Kilroy Gail E, Foster Sandra J, Wu Xiying, Ruiz Joseph, Sherwood Sonya, Heifetz Aaron, Ludlow John W, Stricker Dawn M, Potiny Suma, Green Patrick, Halvorsen Yuan-Di C, Cheatham Bentley, Storms Robert W, Gimble Jeffrey M
Stem Cell Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
J Cell Physiol. 2007 Sep;212(3):702-9. doi: 10.1002/jcp.21068.
Adipose tissue serves as a source of adipokines and cytokines with both local and systemic actions in health and disease. In this study, we examine the hypothesis that multipotent human adipose-derived stem cells (ASCs), capable of differentiating along the adipocyte, chondrocyte, and osteoblast pathways, contribute to adipose tissue-derived cytokine secretion. Following exposure to basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF), the ASCs significantly increase their secretion of hepatocyte growth factor (HGF), a cytokine implicated in hematopoiesis, vasculogenesis, and mammary epithelial duct formation. Ascorbic acid synergizes with these inductive factors, further increasing HGF levels. Following exposure to lipopolysaccharide, ASCs increase their secretion of both hematopoietic (granulocyte/monocyte, granulocyte, and macrophage colony stimulating factors, interleukin 7) and proinflammatory (interleukins 6, 8, and 11, tumor necrosis factor alpha) cytokines based on ELISA and RT-PCR. In co-cultures established with umbilical cord blood-derived CD34(+) cells, the ASCs support long-term hematopoiesis in vitro. Furthermore, in short-term 12-day co-cultures, the ASC maintain and expand the numbers of both myeloid and lymphoid progenitors. These observations are consistent with the functionality of the secreted cytokines and confirm recent reports by other laboratories concerning the hematopoietic supportive capability of ASCs. We conclude that the ASCs display cytokine secretory properties similar to those reported for bone marrow-derived mesenchymal stem cells (MSCs).
脂肪组织是脂肪因子和细胞因子的来源，在健康和疾病状态下均具有局部和全身作用。在本研究中，我们检验了一个假设，即能够沿着脂肪细胞、软骨细胞和成骨细胞途径分化的多能人类脂肪来源干细胞（ASC）有助于脂肪组织衍生细胞因子的分泌。在暴露于碱性成纤维细胞生长因子（bFGF）或表皮生长因子（EGF）后，ASC显著增加其肝细胞生长因子（HGF）的分泌，HGF一种与造血、血管生成和乳腺上皮导管形成有关的细胞因子。抗坏血酸与这些诱导因子协同作用，进一步提高HGF水平。基于酶联免疫吸附测定（ELISA）和逆转录-聚合酶链反应（RT-PCR），在暴露于脂多糖后，ASC增加其造血（粒细胞/单核细胞、粒细胞和巨噬细胞集落刺激因子、白细胞介素7）和促炎（白细胞介素6、8和11、肿瘤坏死因子α）细胞因子的分泌。在用脐带血来源的CD34(+)细胞建立的共培养物中，ASC在体外支持长期造血。此外，在短期的12天共培养中，ASC维持并扩大髓系和淋巴系祖细胞的数量。这些观察结果与分泌细胞因子的功能一致，并证实了其他实验室最近关于ASC造血支持能力的报道。我们得出结论，ASC表现出与骨髓来源间充质干细胞（MSC）报道的类似的细胞因子分泌特性。
