纤维蛋白基质为移植到损伤脊髓中的骨髓基质细胞提供了合适的支架:一种用于中枢神经系统组织工程的新型材料。

Fibrin matrix provides a suitable scaffold for bone marrow stromal cells transplanted into injured spinal cord: a novel material for CNS tissue engineering.

作者信息

Itosaka Hiroyuki, Kuroda Satoshi, Shichinohe Hideo, Yasuda Hiroshi, Yano Shunsuke, Kamei Shintaro, Kawamura Ryoichi, Hida Kazutoshi, Iwasaki Yoshinobu

机构信息

Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

出版信息

Neuropathology. 2009 Jun;29(3):248-57. doi: 10.1111/j.1440-1789.2008.00971.x. Epub 2008 Oct 20.

Abstract

Recent basic experiments have strongly suggested that cell transplantation therapy may promote functional recovery in patients with spinal cord injury (SCI). However, a safe and efficient transplantation technique still remains undetermined. This study, therefore, was aimed to clarify whether fibrin matrix could be a useful scaffold in bone marrow stromal cell (BMSC) transplantation for the injured spinal cord. To clarify the issue, three-dimensional structure of fibrin matrix was assessed and the green fluorescent protein (GFP)-expressing BMSC were cultured in fibrin matrix. The rats were subjected to spinal cord hemisection at T8 level, and the vehicle, BMSC or BMSC-fibrin matrix construct was implanted into the cavity. Neurologic function was serially evaluated. Using immunohistochemistry, we evaluated the survival, migration and differentiation of the transplanted cells at 4 weeks after transplantation. In the initial in vitro study, the BMSC could survive in fibrin matrix for 2 weeks. The animals treated with the BMSC-fibrin matrix construct showed significantly more pronounced recovery of neurologic function than vehicle- or BMSC-treated animals. Fibrin scaffold markedly improved the survival and migration of the transplanted cells. There was no significant difference in the percentage of cells doubly positive for GFP and microtubule-associated protein 2 between the animals treated with BMSC-fibrin matrix construct and those treated with BMSC, but a certain subpopulation of GFP-positive cells morphologically simulated the neurons in the animals treated with BMSC-fibrin matrix construct. These findings strongly suggest that fibrin matrix may be one of the promising candidates for a potential, minimally invasive scaffold for injured spinal cord, and that such strategy of tissue engineering could be a hopeful option in regeneration therapy for patients with SCI.

摘要

近期的基础实验有力地表明,细胞移植疗法可能促进脊髓损伤(SCI)患者的功能恢复。然而,一种安全有效的移植技术仍未确定。因此,本研究旨在阐明纤维蛋白基质是否可作为骨髓基质细胞(BMSC)移植到损伤脊髓中的有用支架。为阐明该问题,评估了纤维蛋白基质的三维结构,并将表达绿色荧光蛋白(GFP)的BMSC培养于纤维蛋白基质中。对大鼠进行T8水平的脊髓半切术,然后将赋形剂、BMSC或BMSC - 纤维蛋白基质构建体植入空洞中。对神经功能进行连续评估。使用免疫组织化学方法,我们在移植后4周评估了移植细胞的存活、迁移和分化情况。在最初的体外研究中,BMSC可在纤维蛋白基质中存活2周。接受BMSC - 纤维蛋白基质构建体治疗的动物,其神经功能恢复明显优于接受赋形剂或BMSC治疗的动物。纤维蛋白支架显著改善了移植细胞的存活和迁移。接受BMSC - 纤维蛋白基质构建体治疗的动物与接受BMSC治疗的动物相比,GFP和微管相关蛋白2双阳性细胞的百分比无显著差异,但在接受BMSC - 纤维蛋白基质构建体治疗的动物中,一定亚群的GFP阳性细胞在形态上模拟了神经元。这些发现有力地表明,纤维蛋白基质可能是用于损伤脊髓的潜在微创支架的有前景的候选者之一,并且这种组织工程策略可能是SCI患者再生治疗中一个有希望的选择。

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