Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation.
Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation.
复制标题
DOI：
10.1371/journal.pone.0002129
复制
发表时间：
2008-05-07
期刊：
影响因子：
3.7
通讯作者：
MacNeil S
中科院分区：
文献类型：
--
作者：
Sun T;McMinn P;Holcombe M;Smallwood R;MacNeil S
临床使用时，通常使用经过辐照的小鼠成纤维细胞和牛血清来扩增自体角质细胞。随着人们对这些异生物质的安全性的日益关注，需要在不含动物源产品的培养基中培养角质形成细胞。更好地了解上皮/间质相互作用可能有助于这一点。通过扩展基于试剂的角质形成细胞集落形成模型以包括角质形成细胞对成纤维细胞和血清的反应，开发了角质形成细胞/成纤维细胞o培养模型。通过比较在 Greens 培养基中单独培养和共培养的角质形成细胞和成纤维细胞的体内和体外多细胞行为，对该模型进行了验证。为了测试模型的稳健性，改变了成纤维细胞的一些特性，以研究它们对角质形成细胞和成纤维细胞的多细胞形态发生的影响。然后使用该模型生成假设，以探索增殖和生长停滞的成纤维细胞与角质形成细胞的相互作用。经体外实验证实的模型得出的关键预测是：1）成纤维细胞与角质形成细胞的比例将严重影响角质形成细胞集落的扩张，2）该比例需要在共培养开始时达到最佳状态，3）增殖的成纤维细胞在扩张角质形成细胞方面比受辐射的细胞更有效，4）在存在足够数量的成纤维细胞的情况下，角质形成细胞的扩张将独立于血清。密切相关的计算和生物学方法是理解复杂生物系统（例如角质形成细胞和成纤维细胞之间的相互作用）的强大工具。这项研究的主要结果是发现，早期添加关键比例的增殖性成纤维细胞可以使角质形成细胞快速扩增，而无需使用受辐射的小鼠成纤维细胞和牛血清。
Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this. A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum. A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum.
登录
查看更多内容
影响因子：
5.8
作者：
Angel, P;Szabowski, A
通讯作者：
Szabowski, A
影响因子：
64.5
作者：
ADAMS, JC;WATT, FM
通讯作者：
WATT, FM
影响因子：
5.8
作者：
Grabe, N;Neuber, K
通讯作者：
Neuber, K
影响因子：
2.2
作者：
BHORA, FY;DUNKIN, BJ;HARMON, JW
通讯作者：
HARMON, JW
影响因子：
2.2
作者：
Chang, CC;Kuo, YF;Jee, SH
通讯作者：
Jee, SH