Mesenchymal stem cells secrete multiple cytokines that promote angiogenesis and have contrasting effects on chemotaxis and apoptosis.
Mesenchymal stem cells secrete multiple cytokines that promote angiogenesis and have contrasting effects on chemotaxis and apoptosis.
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DOI：
10.1371/journal.pone.0035685
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Geenen DL
中科院分区：
文献类型：
--
作者：
Boomsma RA;Geenen DL
我们以前已经证明，间充质干细胞（MSC）改善功能后，整合在缺血心肌。我们研究了MSC产生的特异性细胞因子和生长因子是否能够影响血管生成、细胞迁移和凋亡。通过培养MSC 48小时来制备条件培养基（CM）。与对照培养基相比，CM显示VEGF、单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎性蛋白-1 α（MIP-1α）、MIP-1β和IFN-γ（IFN-γ）诱导的单核因子的水平显著升高。RT-PCR检测到MSC含有这些因子的RNA。CM能够诱导犬血管内皮细胞的血管生成。MCP-1和MIP-1α增加MSC的细胞迁移，而VEGF减少MSC的细胞迁移。与对照组相比，在缺氧条件下用CM处理24小时的H9 c2细胞显示caspase-3活性降低16%。PI 3激酶γ抑制剂对对照组无影响，但可逆转CM对caspase 3活性的影响。单独的MCP-1模拟CM的保护作用，而PI 3-Kγ抑制剂不能逆转MCP-1的作用。CM降低磷酸化BAD（Ser 112）和磷酸化Akt（Ser 473），同时增加磷酸化Akt（Thr 308）。MCP-1降低磷酸化Akt（Ser 473）的水平，而对其他两个没有影响; PI 3-Kγ抑制剂没有改变MCP-1的作用。在CM处理的H9 c2细胞中，ERK 1/2磷酸化减少，并且ERK 1/2的抑制减少Akt（Ser 473）、Akt（Thr 308）和Bad（Ser 112）的磷酸化。总之，MSC合成和分泌多种旁分泌因子，能够影响MSC迁移，促进血管生成和减少凋亡。虽然MCP-1和PI 3-激酶都参与了保护作用，但它们彼此独立。除了MCP-1之外，MSC还可能分泌多种促存活因子，其作用于不同的细胞内信号传导途径。
We have previously shown that mesenchymal stem cells (MSC) improve function upon integration in ischemic myocardium. We examined whether specific cytokines and growth factors produced by MSCs are able to affect angiogenesis, cellular migration and apoptosis. Conditioned media (CM) was prepared by culturing MSC for 48 hours. CM displayed significantly elevated levels of VEGF, Monocyte Chemoattractant Protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), MIP-1β and monokine induced by IFN-γ (MIG) compared to control media. MSC contained RNA for these factors as detected by RT-PCR. CM was able to induce angiogenesis in canine vascular endothelial cells. MCP-1 and MIP-1α increased cell migration of MSC while VEGF reduced it. H9c2 cells treated with CM under hypoxic conditions for 24 hours displayed a 16% reduction in caspase-3 activity compared to controls. PI 3-kinase γ inhibitor had no effect on controls but reversed the effect of CM on caspase-3 activity. MCP-1 alone mimicked the protective effect of CM while the PI 3-Kγ inhibitor did not reverse the effect of MCP-1. CM reduced phospho-BAD (Ser112) and phospho-Akt (Ser473) while increasing phospho-Akt (Thr308). MCP-1 reduced the level of phospho-Akt (Ser473) while having no effect on the other two; the PI 3-Kγ inhibitor did not alter the MCP-1 effect. ERK 1/2 phosphorylation was reduced in CM treated H9c2 cells, and inhibition of ERK 1/2 reduced the phosphorylation of Akt (Ser473), Akt (Thr308) and Bad (Ser112). In conclusion, MSC synthesize and secrete multiple paracrine factors that are able to affect MSC migration, promote angiogenesis and reduce apoptosis. While both MCP-1 and PI3-kinase are involved in the protective effect, they are independent of each other. It is likely that multiple pro-survival factors in addition to MCP-1 are secreted by MSC which act on divergent intracellular signaling pathways.
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影响因子：
5.2
作者：
Lopez Ponte, Adriana;Marais, Emeline;Domenech, Jorge
通讯作者：
Domenech, Jorge
DOI：
10.1016/j.bbrc.2005.06.116
发表时间：
2005-08-26
影响因子：
3.1
作者：
Fiedler, J;Leucht, F;Brenner, RE
通讯作者：
Brenner, RE
影响因子：
4.5
作者：
Schmal, H.;Niemeyer, P.;Mehhorn, A. T.
通讯作者：
Mehhorn, A. T.
DOI：
10.1152/ajpheart.00431.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Singla, Dinender K.;McDonald, Debbie E.
通讯作者：
McDonald, Debbie E.
DOI：
10.1152/ajpheart.00762.2007
发表时间：
2008-05-01
影响因子：
4.8
作者：
Schuleri, Karl H.;Amado, Luciano C.;Hare, Joshua M.
通讯作者：
Hare, Joshua M.