Development of 3 dimensional in vitro models of bone infection (Immunobact)

AO Trauma
M Stoddart, S Zeiter, F Moriarty

Background

Staphylococcus aureus is a prominent pathogen in bone-related infections where it can form staphylococcal abscess communities (SACs). SACs are a dense population of S. aureus within a fibrin pseudocapsule and are implicated in fracture related infection. 

 

A+B: in vivo SACs have been characterized in mice infected with S. aureus and which had a femoral double osteotomy. Around the SAC (A, asterisk) there are cells that cannot reach the bacteria and are entrapped within an encapsulation (A, arrow heads). This encapsulation consisted of fibrin (B, violet) and contained alpha-smooth muscle actin (αSMA)- and F4/80-positive cells (B, yellow and green, respectively).C+D: an in vitro SAC model has been established that resembles in vivo SACs; they have a fibrin pseudocapsule and they are not affected by neutrophils nor antibiotics

 

Goal

To establish an in vitro SAC model that resembles in vivo SACs. 

  • Publication

    Hofstee MI, Riool M, Terjajevs I, Thompson K, Stoddart MJ, Richards RG, Zaat SAJ, Moriarty TF. 3-dimensional in vitro Staphylococcus aureus abscess communities display antibiotic tolerance and protection from neutrophil clearance. Infect Immun. 2020;epub Aug 17

    Hofstee MI, Muthukrishnan G, Atkins GJ, Riool M, Thompson K, Morgenstern M, Stoddart MJ, Richards RG, Zaat SAJ, Moriarty TF. Current Concepts of Osteomyelitis: From Pathologic Mechanisms to Advanced Research Methods. Am J Pathol. 2020 Jun;190(6):1151-1163.

    Hofstee MI, Riool M, Gieling F, Stenger V, Constant C, Nehrbass D, Zeiter S, Richards RG, Zaat SA, Moriarty TF. A murine Staphylococcus aureus fracture-related infection model characterised by fracture non-union, staphylococcal abscess communities and myeloid-derived suppressor cells. Eur Cell Mater. 2021;41:774-92

    Sabaté Brescó M, Berset CM, Zeiter S, Stanic B, Thompson K, Ziegler M, Richards RG, O'Mahony L, Moriarty TF. Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model. Biology Open. 2021;epub July 9. https://doi.org/10.1242/bio.057315

    Constant C, Moriarty TF, Arens D, Pugliese B, Zeiter S. Peri-anesthetic hypothermia in rodents: A factor to consider for accurate and reproducible outcomes in orthopedic device-related infection studies. J Orthop Res. 2022;epub Jun 18. https://doi.org/10.1002/jor.25397 

     

     

     

     

  • Presentation

    Hofstee M, Riool M, Thompson K, Zaat SAJ, Stoddart MJ, Richards RG, Moriarty TJ. "A novel 3-dimensional in vitro model for Staphylococcus aureus abscess communities", Maastricht, the Netherlands, 2-4 October 2019 (oral)

    Hofstee M, Riool M, Thompson K, Zaat SAJ, Stoddart MJ, Richards RG, Moriarty TF. "A novel 3-dimensional in vitro model for Staphylococcus aureus abscess communities", Davos, Switzerland, 26-28 June 2019 (poster)

    Hofstee M, Riool M, Thompson K, Zaat SAJ, Stoddart MJ, Richards RG, Moriarty TF. "A novel 3-dimensional multicellular in vitro model for Staphylococcus aureus microcolony interaction with neutrophils.", Davos, Switzerland, 6-9 April 2019 (poster)

     Hofstee M, Riool M, Terjajevs I, Thompson K, Stoddart M, Zaat SA, Moriarty TF.  3-dimensional in vitro Staphylococcus aureus abscess communities display antibiotic tolerance and protection from neutrophil clearance.  2020 GR forscht virtual (oral) 

    Hofstee MI, Riool M, Gieling F, Stenger V, Constant C, Nehrbass D, Heider A, Zeiter S, Richards RG, Zaat SAJ, Moriarty TF. Staphylococcus aureus abscess communities and myeloid-derived suppressor cells: in vivo and in vitro studies. 2021 WIRM digital (oral)

    Hofstee MI, Riool M, Terjajevs I, Thompson K, Stoddart MJ, Zaat SAJ, Moriarty T.F.  A 3-dimensional in vitro Staphylococcus aureus abscess community model.  2021 KNVM & NVMM virtual (oral) 
     

     
  • Partner

    SAJ Zaat (MD), Amsterdam UMC, Amsterdam, the Netherlands

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