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宫内生长受限(IUGR)作为羊膜腔内干细胞治疗的潜在靶点。

Intrauterine Growth Restriction (IUGR) as a potential target for transamniotic stem cell therapy.

机构信息

Department of Surgery, Boston Children's Hospital/Harvard Medical School, Boston, MA, United States of America.

Department of Surgery, Boston Children's Hospital/Harvard Medical School, Boston, MA, United States of America.

出版信息

J Pediatr Surg. 2022 Jun;57(6):999-1003. doi: 10.1016/j.jpedsurg.2022.01.062. Epub 2022 Feb 14.

DOI:10.1016/j.jpedsurg.2022.01.062
PMID:35277250
Abstract

BACKGROUND

We sought to determine whether intrauterine growth restriction (IUGR) could be a target for mesenchymal stem cell (MSC)-based transamniotic stem cell therapy (TRASCET).

METHODS

Pregnant dams subjected to hypoxia (10.5% O) cycles had their fetuses divided into four groups: untreated (n = 24) and three groups receiving volume-matched intra-amniotic injections of either saline (sham; n = 16), or suspensions of luciferase-labeled, syngeneic amniotic fluid-derived MSCs that were either native (TRASCET-unprimed; n = 29), or primed by exposure to IFNγ and IL-1β (TRASCET-primed; n = 31). Normal fetuses served as additional controls (n = 22). Multiple analyses were performed at term.

RESULTS

Compared to normal, fetal weights were significantly decreased in all hypoxia groups (p = 0.002 to <0.001), except for TRASCET-primed. Placental efficiency (fetal/placental weight) was significantly decreased in all hypoxia groups (p = 0.002 to <0.001), but normalized in both TRASCET groups. A significant increase in metrial expression of IFNγ in both the untreated and sham groups (p = 0.04 to 0.02) was reversed only in the TRASCET-primed group. Luciferase DNA was present in both TRASCET groups' placentas.

CONCLUSIONS

Transamniotic stem cell therapy with primed mesenchymal stem cells reverses some of the effects of intrauterine growth restriction in a rat model. Further study into this novel approach for the treatment of this disease is warranted.

LEVEL OF EVIDENCE

N/A (Animal and Laboratory Study).

摘要

背景

我们旨在确定宫内生长受限(IUGR)是否可以成为基于间充质干细胞(MSC)的经羊膜腔干细胞治疗(TRASCET)的靶点。

方法

将处于缺氧(10.5% O)循环中的孕鼠胎儿分为四组:未治疗组(n=24)和三组接受体积匹配的经羊膜腔内生理盐水(假手术;n=16)或荧光素酶标记的同种异体羊水衍生 MSC 混悬液注射,其分别为未预先处理(TRASCET-未预先处理;n=29)或预先用 IFNγ和 IL-1β处理(TRASCET-预先处理;n=31)。正常胎儿作为额外的对照组(n=22)。在足月时进行了多项分析。

结果

与正常胎儿相比,所有缺氧组的胎儿体重均显著降低(p=0.002 至 <0.001),除 TRASCET-预先处理组外。所有缺氧组的胎盘效率(胎儿/胎盘重量)均显著降低(p=0.002 至 <0.001),但在两个 TRASCET 组中均恢复正常。未治疗组和假手术组的蜕膜 IFNγ表达均显著增加(p=0.04 至 0.02),仅在 TRASCET-预先处理组中得到逆转。荧光素酶 DNA 存在于两个 TRASCET 组的胎盘组织中。

结论

用预先处理的间充质干细胞进行经羊膜腔干细胞治疗可逆转大鼠模型中宫内生长受限的一些影响。有必要进一步研究这种治疗这种疾病的新方法。

证据水平

无(动物和实验室研究)。

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