Immortalized Bone Mesenchymal Stromal Cells With Inducible Galanin Expression Produce Controllable Pain Relief in...

Area of Science:

• Regenerative Medicine
• Neuroscience
• Pharmacology

Background:

• Chronic pain management remains a significant clinical challenge.
• Human telomerase reverse transcriptase-immortalized bone marrow mesenchymal stromal cells (hTERT-BMSCs) offer a potential cell-based therapy.
• Inducible galanin (GAL) expression in hTERT-BMSCs presents a controllable approach for pain relief.

Purpose of the Study:

• To evaluate the feasibility of hTERT-BMSCs engineered for doxycycline (Dox)-inducible GAL secretion for controllable pain relief.
• To investigate the analgesic effects and underlying mechanisms of these modified cells in a rat model of neuropathic pain.

Main Methods:

• Neuropathic pain was induced in rats via spared nerve injury.
• hTERT-BMSCs engineered with Tet-on/GAL system were transplanted into the subarachnoid space.
• Analgesic effects were assessed using behavioral tests, and GAL levels, receptor expression, and signaling pathways were analyzed.

Main Results:

• Transplanted hTERT-BMSCs/Tet-on/GAL cells significantly alleviated mechanical allodynia and thermal hyperalgesia without causing motor deficits.
• The analgesic effects were reversible by a GAL receptor antagonist and controllable via Dox induction.
• Cerebrospinal fluid GAL levels and spinal Galanin Receptor 1 (GalR1) expression correlated with Dox administration, while spinal protein kinase Mζ (PKMζ) expression was inhibited.

Conclusions:

• Inducible GAL release from transplanted hTERT-BMSCs provides controllable pain relief in neuropathic rats.
• The mechanism involves inhibition of PKMζ activation and activation of GalR1, not GalR2.
• This study presents a promising stem cell-based strategy for chronic pain therapy.