Kabagambe Sandra, Keller Benjamin, Becker James, Goodman Laura, Pivetti Christopher, Lankford Lee, Chung Karen, Lee Chelsey, Chen Y Julia, Kumar Priyadarsini, Vanover Melissa, Wang Aijun, Farmer Diana
University of California, Davis Health, Sacramento, CA.
University of California, Davis Health, Sacramento, CA.
J Pediatr Surg. 2017 Oct 12. doi: 10.1016/j.jpedsurg.2017.10.032.
The purpose of this study was to investigate the effects of placental mesenchymal stromal cells (PMSCs) seeded on a clinical grade porcine small intestinal submucosa (SIS)-derived extracellular matrix (ECM) on hindlimb motor function in an ovine fetal repair model of myelomeningocele (MMC).
MMC defects were surgically created in 21 fetuses at median gestational age 78 (range 76-83) days. Fetuses were randomly assigned to repair 25days later with ECM only or PMSC-ECM. Surviving fetuses were delivered at term. Motor function was evaluated using the Sheep Locomotor Rating (SLR) scale (0-15). Histologic analysis of the spinal cord (SC) was completed.
Fetal viability was 71%. 5 of 8 (63%) lambs repaired with PMSC-ECM ambulated independently versus only 1 of 6 (17%) repaired with ECM only (p=0.04, χ test). SLR scores and large neuron densities were higher in the PMSC-ECM group. The cross-sectional areas of the SC and the gray matter were equally preserved.
Fetal repair of MMC with PMSCs seeded on SIS-ECM improves hindlimb motor function in lambs. Using ECM helps to preserve the architecture of the SC, but adding PMSCs improves the lamb's ability to walk and increases large neuron density. Clinical studies are needed to show benefits in humans.
LEVELS OF EVIDENCE/TYPE OF STUDY: Basic Science.
本研究旨在探讨接种于临床级猪小肠黏膜下层（SIS）来源的细胞外基质（ECM）上的胎盘间充质基质细胞（PMSC）对脊柱裂（MMC）绵羊胎儿修复模型后肢运动功能的影响。
在21只孕龄中位数为78天（范围76 - 83天）的胎儿中手术制造MMC缺损。胎儿在25天后被随机分配接受仅ECM或PMSC - ECM修复。存活的胎儿足月分娩。使用绵羊运动评分（SLR）量表（0 - 15）评估运动功能。完成脊髓（SC）的组织学分析。
胎儿存活率为71%。8只接受PMSC - ECM修复的羔羊中有5只（63%）能独立行走，而仅接受ECM修复的6只羔羊中只有1只（17%）能独立行走（p = 0.04，χ检验）。PMSC - ECM组的SLR评分和大神经元密度更高。SC和灰质的横截面积得到同等程度的保留。
在SIS - ECM上接种PMSC对MMC进行胎儿修复可改善羔羊的后肢运动功能。使用ECM有助于保留SC的结构，但添加PMSC可提高羔羊的行走能力并增加大神经元密度。需要进行临床研究以证明对人类有益。
证据水平/研究类型：基础科学。
