Hsiao Hui-Yi, Liu Jia-Wei, Pappalardo Marco, Cheng Ming-Huei
From the Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery.
the Center for Tissue Engineering.
Plast Reconstr Surg. 2023 May 1;151(5):1005-1015. doi: 10.1097/PRS.0000000000010082. Epub 2022 Dec 20.
The pathophysiology of adipose proliferation or differentiation in extremity lymphedema has not been thoroughly studied. This study investigated the impacts of the lymph harvested from lymphedematous limbs on the adipogenesis of adipose-derived stem cells (ASCs).
ASCs were isolated from the adipose tissue of normal extremities and cultured with lymph collected from Cheng lymphedema grade III to IV patients or adipogenic differentiation medium (ADM) and further subjected to differentiation and proliferation assay. The expression of adipogenesis genes was examined by real-time polymerase chain reaction to investigate the effect of lymph on ASCs. The level of adipogenic cytokines in the lymph was also evaluated.
The adipocytes were significantly larger in lymphedema fat tissue compared with that in normal fat tissues ( P < 0.00). The adipogenesis of ASCs cultured in lymph was significantly enhanced compared with in ADM ( P = 0.008) on day 10, suggesting that the adipogenesis of ASCs was promoted under the lymph-cultured environment. The expression of adipogenesis genes, peroxisome proliferator-activated receptor ( P = 0.02), CAAT/enhancer-binding protein α ( P = 0.008); fatty-acid binding protein ( P = 0.004), and lipoprotein lipase ( P = 0.003), was statistically elevated when the ASCs were cultured with lymph. The insulin content in lymph was statistically higher in lymph ( P < 0.001) than in plasma.
The adipogenesis of ASCs was promoted under the lymph-cultured environment with statistically increased adipogenesis genes of peroxisome proliferator-activated receptor, CAAT/enhancer-binding protein α, fatty-acid binding protein, and lipoprotein lipase. The excess lymph accumulated in the lymphedematous extremity contained a greater insulin/insulin-like growth factor-2. These adipogenic factors promoted the expression of early adipogenesis genes and led ASCs to undergo adipogenesis and differentiated into adipocytes.
The accumulation of adipose tissue in the lymphedema region was contributed from the content of excess lymph.
肢体淋巴水肿中脂肪组织增生或分化的病理生理学尚未得到充分研究。本研究调查了从淋巴水肿肢体采集的淋巴液对脂肪来源干细胞（ASC）成脂作用的影响。
从正常肢体的脂肪组织中分离出ASC，并与从Ⅲ至Ⅳ级淋巴水肿患者采集的淋巴液或成脂分化培养基（ADM）一起培养，然后进行分化和增殖测定。通过实时聚合酶链反应检测成脂基因的表达，以研究淋巴液对ASC的影响。同时评估淋巴液中成脂细胞因子的水平。
与正常脂肪组织相比，淋巴水肿脂肪组织中的脂肪细胞明显更大（P < 0.00）。在第10天，与在ADM中培养的ASC相比，在淋巴液中培养的ASC的成脂作用显著增强（P = 0.008），这表明在淋巴液培养环境下ASC的成脂作用得到促进。当ASC与淋巴液一起培养时，成脂基因过氧化物酶体增殖物激活受体（P = 0.02）、CCAAT/增强子结合蛋白α（P = 0.008）、脂肪酸结合蛋白（P = 0.004）和脂蛋白脂肪酶（P = 0.003）的表达在统计学上有所升高。淋巴液中的胰岛素含量在统计学上高于血浆（P < 0.001）。
在淋巴液培养环境下，ASC的成脂作用得到促进，过氧化物酶体增殖物激活受体、CCAAT/增强子结合蛋白α、脂肪酸结合蛋白和脂蛋白脂肪酶的成脂基因在统计学上增加。淋巴水肿肢体中积聚的过量淋巴液含有更多的胰岛素/胰岛素样生长因子-2。这些成脂因子促进了早期成脂基因的表达，并导致ASC发生成脂作用并分化为脂肪细胞。
淋巴水肿区域脂肪组织的积聚是由过量淋巴液的成分导致的。
