The effect of hypoxia on the chondrogenic differentiation of co-cultured articular chondrocytes and mesenchymal stem cells in scaffolds.
The effect of hypoxia on the chondrogenic differentiation of co-cultured articular chondrocytes and mesenchymal stem cells in scaffolds.
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DOI：
10.1016/j.biomaterials.2013.02.064
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发表时间：
2013-06
期刊：
影响因子：
14
通讯作者：
Mikos, Antonios G.
中科院分区：
文献类型：
--
作者：
Meretoja, Ville V.;Dahlin, Rebecca L.;Wright, Sarah;Kasper, F. Kurtis;Mikos, Antonios G.
在这项工作中，我们研究了降低氧张力（20%和5% O2）对关节软骨细胞（ACs）、间充质干细胞（MSCs）及其共培养物（AC:MSC比例为30:70）的软骨形成和肥大的影响。细胞在多孔支架内培养6周，分析其细胞结构、软骨基质生成（胶原II/I表达比、羟脯氨酸和GAG含量）和肥大标志物（胶原X表达、ALP活性、钙积累）。两周后，缺氧培养条件促进了所有类型细胞的软骨形成，胶原II/I表达率和基质合成分别提高了2.5 ~ 11倍和1.5 ~ 3.0倍。后来，缺氧使细胞数量减少，但对基质合成影响不大。ACs和共培养均表现出类似的高胶原II/I表达率和富含GAG的基质形成，而MSCs产生的透明软骨样基质最少，并获得增厚表型，最终钙化。在缺氧条件下，间充质干细胞肥大得到进一步强调。我们得出结论，软骨工程最有希望的细胞来源是共培养，因为它们有可能减少对原代软骨细胞收获和扩增的需求，同时获得稳定的高度软骨性表型，不依赖于培养物中的氧张力。
In this work, we investigated the effects of lowered oxygen tension (20% and 5% O2) on the chondrogenesis and hypertrophy of articular chondrocytes (ACs), mesenchymal stem cells (MSCs) and their co-cultures with a 30:70 AC:MSC ratio. Cells were cultured for six weeks within porous scaffolds, and their cellularity, cartilaginous matrix production (collagen II/I expression ratio, hydroxyproline and GAG content) and hypertrophy markers (collagen X expression, ALP activity, calcium accumulation) were analyzed. After two weeks, hypoxic culture conditions had expedited chondrogenesis with all cell types by increasing collagen II/I expression ratio and matrix synthesis by ~2.5 – 11 and ~1.5 – 3.0 fold, respectively. At later times, hypoxia decreased cellularity but had little effect on matrix synthesis. ACs and co-cultures showed similarly high collagen II/I expression ratio and GAG rich matrix formation, whereas MSCs produced the least hyaline cartilage-like matrix and obtained a hypertrophic phenotype with eventual calcification. MSC hypertrophy was further emphasized in hypoxic conditions. We conclude that the most promising cell source for cartilage engineering was co-cultures, as they have a potential to decrease the need for primary chondrocyte harvest and expansion while obtaining a stable highly chondrogenic phenotype independent of the oxygen tension in the cultures.
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影响因子：
7
作者：
Buckley, C. T.;Vinardell, T.;Kelly, D. J.
通讯作者：
Kelly, D. J.
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
5.6
作者：
Dickhut, Andrea;Pelttari, Karoliina;Richter, Wiltrud
通讯作者：
Richter, Wiltrud
DOI：
10.1002/jor.20816
发表时间：
2009-06
期刊：
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子：
--
作者：
Coyle CH;Izzo NJ;Chu CR
通讯作者：
Chu CR
影响因子：
4.1
作者：
Bian, Liming;Zhai, David Y.;Burdick, Jason A.
通讯作者：
Burdick, Jason A.