缺氧诱导因子-1α促进骨髓基质细胞向损伤部位迁移，并增强大鼠脊髓损伤后的功能恢复。

HIF-1α promotes bone marrow stromal cell migration to the injury site and enhances functional recovery after spinal cord injury in rats.

机构信息

Department of Spine Surgery, Beijing Jishuitan Hospital, Beijing, China.

Orthopedic Center, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, China.

出版信息

J Gene Med. 2018 Dec;20(12):e3062. doi: 10.1002/jgm.3062. Epub 2018 Dec 11.

DOI:10.1002/jgm.3062

PMID:30414229

Abstract

BACKGROUND

Spinal cord injury (SCI) is a severe health problem worldwide, and efficacious strategies to properly repair SCI have not yet been developed. Recently, gene and cell therapies as alternative treatments for SCI have been proposed to comprise safe and promising strategies.

METHODS

The present study investigated the therapeutic effects and underlying mechanisms of hypoxia-inducible factor-1α carried in recombinant adenovirus (Adv-HIF-1α), as administered immediately after SCI in adult rats.

RESULTS

Adv-HIF-1α-treated animals showed better functional recovery and smaller cavity volume than those in the vehicle-treated control group. Both the numbers of green fluorescent protein-labeled bone marrow stromal cells (GFP-BMSCs) and cells double-positive for GFP and a cell lineage marker (NeuN) in the injured spinal cord were larger in the Adv-HIF-1α-treated group. The expression levels of neurotrophins such as neurotrophin-3 and brain-derived neurotrophic factor were also higher in the Adv-HIF-1α-treated group.

CONCLUSIONS

Adv-HIF-1α improves functional recovery in rats with SCI, and the underlying mechanism may be related to the mobilization of BMSCs to the injured area and higher expression levels of neurotrophin-3 and brain-derived neurotrophic factor.

摘要

背景

脊髓损伤（SCI）是一个全球性的严重健康问题，尚未开发出能有效修复 SCI 的策略。最近，基因和细胞治疗作为 SCI 的替代治疗方法已被提出，作为安全且有前景的策略。

方法

本研究探讨了缺氧诱导因子-1α（HIF-1α）在重组腺病毒（Adv-HIF-1α）中的治疗作用及其潜在机制，在成年大鼠 SCI 后立即给予 Adv-HIF-1α。

结果

与对照组相比，Adv-HIF-1α 治疗的动物表现出更好的功能恢复和更小的空洞体积。在 Adv-HIF-1α 治疗组中，绿色荧光蛋白标记的骨髓基质细胞（GFP-BMSCs）和 GFP 与细胞谱系标志物（NeuN）双阳性的细胞数量更多。Adv-HIF-1α 治疗组中神经生长因子如神经营养因子-3 和脑源性神经营养因子的表达水平也更高。