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水凝胶携带的人骨髓基质细胞异种移植意外地在大鼠脊髓损伤的功能恢复中发挥了重要作用。

The hetero-transplantation of human bone marrow stromal cells carried by hydrogel unexpectedly demonstrates a significant role in the functional recovery in the injured spinal cord of rats.

作者信息

Li Yanbin, Yu Hao, Huang Hua, Guo Muyao, Hua Rongrong, Jiang Fenjun, Zhang Kaihua, Li Hailong, Wang Fei, Li Lusheng, Cui FuZhai, An Yihua

机构信息

Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.

Beijing Di Tan Hospital, Capital Medical University, Beijing 100050, China.

出版信息

Brain Res. 2016 Mar 1;1634:21-33. doi: 10.1016/j.brainres.2015.10.038. Epub 2015 Oct 30.

Abstract

Spinal cord injury (SCI) often causes a disturbance in the microenvironment in the lesion site resulting in sudden loss of sensory and motor function. Transplantation of stem cells provides a promising strategy in the treatment of SCI. But limited growth and immunological incompatibility of the stem cells with the host limits the application of this strategy. In order to get better survival and integration with the host, we employed a hyaluronic acid (HA) based scaffold covalently modified by poly-l-Lysine (PLL) as a vehicle to deliver the human bone marrow stromal cells (BMSCs) to the injured spinal cord of rats. The BMSCs were chosen as an ideal candidate for its advantage of low expression of major histocompatibility complex II. The data unexpectedly showed that the hetero-transplanted cells survived well in the lesion site even at 8 weeks post injury. Both the immunofluorescent and the electrophysiological assay indicated better survival of the transplanted cells and improved axonal growth in SCI rats transplanted with BMSCs in HA-PLL in contrast to the groups without either BMSCs or the HA scaffold transplantation. These promotions may account for the functional recovery assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale in the HA-PLL seeded with BMSCs group. These data suggests that hetero-transplantation of human BMSCs delivered by HA scaffold demonstrates a significant role in the functional recovery in the injured spinal cord of rats.

摘要

脊髓损伤(SCI)常导致损伤部位的微环境紊乱,从而致使感觉和运动功能突然丧失。干细胞移植为脊髓损伤的治疗提供了一种有前景的策略。但干细胞有限的生长能力以及与宿主的免疫不相容性限制了该策略的应用。为了使干细胞更好地存活并与宿主整合,我们采用了一种由聚赖氨酸(PLL)共价修饰的基于透明质酸(HA)的支架作为载体,将人骨髓基质细胞(BMSCs)输送到大鼠受损脊髓。由于主要组织相容性复合体II低表达的优势,BMSCs被选为理想的候选细胞。数据意外地显示,即使在损伤后8周,异种移植细胞在损伤部位仍存活良好。免疫荧光和电生理检测均表明,与未进行BMSCs或HA支架移植的组相比,在HA-PLL中移植BMSCs的SCI大鼠中,移植细胞存活更好,轴突生长得到改善。这些促进作用可能是通过Basso-Beattie-Bresnahan(BBB)运动评分量表评估的BMSCs接种于HA-PLL组功能恢复的原因。这些数据表明,由HA支架递送的人BMSCs异种移植在大鼠受损脊髓的功能恢复中发挥了重要作用。

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