Open AccessTherapeutic Lymphangiogenesis With Implantation of Adipose‐Derived Regenerative Cells
Author(s) -
Shimizu Yuuki,
Shibata Rei,
Shintani Satoshi,
Ishii Masakazu,
Murohara Toyoaki
Publication year - 2012
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.112.000877
Subject(s) - medicine , lymphangiogenesis , lymphedema , lymphatic system , saline , vascular endothelial growth factor , vascular endothelial growth factor c , surgery , angiogenesis , pathology , breast cancer , cancer , vascular endothelial growth factor a , metastasis , vegf receptors
Background 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. Methods and Results 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. Conclusions 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/JAHA.112.000877.)