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食蟹猴子宫同种异体移植:非人灵长类动物模型的初步经验

Uterus allotransplantation in cynomolgus macaque: a preliminary experience with non-human primate models.

作者信息

Kisu Iori, Mihara Makoto, Banno Kouji, Hara Hisako, Masugi Yohei, Araki Jun, Iida Takuya, Yamada Yohei, Kato Yojiro, Shiina Takashi, Suganuma Nobuhiko, Aoki Daisuke

机构信息

Department of Obstetrics and Gynecology, Keio University, Tokyo, Japan.

出版信息

J Obstet Gynaecol Res. 2014 Apr;40(4):907-18. doi: 10.1111/jog.12302. Epub 2014 Feb 26.

DOI:10.1111/jog.12302
PMID:24612366
Abstract

AIM

Uterine transplantation (UTx) is a potential option for child-bearing in women with uterine infertility. Recovery of uterine function after allogeneic UTx in non-human primates has not been reported. The objective of this study is to establish the functional uterine transplant model in non-human primates.

METHODS

Uteri of two cynomolgus monkeys were simultaneously removed, cooled at 4°C and perfused with heparin saline. The uteri were interchanged with each other and then orthotopically transplanted. Immunosuppressive protocols included use of three agents (tacrolimus, mycophenolate mofetil and methylprednisolone) in case 1 and two agents (tacrolimus and methylprednisolone) in case 2. Transabdominal ultrasonography, vaginoscopy and biopsy of the transplanted uterine cervix were routinely conducted to monitor rejection after surgery.

RESULTS

The blood concentration of tacrolimus decreased 11 days after surgery and evidence of rejection was found in biopsy of the uterine cervix in both cases. The suspected rejection disappeared 23 days after surgery in case 1 and temporary menstruation resumed at 3 months after surgery. In case 2, blood flow to the uterine artery gradually decreased and the uterus resulted in atrophy due to ischemia, which has been triggered by rejection.

CONCLUSION

Allogeneic UTx in the cynomolgus monkeys resulted in temporary recovery of menstruation with three immunosuppressants and uterine atrophy with two immunosuppressants. This preliminary experience suggests that recovery of uterine function after allogeneic UTx in non-human primates is possible but more experiments are required.

摘要

目的

子宫移植(UTx)是子宫性不孕女性生育的一种潜在选择。非人灵长类动物同种异体子宫移植后子宫功能的恢复情况尚未见报道。本研究的目的是建立非人灵长类动物功能性子宫移植模型。

方法

同时切除两只食蟹猴的子宫,在4℃下冷却并用肝素盐水灌注。将子宫相互交换后进行原位移植。免疫抑制方案在病例1中包括使用三种药物(他克莫司、霉酚酸酯和甲泼尼龙),在病例2中包括使用两种药物(他克莫司和甲泼尼龙)。术后常规进行经腹超声检查、阴道镜检查及移植子宫宫颈活检以监测排斥反应。

结果

术后11天他克莫司血药浓度下降,两例子宫颈活检均发现排斥反应证据。病例1术后23天疑似排斥反应消失,术后3个月恢复短暂月经。病例2中,子宫动脉血流逐渐减少,子宫因排斥反应引发的缺血而萎缩。

结论

食蟹猴同种异体子宫移植使用三种免疫抑制剂时月经有短暂恢复,使用两种免疫抑制剂时子宫发生萎缩。这一初步经验表明,非人灵长类动物同种异体子宫移植后子宫功能有可能恢复,但还需要更多实验。

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