Molecular Analysis and Differentiation Capacity of Adipose-Derived Stem Cells from Lymphedema Tissue

被引：31
作者：
Levi, Benjamin
Glotzbach, Jason P.
Sorkin, Michael
Hyun, Jeong
Januszyk, Michael
Wan, Derrick C.
Li, Shuli
Nelson, Emily R.
Longaker, Michael T.
Gurtner, Geoffrey C. [1 ]
机构：
[1] Stanford Univ, Sch Med, Div Plast & Reconstruct Surg, Dept Surg, Stanford, CA 94305 USA
来源：
PLASTIC AND RECONSTRUCTIVE SURGERY | 2013年 / 132卷 / 03期
基金：
美国国家卫生研究院;
关键词：
D O I：
10.1097/PRS.0b013e31829ace13
中图分类号：
R61 [外科手术学];
学科分类号：
摘要：
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
引用
收藏
页码：580 / 589
页数：10
相关论文
共 41 条
  • [1] Cancer Facts & Figures, (2010)
  • [2] Brorson H., Ohlin K., Olsson G., Karlsson M.K., Breast cancer-related chronic arm lymphedema is associated with excess adipose and muscle tissue, Lymphat Res Biol, 7, pp. 3-10, (2009)
  • [3] Brorson H., Liposuction in arm lymphedema treatment, Scandinavian Journal of Surgery, 92, 4, pp. 287-295, (2003)
  • [4] Brorson H., Svensson H., Complete reduction of lymphoedema of the arm by liposuction after breast cancer, Scand J Plast Reconstr Surg Hand Surg, 31, pp. 137-143, (1997)
  • [5] Brorson H., Svensson H., Liposuction combined with controlled compression therapy reduces arm lymphedema more effectively than controlled compression therapy alone, Plastic and Reconstructive Surgery, 102, 4, pp. 1058-1067, (1998)
  • [6] De Ugarte D.A., Alfonso Z., Zuk P.A., Elbarbary A., Zhu M., Ashjian P., Benhaim P., Hedrick M.H., Fraser J.K., Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow, Immunology Letters, 89, 2-3, pp. 267-270, (2003)
  • [7] De Ugarte D.A., Morizono K., Elbarbary A., Alfonso Z., Zuk P.A., Zhu M., Dragoo J.L., Ashjian P., Thomas B., Benhaim P., Chen I., Fraser J., Hedrick M.H., Comparison of multi-lineage cells from human adipose tissue and bone marrow, Cells Tissues Organs, 174, 3, pp. 101-109, (2003)
  • [8] Zuk P.A., Zhu M., Ashjian P., De Ugarte D.A., Huang J.I., Mizuno H., Alfonso Z.C., Fraser J.K., Benhaim P., Hedrick M.H., Human adipose tissue is a source of multipotent stem cells, Molecular Biology of the Cell, 13, 12, pp. 4279-4295, (2002)
  • [9] Zuk P.A., Zhu M., Mizuno H., Huang J., Futrell J.W., Katz A.J., Benhaim P., Lorenz H.P., Hedrick M.H., Multilineage cells from human adipose tissue: Implications for cell-based therapies, Tissue Engineering, 7, 2, pp. 211-228, (2001)
  • [10] Jaager K., Neuman T., Human dermal fibroblasts exhibit delayed adipogenic differentiation compared with mesenchymal stem cells, Stem Cells Dev, 20, pp. 1327-1336, (2011)
12345