Therapeutic lymphangiogenesis with implantation of adipose-derived regenerative cells.
Therapeutic lymphangiogenesis with implantation of adipose-derived regenerative cells.
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DOI：
10.1161/jaha.112.000877
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发表时间：
2012-08
影响因子：
5.4
通讯作者：
Murohara T
中科院分区：
文献类型：
--
作者：
Shimizu Y;Shibata R;Shintani S;Ishii M;Murohara T
淋巴水肿是乳腺癌或盆腔内癌等恶性肿瘤手术切除后可能出现的严重临床问题之一。然而，目前尚无有效的治疗方案。在这里，我们报告植入脂肪源性再生细胞（ADRC）可以在修复性淋巴水肿小鼠模型中诱导淋巴管生成。 ADRCs 是从 C57BL/6J 小鼠中分离出来的。为了检验 ADRC 植入体内的治疗效果，我们建立了一种新的尾部淋巴水肿小鼠模型。局部注射ADRCs可显着改善淋巴水肿（P<0.05）。组织学分析显示，ADRC 组的毛细淋巴管密度高于磷酸盐缓冲盐水对照组（P<0.01）。 ADRC组血管内皮生长因子C mRNA的组织表达量和血浆血管内皮生长因子C水平均高于对照组（分别P<0.01和P<0.05）。 ADRC 释放血管内皮生长因子 C，直接刺激淋巴管生成。 ADRC 的植入还增强了骨髓来源的 M2 巨噬细胞的募集，这些巨噬细胞充当淋巴管内皮祖细胞。对于通过介导淋巴管生成而导致严重淋巴水肿的患者，植入自体 ADRC 可能是一种有用的治疗选择。 （美国心脏协会。2012 年；1:e000877 doi: 10.1161/JAHA.112.000877。）
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/JAHA.112.000877.)