Therapeutic effects of 3D-bioprinted mesenchymal stem cell-based artificial lymph nodes on lymphedema

Abstract

Lymphedema is a condition resulting from impaired lymphatic function, with limited effective treatment options available. This study investigates the potential of 3D-bioprinted scaffolds, utilizing biomaterials and human adipose-derived stem cells (hADSCs), as a novel approach to promote lymphangiogenesis and improve treatment outcomes in lymphedema. Scaffolds were characterized for cell viability, mechanical properties through compressive strength testing, and structural integrity after printing. In vivo therapeutic effects were assessed in Sprague-Dawley rats through fluorescence imaging, histopathological analysis, and immunofluorescence staining. Additionally, protein and gene expression of lymphangiogenic markers (LYVE-1, VEGF-C, VEGF-A) were analyzed using Western blotting and quantitative polymerase chain reaction. The scaffolds demonstrated high cell viability, structural integrity, and mechanical stability, with enhanced cell distribution and extracellular matrix deposition over time. Scaffolds containing hADSCs showed the most lymph node-like characteristics, with a well-defined capsule and increased lymphocytic infiltration. Immunofluorescence analysis revealed enhanced expression of LYVE-1, Prox1, and CD31, indicating significant lymphatic and vascular remodeling. Additionally, upregulation of LYVE-1, VEGF-C, and VEGF-A protein and mRNA levels highlighted the scaffolds’ potential in promoting lymphangiogenesis and angiogenesis. These findings highlight the significant potential of hADSCs-loaded scaffolds in enhancing tissue regeneration, particularly in restoring lymphatic function in lymphedema.

Keywords

Bioprinting / Lymphedema / Lymph nodes / Lymphangiogenesis / Mesenchymal stem cells / Tissue engineering

Funding

This research was supported by a Seoul National University Bundang Hospital grant (No. 14-2019-0010) and a research fund from Honam University, 2023 (No. 2023-0151).

Conflict of interest

The authors declare they have no competing interests.

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