Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.
Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.
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在啮齿动物模型中使用胎儿定向胎盘注射的免疫耐受性诱导：鼠模型。
DOI：
10.1371/journal.pone.0123712
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kimura T
中科院分区：
文献类型：
--
作者：
Takahashi K;Endo M;Miyoshi T;Tsuritani M;Shimazu Y;Hosoda H;Saga K;Tamai K;Flake AW;Yoshimatsu J;Kimura T
免疫应答的诱导是遗传性蛋白质缺乏症的替代疗法中的主要问题。子宫内产生的耐受性有助于产后治疗。在这项研究中，我们的目的是诱导免疫耐受的外源蛋白与早期妊娠细胞移植到绒毛膜绒毛超声引导下在小鼠模型。将妊娠第10天的妊娠C57 BL/6（B6）小鼠麻醉并通过高分辨率超声成像。小鼠胚胎及其胎盘被定位以在B模式下获得迷路的清晰视图，其相当于人类的绒毛膜绒毛。将来自B6-绿色荧光蛋白（B6 GFP）转基因小鼠的骨髓细胞（BMC）用玻璃微毛细管移液器注射到胎盘的胎儿侧，包括迷路。每只胎鼠接受2x 105个活GFP-BMC。出生后，我们评估了针对GFP的体液和细胞介导的免疫应答。将骨髓移植到胎盘胎侧可有效地将供体细胞分布到胎鼠体内。手术存活率为13.5%（5/37）。出生后6周，在所有受体小鼠（5/5）中观察到B6-GFP供体皮肤移植物的成功植入。抗GFP抗体的诱导被完全抑制。ELISPOT检测抑制了胸腺细胞对携带GFP的细胞的细胞毒性免疫反应。在这项研究中，我们利用早期妊娠胎盘注射针对小鼠胎儿，转移供体细胞携带外源蛋白进入胎儿循环。这种方法足以诱导针对外源蛋白的体液和细胞介导的免疫耐受。
Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transplantation into the chorionic villi under ultrasound guidance in the murine model. Pregnant C57BL/6 (B6) mice on day 10 of gestation were anesthetized and imaged by high resolution ultrasound. Murine embryos and their placenta were positioned to get a clear view in B-mode with power mode of the labyrinth, which is the equivalent of chorionic villi in the human. Bone marrow cells (BMCs) from B6-Green Fluorescence Protein (B6GFP) transgenic mice were injected into the fetal side of the placenta which includes the labyrinth with glass microcapillary pipettes. Each fetal mouse received 2 x 105 viable GFP-BMCs. After birth, we evaluated the humoral and cell-mediated immune response against GFP. Bone marrow transfer into fetal side of placenta efficiently distributed donor cells to the fetal mice. The survival rate of this procedure was 13.5%(5 out of 37). Successful engraftment of the B6-GFP donor skin grafts was observed in all recipient (5 out of 5) mice 6 weeks after birth. Induction of anti-GFP antibodies was completely inhibited. Cytotoxic immune reactivity of thymic cells against cells harboring GFP was suppressed by ELISPOT assay. In this study, we utilized early gestational placental injection targeting the murine fetus, to transfer donor cells carrying a foreign protein into the fetal circulation. This approach is sufficient to induce both humoral and cell-mediated immune tolerance against the foreign protein.
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DOI：
10.1016/j.bpobgyn.2012.06.005
发表时间：
2012-10-01
影响因子：
5.5
作者：
Mattar, Citra N.;Biswas, Arijit;Chan, Jerry K. Y.
通讯作者：
Chan, Jerry K. Y.
影响因子：
20.3
作者：
Peranteau, William H.;Endo, Masayuki;Flake, Alan W.
通讯作者：
Flake, Alan W.
影响因子：
4.4
作者：
Soper, BW;Lessard, MD;Barker, JE
通讯作者：
Barker, JE
影响因子：
12.4
作者：
Endoh, M;Koibuchi, N;Kaneda, Y
通讯作者：
Kaneda, Y
DOI：
10.1073/pnas.76.11.5736
发表时间：
1979-01-01
影响因子：
11.1
作者：
FLEISCHMAN, RA;MINTZ, B
通讯作者：
MINTZ, B