Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Tissue Eng Part A. 2010 May;16(5):1595-606. doi: 10.1089/ten.TEA.2009.0616.
Human adipose-derived stromal cells (ASCs) have been shown to possess therapeutic potential in a variety of settings, including cutaneous wound healing; however, it is unknown whether the regenerative properties of this cell type can be applied to diabetic ulcers. ASCs collected from elective surgical procedures were used to treat full-thickness dermal wounds in leptin receptor-deficient (db/db) mice. Cells were delivered either as multicellular aggregates or as cell suspensions to determine the impact of cell formulation and delivery methods on biological activity and in vivo therapeutic effect. After treatment with ASCs that were formulated as multicellular aggregates, diabetic wounds experienced a significant increase in the rate of wound closure compared to wounds treated with an equal number of ASCs delivered in suspension. Analysis of culture supernatant and gene arrays indicated that ASCs formulated as three-dimensional aggregates produce significantly more extracellular matrix proteins (e.g., tenascin C, collagen VI alpha3, and fibronectin) and secreted soluble factors (e.g., hepatocyte growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-14) compared to monolayer culture. From these results, it is clear that cell culture, formulation, and delivery method have a large impact on the in vitro and in vivo biology of ASCs.
人脂肪来源的基质细胞（ASCs）已被证明在多种环境中具有治疗潜力，包括皮肤伤口愈合；然而，尚不清楚这种细胞类型的再生特性是否可以应用于糖尿病溃疡。从择期手术中收集的 ASC 用于治疗瘦素受体缺陷（db/db）小鼠的全层真皮伤口。将细胞作为多细胞聚集体或细胞悬浮液进行递送，以确定细胞配方和递送方法对生物活性和体内治疗效果的影响。在用多细胞聚集体形式配制的 ASC 处理后，与用悬浮液递送的相同数量的 ASC 处理的伤口相比，糖尿病伤口的闭合速度显著增加。对培养上清液和基因阵列的分析表明，与单层培养相比，ASC 作为三维聚集体产生的细胞外基质蛋白（例如，腱蛋白 C、胶原 VI alpha3 和纤维连接蛋白）和分泌的可溶性因子（例如，肝细胞生长因子、基质金属蛋白酶-2 和基质金属蛋白酶-14）明显更多。从这些结果可以清楚地看出，细胞培养、配方和递送方法对 ASC 的体外和体内生物学有很大影响。
