What question did this study set out to answer?

The aim is to explore the effects of NT-3 modified BMSCs and PCL scaffolds on muscle atrophy post sciatic nerve injury in rats.

January 24, 20260 citations

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Neurotrophin-3 modified bone marrow mesenchymal stem cells combined with polycaprolactone scaffold can treat denervation-induced muscle atrophy in rats by regulating FasL.

RTR H TianQingdao University CZC X ZhengQingdao University

Key Points

The aim is to explore the effects of NT-3 modified BMSCs and PCL scaffolds on muscle atrophy post sciatic nerve injury in rats.
Developed an SNI rat model to test therapeutic efficacy.
Utilized serial SFI measurements for functional recovery assessment.
Performed histopathological analyses for nerve and muscle evaluation.
Employed RT-qPCR and Western blot to study molecular mechanisms.
Investigated the role of FasL expression in therapeutic outcomes.
BMSCs and NT-3 modified PCL scaffolds improved peripheral nerve recovery.
Muscle preservation and regeneration were significantly enhanced.
FasL expression decreased following the composite treatment.
The combined approach demonstrated superior neurorestorative effects compared to individual treatments.
Lentiviral overexpression of FasL negated the therapeutic benefits.

Abstract

We investigated the effects and mechanisms of neurotrophin-3 (NT-3)-modified bone marrow mesenchymal stem cells (BMSCs) combined with a polycaprolactone (PCL) scaffold to repair denervation-induced muscle atrophy following sciatic nerve injury (SNI) in rats. An established SNI rat model was utilized to evaluate the therapeutic efficacy of BMSCs, pcDNA3.1-NT-3, and NT-3-modified BMSCs scaffold complexes. Functional recovery of peripheral nerves was assessed through serial sciatic functional index (SFI) measurements. Histopathological analyses evaluated nerve regeneration and gastrocnemius muscle preservation, complemented by quantification of muscle wet weight and fiber cross-sectional area. Molecular mechanisms were investigated via RT-qPCR and Western blot to determine expression profiles of NT-3, FasL, Cleaved Caspase-3, Bcl-2, and Bax. Both individual and combined applications of BMSCs and pcDNA3.1-NT-3 composite PCL scaffolds demonstrated therapeutic efficacy in ameliorating SNI, enhancing nerve regeneration, and restoring neurological function while attenuating denervation-induced skeletal muscle atrophy. The combinatorial BMSCs/pcDNA3.1-NT-3 intervention exhibited superior neurorestorative effects through synergistic mechanisms, suggesting clinical potential for optimizing functional recovery in peripheral nerve injury (PNI) patients. Notably, SNI rats exhibited upregulated FasL expression in neuromuscular tissues, which was significantly suppressed following BMSCs/pcDNA3.1-NT-3 scaffold treatment. Lentiviral-mediated FasL overexpression (Lv-FasL) abolished the therapeutic benefits of the composite scaffold, confirming FasL's critical role in mediating these neuroprotective effects. We found out that NT-3 modified BMSCs combined with PCL scaffolds promoted nerve regeneration, repaired nerve function, and inhibited skeletal muscle atrophy in rats after sciatic nerve injury by regulating FasL expression.

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Cite This Study

Tian et al. (Thu,) studied this question.

synapsesocial.com/papers/69746187bb9d90c67120b6bc https://doi.org/https://doi.org/10.26402/jpp.2025.6.03

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