The matrix microenvironment influences but does not dominate tissue-specific stem cell lineage differentiation.
The matrix microenvironment influences but does not dominate tissue-specific stem cell lineage differentiation.
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DOI：
10.1016/j.mtbio.2023.100805
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发表时间：
2023-12
影响因子：
8.2
通讯作者：
Pei, Ming
中科院分区：
文献类型：
--
作者：
Pei, Yixuan Amy;Mikaeiliagah, Elmira;Wang, Bin;Zhang, Xiaobing;Pei, Ming
关键词：
间充质干细胞（Mesenchymal stem cells，MSCs）在组织工程和再生医学中发挥着重要作用，但其体外扩增过程中细胞衰老往往阻碍其临床应用。最近的研究表明，MSC沉积的脱细胞细胞外基质（dECM）提供了一个有益的微环境，促进细胞增殖和强调干细胞分化。然而，这种基质环境管理组织特异性干细胞谱系分化的能力仍然不明确。本研究采用人脂肪源性间充质干细胞（ADSC）和滑膜源性间充质干细胞（SDSC）分别作为脂肪形成和软骨形成分化途径的模型。研究了由SV 40 LT转导的永生化细胞产生的遗传修饰的dECM（GMdECM）对细胞分化的影响。两种类型的永生化细胞显示软骨形成能力降低，但脂肪形成潜力增强。在ADSC沉积的dECM上生长的ADSC显示出稳定的软骨形成潜力，但增加了脂肪形成能力;相反，在SDSC产生的dECM上扩增的SDSC显示出升高的软骨形成能力和降低的脂肪形成潜力。通过GMdECM扩增证实了这种细胞依赖性反应，SDSC显示出增强的软骨形成。然而，ADSC在GMdECM上没有表现出改善的软骨形成潜力，这表明基质微环境并不决定组织特异性干细胞的最终分化途径。潜在的分子机制，如GMdECM中基底膜蛋白表达升高以及扩增和软骨诱导过程中TWIST 1的动态表达，可能支持GMdECM扩增的SDSC的强软骨分化。
Mesenchymal stem cells (MSCs) play a pivotal role in tissue engineering and regenerative medicine, with their clinical application often hindered by cell senescence during ex vivo expansion. Recent studies suggest that MSC-deposited decellularized extracellular matrix (dECM) offers a conducive microenvironment that fosters cell proliferation and accentuates stem cell differentiation. However, the ability of this matrix environment to govern lineage differentiation of tissue-specific stem cells remains ambiguous. This research employs human adipose-derived MSCs (ADSCs) and synovium-derived MSCs (SDSCs) as models for adipogenesis and chondrogenesis differentiation pathways, respectively. Genetically modified dECM (GMdECM), produced by SV40LT-transduced immortalized cells, was studied for its influence on cell differentiation. Both types of immortalized cells displayed a reduction in chondrogenic ability but an enhancement in adipogenic potential. ADSCs grown on ADSC-deposited dECM showed stable chondrogenic potential but increased adipogenic capacity; conversely, SDSCs expanded on SDSC-generated dECM displayed elevated chondrogenic capacity and diminished adipogenic potential. This cell-dependent response was confirmed through GMdECM expansion, with SDSCs showing enhanced chondrogenesis. However, ADSCs did not exhibit improved chondrogenic potential on GMdECM, suggesting that the matrix microenvironment does not dictate the final differentiation path of tissue-specific stem cells. Potential molecular mechanisms, such as elevated basement membrane protein expression in GMdECMs and dynamic TWIST1 expression during expansion and chondrogenic induction, may underpin the strong chondrogenic differentiation of GMdECM-expanded SDSCs.
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DOI：
10.1088/1748-6041/11/4/045009
发表时间：
2016-08-10
期刊：
Biomedical materials (Bristol, England)
影响因子：
--
作者：
Pizzute T;Zhang Y;He F;Pei M
通讯作者：
Pei M
影响因子：
56.9
作者：
Bunz, F;Dutriaux, A;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
11.8
作者：
Bialek, P;Kern, B;Karsenty, G
通讯作者：
Karsenty, G
影响因子：
14
作者：
Li, Jingting;Narayanan, Karthikeyan;Pei, Ming
通讯作者：
Pei, Ming
影响因子：
5.3
作者：
Niculescu, AB;Chen, XB;Reed, SI
通讯作者：
Reed, SI