中文摘要：

盡管生長因子是再生醫(yī)學(xué)的核心功能分子，但遞送體系效果不佳、信號(hào)動(dòng)態(tài)調(diào)控機(jī)制尚不明確等問題，極大限制了其臨床應(yīng)用。本研究探究了促炎信號(hào)對生長因子再生修復(fù)能力的影響。通過小鼠骨再生模型研究發(fā)現(xiàn)，兩種具有臨床應(yīng)用價(jià)值的生長因子（BMP-2、PDGF-BB）的再生功能會(huì)受到白介素 - 1 受體（IL-1R1）的抑制。

英文摘要：

Although growth factors (GFs) are key molecules for regenerative medicine, their use has been limited by issues associated with suboptimal delivery systems and incomplete understanding of their signaling dynamics. Here, we explored how proinflammatory signals affect GF regenerative potential. Using bone regeneration in mouse, we found that the regenerative capacity of two clinically relevant GFs (BMP-2 and PDGF-BB) is impaired by interleukin-1 receptor (IL-1R1). Mechanistically, IL-1R1 activation in bone-forming cells desensitizes them to GFs and accelerates senescence. Moreover, administration of the GFs triggers IL-1 release by macrophages. To provide localized and sustained IL-1R1 inhibition, we engineered IL-1R antagonist (IL-1Ra) to bind the extracellular matrix (ECM) very strongly and demonstrate that codelivering GFs with ECM-binding IL-1Ra induces superior regeneration. Thus, we highlight that GF regenerative activity is hindered by proinflammatory signals, and GF-based therapies should integrate immunomodulation. Particularly, ECM-binding IL-1Ra holds clinical translational potential by enhancing efficacy of GF therapies.

論文信息：

論文題目：Enhancing the regenerative effectiveness of growth factors by local inhibition of interleukin-1 receptor signaling

期刊名稱：Science Advances

時(shí)間期卷：Vol 6, Issue24(2020)

在線時(shí)間：2020年6月12日

DOI: 10.1126/sciadv.aba76

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點(diǎn)科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除小鼠骨再生模型里巨噬細(xì)胞。荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見刊于Science Advances：通過局部抑制IL-1受體信號(hào)通路提升生長因子的再生修復(fù)效能。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)胞的材料和方法：

In vivo macrophage depletion

One day before surgery, 200 μl of clodronate liposomes (5 mg/ml) or empty liposomes (Liposoma) was intravenously injected in C57BL/6 mice (10 to 12 weeks old). An additional 200 μl of clodronate liposomes or empty liposomes were intraperitoneally injected every 2 days until day 6. Mouse spleens were harvested and crushed, and red blood cells were lysed with red blood cell lysis buffer [ammonium chloride (8.3 g/liter) and 10 mM tris-HCl in distilled water]. Macrophage depletion was verified by resuspending splenocytes in TruStain FcX anti-CD16/32 (1 μg/ml; clone 93, BioLegend) antibodies to block nonspecific binding and 1:500 dilution of Zombie Aqua (BioLegend) diluted in PBS. Subsequently, splenocytes were labeled with the following antibodies: anti-CD11b PE (1 μg/ml; clone M1/70, BioLegend), anti-Ly6G BV421 (1 μg/ml; clone 1A8, BioLegend), and anti-F4/80 biotin (3 μg/ml; clone REA126, Miltenyi Biotech) conjugated to streptavidin APC/Fire 750 (0.4 μg/ml; BioLegend) diluted in flow cytometry buffer (PBS with 1% BSA and 5 mM EDTA). Samples were acquired on a BD FACS Fortessa X20 and analyzed with FlowJo software (TreeStar Inc.).

巨噬細(xì)胞清除材料和方法文獻(xiàn)截圖：通過局部抑制IL-1受體信號(hào)通路提升生長因子的再生修復(fù)效能。