Therapeutic lymphangiogenesis with implantation of adipose-derived regenerative cells.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Lymphedema is one of the serious clinical problems that can occur after surgical resection of malignant tumors such as breast cancer or intra-pelvic cancers. However, no effective treatment options exist at present. Here, we report that implantation of adipose-derived regenerative cells (ADRCs) can induce lymphangiogenesis in a mouse model of reparative lymphedema. ADRCs were isolated from C57BL/6J mice. To examine the therapeutic efficacy of ADRC implantation in vivo, we established a new mouse model of tail lymphedema. Lymphedema was improved significantly by local injection of ADRCs (P<0.05). Histological analysis revealed that lymphatic capillary density was greater in the ADRC group than in the phosphate-buffered saline control group (P<0.01). Tissue expression of vascular endothelial growth factor C mRNA and plasma levels of vascular endothelial growth factor C were greater in the ADRC group than in the control group (P<0.01 and P<0.05, respectively). ADRCs released vascular endothelial growth factor C, which directly stimulated lymphangiogenesis. Implantation of ADRCs also enhanced recruitment of bone marrow-derived M2 macrophages, which served as lymphatic endothelial progenitor cells. Implantation of autologous ADRCs could be a useful treatment option for patients with severe lymphedema via mediation of lymphangiogenesis. (J Am Heart Assoc. 2012;1:e000877 doi: 10.1161/

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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