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在体治疗脊髓脊膜膨出的胎盘间充质基质细胞 - 为临床试验做准备选择最佳细胞系。

In utero treatment of myelomeningocele with placental mesenchymal stromal cells - Selection of an optimal cell line in preparation for clinical trials.

机构信息

University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA.

University of California-Davis, 4625 2nd Ave, Suite 3005, Sacramento, CA 95817, USA; Shriners Hospitals for Children Northern California, 2425 Stockton Blvd, Sacramento, CA 95817, USA.

出版信息

J Pediatr Surg. 2020 Sep;55(9):1941-1946. doi: 10.1016/j.jpedsurg.2019.09.029. Epub 2019 Oct 21.

DOI:10.1016/j.jpedsurg.2019.09.029
PMID:31672407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7170747/
Abstract

BACKGROUND

We determined whether in vitro potency assays inform which placental mesenchymal stromal cell (PMSC) lines produce high rates of ambulation following in utero treatment of myelomeningocele in an ovine model.

METHODS

PMSC lines were created following explant culture of three early-gestation human placentas. In vitro neuroprotection was assessed with a neuronal apoptosis model. In vivo, myelomeningocele defects were created in 28 fetuses and repaired with PMSCs at 3 × 10 cells/cm of scaffold from Line A (n = 6), Line B (n = 7) and Line C (n = 5) and compared to no PMSCs (n = 10). Ambulation was scored as ≥13 on the Sheep Locomotor Rating Scale.

RESULTS

In vitro, Line A and B had higher neuroprotective capability than no PMSCs (1.7 and 1.8 respectively vs 1, p = 0.02, ANOVA). In vivo, Line A and B had higher large neuron densities than no PMSCs (25.2 and 27.9 respectively vs 4.8, p = 0.03, ANOVA). Line C did not have higher neuroprotection or larger neuron density than no PMSCs. In vivo, Line A and B had ambulation rates of 83% and 71%, respectively, compared to 60% with Line C and 20% with no PMSCs.

CONCLUSION

The in vitro neuroprotection assay will facilitate selection of optimal PMSC lines for clinical use.

LEVEL OF EVIDENCE

n/a.

TYPE OF STUDY

Basic science.

摘要

背景

我们旨在确定体外效力测定是否能预测哪种胎盘间充质基质细胞(PMSC)系在羊膜内治疗脊髓脊膜膨出的模型中能提高运动能力。

方法

通过对三个早期妊娠胎盘进行外植体培养来创建 PMSC 系。用神经元凋亡模型评估体外神经保护作用。在体内,在 28 个胎儿中创建脊髓脊膜膨出缺陷,并使用来自 Line A(n=6)、Line B(n=7)和 Line C(n=5)的 PMSC 修复,细胞密度为 3×10 细胞/cm 支架,与不使用 PMSC 修复(n=10)进行比较。将运动能力评分≥13 分作为羊运动评分量表的评分标准。

结果

在体外,Line A 和 Line B 的神经保护能力均高于无 PMSC(分别为 1.7 和 1.8 比 1,p=0.02,ANOVA)。在体内,Line A 和 Line B 的大神经元密度均高于无 PMSC(分别为 25.2 和 27.9 比 4.8,p=0.03,ANOVA)。Line C 的神经保护或更大神经元密度均不如无 PMSC。在体内,Line A 和 Line B 的运动能力分别为 83%和 71%,而 Line C 为 60%,无 PMSC 为 20%。

结论

体外神经保护测定将有助于选择用于临床的最佳 PMSC 系。

证据水平

无。

研究类型

基础科学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6f/7170747/744bc69c9868/nihms-1577025-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6f/7170747/7e7c556713f9/nihms-1577025-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6f/7170747/d036e5279701/nihms-1577025-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6f/7170747/263835c94b55/nihms-1577025-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6f/7170747/9d3b3b2fea5b/nihms-1577025-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6f/7170747/744bc69c9868/nihms-1577025-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6f/7170747/7e7c556713f9/nihms-1577025-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6f/7170747/d036e5279701/nihms-1577025-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6f/7170747/263835c94b55/nihms-1577025-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6f/7170747/9d3b3b2fea5b/nihms-1577025-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6f/7170747/744bc69c9868/nihms-1577025-f0005.jpg

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3
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Stem Cell Res Ther. 2024 Nov 20;15(1):444. doi: 10.1186/s13287-024-03991-y.
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The Placenta as a Source of Human Material for Neuronal Repair.胎盘作为用于神经元修复的人类材料来源。
Biomedicines. 2024 Jul 15;12(7):1567. doi: 10.3390/biomedicines12071567.
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