PTX-3 Secreted by Intra-Articular-Injected SMUP-Cells Reduces Pain in an Osteoarthritis Rat Model

Cells. 2021 Sep 14;10(9):2420. doi: 10.3390/cells10092420.


Mesenchymal stem cells (MSCs) are accessible, abundantly available, and capable of regenerating; they have the potential to be developed as therapeutic agents for diseases. However, concerns remain in their further application. In this study, we developed a SMall cell+Ultra Potent+Scale UP cell (SMUP-Cell) platform to improve whole-cell processing, including manufacturing bioreactors and xeno-free solutions for commercialization. To confirm the superiority of SMUP-Cell improvements, we demonstrated that a molecule secreted by SMUP-Cells is capable of polarizing inflammatory macrophages (M1) into their anti-inflammatory phenotype (M2) at the site of injury in a pain-associated osteoarthritis (OA) model. Lipopolysaccharide-stimulated macrophages co-cultured with SMUP-Cells expressed low levels of M1-phenotype markers (CD11b, tumor necrosis factor-α, interleukin-1α, and interleukin-6), but high levels of M2 markers (CD163 and arginase-1). To identify the paracrine action underlying the anti-inflammatory effect of SMUP-Cells, we employed a cytokine array and detected increased levels of pentraxin-related protein-3 (PTX-3). Additionally, PTX-3 mRNA silencing was applied to confirm PTX-3 function. PTX-3 silencing in SMUP-Cells significantly decreased their therapeutic effects against monosodium iodoacetate (MIA)-induced OA. Thus, PTX-3 expression in injected SMUP-Cells, applied as a therapeutic strategy, reduced pain in an OA model.

Keywords: PTX-3; SMUP-Cells; bioreactor; cell therapy; macrophage polarization; mesenchymal stem cells; osteoarthritis; pain relief.

MeSH terms

  • Animals
  • C-Reactive Protein / metabolism*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / therapy
  • Injections, Intra-Articular
  • Iodoacetic Acid / toxicity
  • Macrophage Activation / immunology
  • Macrophages / immunology*
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology*
  • Osteoarthritis / chemically induced
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Osteoarthritis / therapy*
  • Osteocytes / cytology*
  • Pain / etiology
  • Pain / metabolism
  • Pain / pathology
  • Pain / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Serum Amyloid P-Component / metabolism*


  • Cytokines
  • Serum Amyloid P-Component
  • PTX3 protein
  • C-Reactive Protein
  • Iodoacetic Acid