Adipose-derived stem cells decrease pain in a rat model of oxaliplatin-induced neuropathy: Role of VEGF-A modulation

Area of Science:

• Neuroscience
• Regenerative Medicine
• Oncology

Background:

• Oxaliplatin chemotherapy for colorectal cancer causes dose-dependent neuropathic pain in 50% of patients.
• Current pharmacological treatments provide limited relief, necessitating novel therapeutic strategies.
• Mesenchymal stem cells (MSCs) and their secretome are explored for pain-relieving properties.

Purpose of the Study:

• To evaluate the efficacy of rat adipose stem cells (rASCs) and their secretome in a preclinical model of oxaliplatin-induced neuropathy.
• To investigate the role of vascular endothelial growth factor (VEGF) in oxaliplatin-induced neuropathic pain and its modulation by rASCs.

Main Methods:

• Administration of rASCs intravenously in a rat model of oxaliplatin-induced neuropathy.
• Assessment of pain hypersensitivity to mechanical stimuli.
• Analysis of VEGF-A and VEGF165b levels in plasma and spinal cord.
• Treatment with anti-VEGF-A antibody (bevacizumab) and anti-VEGF165b antibody.

Main Results:

• A single intravenous injection of rASCs significantly reduced mechanical hypersensitivity for 5 days.
• rASCs administration reverted increased plasma VEGF-A and spinal cord VEGF165b levels.
• Intrathecal bevacizumab and anti-VEGF165b antibody also reduced pain, indicating VEGF's pro-algesic role.

Conclusions:

• Adult adipose-derived MSCs demonstrate significant pain-relieving effects in oxaliplatin-induced neuropathy.
• VEGF-A regulation by MSCs is a key mechanism in mitigating chemotherapy-induced neuropathic pain.
• MSCs represent a promising novel therapeutic avenue for neuropathic pain management.