Lymphatic tissue engineering: experience of the laboratory of tissue engineering and cell culture at Nicolae Testemitanu State University of Medecine and Pharmacy

Abstract

Introduction: Lymphedema (LE) is a chronic and progressive disease caused by damage to lymphatic vessels and/or lymph nodes (LNs). Conservative treatment includes complex decongestive therapy, physiotherapy, exercise, and skin care, while surgical treatment options include lymphovenous anastomosis, vascularized LN transfer, and reductive procedures such as liposuction and excisional techniques. Although these approaches provide symptomatic relief, they do not restore damaged lymphatic structures. Lymphatic tissue engineering (LTE) represents a promising regenerative strategy, combining biomaterials, scaffolds, cells, growth factors, and in vitro and in vivo models to promote the regeneration of lymphatic structures. Materials and methods: This work is based on a literature review in LTE and presents our experience in LNs-based TE. The literature review focused on current strategies in LTE, with an emphasis on LNs decellularization, decellularized scaffold, lymphatic endothelial cell culture, and preclinical animal models. Articles were selected from PubMed, Google Scholar, and Scopus, without time restrictions. Our experience at the Laboratory of Tissue Engineering and Cell Culture involves decellularization method applied to nonvascularized lymph nodes (NLNs) in small animal models, assessing their potential for regenerative applications. Results: Anatomical studies of the lymphatic system in small animal models (rats) were performed to identify suitable models for LN-based TE. Among the LN examined, the axillary LN was found to be the most practical and accessible for experimental procedures. A low-concentration detergent protocol was developed for decellularization of NLNs. This protocol allowed effective removal of cellular components while preserving the extracellular matrix architecture, providing a suitable scaffold for potential regenerative applications, as demonstrated in our previous experience. The literature review revealed that similar approaches have been explored in other preclinical models, showing that decellularization and decellularized scaffold-based strategies can preserve LN microarchitecture and support regenerative applications. Conclusion: (i) Axillary LN in small animal models are practical for LN-based TE; (ii) Lowconcentration detergent decellularization preserves extracellular matrix structure, providing scaffolds for regenerative applications; (iii) Preclinical studies support these strategies, highlighting their potential to promote lymphatic regeneration and improve treatments for lymphedema. Funding. This research was supported by grants from Project No. 25.80012.8007.03TC within the Young Researchers Project Competition 2025–2026, Chisinau, Republic of Moldova.