# Multilineage differentiating stress-enduring cells alleviate neuropathic pain in mice through TGF-β and IL-10-dependent anti-inflammatory signaling

## TL;DR

Multilineage-differentiating stress-enduring (Muse) cells reduce neuropathic pain in mice by suppressing inflammation through TGF-β and IL-10.

## Contribution

Muse cells show superior analgesic effects compared to BMSCs via TGF-β and IL-10-dependent anti-inflammatory mechanisms.

## Key findings

- Muse cells effectively reduce neuropathic pain in mouse models better than low-dose BMSCs.
- Muse cells inhibit spinal cord neuroinflammation via TGF-β and IL-10 secretion.
- Muse cells migrate to injured dorsal root ganglion via the CCR7–CCL21 chemotactic axis.

## Abstract

Neuropathic pain is a chronic condition characterized by damage to and dysfunction of the peripheral or central nervous system. There are currently no effective treatment options available for neuropathic pain, and existing drugs often provide only temporary relief with potential side effects. Multilineage-differentiating stress-enduring (Muse) cells are characterized by high expansion potential, a stable phenotype and strong immunosuppression. These properties make them attractive candidates for therapeutics for neuropathic pain management. Muse cells from different species demonstrated analgesic potential by reversing chronic constriction injury model (CCI)-induced neuropathic pain. Protein profiling revealed a high degree of similarity between Muse cells and bone marrow stromal cells (BMSCs). The intrathecal injection of Muse cells effectively reduced neuropathic pain in various mouse models, resulting in better analgesic effects than the administration of equivalent low doses of BMSCs. Immunohistochemical analysis and quantitative real-time PCR revealed the ability of Muse cells to inhibit spinal cord neuroinflammation caused by spared nerve injury model. In addition, Transwell and ELISA revealed that Muse cells migrated through the injured dorsal root ganglion via the CCR7–CCL21 chemotactic axis. In addition, the secretion of transforming growth factor-beta (TGF-β) and interleukin 10 (IL-10) by Muse cells was identified as the mechanism underlying the analgesic effect of Muse cells. The capacity of Muse cells to mitigate neuroinflammation and produce analgesic effects via the modulation of TGF-β and IL-10 underscores their potential as promising therapeutic approaches for the treatment of neuropathic pain.