Molecular analysis and differentiation capacity of adipose-derived stem cells from lymphedema tissue.
Molecular analysis and differentiation capacity of adipose-derived stem cells from lymphedema tissue.
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DOI：
10.1097/prs.0b013e31829ace13
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发表时间：
2013-09
影响因子：
3.6
通讯作者：
Gurtner GC
中科院分区：
文献类型：
--
作者：
Levi B;Glotzbach JP;Sorkin M;Hyun J;Januszyk M;Wan DC;Li S;Nelson ER;Longaker MT;Gurtner GC
许多乳腺癌患者在腋窝手术后都受到上肢水肿这一致残性并发症的困扰。使用按摩和压迫疗法的保守治疗不能提供持久的缓解，因为它们无法解决水肿向多余脂肪组织的慢性转化。抽脂术，以解决脂肪性质的水肿提供了一个机会，详细分析基质部分水肿相关的脂肪，以澄清这种脂肪转化的分子机制。脂肪来源的干细胞从来自患有水肿的年龄匹配患者（n = 3）的上肢的人脂肪抽吸物或来自经历美容手术的对照患者（n = 3）的皮下脂肪组织中收获。收获后立即使用单细胞转录谱分析技术分析脂肪来源的干细胞。通过实时定量聚合酶链反应和标准体外分化试验评估成骨、成脂和血管生成基因表达和分化。在水肿和皮下脂肪之间发现了脂肪源性干细胞的差异转录簇。有趣的是，水肿相关干细胞具有更高的成脂基因表达和增强的成脂分化能力。相反，它们具有较低的血管生成基因表达和体外形成小管的能力减弱，而成骨分化能力没有显著改变。脂肪干细胞从四肢受累的水肿似乎表现出类似的腹部脂肪干细胞的转录谱，然而，他们的脂肪分化潜力大大增加，他们的血管生成能力受到损害。这些结果表明，水肿的潜在病理生理驱动脂肪源性干细胞向成脂分化。
Many breast cancer patients are plagued by the disabling complication of upper limb lymphedema after axillary surgery. Conservative treatments using massage and compression therapy do not offer a lasting relief, as they fail to address the chronic transformation of edema into excess adipose tissue. Liposuction to address the adipose nature of the lymphedema has provided an opportunity for a detailed analysis of the stromal fraction of lymphedema-associated fat to clarify the molecular mechanisms for this adipogenic transformation. Adipose-derived stem cells were harvested from human lipoaspirate of the upper extremity from age-matched patients with lymphedema (n = 3) or subcutaneous adipose tissue from control patients undergoing cosmetic procedures (n = 3). Immediately after harvest, adipose-derived stem cells were analyzed using single-cell transcriptional profiling techniques. Osteogenic, adipogenic, and vasculogenic gene expression and differentiation were assessed by quantitative real-time polymerase chain reaction and standard in vitro differentiation assays. Differential transcriptional clusters of adipose-derived stem cells were found between lymphedema and subcutaneous fat. Interestingly, lymphedema-associated stem cells had a much higher adipogenic gene expression and enhanced ability to undergo adipogenic differentiation. Conversely, they had lower vasculogenic gene expression and diminished capability to form tubules in vitro, whereas the osteogenic differentiation capacity was not significantly altered. Adipose-derived stem cells from extremities affected by lymphedema appear to exhibit transcriptional profiles similar to those of abdominal adipose-derived stem cells; however, their adipogenic differentiation potential is strongly increased and their vasculogenic capacity is compromised. These results suggest that the underlying pathophysiology of lymphedema drives adipose-derived stem cells toward adipogenic differentiation.