Background: As a promising investigational therapy for stroke recovery, mesenchymal stromal cells (MSCs) are in various stages of clinical trials. MSCs may promote recovery through cytokine release and immunomodulation. Stroke patients typically are treated with antiplatelets and medications for hypertension and hyperlipidemia. We explored the effect of commonly prescribed drugs at physiological concentrations on MSCs.
Methods: Clinical grade bone marrow MSCs from healthy donor at passage 2 were thawed and re-suspended in serum free media. Monocytes (Mo) were isolated from peripheral blood of healthy humans. MSCs and Mo were cultured alone as well as in co-culture and exposed to simvastatin, atenolol, losartan, captopril, or aspirin. They were also exposed to high glucose (upto 40mM) to simulate hyperglycemia. At 24 hours of incubation, media was collected and TNF-α concentration was measured, as an index of immunomodulation of Mo by MSCs. Cell viability was also measured (using MTT assay and flow cytometry).
Results: There were significant effects of all drugs on viability of MSCs but with no impact on Mo. More importantly, Losartan (dose independent), Simvastatin and Atenolol (dose-dependent) reduced the viability of MSCs even at the pharmacologically relevant concentrations (Fig 1). High glucose had no effect on viability of MSCs or Mo. TNF-α secretion from co-culture of MSCs and Mo at 24 hours showed differences at very high doses of aspirin (2-fold increase), atenolol (0.5 fold decrease), and glucose (0.5 fold decrease) (data not shown). However, these high concentrations are unlikely to be achieved pharmacologically in plasma of patients treated with these drugs.
Conclusion: Exposure of MSCs to clinically relevant drugs can alter their viability and function. Our results suggest that stroke trials involving use of intravenous MSCs should consider the differential impact of commonly prescribed medications on MSCs function.