Stem Cell Biotechnologies, U976 et Centre d'Investigation Clinique en Biothérapies CIC-BT CBT501, INSERM, Paris, France.
Department of Fetal Medicine, APHP, Trousseau Hospital, DMU ORIGYNE, Sorbonne University, Paris, France.
Stem Cell Res Ther. 2022 Jul 15;13(1):300. doi: 10.1186/s13287-022-02991-0.
Myelomeningocele (MMC) is a spinal cord congenital defect that leads to paraplegia, sphincter disorders and potential neurocognitive disabilities. Prenatal surgery of MMC provides a significant benefit compared to surgery at birth. Mesenchymal stromal cell (MSC) therapy as an adjuvant treatment for prenatal surgery showed promising results in animal experiments which could be considered for clinical use in human fetuses. Despite numerous reassuring studies on the safety of MSCs administration in humans, no study focused on MSCs biodistribution after a local MSCs graft on the fetal spinal cord.
The purpose of our study was to assess the biodistribution of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) at birth in lambs who had a prenatal myelomeningocele repair using a fibrin patch seeded with allogenic UC-MSCs.
After isolation, UC-MSCs were tagged using a green fluorescent protein (GFP)-containing lentiviral vector. MMC defects were surgically created at 75 days of gestation and repaired 15 days later using UC-MSCs patch. Lambs were delivered at 142 days and sacrificed. DNA extraction was performed among biopsies of the different organs and q-PCR analysis was used to detect the expression of GFP (GFP DNA coding sequence).
In our 6 surviving lambs grafted with UC-MSCs, GFP lentivirus genomic DNA was not detected in the organs.
These reassuring data will support translational application in humans, especially since the first human clinical trial using mesenchymal stromal cells for in-utero treatment of MMC started recently in U.S.A.
脊髓脊膜膨出（MMC）是一种脊髓先天性缺陷，可导致截瘫、括约肌功能障碍和潜在的神经认知障碍。与出生后手术相比，产前手术对 MMC 有显著益处。间充质基质细胞（MSC）治疗作为产前手术的辅助治疗，在动物实验中显示出良好的效果，这可以考虑用于人类胎儿的临床应用。尽管有大量关于 MSC 给药在人体安全性的令人放心的研究，但没有研究关注在胎儿脊髓局部 MSC 移植物后 MSC 的生物分布。
我们的研究目的是评估在使用纤维蛋白贴片接种同种异体脐带间充质基质细胞（UC-MSCs）修复产前脊髓脊膜膨出的羔羊中，出生时 UC-MSCs 的生物分布。
UC-MSCs 分离后，使用含有绿色荧光蛋白（GFP）的慢病毒载体进行标记。在妊娠 75 天时，在 MMC 缺陷处进行手术，并在 15 天后使用 UC-MSCs 贴片进行修复。在妊娠 142 天时分娩并进行安乐死。对不同器官的活检进行 DNA 提取，并使用 q-PCR 分析检测 GFP 的表达（GFP DNA 编码序列）。
在我们的 6 只接受 UC-MSCs 移植的存活羔羊中，未在器官中检测到 GFP 慢病毒基因组 DNA。
这些令人放心的数据将支持在人体中的转化应用，特别是因为最近在美国开始了首例使用间充质基质细胞对 MMC 进行宫内治疗的人类临床试验。
