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脊髓修复的细胞治疗:优化生物支架以提高人骨髓基质细胞的存活和神经分化能力。

Cell therapy for spinal cord repair: optimization of biologic scaffolds for survival and neural differentiation of human bone marrow stromal cells.

机构信息

Neuroscience Research Unit of Surgical Research Service, Hospital Puerta de Hierro-Majadahonda, Madrid, Spain.

出版信息

Cytotherapy. 2010 Jul;12(4):522-37. doi: 10.3109/14653241003615164.

DOI:10.3109/14653241003615164
PMID:20465485
Abstract

BACKGROUND AIMS

The suppression of cell apoptosis using a biodegradable scaffold to replace the missing or altered extracellular matrix (ECM) could increase the survival of transplanted cells and thus increase the effectiveness of cell therapy.

METHODS

We studied the best conditions for the proliferation and differentiation of human bone marrow stromal cells (hBMSC) when cultured on different biologic scaffolds derived from fibrin and blood plasma, and analyzed the best concentrations of fibrinogen, thrombin and calcium chloride for favoring cell survival. The induction of neural differentiation of hBMSC was done by adding to these scaffolds different growth factors, such as nerve growth factor (NGF), brain-derived-neurotrophic factor (BDNF) and retinoic acid (RA), at concentrations of 100 ng/mL (NGF and BDNF) and 1 micro/mL (RA), over 7 days.

RESULTS

Although both types of scaffold allowed survival and neural differentiation of hBMSC, the results showed a clear superiority of platelet-rich plasma (PRP) scaffolds, mainly after BDNF administration, allowing most of the hBMSC to survive and differentiate into a neural phenotype.

CONCLUSIONS

Given that clinical trials for spinal cord injury using hBMSC are starting, these findings may have important clinical applications.

摘要

背景目的

使用可生物降解的支架来抑制细胞凋亡,以替代缺失或改变的细胞外基质(ECM),可以增加移植细胞的存活率,从而提高细胞治疗的效果。

方法

我们研究了人骨髓基质细胞(hBMSC)在不同的纤维蛋白和血浆衍生的生物支架上培养时增殖和分化的最佳条件,并分析了纤维蛋白原、凝血酶和氯化钙的最佳浓度,以有利于细胞存活。通过在这些支架上添加不同的生长因子,如神经生长因子(NGF)、脑源性神经营养因子(BDNF)和维甲酸(RA),诱导 hBMSC 向神经分化,浓度为 100ng/mL(NGF 和 BDNF)和 1μg/mL(RA),持续 7 天。

结果

尽管两种支架都允许 hBMSC 的存活和神经分化,但结果显示富含血小板的血浆(PRP)支架具有明显的优势,特别是在给予 BDNF 后,大多数 hBMSC 得以存活并分化为神经表型。

结论

鉴于使用 hBMSC 进行脊髓损伤的临床试验即将开始,这些发现可能具有重要的临床应用价值。

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