Lymphedema is a chronic progressive disease ultimately resulting in severe, disfiguring swelling and permanent changes of the affected tissues. Presently, there is no causal treatment approach of lymphedema. Therefore, most therapies are purely symptomatic. However, the recent use of stem cell-based therapies has offered new prospects for alternative treatment options. The present study was performed to investigate the effects of human adipose-derived stem cells (ADSCs) on human dermal lymphatic endothelial cells (HDLECs) in terms of basic in vitro lymphangiogenic assays (WST-8 assay, scratch assay, transmigration assay, sprouting assay, tube formation assay). The influence of ADSC-conditioned medium (ADSC-CM) on HDLECs was compared to recombinant VEGF-C, bFGF and HGF. Further ADSC-CM was characterized by protein microarray and enzyme-linked immunosorbent assay (ELISA). Although key-lymphangiogenic growth factors - like VEGF-C - could only be detected in low concentrations within the conditioned medium (CM), HDLECs were potently stimulated to proliferate, migrate and to form tube like structures by ADSC-CM. Despite concentrations more than hundredfold higher than those found in the conditioned medium, stimulation with recombinant VEGF-C, bFGF and HGF was still weaker compared to ADSC-CM. These results highlight the effectiveness of growth factors secreted by ADSC to stimulate HDLEC, potentially providing a promising new therapeutic approach for the treatment of lymphedema.

中文翻译：

---

人脂肪来源的干细胞通过淋巴管生成因子的分泌在体外支持淋巴管生成。

淋巴水肿是一种慢性进行性疾病，最终导致受影响组织的严重，毁容性肿胀和永久性变化。目前，尚无因果关系的淋巴水肿治疗方法。因此，大多数疗法纯粹是对症治疗。但是，最近基于干细胞疗法的使用为替代疗法提供了新的前景。本研究旨在通过基本的体外淋巴管生成测定（WST-8测定，刮擦测定，转运测定，发芽测定）研究人脂肪干细胞（ADSCs）对人真皮淋巴内皮细胞（HDLECs）的影响，试管形成试验）。将ADSC条件培养基（ADSC-CM）对HDLEC的影响与重组VEGF-C，bFGF和HGF进行了比较。进一步的ADSC-CM通过蛋白质微阵列和酶联免疫吸附测定（ELISA）进行表征。尽管只能在条件培养基（CM）中以低浓度检测到关键的淋巴管生成因子-VEGF-C，但ADSC-CM可以有效刺激HDLEC增殖，迁移并形成管状结构。尽管其浓度比条件培养基中的浓度高一百倍以上，但与ADSC-CM相比，重组VEGF-C，bFGF和HGF的刺激作用仍然较弱。这些结果突显了ADSC分泌的生长因子刺激HDLEC的有效性，可能为淋巴水肿的治疗提供有希望的新治疗方法。尽管只能在条件培养基（CM）中以低浓度检测到关键的淋巴管生成因子-VEGF-C，但ADSC-CM可以有效刺激HDLEC增殖，迁移并形成管状结构。尽管其浓度比条件培养基中的浓度高一百倍以上，但与ADSC-CM相比，重组VEGF-C，bFGF和HGF的刺激作用仍然较弱。这些结果突显了ADSC分泌的生长因子刺激HDLEC的有效性，可能为淋巴水肿的治疗提供有希望的新治疗方法。尽管只能在条件培养基（CM）中以低浓度检测到关键的淋巴管生成因子-VEGF-C，但ADSC-CM可以有效刺激HDLEC增殖，迁移并形成管状结构。尽管其浓度比条件培养基中的浓度高一百倍以上，但与ADSC-CM相比，重组VEGF-C，bFGF和HGF的刺激作用仍然较弱。这些结果突显了ADSC分泌的生长因子刺激HDLEC的有效性，可能为淋巴水肿的治疗提供有希望的新治疗方法。与ADSC-CM相比，重组VEGF-C，bFGF和HGF的刺激作用仍然较弱。这些结果突显了ADSC分泌的生长因子刺激HDLEC的有效性，可能为淋巴水肿的治疗提供有希望的新治疗方法。与ADSC-CM相比，重组VEGF-C，bFGF和HGF的刺激作用仍然较弱。这些结果突显了ADSC分泌的生长因子刺激HDLEC的有效性，可能为淋巴水肿的治疗提供有希望的新治疗方法。