M-Sec Overexpressed Stem Cells Growing Abundant Tunneling Nanotubes for Diverse Active Transferring.

Abstract

Stem cell-based therapy holds immense potential for treating patients with intractable diseases and injuries, while its benefit is often limited by the inefficient delivery of therapeutic actives. In this study, using mRNA analysis and validation, we discovered that the M-sec protein can interact with the Ral-exocyst pathway to induce tunneling nanotubes (TNTs) in stem cells, which could represent a pathway for the direct transfer of bioactive agents to damaged cells for therapeutic purposes. With this, we constructed a genetically engineered stem cell delivery system overexpressing M-sec (MSCs^M-sec), which forms abundant TNTs. We demonstrated that MSCs^M-sec enabled selective, direct, and efficient delivery of diverse actives to various types of damaged recipient cells via TNT transport channels. Based on these features, we verified MSCs^M-sec mediated codelivery of mitochondria and cerium oxide nanozymes to impaired chondrocytes in osteoarthritis, which restored cell function and produced strong protection against the pathological progression of osteoarthritis. We believe that MSCs^M-sec offer a universal platform for the delivery of therapeutic actives in the treatment of diverse diseases.