Niemelä Sanna-Mari, Miettinen Susanna, Konttinen Yrjö, Waris Timo, Kellomäki Minna, Ashammakhi Nureddin A, Ylikomi Timo
Department of Cell Biology, Medical School, University of Tampere, Tampere, and Department of Surgery, Oulu University Hospital, Oulu, Finland.
J Craniofac Surg. 2007 Mar;18(2):325-35. doi: 10.1097/scs.0b013e3180333b6a.
Transplantation of autologous fat as pedicle or transposition flaps has been a classical method in plastic surgery for tissue reconstruction. The injection of fat for soft tissue reconstruction is also an old innovation. This approach has some significant drawbacks such as resorption of the fat transplant. To regenerate additional and self-regenerating adipose tissue for reconstructive purposes, a thorough understanding of adipose tissue (mesodermal stem cells, adipoblasts, pre-adipocytes, mature, lipid-synthesizing, and lipid-storing white or brown adipocytes) on cellular and molecular levels is required. Several transcription factors that play a central role in the control of adipogenesis have been identified. Among these are the CCAAT/enhancer binding protein gene family and peroxisome proliferator-activated receptor-gamma. Hormones and growth factors, such as insulin and insulin-like growth factor (IGF), transfer external signals to differentiating adipocytes. In an attempt to improve the quality of tissue-engineered fat by culture-expanded adipocytes, various pre-adipocyte and stem cell culture conditions and expansion methods have been developed. In the presence of fetal calf serum, spontaneous differentiation of pre-adipocytes into fat cell clusters occurs to some degree. This in vitro differentiation can be enhanced by addition of inducing agents such as dexamethasone, isobutylmethylxantine, and insulin into the culture medium. Recent work has shown the multipotency of pre-adipocytes, which are fibroblast-like precursors of adipocytes. With use of specific culture conditions, human adipose tissue-derived stem cells can be induced to express markers of adipocyte, osteoblast, and myocyte cell lineages. The multipotent characteristics of adipose tissue-derived stem cells, as well as their abundance and accessibility in the human body, make them a potential cell source for tissue engineering applications.
自体脂肪作为带蒂皮瓣或转位皮瓣进行移植,一直是整形外科组织重建的经典方法。注射脂肪进行软组织重建也是一项古老的创新技术。这种方法存在一些显著缺点,比如脂肪移植会被吸收。为了再生额外的、自我更新的脂肪组织用于重建目的,需要在细胞和分子水平上深入了解脂肪组织(中胚层干细胞、成脂细胞、前脂肪细胞、成熟的、合成脂质和储存脂质的白色或棕色脂肪细胞)。已经确定了几种在脂肪生成控制中起核心作用的转录因子。其中包括CCAAT/增强子结合蛋白基因家族和过氧化物酶体增殖物激活受体-γ。激素和生长因子,如胰岛素和胰岛素样生长因子(IGF),将外部信号传递给分化中的脂肪细胞。为了通过培养扩增的脂肪细胞提高组织工程脂肪的质量,已经开发了各种前脂肪细胞和干细胞培养条件及扩增方法。在胎牛血清存在的情况下,前脂肪细胞会在一定程度上自发分化为脂肪细胞簇。通过向培养基中添加诱导剂,如地塞米松、异丁基甲基黄嘌呤和胰岛素,可以增强这种体外分化。最近的研究表明前脂肪细胞具有多能性,它们是脂肪细胞的成纤维细胞样前体。利用特定的培养条件,可以诱导人脂肪组织来源的干细胞表达脂肪细胞、成骨细胞和心肌细胞系的标志物。脂肪组织来源的干细胞的多能特性,以及它们在人体中的丰富性和易获取性,使其成为组织工程应用的潜在细胞来源。