Clonal analysis of the proliferation potential of human bone marrow mesenchymal stem cells as a function of potency.
Clonal analysis of the proliferation potential of human bone marrow mesenchymal stem cells as a function of potency.
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DOI：
10.1002/bit.23193
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发表时间：
2011-11
影响因子：
3.8
通讯作者：
OConnor, Kim C.
中科院分区：
文献类型：
--
作者：
Russell, Katie C.;Lacey, Michelle R.;Gilliam, Jennifer K.;Tucker, H. Alan;Phinney, Donald G.;OConnor, Kim C.
来自骨髓的人间充质干细胞（MSCs）是一个由祖细胞和谱系细胞组成的异质集合，具有广泛的再生特性。体外扩增以产生足够数量的间充质干细胞对于大多数治疗应用是必不可少的。本研究解决了间充质干细胞的增殖潜能与其效力之间的关系。克隆分析产生了单细胞衍生的MSCs集落，根据它们的三龄潜力进行分类，表现出脂肪-(A)，软骨-(C)和成骨(O)作为效力的衡量标准。多能OAC克隆增殖能力强，集落形成效率为35% ~ 90%；而0个无性系形成菌落的效率不超过5% （P<0.01）。在离体培养过程中也有类似的趋势：例如，接种OAC克隆的培养物的中位特定生长率为0.85天−1（20小时加倍时间），接种O克隆的培养物的中位特定生长率为0的1 / 5 （P<0.01）。OA和OC克隆具有相似的增殖潜能。在亚融合培养中，接种O克隆的细胞中有75%以上的细胞呈衰老相关β-半乳糖苷酶活性阳性，而OAC克隆的细胞则不到10% （P<0.001）。在所有效价组中，凋亡细胞均为少数。克隆分析过程中产生的初步数据表明，MSCs产生矿化基质的成骨潜能也是效力的函数。这些结果在制备有效的MSC体外扩增疗法的背景下进行了讨论。
Human mesenchymal stem cells (MSCs) from bone marrow are a heterogeneous ensemble of progenitors and lineage-committed cells, with a broad range of regenerative properties. Ex vivo expansion to produce sufficient quantities of MSCs is essential for most therapeutic applications. The present study resolves the relationship between proliferation potential of MSCs and their potency. Clonal analysis generated single-cell derived colonies of MSCs that were classified according to their trilineage potential to exhibit adipo- (A), chondro-(C) and osteogenesis (O) as a measure of potency. Multipotent OAC clones were highly proliferative with colony-forming efficiencies that ranged from 35% to 90%; whereas, O clones formed colonies with an efficiency of 5% or less (P<0.01). Similar trends were evident during ex vivo expansion: for example, the median specific growth rate was 0.85 day−1 (20 h doubling time) for cultures inoculated with OAC clones and was 5-fold less for inocula of O clones (P<0.01). OA and OC clones had similar proliferation potentials. More than 75% of cells in subconfluent cultures inoculated with O clones stained positive for senescence-associated β-galactosidase activity vs. less than 10% for OAC clones (P<0.001). Apoptotic cells were in the minority for all potency groups. Preliminary data generated during clonal analysis suggest that osteogenic potential of MSCs to produce mineralized matrix is a function of potency, as well. These results are discussed in the context of the preparation of efficacious MSC therapies by ex vivo expansion.
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影响因子：
--
作者：
Kretlow JD;Jin YQ;Liu W;Zhang WJ;Hong TH;Zhou G;Baggett LS;Mikos AG;Cao Y
通讯作者：
Cao Y
影响因子：
4
作者：
Gronthos, S;Zannettino, ACW;Simmons, PJ
通讯作者：
Simmons, PJ
影响因子：
4
作者：
Caplan, Arnold I.;Dennis, James E.
通讯作者：
Dennis, James E.
影响因子：
4
作者：
D'Ippolito, G;Diabira, S;Schiller, PC
通讯作者：
Schiller, PC
DOI：
10.3324/haematol.13740
发表时间：
2009-02-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Battula, Venkata Lokesh;Treml, Sabrina;Buehring, Hans-Joerg
通讯作者：
Buehring, Hans-Joerg