Human mesenchymal stromal cells can uptake and release ciprofloxacin, acquiring in vitro anti-bacterial activity.
OBJECTIVE
Traditional antibiotic therapy is based on the oral or systemic injection of antibiotics that are often unable to stop a deep infection (eg, osteomyelitis). We studied whether or not bone marrow stromal cells (BM-MSCs) are able to uptake and release ciprofloxacin (CPX), a fluoroquinolone considered the drug of choice for the treatment of chronic osteomyelitis because of its favorable penetration into poorly vascularized sites of infection.


METHODS
Human bone marrow stromal cells (BM-MSCs) were primed with CPX (BM-MSCsCPX) according to a methodology previously standardized in our laboratory for paclitaxel (PTX). The anti-microbial activity of CPX released from BM-MSCs cells (BM-MSCsCPX-CM) or supernatant from cell lysate (BM-MSCsCPX-LYS) was evaluated by agar dilution and microdilution methods on three bacterial strains (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa). To investigate whether or not primed cells (BM-MSCsCPX) were able to directly act on the bacterial growth, co-colture was performed by mixing E. coli suspension to an increasing number of BM-MSCsCPX. The anti-bacterial activity was determined as number of BM-MSCsCPX that completely inhibited bacterial growth.


RESULTS
The results demonstrated that BM-MSCsCPX are able to uptake and then release CPX in the conditioned medium. The loaded antibiotic maintains its active form throughout the process as tested on bacteria.


CONCLUSIONS
Our findings suggest that CPX-loaded MSCs may represent an important device for carrying and delivering CPX (and perhaps other antibiotics) into infected deep microenvironments; they could be used for local application and by systemic infusion when their homing capacity into the bone is cleared.
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy.
Francesca
F
Sisto
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy.
Arianna
A
Bonomi
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy.
Loredana
L
Cavicchini
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy.
Valentina
V
Coccè
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy.
Maria Maddalena
MM
Scaltrito
Department of Medical Biotechnology and Translational Medicine, University of Milan, Italy.
Gianpietro
G
Bondiolotti
Fondazione IRCCS, Neurological Institute Carlo Besta, Milan, Italy.
Giulio
G
Alessandri
Fondazione IRCCS, Neurological Institute Carlo Besta, Milan, Italy.
Eugenio
E
Parati
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy. Electronic address: augusto.pessina@unimi.it.
Augusto
A
Pessina
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000627:therapeutic use*; D001770:Blood Bactericidal Activity / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D002908:Chronic Disease; D002939:Ciprofloxacin / Q000378:metabolism / Q000627:therapeutic use*; D004705:Endocytosis; D005089:Exocytosis; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D010019:Osteomyelitis / Q000628:therapy*
D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin
ciprofloxacin; in vitro anti-bacterial activity; mesenchymal stromal cells