Cultivation in Human Serum Reduces Adipose Tissue-Derived Mesenchymal Stromal Cell Adhesion to Laminin and Endothelium and Reduces Capillary Entrapment
Cultivation in Human Serum Reduces Adipose Tissue-Derived Mesenchymal Stromal Cell Adhesion to Laminin and Endothelium and Reduces Capillary Entrapment
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DOI：
10.1089/scd.2012.0051
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发表时间：
2013-03-01
影响因子：
4
通讯作者：
Bieback, Karen
中科院分区：
文献类型：
--
作者：
Dreher, Lena;Elvers-Hornung, Susanne;Bieback, Karen
间充质基质细胞（MSC）在临床细胞治疗中的使用越来越多，需要符合良好生产规范指南的安全和受控的生产过程。混合AB血型人血清（HS）已被用于取代胎牛血清（FBS），这受到监管机构的严格评价，因为它可以支持脂肪组织来源的间充质基质细胞（ASC）的扩增。然而，血清的选择是否会影响ASC的应用相关特性仍是未知数。基于微阵列的筛选揭示了HS-和FBS-ASC中差异表达的粘附和细胞外基质相关分子。由于细胞疗法依赖于细胞归巢和移植的功效，因此通过分析粘附、迁移和移行以及体内短期归巢来比较HS-和FBS-ASC。HS培养的ASC表现出较高的粘附塑料，但减少粘附细胞外基质分子，即层粘连蛋白，和内皮细胞在静态和流动条件下。迁移和迁移试验证实了ASC的肿瘤条件培养基的吸引力，无论补充。将不同标记的HS-和FBS-ASC共注射到非肥胖糖尿病、严重联合免疫缺陷小鼠中，发现肺和肝中的HS-ASC数量减少。这已被解释为减少毛细截留。我们的数据表明，不同的血清补充可能会改变ASC的应用相关特性，如粘附，以及输注后的肺截留。需要适当的损伤模型和进一步的分子分析来提供HS与FBS对ASC培养物的不同作用的机制见解。
The increasing use of mesenchymal stromal cells (MSC) in clinical cellular therapy requires a safe and controlled production process compliant with Good Manufacturing Practice guidelines. Pooled blood group AB human serum (HS) has been used to replace fetal bovine serum (FBS), critically rated by the regulatory agencies, since it can support the expansion of adipose tissue-derived mesenchymal stromal cells (ASC). However, it remains unknown whether the choice of serum affects application-relevant characteristics of ASC. A microarray-based screen has revealed differentially expressed adhesion and extracellular matrix-associated molecules in HS- and FBS-ASC. Since cell therapy relies on the cells' efficacy to home and engraft, HS- and FBS-ASC were compared by analyzing adhesion, migration, and transmigration as well as short-term homing in vivo. HS-cultivated ASC demonstrated a higher adhesion to plastic, but reduced adhesion to extracellular matrix molecules, that is, laminin, and to endothelial cells both under static and flow conditions. Migration and transmigration assays confirmed the attraction of ASC by the tumor conditioned medium irrespective of the supplement. Coinjecting differently labeled HS- and FBS-ASC into nonobese diabetic, severe combined immunodeficiency mice revealed reduced numbers of HS-ASC in lungs and liver. This has been interpreted as reduced capillary entrapment. Our data indicate that varying the serum supplement may alter application-relevant characteristics of ASC, such as adhesion, as well as lung entrapment after infusion. Appropriate injury models and further molecular analyses are required to provide mechanistic insight into the differential effects of HS versus FBS on ASC cultures.