2. Academic Validation
  3. M-Sec Overexpressed Stem Cells Growing Abundant Tunneling Nanotubes for Diverse Active Transferring

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

  • ACS Nano. 2025 Aug 12;19(31):28644-28659. doi: 10.1021/acsnano.5c08001.
Junyi Che 1,  Yi Cheng 1,  Xiangyi Wu 1,  Zhuhao Wu 1,  Luoran Shang 2,  Yuanjin Zhao 1 3
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
  • 2 Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • 3 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China.
PMID: 40743507 DOI: 10.1021/acsnano.5c08001
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 (MSCsM-sec), which forms abundant TNTs. We demonstrated that MSCsM-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 MSCsM-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 MSCsM-sec offer a universal platform for the delivery of therapeutic actives in the treatment of diverse diseases.

Keywords

delivery system; genetic engineering; osteoarthritis; stem cell; tunneling nanotube.

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