Human Adipose-Derived Stromal Cells Accelerate Diabetic Wound Healing: Impact of Cell Formulation and Delivery
Human Adipose-Derived Stromal Cells Accelerate Diabetic Wound Healing: Impact of Cell Formulation and Delivery
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DOI：
10.1089/ten.tea.2009.0616
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发表时间：
2010-05-01
影响因子：
4.1
通讯作者：
Katz, Adam J.
中科院分区：
文献类型：
--
作者：
Amos, Peter J.;Kapur, Sahil K.;Katz, Adam J.
人脂肪源性基质细胞（ASCs）已被证明在多种情况下具有治疗潜力，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应用于糖尿病溃疡。从选择性外科手术中收集的ASC用于治疗瘦素受体缺陷（db/db）小鼠的全层皮肤伤口。将细胞作为多细胞聚集体或作为细胞悬浮液递送，以确定细胞制剂和递送方法对生物活性和体内治疗效果的影响。在用配制成多细胞聚集体的ASC治疗后，与用相同数量的悬浮液中递送的ASC治疗的伤口相比，糖尿病伤口的伤口闭合率显著增加。对培养上清液和基因阵列的分析表明，配制成三维聚集体的ASC产生显著更多的细胞外基质蛋白（例如，腱生蛋白C，胶原VI α 3，和纤连蛋白）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）。从这些结果可以清楚地看出，细胞培养、制剂和递送方法对ASC的体外和体内生物学具有很大影响。
Human adipose-derived stromal cells (ASCs) have been shown to possess therapeutic potential in a variety of settings, including cutaneouswound healing; however, it is unknownwhether 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 alpha 3, 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.