mechanisms of lipedema are being developed, though formal evaluation in clinical trials is still needed. Overall, a multidisciplinary approach combining conservative management with surgical interventions in selected cases is crucial for effective lipedema treatment.
This Special Issue aims to summarize our current understanding of the molecular mechanisms underlining the pathophysiology of secondary lymphedema and lipedema and how this knowledge is used in designing novel targeted therapies to treat these chronic diseases.
Dr. Raghu P. Kataru
Dr. Geoffrey E. Hespe
Guest Editors
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Keywords
- secondary lymphedema
- breast cancer related lymphedema
- chronic CD4+ T cell inflammtion Th2 driven fribrosis
- lymphatic pathophysiology
- tissue fibrosis
- lymphovenous bypass
- lymph node transplanatation
- targeted therapies
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