PDGF-BB and IL-4 co-overexpression is a potential strategy to enhance mesenchymal stem cell-based bone regeneration.
PDGF-BB and IL-4 co-overexpression is a potential strategy to enhance mesenchymal stem cell-based bone regeneration.
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DOI：
10.1186/s13287-020-02086-8
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发表时间：
2021-01-07
影响因子：
7.5
通讯作者：
Goodman SB
中科院分区：
文献类型：
--
作者：
Zhang N;Lo CW;Utsunomiya T;Maruyama M;Huang E;Rhee C;Gao Q;Yao Z;Goodman SB
间充质干细胞（MSC）为基础的治疗具有免疫调节和增强组织再生的潜力。过表达特定细胞因子、生长因子或趋化因子的遗传修饰的MSC在临床前研究中显示出巨大的前景。在这方面，抗炎细胞因子白细胞介素（IL）-4将促炎M1巨噬细胞转化为抗炎M2表型; M2巨噬细胞减轻慢性炎症并增强MSC谱系细胞的成骨作用。然而，暴露于IL-4过早地抑制骨髓间充质干细胞在体外的成骨;此外，IL-4过表达的骨髓间充质干细胞在体内抑制成骨在急性炎症期。血小板衍生生长因子（PDGF）-BB已被证明可以增强MSC的成骨作用，并具有剂量依赖性效应。在这项研究中，我们产生了一种慢病毒载体，产生PDGF-BB下的弱启动子（磷酸甘油酸激酶，PGK）和慢病毒载体产生IL-4下的强启动子（巨细胞病毒，CMV）。我们用PDGF-BB和IL-4产生慢病毒载体分别或联合感染MSC，以研究细胞增殖和活力、蛋白表达和成骨能力。在共感染的MSC中观察到PDGF-BB和IL-4共过表达，并且与单独的IL-4过表达MSC相比，显示出增强细胞增殖和活力以及骨生成。PDGF-BB与IL-4一起过表达减轻了IL-4对过表达IL-4的MSCS的成骨抑制作用。PDGF-BB和IL-4过表达MSC可能是促进急性和慢性炎症情况下骨生成的潜在策略。
Mesenchymal stem cell (MSC)-based therapy has the potential for immunomodulation and enhancement of tissue regeneration. Genetically modified MSCs that over-express specific cytokines, growth factors, or chemokines have shown great promise in pre-clinical studies. In this regard, the anti-inflammatory cytokine interleukin (IL)-4 converts pro-inflammatory M1 macrophages into an anti-inflammatory M2 phenotype; M2 macrophages mitigate chronic inflammation and enhance osteogenesis by MSC lineage cells. However, exposure to IL-4 prematurely inhibits osteogenesis of MSCs in vitro; furthermore, IL-4 overexpressing MSCs inhibit osteogenesis in vivo during the acute inflammatory period. Platelet-derived growth factor (PDGF)-BB has been shown to enhance osteogenesis of MSCs with a dose-dependent effect. In this study, we generated a lentiviral vector that produces PDGF-BB under a weak promoter (phosphoglycerate kinase, PGK) and lentiviral vector producing IL-4 under a strong promoter (cytomegalovirus, CMV). We infected MSCs with PDGF-BB and IL-4-producing lentiviral vectors separately or in combination to investigate cell proliferation and viability, protein expression, and the capability for osteogenesis. PDGF-BB and IL-4 co-overexpression was observed in the co-infected MSCs and shown to enhance cell proliferation and viability, and osteogenesis compared to IL-4 overexpressing MSCs alone. Overexpression of PDGF-BB together with IL-4 mitigates the inhibitory effect of IL-4 on osteogenesis by IL-4 overexpressing MSCS. PDGF-BB and IL-4 overexpressing MSCs may be a potential strategy to facilitate osteogenesis in scenarios of both acute and chronic inflammation.
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DOI：
10.1002/stem.2060
发表时间：
2015-09
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Hung BP;Hutton DL;Kozielski KL;Bishop CJ;Naved B;Green JJ;Caplan AI;Gimble JM;Dorafshar AH;Grayson WL
通讯作者：
Grayson WL
影响因子：
5.4
作者：
Fischer, JE;Johnson, JE;Graham, BS
通讯作者：
Graham, BS
影响因子：
9.7
作者：
Lin TH;Pajarinen J;Sato T;Loi F;Fan C;Córdova LA;Nabeshima A;Gibon E;Zhang R;Yao Z;Goodman SB
通讯作者：
Goodman SB
影响因子：
2.8
作者：
CAPLAN, AI
通讯作者：
CAPLAN, AI
影响因子：
4.6
作者：
Nathan, K.;Lu, L. Y.;Goodman, S. B.
通讯作者：
Goodman, S. B.