Aging bone marrow mesenchymal stromal cells have altered membrane glycerophospholipid composition and functionality
Aging bone marrow mesenchymal stromal cells have altered membrane glycerophospholipid composition and functionality
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DOI：
10.1194/jlr.m030650
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发表时间：
2013-03-01
影响因子：
6.5
通讯作者：
Laitinen, Saara
中科院分区：
文献类型：
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作者：
Kilpinen, Lotta;Tigistu-Sahle, Feven;Laitinen, Saara
人类间充质干/基质细胞（hMSC）越来越多地用于先进的细胞疗法。hMSC的临床应用需要连续的细胞扩增。由于它是公认的膜甘油磷脂（GPL）提供前体信号脂质，调节细胞功能，我们研究了供体的年龄和细胞增殖对人骨髓间充质干细胞（hBMSC）的GPL配置文件的影响。从5个年轻人和5个老年人中收获的hBMSCs在脂质类、脂质种类和酰基链的水平上观察到扩增期间显示出明显的组成变化。磷脂酰肌醇与磷脂酰丝氨酸的比例在传代后期样品中增加。此外，在传代过程中，含有20：4 n-6的磷脂酰胆碱和磷脂酰乙醇胺的种类积累，而含有单不饱和脂肪酸（FA）的种类减少。此外，在细胞的总FA池中，20：4 n-6增加，这是以牺牲n-3多不饱和FA（尤其是22：6 n-3）为代价的。GPL和FA与hBMSCs扩增过程中免疫抑制能力的下降相关。参与脂质代谢和免疫调节的几种酶的基因表达水平的改变进一步支持了我们的观察结果。结果表明，hBMSC的广泛扩增有害地调节膜GPL，影响脂质信号传导并最终损害功能。基尔皮宁湖F. Tigistu-Sahle，S. Oja，D. Greco，A. Parmar，P. Saavalainen，J. Nikkila，M. Korhonen，P. Lehenkari，R. Kakela和S.莱蒂宁衰老的骨髓间充质干细胞改变了膜甘油磷脂的组成和功能。J. Lipid Res. 2013. 54：622-635。
Human mesenchymal stem/stromal cells (hMSC) are increasingly used in advanced cellular therapies. The clinical use of hMSCs demands sequential cell expansions. As it is well established that membrane glycerophospholipids (GPL) provide precursors for signaling lipids that modulate cellular functions, we studied the effect of the donor's age and cell doublings on the GPL profile of human bone marrow MSC (hBMSC). The hBMSCs, which were harvested from five young and five old adults, showed clear compositional changes during expansion seen at the level of lipid classes, lipid species, and acyl chains. The ratio of phosphatidylinositol to phosphatidylserine increased toward the late-passage samples. Furthermore, 20:4n-6-containing species of phosphatidylcholine and phosphatidylethanolamine accumulated while the species containing monounsaturated fatty acids (FA) decreased during passaging. Additionally, in the total FA pool of the cells, 20:4n-6 increased, which happened at the expense of n-3 polyunsaturated FAs, especially 22:6n-3. The GPL and FA correlated with the decreased immunosuppressive capacity of hBMSCs during expansion. Our observations were further supported by alterations in the gene expression levels of several enzymes involved in lipid metabolism and immunomodulation. The results show that extensive expansion of hBMSCs harmfully modulates membrane GPLs, affecting lipid signaling and eventually impairing functionality.-Kilpinen, L., F. Tigistu-Sahle, S. Oja, D. Greco, A. Parmar, P. Saavalainen, J. Nikkila, M. Korhonen, P. Lehenkari, R. Kakela, and S. Laitinen. Aging bone marrow mesenchymal stromal cells have altered membrane glycerophospholipid composition and functionality. J. Lipid Res. 2013. 54: 622-635.