title: Fentanyl is less toxic on adult human mesenchymal stem cells compared to ropivacaine when used intraarticularly. A controlled in vitro study.
abstract: The purpose of this study was to evaluate the toxicity of ropivacaine and fentanyl on adult human mesenchymal stem cells (hMSC). hMSC's were seeded in monolayer triple-flasks and then plated into 96-well plates at a density of 5000 cells per well. After fully aspirating the culture medium, ropivacaine or fentanyl in its corresponding concentration (0.5%, 0.25%, 0.125% for ropivacaine and 0.05%, 0.025%, 0.0125% for fentanyl) or culture medium only was added to each well. After 30 min, the anaesthetic was removed and fresh culture medium was added. hMSCs mitochondrial activity as a marker of cell proliferation and apoptosis marker was evaluated after 1, 24 h and 7 days. Proliferation was significantly decreased after a 30 min exposure to 0.5% and 0.125% ropivacaine, respectively compared to the control group after 24 h (p < 0.001). Simultaneously, apoptosis was significantly induced. Proliferation of hMSC's was decreased after 24 h when exposed to 0.05%, 0.025% and 0.0125% fentanyl (p < 0.001). Apoptosis was only induced 24 h after an exposure to 0.05% fentanyl. Our data suggest that both drugs have a concentration-dependent effect on proliferation in adult hMSC's in vitro. This effect was more distinct with ropivacaine compared to fentanyl. Translating these results into clinical practice, this in vitro study suggests fentanyl as a potentially less toxic analgetic drug for intraarticular application after arthroscopic bone marrow stimulation or rotator cuff repair with comparable to prolonged pain reduction.
authors.affiliation: Department of Orthopaedic Surgery, University Hospital of Munich (LMU) , Munich , Germany and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ficklscherer
authors.forename: Peter C
authors.initials: PC
authors.lastname: Kreuz
authors.forename: Birte
authors.initials: B
authors.lastname: Sievers
authors.forename: Mehmet F
authors.initials: MF
authors.lastname: Gülecyüz
authors.forename: Volkmar
authors.initials: V
authors.lastname: Jansson
authors.forename: Peter E
authors.initials: PE
authors.lastname: Müller
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D000577:Amides / Q000008:administration & dosage / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005283:Fentanyl / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D007270:Injections, Intra-Articular; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D000077212:Ropivacaine
chemical_list: D000577:Amides; D015415:Biomarkers; D000077212:Ropivacaine; D053148:Caspase 3; D005283:Fentanyl