The Effect of Umbilical Cord Blood Cells on Outcomes After Experimental Traumatic Spinal Cord Injury

The Effect of Umbilical Cord Blood Cells on Outcomes After Experimental Traumatic Spinal Cord Injury
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DOI:
10.1097/brs.0b013e3181c3e963
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发表时间:
2010-07-15
期刊:
影响因子:
3
通讯作者:
Casper, Robert F.
Casper, Robert F.
中科院分区:
医学2区
文献类型:
--
作者:
Chua, Shawn J.;Bielecki, Ryszard;Casper, Robert F.

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研究设计.产生了脐带血(UCB)来源的多能干细胞(MPSC)的细胞因子表达谱。然后,我们将MPSCs移植到脊髓损伤(SCI)的大鼠模型中,并评估神经功能和脊髓组织学。为了确定MPSC移植到急性SCI大鼠模型中是否会产生有益的神经学效应。脐带血条件培养液含有促进内源性神经组织愈合的因子。以前,我们的实验室已经证明UCB造血细胞可以发育成能够分化成包括少突胶质细胞样细胞在内的多种细胞类型的MPSC。我们使用成纤维细胞生长因子4、干细胞因子和fms样酪氨酸激酶受体-3配体补充的无血清培养基从UCB细胞培养MPSCs。使用细胞因子抗体阵列,我们产生了MPSC的细胞因子表达谱。然后,我们将MPSC移植到免疫抑制的SCI大鼠模型中,并通过Basso,Beattie和Bresnahan运动试验每周评估神经功能,持续6周。对脊髓进行组织学检查并量化病变面积。我们检测到MPSC条件培养基中细胞因子和生长因子水平升高,具有已知的神经保护、血管生成和抗炎作用。与仅接受载体的组相比,用MPSC治疗的SCI大鼠在6周后显示出Basso、Beattie和Bresnahan评分的显著改善。免疫组织化学显示,移植的人细胞在1周后存在于损伤的脊髓中,但在6周时不再存在。治疗组大鼠的病灶大小有小于对照组的趋势。结论。我们的结论是,脐带MPSCs改善急性SCI大鼠的神经功能,可能是通过释放减少继发性损伤的因子。
Study Design. A cytokine expression profile of umbilical cord blood (UCB) derived multipotential stem cells (MPSC) was produced. We then transplanted MPSCs into a rat model of spinal cord injury (SCI) and assessed neurologic function as well as spinal cord histology.Objective. To determine if MPSCs transplanted into a rat model of acute SCI would lead to a beneficial neurologic effect.Summary of Background Data. Conditioned medium from UCB contains factors that could promote healing of endogenous neural tissues. Previously, our laboratory has demonstrated that UCB hematopoietic cells can develop into MPSCs capable of differentiating into multiple cell types including oligodendrocyte-like cells.Methods. We cultured MPSCs from UCB cells using fibroblast growth factor 4, stem cell factor and fms-like tyrosine kinase receptor-3 ligand supplemented serum-free medium. Using a cytokine antibody array, we produced a cytokines expression profile of MPSCs. We then transplanted MPSCs into an immunosuppressed rat model of SCI and assessed neurologic function weekly for 6 weeks by the Basso, Beattie, and Bresnahan locomotor test. The spinal cords were examined histologically and lesion areas quantified.Results. We detected elevated levels of cytokines and growth factors with known neuroprotective, angiogenic, and anti-inflammatory effects in the MPSC conditioned media. The SCI rats treated with MPSCs showed a significant improvement in Basso, Beattie, and Bresnahan scores after 6 weeks compared with the group that received vehicle only. Immunohistochemistry revealed transplanted human cells were present in the injured spinal cord after 1 week, but were no longer present by 6 weeks. There was a trend for the lesion size in treated rats to be smaller than that of the control group.Conclusion. We conclude that UCB MPSCs improve neurologic function of rats with acute SCI, possibly by the release of factors that reduce secondary injury.