Scholarlink

Background: <p>Peripheral nerve injuries are a major clinical challenge because of their complex nature and limited regenerative capacity. This study aimed to improve peripheral nerve regeneration using Wharton’s jelly mesenchymal stem cells (WJ-MSCs) engineered to express brain-derived neurotrophic factor (BDNF) via a baculovirus (BV) vector. The cells were evaluated for efficacy when seeded into acellular nerve grafts (ANGs) in a rat sciatic nerve defect model.</p> Methods: <p>WJ-MSCs were transfected with recombinant BV to upregulate BDNF expression. Conditioned medium (CM) from these cells was utilized to treat Schwann cells (SCs), and the impact on myelination-related markers, including KROX20, myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein β (S100β), and the activation of the mammalian target of rapamycin (mTOR)/ protein kinase B (AKT)/p38 signaling pathways were evaluated. <i>In vivo</i>, BDNF-expressing WJ-MSCs were seeded into ANGs and implanted into a rat sciatic nerve defect model. Functional recovery was evaluated via video gait analysis, isometric tetanic force measurement, muscle weight evaluation, ankle contracture angle measurement, and histological analysis using toluidine blue staining.</p> Results: <p>BDNF expression was significantly upregulated in WJ-MSCs post-transfection. BDNF-MSC CM substantially promoted the expression of myelination markers in SCs and activated the mTOR/AKT/p38 signaling pathway. In the rat model, seeding of ANGs with BDNF-expressing WJ-MSCs resulted in improved functional outcomes, including enhanced toe-off angles, increased isometric tetanic force, greater muscle weight recovery, and a higher total number of myelinated axons compared with controls.</p> Conclusion: <p>WJ-MSCs engineered to express BDNF significantly enhanced peripheral nerve regeneration when utilized in conjunction with ANGs. These findings indicate BDNF-expressing WJ-MSCs are a promising therapeutic approach for treating peripheral nerve injuries.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Mesenchymal Stem Cells Expressing Baculovirus-Engineered Brain-Derived Neurotrophic Factor Improve Peripheral Nerve Regeneration in a Rat Model

  • 期刊论文

  • 发表日期：

    2025年2月17日

查看全文
  • Won Sun Lee,
  • Soon Jin Choi,
  • Young Ho Shin,
  • Jae Kwang Kim

摘要

Background:

Peripheral nerve injuries are a major clinical challenge because of their complex nature and limited regenerative capacity. This study aimed to improve peripheral nerve regeneration using Wharton’s jelly mesenchymal stem cells (WJ-MSCs) engineered to express brain-derived neurotrophic factor (BDNF) via a baculovirus (BV) vector. The cells were evaluated for efficacy when seeded into acellular nerve grafts (ANGs) in a rat sciatic nerve defect model.

Methods:

WJ-MSCs were transfected with recombinant BV to upregulate BDNF expression. Conditioned medium (CM) from these cells was utilized to treat Schwann cells (SCs), and the impact on myelination-related markers, including KROX20, myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein β (S100β), and the activation of the mammalian target of rapamycin (mTOR)/ protein kinase B (AKT)/p38 signaling pathways were evaluated. In vivo, BDNF-expressing WJ-MSCs were seeded into ANGs and implanted into a rat sciatic nerve defect model. Functional recovery was evaluated via video gait analysis, isometric tetanic force measurement, muscle weight evaluation, ankle contracture angle measurement, and histological analysis using toluidine blue staining.

Results:

BDNF expression was significantly upregulated in WJ-MSCs post-transfection. BDNF-MSC CM substantially promoted the expression of myelination markers in SCs and activated the mTOR/AKT/p38 signaling pathway. In the rat model, seeding of ANGs with BDNF-expressing WJ-MSCs resulted in improved functional outcomes, including enhanced toe-off angles, increased isometric tetanic force, greater muscle weight recovery, and a higher total number of myelinated axons compared with controls.

Conclusion:

WJ-MSCs engineered to express BDNF significantly enhanced peripheral nerve regeneration when utilized in conjunction with ANGs. These findings indicate BDNF-expressing WJ-MSCs are a promising therapeutic approach for treating peripheral nerve injuries.