Service de médecine foetale, DMU ORIGYN, APHP, Hôpital Trousseau, Sorbonne Université, Paris, France.
Unité de Thérapie Cellulaire, Université Paris Cité, AP-HP, Hôpital Saint-Louis, U976 et CIC de Biothérapies, INSERM, Paris, France.
Stem Cell Res Ther. 2024 Nov 20;15(1):444. doi: 10.1186/s13287-024-03991-y.
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.
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.
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/mm 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.
Ovine fetal repair of MMC using human UC-MSCs seems to be an effective and safe procedure.
本研究旨在评估人脐带间充质干细胞(hUC-MSCs)贴剂作为辅助治疗在羊膜膨出(MMC)手术中的安全性和有效性。
采用组织块法分离人脐带(UC)中的 hUC-MSCs,进行培养和鉴定。然后将 hUC-MSCs 嵌入纤维蛋白贴片。在妊娠 75 天时在绵羊胎儿中创建 MMC,并在妊娠 89 天时进行修复。比较两组:用细胞贴片修复 MMC 的 hUC-MSCs 组和用无细胞贴片修复 MMC 的对照组。通过妊娠期间对母羊的临床监测以及出生后羔羊的临床和组织学检查来评估安全性。通过绵羊运动评分量表在出生后 2 小时和 24 小时进行临床神经评估以及组织学分析来评估疗效。
在 17 只接受手术的羔羊中,有 9 只出生存活:hUC-MSCs 组 6 只,对照组 3 只。总胎儿死亡率为 47%(8/17),两组之间无差异。母羊无发热。羔羊的临床和组织学检查均未发现肿瘤。出生后 24 小时,hUC-MSCs 组的绵羊运动评分中位数高于对照组:15.0 比 2.0(p=0.07)。组织学分析显示,hUC-MSCs 组的大神经元密度高于对照组:灰质 9.9 比 6.3/mm(p=0.04)。hUC-MSCs 组的羔羊脊髓周围和 MMC 瘢痕处的纤维化程度较低:70.9 比 253.7μm(p=0.10)和 691.3 比 1684.4μm(p=0.18)。
使用人 UC-MSCs 修复绵羊胎儿 MMC 似乎是一种有效且安全的方法。