The migration and differentiation of hUC-MSCsCXCR4/GFP encapsulated in BDNF/chitosan scaffolds for brain tissue engineering

The migration and differentiation of hUC-MSCsCXCR4/GFP encapsulated in BDNF/chitosan scaffolds for brain tissue engineering
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脑组织工程中 BDNF/壳聚糖支架封装的 hUC-MSCsCXCR4/GFP 的迁移和分化

DOI:
10.1088/1748-6041/11/3/035004
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发表时间:
2016-06-01
影响因子:
4
通讯作者:
Shi, Wei
Shi, Wei
中科院分区:
工程技术3区
文献类型:
--
作者:
Huang, Chuanjun;Zhao, Longxiang;Shi, Wei

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我们以前开发了一种生物材料支架,可以有效地提供种子细胞到创伤性脑损伤造成的病变腔。然而,我们随后发现,很少有移植的人脐带间充质干细胞(hUC-MSCs)能够从支架迁移到病变边界。基质衍生细胞因子-1 α及其受体趋化因子(C-X-C基序)受体(CXCR)4是控制细胞迁移和干细胞募集到靶区域的趋化因子。鉴于hUC-MSC膜上CXCR 4的低表达水平,使用慢病毒载体来产生稳定表达与绿色荧光蛋白(GFP)融合的CXCR 4的hUC-MSC(hUC-MSCsCXCR 4/GFP)。我们构建了一个支架,其中重组人脑源性神经营养因子(BDNF)连接到壳聚糖支架与交联剂京尼平(CGB支架)。将含有hUC-MSCsCXCR 4/GFP的支架移植到大鼠脑损伤腔中,向损伤边界和腔提供外源性hUC-MSC。这些结果证明了一种新的策略,用于诱导创伤性脑损伤后的组织再生。
We previously developed a biomaterial scaffold that could effectively provide seed cells to a lesion cavity resulting from traumatic brain injury. However, we subsequently found that few transplanted human umbilical cord mesenchymal stem cells (hUC-MSCs) are able to migrate from the scaffold to the lesion boundary. Stromal derived-cell factor-1 alpha and its receptor chemokine (C-X-C motif) receptor (CXCR) 4 are chemotactic factors that control cell migration and stem cell recruitment to target areas. Given the low expression level of CXCR4 on the hUC-MSC membrane, lentiviral vectors were used to generate hUC-MSCs stably expressing CXCR4 fused to green fluorescent protein (GFP) (hUC-MSCsCXCR4/GFP). We constructed a scaffold in which recombinant human brain-derived neurotrophic factor (BDNF) was linked to chitosan scaffolds with the crosslinking agent genipin (CGB scaffold). The scaffold containing hUC-MSCsCXCR4/GFP was transplanted into the lesion cavity of a rat brain, providing exogenous hUC-MSCs to both lesion boundary and cavity. These results demonstrate a novel strategy for inducing tissue regeneration after traumatic brain injury.