Safety and efficacy of human umbilical cord-derived mesenchymal stromal cells in fetal ovine myelomeningocele repair.

IF 7.1 2区 医学 Q1 CELL & TISSUE ENGINEERING
Yoann Athiel, Laura Cariot, Jean-Marie Jouannic, Corentin Maillet, Vincent Mauffré, Clovis Adam, Hélène Huet, Jérôme Larghero, Justine Nasone, Lucie Guilbaud
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Abstract

Background: The aim of this study was to assess the safety and efficacy of human umbilical cord mesenchymal stromal cells (hUC-MSCs) patch used as an adjuvant therapy in fetal myelomeningocele (MMC) surgery in the ovine model.

Methods: hUC-MSCs were isolated from human umbilical cords (UC) using the explant method, cultured and characterized. hUC-MSCs were then embedded in a fibrin patch. MMC were surgically created at 75 days of gestation and repaired at 89 days of gestation in sheep fetuses. Two groups were compared: the hUC-MSCs group in which MMC was repaired using a cellular patch and the control group, in which MMC was repaired using an acellular patch. Safety was evaluated by clinical ewes' monitoring during gestation, and clinical and histological examinations of lambs after birth. Efficacy was assessed by clinical neurological evaluation at 2 and 24 h of life using the sheep locomotor rating scale and by histological analyses.

Results: Among the 17 operated lambs, nine were born alive: six in the hUC-MSCs group and three in the control group. Overall fetal loss was 47% (8/17) without differences between the two groups. No fever was reported in ewes. No tumors were detected in clinical and histological examinations in the lambs. At 24 h of life, mean Sheep Locomotor Rating score was higher in the hUC-MSCs group than in the control group: 15.0 versus 2.0 (p = 0.07). Histological analyses showed a higher large neurons density in the hUC-MSCs group in comparison with the control group: 9.9 versus 6.3/mm2 of gray matter (p = 0.04). Lambs in the hUC-MSCs group had lower fibrosis around the spinal cord and at the level of the MMC scar: 70.9 versus 253.7 μm (p = 0.10) and 691.3 versus 1684.4 μm (p = 0,18), respectively.

Conclusions: Ovine fetal repair of MMC using human UC-MSCs seems to be an effective and safe procedure.

人类脐带间充质基质细胞在胎儿绵羊骨髓膜缺损修复中的安全性和有效性。
研究背景本研究旨在评估人脐带间充质基质细胞(hUC-MSCs)补片在绵羊模型中作为胎儿骨髓脊膜膨出(MMC)手术辅助疗法的安全性和有效性。绵羊胎儿在妊娠 75 天时通过手术形成 MMC,并在妊娠 89 天时进行修复。两组绵羊胎儿进行了比较:使用细胞补片修复 MMC 的 hUC 间充质干细胞组和使用无细胞补片修复 MMC 的对照组。安全性通过对妊娠期母羊的临床监测以及羔羊出生后的临床和组织学检查进行评估。疗效通过羔羊出生后 2 小时和 24 小时的临床神经评估(使用绵羊运动评分量表)和组织学分析进行评估:结果:在 17 只接受手术的羔羊中,有 9 只活了下来,其中 6 只在 hUC 间充质干细胞组,3 只在对照组。胎儿总损失率为 47%(8/17),两组之间无差异。母羊没有发烧报告。羔羊的临床和组织学检查均未发现肿瘤。出生 24 小时后,hUC-间充质干细胞组的绵羊运动能力平均评分高于对照组:15.0 对 2.0(p = 0.07)。组织学分析显示,hUC-间充质干细胞组的大神经元密度高于对照组:9.9 对 6.3/mm2(p = 0.04)。hUC-间充质干细胞组羔羊脊髓周围和MMC瘢痕水平的纤维化程度较低:分别为70.9对253.7 μm(p = 0.10)和691.3对1684.4 μm(p = 0.18):结论:利用人体 UC 间充质干细胞修复脐带间充质干细胞似乎是一种有效而安全的方法。
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来源期刊
Stem Cell Research & Therapy
Stem Cell Research & Therapy CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
13.20
自引率
8.00%
发文量
525
审稿时长
1 months
期刊介绍: Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.
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