Polycaprolactone electrospun mesh conjugated with an MSC affinity peptide for MSC homing in vivo

CD90型 间充质干细胞 体内 材料科学 聚己内酯 归巢(生物学) 生物医学工程 CD44细胞 体外 化学 细胞生物学 生物化学 医学 生物 复合材料 生物技术 聚合物 生态学
作者
Zhenxing Shao,Xin Zhang,Yanbin Pi,Xiaokun Wang,Zhuqing Jia,Jingxian Zhu,Linghui Dai,Wenqing Chen,Ling Yin,Haifeng Chen,Chunyan Zhou,Yingfang Ao
出处
期刊:Biomaterials [Elsevier]
卷期号:33 (12): 3375-3387 被引量:153
标识
DOI:10.1016/j.biomaterials.2012.01.033
摘要

Mesenchymal stem cell (MSC) is a promising cell source candidate in tissue engineering (TE) and regenerative medicine . However, the inability to target MSCs in tissues of interest with high efficiency and engraftment has become a significant barrier for MSC-based therapies. The mobilization and transfer of MSCs to defective/damaged sites in tissues or organs in vivo with high efficacy and efficiency has been a major concern. In the present study, we identified a peptide sequence (E7) with seven amino acids through phage display technology, which has a high specific affinity to bone marrow-derived MSCs. Subsequent analysis suggested that the peptide could efficiently interact specifically with MSCs without any species specificity. Thereafter, E7 was covalently conjugated onto polycaprolactone (PCL) electrospun meshes to construct an “MSC-homing device” for the recruitment of MSCs both in vitro and in vivo. The E7-conjugated PCL electrospun meshes were implanted into a cartilage defect site of rat knee joints, combined with a microfracture procedure to mobilize the endogenous MSCs. After 7 d of implantation, immunofluorescence staining showed that the cells grown into the E7-conjugated PCL electrospun meshes yielded a high positive rate for specific MSC surface markers (CD44, CD90 , and CD105) compared with those in arginine-glycine-aspartic acid (RGD)-conjugated PCL electrospun meshes (63.67% vs. 3.03%; 59.37% vs. 2.98%; and 61.45% vs. 3.82%, respectively). Furthermore, the percentage of CD68 positive cells in the E7-conjugated PCL electrospun meshes was much lower than that in the RGD-conjugated PCL electrospun meshes (5.57% vs. 53.43%). This result indicates that E7-conjugated PCL electrospun meshes absorb much less inflammatory cells in vivo than RGD-conjugated PCL electrospun meshes. The results of the present study suggest that the identified E7 peptide sequence has a high specific affinity to MSCs. Covalently conjugating this peptide on the synthetic PCL mesh significantly enhanced the MSC recruitment of PCL in vivo. This method provides a wide range of potential applications in TE.
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