Efficacy and safety of intrathecal human umbilical cord-derived mesenchymal stromal cell therapy for bone cancer pain: a preclinical study.

BACKGROUND: Bone cancer pain (BCP) is a severe complication in patients with advanced cancer, for which current therapies remain inadequate and often lead to significant adverse effects. Mesenchymal stromal cell (MSC)-based therapy has recently emerged as a promising strategy for pain management. However, the safety profile of MSC therapy for BCP treatment has not yet been verified in preclinical studies. METHODS: In this study, clinical-grade human umbilical cord-derived MSCs (hUC-MSCs) at doses of 1 × 10⁶ or 4 × 10⁶ were administered intrathecally to BCP rats to evaluate analgesic efficacy, acute toxicity, and in vivo biodistribution. Additional assessments in nude mice investigated the tumorigenicity and tumor-promoting potential of hUC-MSCs. RESULTS: Intrathecal administration of hUC-MSCs effectively alleviated mechanical allodynia, heat hyperalgesia, spontaneous flinching, and gait abnormalities in BCP rats, while attenuating hyperactivation of neurons and glial cells in the spinal dorsal horn. The higher dose of 4 × 10⁶ hUC-MSCs demonstrated superior analgesic efficacy compared to the 1 × 10⁶ dose. Importantly, comprehensive safety evaluations confirmed a favorable preclinical safety profile for intrathecal hUC-MSC administration, demonstrating absence of acute toxicity, restricted distribution, and no tumorigenicity or tumor-promoting potential. CONCLUSIONS: Intrathecal hUC-MSC therapy demonstrates marked analgesic efficacy and a favorable safety profile in BCP, showing strong potential for clinical translation. This preclinical study provides compelling evidence to support future clinical trials and therapeutic applications of hUC-MSC therapy for BCP.