Platelet-Derived Growth Factor-BB Protects Mesenchymal Stem Cells (MSCs) Derived From Immune Thrombocytopenia Patients Against Apoptosis and Senescence and Maintains MSC-Mediated Immunosuppression
Platelet-Derived Growth Factor-BB Protects Mesenchymal Stem Cells (MSCs) Derived From Immune Thrombocytopenia Patients Against Apoptosis and Senescence and Maintains MSC-Mediated Immunosuppression
复制标题
血小板衍生生长因子-BB 保护免疫性血小板减少症患者来源的间充质干细胞 (MSC) 免受细胞凋亡和衰老，并维持 MSC 介导的免疫抑制
DOI：
10.5966/sctm.2015-0360
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发表时间：
2016-12-01
影响因子：
6
通讯作者：
Zhang, Xiao-hui
中科院分区：
文献类型：
--
作者：
Zhang, Jia-min;Feng, Fei-er;Zhang, Xiao-hui
免疫性血小板减少症（ITP）的特征是血小板破坏和巨核细胞功能障碍。来自ITP患者的间充质干细胞（MSC-ITP）不表现出常规的增殖能力，因此表现出免疫调节缺陷，这表明MSC损伤可能是ITP的一个机制。血小板衍生生长因子 (PDGF) 可改善各种细胞类型的生长和存活。此外，PDGF还能促进MSC增殖。本研究的目的是分析PDGF-BB对MSC-ITP的影响。我们发现 MSC-ITP 的扩张速度更慢，并且显得扁平且更大。与对照组相比，MSC-ITP 表现出细胞凋亡和衰老增加。内在和外在途径均导致细胞凋亡增强。 P53 和 p21 表达在 MSC-ITP 中上调，但用 Pifithrin-α 抑制 p53 可显着抑制细胞凋亡和衰老。此外，来自ITP患者的MSC表现出较低的抑制诱导调节性T细胞（Treg）的活化T细胞增殖和抑制抗糖蛋白（GP）IIb-IIIa抗体合成的能力。 PDGF-BB处理显着降低MSC-ITP中p53和p21的表达并增加生存素表达。此外，ITP MSCs中的凋亡率和衰老细胞数量也减少。 PDGF-BB 治疗后，它们抑制活化 T 细胞、诱导 Tregs 和抑制抗 GPIIb-IIIa 抗体合成的能力受损。总之，我们证明 PDGF-BB 可以保护 ITP 患者来源的 MSC 免受细胞凋亡、衰老和免疫调节缺陷的影响。 PDGF-BB 的这种保护作用可能是通过 p53/p21 途径介导的，因此有可能为 ITP 提供一种新的治疗方法。
Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Mesenchymal stem cells (MSCs) from ITP patients (MSC-ITP) do not exhibit conventional proliferative abilities and thus exhibit defects in immunoregulation, suggesting that MSC impairment might be a mechanism involved in ITP. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types. Moreover, PDGF promotes MSC proliferation. The aim of the present study was to analyze the effects of PDGF-BB on MSC-ITP. We showed that MSC-ITP expanded more slowly and appeared flattened and larger. MSC-ITP exhibited increased apoptosis and senescence compared with controls. Both the intrinsic and extrinsic pathways account for the enhanced apoptosis. P53 and p21 expression were upregulated in MSC-ITP, but inhibition of p53 with pifithrin-alpha markedly inhibited apoptosis and senescence. Furthermore, MSCs from ITP patients showed a lower capacity for inhibiting the proliferation of activated T cells inducing regulatory T cells (Tregs) and suppressing the synthesis of anti-glycoprotein (GP) IIb-IIIa antibodies. PDGF-BB treatment significantly decreased the expression of p53 and p21 and increased survivin expression in MSC-ITP. In addition, the apoptotic rate and number of senescent cells in ITP MSCs were reduced. Their impaired ability for inhibiting activated T cells, inducing Tregs, and suppressing the synthesis of anti-GPIIb-IIIa antibodies was restored after PDGF-BB treatment. In conclusion, we have demonstrated that PDGF-BB protects MSCs derived from ITP patients against apoptosis, senescence, and immunomodulatory defects. This protective effect of PDGF-BB is likely mediated via the p53/p21 pathway, thus potentially providing a new therapeutic approach for ITP.