類器官transplantation通過L-蘋果酸介導(dǎo)的M2型巨噬細(xì)胞極化減輕小鼠腸道缺血/再灌注損傷

中文摘要：

腸道類器官transplantation是一種治療黏膜損傷的有前景的療法。然而，移植的類器官如何調(diào)節(jié)受體小鼠的免疫微環(huán)境，以及它們?cè)谥委熌c道缺血-再灌注（I/R）損傷中的作用仍然不清楚。在這里，我們建立了一種將腸道類器官transplantation到腸道I/R小鼠的方法。我們發(fā)現(xiàn)移植能夠改善小鼠的生存率，促進(jìn)腸道干細(xì)胞的自我更新，并調(diào)節(jié)腸道I/R后的免疫微環(huán)境，這取決于巨噬細(xì)胞極化為抗炎性M2表型的增強(qiáng)能力。具體來說，我們報(bào)告L-蘋果酸（MA）在移植小鼠的類器官衍生條件培養(yǎng)基和盲腸內(nèi)容物中表達(dá)量高且富集，證明類器官在移植過程中分泌MA。體內(nèi)和體外實(shí)驗(yàn)都表明，MA誘導(dǎo)M2巨噬細(xì)胞極化，并以SOCS2依賴的方式恢復(fù)白細(xì)胞介素-10水平。這項(xiàng)研究為腸道I/R損傷提供了一種治療策略。

英文摘要：

Intestinal organoid transplantation is a promising therapy for the treatment of mucosal injury. However, how the transplanted organoids regulate the immune microenvironment of recipient mice and their role in treating intestinal ischemia-reperfusion (I/R) injury remains unclear. Here, we establish a method for transplanting intestinal organoids into intestinal I/R mice. We find that transplantation improve mouse survival, promote self-renewal of intestinal stem cells and regulate the immune microenvironment after intestinal I/R, depending on the enhanced ability of macrophages polarized to an anti-inflammatory M2 phenotype. Specifically, we report that L-Malic acid (MA) is highly expressed and enriched in the organoids-derived conditioned medium and cecal contents of transplanted mice, demonstrating that organoids secrete MA during engraftment. Both in vivo and in vitro experiments demonstrate that MA induces M2 macrophage polarization and restores interleukin-10 levels in a SOCS2-dependent manner. This study provides a therapeutic strategy for intestinal I/R injury.

論文信息：

論文題目：Organoids transplantation attenuates intestinal ischemia/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization

期刊名稱：Nature Communications

時(shí)間期卷：14, Article number: 6779 (2023)

在線時(shí)間：2023年10月25日

DOI：doi.org/10.1038/s41467-023-42502-0

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 and Control Liposomes

辦事處：Target Technology(靶點(diǎn)科技)

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除腸道巨噬細(xì)胞，在腸道缺血再灌注的炎性模型中單核巨噬細(xì)胞功能研究，荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：類器官transplantation通過L-蘋果酸介導(dǎo)的M2型巨噬細(xì)胞極化減輕小鼠腸道缺血/再灌注損傷

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

Depletion of intestinal macrophages

Two hundred microliters of clodronate- or PBS-loaded liposomes (CP-005-005, LIPOSOMA, Groningen, The Netherlands) were intravenously injected into mice thrice on alternating days prior to intestinal I/R to deplete intestinal macrophages.

材料和方法文獻(xiàn)截圖：