人脂肪来源基质细胞成骨和成脂分化潜能的基质细胞特异性差异。
Depot-specific variation in the osteogenic and adipogenic potential of human adipose-derived stromal cells.
机构信息
Stanford and Los Angeles, Calif. From the Hagey Pediatric Regenerative Medicine Research Laboratory, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, and the Division of Plastic and Reconstructive Surgery, University of California, Los Angeles.
出版信息
Plast Reconstr Surg. 2010 Sep;126(3):822-834. doi: 10.1097/PRS.0b013e3181e5f892.
BACKGROUND
Adipose-derived stromal cells hold promise for use in tissue regeneration. However, multiple facets of their biology remain unclear. The authors examined the variations in osteogenesis and adipogenesis in adipose-derived stromal cells between subcutaneous fat depots and potential molecular causes.
METHODS
Adipose-derived stromal cells were isolated from human patients from subcutaneous fat depots, including arm, flank, thigh, and abdomen (n = 5 patients). Osteogenic and adipogenic differentiation was performed (alkaline phosphatase, alizarin red, and oil red O staining, and quantitative real-time polymerase chain reaction). Co-cultures were established to assess the paracrine effect of human adipose-derived stromal cells on mouse osteoblasts. Finally, HOX gene expression was analyzed by quantitative real-time polymerase chain reaction.
RESULTS
Subcutaneous fat depots retain markedly different osteogenic and adipogenic potentials. Osteogenesis was most robust in adipose-derived stromal cells from the flank and thigh, as compared with those from the arm and abdomen (p < 0.05 by all markers examined). This was accompanied by elevations of BMP4 and BMPR1B (p < 0.05 by all markers examined). The osteogenic advantage of cells from the flank and thigh was again observed when analyzing the paracrine effects of these cells. Conversely, those cells isolated from the flank had a lesser ability to undergo adipogenic differentiation. Adipose-associated HOX genes were less expressed in flank-derived adipose-derived stromal cells.
CONCLUSIONS
Variations exist between fat depots in terms of adipose-derived stromal cell osteogenic and adipogenic differentiation. Differences in HOX expression and bone morphogenetic protein signaling may underlie these observations. This study indicates that the choice of fat depot derivation of adipose-derived stromal cells may be an important one for future efforts in tissue engineering.
背景
脂肪来源的基质细胞在组织再生中具有应用前景。然而，它们的生物学特性仍有许多方面尚不清楚。作者研究了皮下脂肪组织中脂肪来源的基质细胞在成骨和成脂分化方面的差异及其潜在的分子原因。
方法
从包括手臂、侧腹、大腿和腹部在内的皮下脂肪组织中分离出 5 名患者的脂肪来源的基质细胞。进行成骨和成脂分化（碱性磷酸酶、茜素红和油红 O 染色以及实时定量聚合酶链反应）。建立共培养物以评估人脂肪来源的基质细胞对小鼠成骨细胞的旁分泌作用。最后，通过实时定量聚合酶链反应分析 HOX 基因表达。
结果
皮下脂肪组织保留了明显不同的成骨和成脂潜能。与手臂和腹部的脂肪来源的基质细胞相比，来自侧腹和大腿的脂肪来源的基质细胞具有更强的成骨能力（所有标记物检测均 p < 0.05）。这伴随着 BMP4 和 BMPR1B 的升高（所有标记物检测均 p < 0.05）。当分析这些细胞的旁分泌作用时，再次观察到来自侧腹和大腿的细胞的成骨优势。相反，来自侧腹的细胞在成脂分化方面的能力较弱。脂肪相关的 HOX 基因在来自侧腹的脂肪来源的基质细胞中表达较少。
结论
脂肪来源的基质细胞的成骨和成脂分化在不同脂肪组织中存在差异。HOX 表达和骨形态发生蛋白信号的差异可能是造成这些差异的原因。本研究表明，脂肪来源的基质细胞的脂肪组织来源的选择可能对未来的组织工程研究具有重要意义。
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