Bone Marrow‐Derived Mesenchymal Stem Cells Enhance Bacterial Clearance and Preserve Bioprosthetic Integrity in a Rat Model of Mesh Infection
Authors: Pierce Lisa , Criman Erik , Matsumoto Karen , Aubin Harry , Campbell Carmen , Kurata Wendy 
Published: November 2023

Infection remains a feared complication of any surgery involving implantation of a foreign body. While bioprosthetic materials are generally favored over synthetic meshes when confronted with a grossly contaminated field, bacterial clearance and rates of clinical resolution are variable. Previous work in our laboratory (Hernia 2015;19:197–205) determined that bioprosthetics may not, in fact, be more resistant to bacterial colonization than reduced‐weight synthetics, particularly in the presence of E. coli. Recently, multipotent mesenchymal stem cells (MSCs) derived from bone marrow and other tissue sources have been shown to possess immunomodulatory properties and improve cellular and vascular infiltration when seeded onto bioprosthetic materials. In this study, we investigated whether seeding noncrosslinked bovine pericardium (VeritasTM, Synovis) with allogeneic bone marrow‐derived MSCs improves infection resistance in vivo after inoculation with E. coli. Rat bone marrow‐derived MSCs at passage 3 were seeded onto 2.5 × 1.5 cm pieces of mesh (7.5 × 105 cells/side) and cultured for 7 days prior to implantation. Rats were implanted subcutaneously with two pieces of seeded or unseeded mesh and inoculated with E. coli [(7 × 105 colony forming units (cfu)] or saline prior to wound closure (Group 1, unseeded mesh/saline; Group 2, unseeded mesh/E. coli; Group 3, MSC‐seeded mesh/E. coli; n=8 rats per group). Meshes were explanted at 4 weeks and underwent microbiological and histological analyses. E. coli‐inoculated MSC‐seeded meshes showed superior bacterial clearance and improved tissue incorporation compared to E. coli‐inoculated unseeded meshes (87.5% vs. 0% clearance, respectively; p=0.001). Likewise, complete mesh degradation concomitant with abscess formation was observed in 100% of meshes (16/16) in the unseeded/E. coli group, in contrast to 6.3% of meshes (1/16) in the MSC‐seeded/E. coli group (p<0.001). In a separate in vitro experiment, incubation of MSCs for 6 hours with 103 cfu E. coli induced the upregulation (>3‐fold change, p<0.05) of 17 genes involved in the innate immune response to bacteria, including those encoding inflammatory cytokines, the antimicrobial peptide cathelicidin (4.2‐fold increase, p=0.04), and genes associated with toll‐like receptor (TLR) signaling, NOD‐like receptor (NLR) signaling, the NFκB pathway, and apoptosis. TLR2 was upregulated 88‐fold (p=0.02), and the NLRs NOD2 and NLRP3 were upregulated 7.7‐fold (p=0.009) and 12.2‐fold (p=0.02), respectively, indicating that these receptors play a significant role in regulating the antibacterial response of MSCs to E. coli. Results from this study suggest that augmenting a bioprosthetic mesh with MSCs enables in vivo down‐modulation of the inflammatory response and enhanced bacterial clearance, in part mediated by TLR2 and NLR signaling and the upregulation of the antimicrobial peptide cathelicidin.

Support or Funding Information

Financial support was obtained from the Department of Clinical Investigation, Tripler Army Medical Center. VeritasTM Collagen Matrix (Synovis) was a gift from Medical Innovative Technologies Hawaii.