Abstract
Background. This study aimed to investigate the use of human bone marrow mesenchymal stem cells (hBMSCs) genetically engineered with the human proenkephalin (hPPE) gene to treat bone cancer pain (BCP) in a rat model. Methods. Primary cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 × 106) were then intrathecally injected into a rat model of BCP. Paw mechanical withdrawal threshold (PMWT) was measured before and after BCP. The effects of hPPE gene transfer on hBMSC bioactivity were analyzed in vitro and in vivo. Results. No changes were observed in the surface phenotypes and differentiation of hBMSCs after gene transfer. The hPPE-hBMSC group showed improved PMWT values on the ipsilateral side of rats with BCP from day 12 postoperatively, and the analgesic effect was reversed by naloxone. The levels of proinflammatory cytokines such as IL-1β and IL-6 were ameliorated, and leucine-enkephalin (L-EK) secretion was augmented, in the hPPE-engineered hBMSC group. Conclusion. The intrathecal administration of BMSCs modified with the hPPE gene can effectively relieve pain caused by bone cancer in rats and might be a potentially therapeutic tool for cancer-related pain in humans.
Highlights
Cancer-related pain is extremely troubling for patients and for their families, often being one of the most burdensome symptoms experienced by cancer patients and severely influencing their quality of life
This study demonstrates the pain-relieving effect of the intrathecal injection of human bone marrow mesenchymal stem cells (hBMSCs) modified with the hPPE gene in a rat bone cancer model
A therapeutic transgene was expressed for an extended time in hBMSCs and induced the enhanced relief provided by L-EK ex vivo and in vivo
Summary
Cancer-related pain is extremely troubling for patients and for their families, often being one of the most burdensome symptoms experienced by cancer patients and severely influencing their quality of life. According to a recent systematic review, approximately 60% of advanced cancer patients suffer from severe cancer-related pain [1]. This study aimed to investigate the use of human bone marrow mesenchymal stem cells (hBMSCs) genetically engineered with the human proenkephalin (hPPE) gene to treat bone cancer pain (BCP) in a rat model. Primary cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 × 106) were intrathecally injected into a rat model of BCP. The hPPE-hBMSC group showed improved PMWT values on the ipsilateral side of rats with BCP from day 12 postoperatively, and the analgesic effect was reversed by naloxone. The intrathecal administration of BMSCs modified with the hPPE gene can effectively relieve pain caused by bone cancer in rats and might be a potentially therapeutic tool for cancer-related pain in humans
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