Combined mesenchymal and neural stem cell therapy enhances neurological recovery in cerebral infarction

Abstract

BACKGROUND

Acute cerebral infarction (ACI), a leading cause of death and disability, causes brain ischemia due to vessel blockage. Current time-limited interventions, such as clot removal, often fail to restore full function. Neurorestoration is vital, but complicated. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) promote angiogenesis and neuroprotection. Stem cell therapy has potential to promote neurorestoration. Specifically, neural stem cells (NSC) reconstruct neural tissue, while mesenchymal stem cells (MSCs) provide support and secrete beneficial factors. Combining NSCs and MSCs in stem cell therapy may synergistically enhance ACI recovery, potentially via the regulation of VEGF and bFGF. However, the mechanisms underlying this combined approach remain unclear.

AIM

To investigate the therapeutic effect of combined NSC and MSC transplantation on neurological recovery and bFGF/VEGF expression in ACI patients.

METHODS

This study enrolled 156 patients with ACI treated from June 2022 to June 2023. Patients were randomly assigned to two groups: The control group (n = 78) received conventional drug therapy, while the observation group (n = 78) received conventional therapy and combined NSC and MSC transplantation. The following outcomes were compared between groups: National Institutes of Health Stroke Scale (NIHSS) score, Barthel index, cerebral perfusion and diffusion on magnetic resonance imaging, serum bFGF and VEGF levels, clinical efficacy, and adverse events.

RESULTS

Serum VEGF and bFGF levels negatively correlated with NIHSS scores in patients with ACI (r = -0.388, r = -0.239; P < 0.05). The observation group (NSC and MSC) showed a significantly higher clinical efficacy of treatment than the controls (85.9% vs 69.2%; P < 0.05). Both groups showed improved cerebral perfusion, increased Barthel index, and decreased NIHSS scores post-treatment (P < 0.05), with significantly greater improvements in the observation group. Serum VEGF and bFGF levels increased significantly in both groups (P < 0.05), but were higher in the observation group. Adverse events in the observation group (transient fever: 4 cases; agitation: 1 case; headache: 2 cases) were mild and resolved with symptomatic treatment. Six-month follow-up revealed no abnormalities in magnetic resonance imaging, electrocardiogram, or blood tests.

CONCLUSION

NSC-MSC combination therapy enhances neurological function and cerebral perfusion in patients with ACI by upregulating VEGF and bFGF expression, demonstrating favorable clinical efficacy and safety.

Keywords: Acute cerebral infarction; Neural stem cells; Mesenchymal stem cells; Vascular endothelial growth factor; Basic fibroblast growth factor; Neurological function

Core Tip: Combination therapy with neural stem cell (NSC) and mesenchymal stem cell (MSC) promotes neurological recovery in patients with acute cerebral infarction (ACI) by modulating vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression, thereby enhancing cerebral perfusion, daily living capacity, and neurological function scores. This study validated the efficacy and safety of NSC/MSC stem cell combination therapy, and systematically elucidated the mechanistic roles of VEGF and bFGF in the NSC-MSC-mediated treatment of ACI. These findings further demonstrate the central regulatory roles of VEGF and bFGF in angiogenesis and neural repair, thereby advancing the application of precision medicine in ACI treatment, and providing a robust theoretical foundation and future directions for clinical translation.