Characterisation of human bone marrow stromal cell heterogeneity for skeletal regeneration strategies using a two-stage colony assay and computational modelling.
Characterisation of human bone marrow stromal cell heterogeneity for skeletal regeneration strategies using a two-stage colony assay and computational modelling.
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使用两阶段集落测定和计算模型表征骨骼再生策略的人骨髓基质细胞异质性。
DOI：
10.1016/j.bone.2009.10.002
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发表时间：
2010
期刊：
影响因子：
4.1
通讯作者：
Sengers BG
中科院分区：
文献类型：
--
作者：
Sengers BG
骨骼再生和组织工程策略主要依赖于祖细胞群的有效扩增，同时保持多能性和诱导骨和软骨分化的能力。细胞群体异质性对这一过程有重大影响，但目前量化不足，阻碍了实验结果的解释和优化扩增方案的设计。本研究的目的是表征个体人骨髓基质细胞在集落扩增潜力方面的异质性。为此，开发了一种新的两阶段CFU-F试验，其中从原代单细胞衍生的菌落中分离细胞，并以克隆密度作为单细胞再次播种，以形成新的继代菌落。这清楚地证明了继发菌落生长潜力在原发菌落之间和内部是如何显著变化的。根据主要菌落的不同，细胞要么只产生小的次级菌落，要么产生大范围的菌落大小。使用计算模型显示了这种群体异质性是如何从分层祖细胞群体中产生的，以及这种群体结构在解释实验数据时的局限性。此外，该模型还证明了细胞迁移对扩增潜力的潜在影响及其对诱导群体异质性的影响。这种结合实验计算的方法将确定细胞培养方案对异质祖细胞群体的扩增潜力和功能组成的影响。这样的见解可能对骨骼再生策略的成功至关重要。
Skeletal regeneration and tissue engineering strategies rely critically on the efficient expansion of progenitor cell populations whilst simultaneously preserving multipotentiality and the ability to induce differentiation towards bone and cartilage. Cell population heterogeneity has a significant impact on this process, but is currently poorly quantified, hampering the interpretation of experimental results and the design of optimised expansion protocols. The objective of this study was to characterise individual human bone marrow stromal cell heterogeneity in terms of colony expansion potential. For this purpose, a novel two-stage CFU-F assay was developed in which cells from primary single cell-derived colonies were detached and reseeded again at clonal density as single cells to form new secondary colonies. This clearly demonstrated how secondary colony growth potential varies markedly both between and within primary colonies. Depending on the primary colony, cells either generated small secondary colonies only, or else a wide range of colony sizes. Using computational modelling it was shown how such colony heterogeneity could arise from hierarchical progenitor cell populations and what the limits of such a population structure were in explaining the experimental data. In addition the model demonstrated the significant potential impact of cell mobility on expansion potential and its implications for inducing population heterogeneity. This combined experimental-computational approach will ascertain the impact of cell culture protocols on the expansion potential and functional composition of heterogeneous progenitor populations. Such insights are likely to be of crucial importance for the success of skeletal regeneration strategies.
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DOI：
--
发表时间：
2008
期刊：
影响因子：
--
作者：
V. Zhdanov;V. Zhdanov
通讯作者：
V. Zhdanov
影响因子：
3.5
作者：
Cai, AQ;Landman, KA;Hughes, BD
通讯作者：
Hughes, BD
平衡状态下分层结构细胞群的数学模型应用于表皮
影响因子：
8.5
作者：
N. Savill
通讯作者：
N. Savill
同时检测成骨细胞分化过程中多种骨相关 mRNA 和蛋白质表达：单细胞水平的聚合酶链反应和免疫细胞化学研究。
影响因子：
2.7
作者：
F. Liu;L. Malaval;A. Gupta;J. Aubin
通讯作者：
J. Aubin
细胞层次结构中的细胞周期。
DOI：
--
发表时间：
1986
期刊：
International Journal of Radiation Biology and Related Studies in Physics Chemistry and Medicine
影响因子：
--
作者：
C. Potten
通讯作者：
C. Potten