Loeffler M, Potten C S, Wichmann H E
Medizinische Universitätsklinik I, Köln, Federal Republic of Germany.
Virchows Arch B Cell Pathol Incl Mol Pathol. 1987;53(5):286-300.
The clustering of 3HTdR labelled cells in the epidermal basal layer and their changes with time have been modelled mathematically and cannot be adequately fitted by an earlier model of the cell kinetic organisation of the skin. A more refined model analysis was performed based on Monte Carlo computer simulations of cell layers which take cell division, cell aging and lateral as well as vertical cell migration into account. A large variety of hypothetical scenarios was tested to see if each could provide a fit to the clustering data. The analysis provides further support for the concept of a cell kinetic heterogeneity with a stem-transit-postmitotic differentiation scheme. In the best overall model scheme three transit divisions are predicted but unlike in the earlier model it is now postulated that postmitotic cells can be produced at all stages in the lineage rather than only at the end of the amplification scheme. Most important, the model predicts that stem cells and most of the transit cells differ in the way they process 3HTdR label. Grain dilution is an important mechanism to explain the fate of some labelled cells in the tissue, but on its own it can only consistently explain the data if the stem cells have a very low labelling index (LI less than or equal to 1%) which implies a very short biologically unreasonable S-phase. If a higher LI (longer S-phase) is assumed for the stem-cells other mechanisms must be predicted to explain the lack of large clusters and the increase in time of the singles. The selective segregation of chromosomes at mitosis is one such mechanism. However, on its own a large number of cells would have to behave in this way (i.e. both stem and T1 cells). If combined with other assumptions such as some grain dilution this selective segregation may be restricted only to stem cells. In addition the model allows cell production and migration rates to be estimated and the analysis can be related to the EPU-concept. Indeed the model itself would tend to automatically generate an EPU like structure. The model quantitatively reproduces LI, PLM, CL and clustering data.
已对表皮基底层中3HTdR标记细胞的聚集及其随时间的变化进行了数学建模，早期的皮肤细胞动力学组织模型无法对其进行充分拟合。基于细胞层的蒙特卡罗计算机模拟进行了更精细的模型分析，该模拟考虑了细胞分裂、细胞衰老以及细胞的横向和纵向迁移。测试了大量假设情景，以查看每种情景是否能拟合聚集数据。该分析为具有干细胞-过渡细胞-有丝分裂后分化方案的细胞动力学异质性概念提供了进一步支持。在最佳的总体模型方案中，预测有三个过渡分裂，但与早期模型不同的是，现在假设在谱系的所有阶段都可以产生有丝分裂后细胞，而不仅仅是在扩增方案结束时。最重要的是，该模型预测干细胞和大多数过渡细胞在处理3HTdR标记的方式上存在差异。颗粒稀释是解释组织中一些标记细胞命运的重要机制，但仅靠它自身，只有在干细胞具有非常低的标记指数（LI小于或等于1%）时才能一致地解释数据，这意味着生物学上不合理的非常短的S期。如果假设干细胞具有更高的LI（更长的S期），则必须预测其他机制来解释缺乏大的细胞簇以及单个细胞数量随时间的增加。有丝分裂时染色体的选择性分离就是这样一种机制。然而，仅靠它自身，大量细胞将不得不以这种方式表现（即干细胞和T1细胞都如此）。如果与其他假设（如一些颗粒稀释）相结合，这种选择性分离可能仅局限于干细胞。此外，该模型允许估计细胞产生和迁移速率，并且该分析可以与表皮增殖单位（EPU）概念相关。实际上，该模型本身倾向于自动生成类似EPU的结构。该模型定量地再现了标记指数（LI）、标记有丝分裂百分数（PLM）、克隆形成率（CL）和聚集数据。
