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HIF‐1α promotes bone marrow stromal cell migration to the injury site and enhances functional recovery after spinal cord injury in rats
Author(s) -
Han Xiaoguang,
Chen Yong,
Liu Yajun,
Wang Zhuo,
Tang Guoqing,
Tian Wei
Publication year - 2018
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3062
Subject(s) - neurotrophin 3 , spinal cord injury , neurotrophic factors , stromal cell , neun , brain derived neurotrophic factor , medicine , bone marrow , spinal cord , neurotrophin , pathology , immunohistochemistry , receptor , psychiatry
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.