2. Academic Validation
  3. ShK-modified UCMSCs Inhibit M1-Like Macrophage Polarization and Alleviate Osteoarthritis Progression via PI3K/Akt Axis

ShK-modified UCMSCs Inhibit M1-Like Macrophage Polarization and Alleviate Osteoarthritis Progression via PI3K/Akt Axis

  • Adv Sci (Weinh). 2024 Dec 25:e2406822. doi: 10.1002/advs.202406822.
Wenshu Wu 1 2 3 4 5,  Xueying An 1 2 3 4 5,  Wang Gong 1 2 3 4 5,  Lin Yang 1 2 3 4 5 6,  Na Liu 1 2 3 4 5,  Bin Liu 1 2 3 4 5,  Baosheng Guo 1 2 3 4 5,  Qing Jiang 1 2 3 4 5 6,  Lan Li 1 2 3 4 5
Affiliations

Affiliations

  • 1 Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, P. R. China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, P. R. China.
  • 3 Branch of National Clinical Research Center for Orthopedics Sports Medicine and Rehabilitation, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, P. R. China.
  • 4 Institute of Medical 3D Printing, Nanjing University, Nanjing, 211166, P. R. China.
  • 5 Jiangsu Engineering Research Center for 3D Bioprinting, 321 Zhongshan Road, Nanjing, 210000, P. R. China.
  • 6 Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, 210008, P.R. China.
PMID: 39721037 DOI: 10.1002/advs.202406822
Abstract

The Potassium Channel Kv1.3 plays an important role in regulating immune cell functions in many inflammatory diseases whereas rarely in osteoarthritis (OA). Here, it is demonstrated that the Kv1.3 of macrophages is upregulated in response to LPS stimulation, as well as in human OA synovium samples than non-OA. Administration of Stichodactyla toxin (ShK), a Kv1.3 blocker, significantly inhibited cartilage degeneration and synovial inflammation in animal models of OA in vivo by inhibiting M1 macrophage polarization and reducing the production of inflammatory factors. In this study, a transgenically engineered human umbilical cord mesenchymal stem cell (UCMSC) delivery system is developed that secreted a peptide ShK, a Kv1.3 potassium blocker, into the knee articular cavity. Collectively, the results identified Kv1.3 as a potential therapeutic target for OA and demonstrated the efficacy of using ShK transgenic engineered UCMSCs as a delivery for the peptide in OA treatment.

Keywords

Kv1.3; Macrophage; Osteoarthritis; UCMSC.

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