IADR Abstract Archives

Cytotoxicity Of Various Bisphosphonates On Human Umbilical Cord-Derived Stem Cells

Objective: Bisphosphonates (BPs) are a group of drugs primarily used to prevent bone resorption in a variety of clinical situations including osteoporosis, Paget’s disease and invasive malignancy- related bone resorption. BP use has been associated with osteonecrosis of the jaw (BRONJ and the biological mechanisms leading to this condition are not fully understood.  This in vitro study aimed to evaluate the effect of different classes of BPs (non-nitrogen containing clodronate, and the nitrogen containing BPs alendronate and zoledronate) on human umbilical cord-derived stem cells (UCSCs).

Method: UCSCs were cultured in-vitro with clodronate, alendronate and zoledronate at 0.25µM, 0.5µM, 1µM, 2µM and 3µM in culture media for 10 days and an Alamar Blue assay was conducted to assess the effects of the drugs on cell proliferation. To assess the cytotoxicity of the drugs, live/dead staining was used at 24 and 48 hours’ time point.  Further, to evaluate the effects of these drugs on cell migration, scratch wound healing assays were conducted at 6 and 24 hours. 

Result: All of the BPs tested were found to negatively affect UCSC cell proliferation with the lowest effect shown by clodronate (0.25 µM) and the highest with zoledronate at 5 µM concentration. Live/dead staining also revealed a similar trend with the high potency drug zoledronate causing the highest cytotoxicity. Further, the scratch wound healing assay showed that zoledronate significantly inhibited cellular migration at both time points compared to minimal or no effect of clodronate at any concentration.  

Conclusion: The non-nitrogen containing BPs are less cytotoxic and have minimum inhibition of proliferation and migration of UCSC as compared to the more potent nitrogen-containing BPs alendronate and zoledronate.

Australian/New Zealand Division Meeting
2014 Australian/New Zealand Division Meeting (Brisbane, Australia)
Brisbane, Australia
2014

Scientific Groups
  • Sharma, Chakrabhavi Gundurao Dileep  ( Griffith University, Griffith Health Institute, Southport, , Australia )
  • Hamlet, Stephen  ( Griffith University, Southport, N/A, Australia )
  • Petcu, Eugen  ( Griffith University School of Medicine, Griffith Health Institute, Southport, , Australia )
  • Ivanovski, Saso  ( Griffith University, Gold Coast, QLD, , Australia )
    • Pharmacology/Therapeutics/Toxicology