Approach to develop a new treatment for patients with implantationfailure using peripheral blood mononuclear cells

利用外周血单核细胞开发治疗植入失败患者的新方法

• 批准号: 09671673
• 负责人: NAKAYAMA Takahiro
• 金额: $ 2.18万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671673/
• 关键词: implantation failure; endometrium; Peripheral blood mononuclear cell; BeWo cell; implantation; LIF; splenocyte; 着床障害; 不妊症; 体外受精-胚移植法; 胚; リンパ球; leukemia inhibitory factor

Systemic administration of splenocytes from ICR mice in the early stages of pregnancy promoted the receptivity of the uterus on pseudopregnant day 2. Splenocytes derived from pregnancy day 4 mice more effectively facilitated embryo implantation than splenocytes derived from pseudopregnancy day 4 and diestrous day 2 mice, suggesting that the presence of an embryo in the donor mice for splenocyte preparation is important for the effect of splenocytes on implantation. To investigate the effect of splenocytes on endometrial differentiation, the expression of LIFmRNA in the uterus was examined. In ovariectomized mice, administration of splenocytes from early pregnant mice induced the expression of LIFmRNA which was also observed with estradiol administration. Intra-endometrial injection of splenocytes from early pregnant mice also enhanced embryo implantation. These findings suggest that the effects of splenocytes from early pregnant mice on implantation are independent of the ovary, and di … More rectly facilitate endometrial differentiation. To estimate whether immune cells promote embryo implantation by direct action on embryos or not, we examined the effect of human peripheral blood mononuclear cells (PBMC) derived from early pregnant women on BeWo cell invasion and, outgrowth and invasion of murine blastocysts using in vitro invasion assay. PBMC promoted the invaded cell number of BeWo cells and facilitated outgrowth and invasion of murine blastocysts. Furthermore, the promoting effect of PBMC derived from non-pregnant women. These promotion effects on BeWo cells and murine blastocyst invasion could by induced by the coculture with r-hCG in PBMC derived from non-pregnant women, suggesting that the promoting effect of peripheral immune cells, which are observed in the presence of an embryo, is induced by hCG.Based on these results, we proposed a new treatment for implantation failure in which autologous peripheral immune cells pretreated with r-hCG are injected into the endometrium to facilitate endometrial defferentiation and embryo implantation in cases of implantation failure. Less

在妊娠早期全身给予ICR小鼠脾细胞可促进假孕第2天子宫的容受性。来自妊娠第4天小鼠的脾细胞比来自假孕第4天和间情第2天小鼠的脾细胞更有效地促进胚胎植入，这表明供体小鼠中胚胎的存在对于脾细胞对植入的影响是重要的。为了研究脾细胞对子宫内膜分化的影响，检测了子宫中LIFmRNA的表达。在卵巢切除的小鼠中，给予早孕小鼠的脾细胞诱导了LIFmRNA的表达，这在给予雌二醇时也观察到。子宫内膜内注射早孕小鼠脾细胞也能促进胚胎着床。这些研究结果表明，早孕小鼠脾细胞对着床的影响不依赖于卵巢，并且与胚胎着床有关。 ...更多信息 直接促进子宫内膜分化。为了探讨免疫细胞是否通过直接作用于胚胎而促进胚胎着床，我们采用体外侵袭实验检测了来自早孕妇女的人外周血单个核细胞（PBMC）对BeWo细胞侵袭以及小鼠囊胚生长和侵袭的影响。PBMC可促进BeWo细胞的侵袭，促进小鼠囊胚的生长和侵袭。此外，来自非妊娠妇女的PBMC的促进作用。这些对BeWo细胞和小鼠胚泡侵袭的促进作用可以通过与来自非妊娠妇女的PBMC中的r-hCG共培养来诱导，这表明在胚胎存在下观察到的外周免疫细胞的促进作用是由hCG诱导的。我们提出了一种新的治疗植入失败的方法，其中自体外周免疫细胞用R-在着床失败的情况下，将hCG注射到子宫内膜中以促进子宫内膜分化和胚胎着床。少

项目成果

Nakayama T, Fujiwara H, Yamada S, Tatsumi K, Honda T, Fujii S: "Clinical application of a new assisted hatching method using a piezo-micromanipulator for morphologically low-quality embryos in poor-prognosis infertile patients."Fertil Steril. 69. 784-788

Nakayama T、Fujiwara H、Yamada S、Tatsumi K、Honda T、Fujii S：“使用压电显微操作器对预后不良的不孕患者形态低质量胚胎进行新型辅助孵化方法的临床应用。”Fertil Steril。

Nakayama,T: "Clinical application of a new assisted hatching method using a piezo-micromanipulator for morphologically low-quality embryos in poor-prognosis infertile patients Fertil Steril in press." Fertility and Sterility. (in press).

Nakayama,T：“使用压电显微操作器的新型辅助孵化方法在预后不良的不孕症患者 Fertil Steril 中的形态低质量胚胎的临床应用正在出版。”

Yamada S, Fujiwara H, Ueda M, Honda T, Nkayama T, Higuchi T, Mori T, Maeda M: "A monoclonal antibody, HCL-2, raised against human luteal cells reacts with apolipoprotein-B and detects the uptake of low density lipoprotein by luteinizing granulosa cells."H

Yamada S、Fujiwara H、Ueda M、Honda T、Nkayama T、Higuchi T、Mori T、Maeda M：“针对人黄体细胞的单克隆抗体 HCL-2 与载脂蛋白 B 发生反应，并检测低密度脂蛋白的摄取

Nakayama,T: "A new assisted hatching technique using a piezo-micromanipulator." Fertility and Sterility. 69. 784-788 (1998)

Nakayama,T：“一种使用压电显微操作器的新辅助孵化技术。”

Fujita K: "Tymocytes promote embryoimplantation by regulating endometrial differentiation." Hum Reprod.(in press.).

Fujita K：“鼓室细胞通过调节子宫内膜分化来促进胚胎着床。”