Cyclosporine

Cell lines

EMG7 mouse ES cells, systematically induced from mesodermal precursor, Flk1 (also designated as vascular endothelial growth factor receptor-2 (VEGFR2))-expressing cells.

Preparation method

The solubility of this compound in DMSO is >53mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

1–3μg/mL

Applications

Addition of cyclosporine (1–3 μg/mL) to Flk1+ cells showed a striking effect to increase beating cells at Flk-d6 and induced approximately 13 times increase in cardiac troponin-T (cTnT)-positive cardiomyocyte appearance than control. These results indicated that functional cardiomyocytes were successfully induced and expanded by cyclosporine treatment. Addition of cyclosporine to Flk1+ cells specifically increased FCV (Flk1+/CXCR4+/vascular) population to approximately 10–20 times more than control. The maximum percentage of FCV cells within total Flk1+ cell-derived cells was increased up to 40% by cyclosporine. The yield of purified FCV progenitor cells was increased approximately 22 times by cyclosporine treatment. These results indicate that cyclosporine-expanded FCV cells retained their high cardiogenic potentials. Taken together, cyclosporine showed a novel effect specifically acting on mesoderm cells to drastically increase cardiac progenitors as well as cardiomyocytes by 10–20 times. Expanded FCV cardiac progenitors showed differentiation potentials to cardiomyocytes in vivo after cell transplantation to rat myocardial infarction model.

Animal models

mice of 7-12 weeks (the inbred strains C3H,C57BL/6 and BALB/c);outbred guinea-pigs of both sexes

Dosage form

Male mice (SIM and C3H) , gavage 250 mg/kg/day on 5 consecutive days; Guinea-pigs i.p. 20-50mg/kg/day on 4 consecutive days.

Application

Doses of cyclosporin on consecutive days strongly depressed direct PFC (plaque-forming cells) in rats in a dose-dependent manner. cyclosporin markedly depresses both direct and indirect PFC in mice on day 4.In another similar skin contact sensitivity model using DNCB (1-chlor-2,4-dinitrobenzene) in guinea pigs, i.p. Treatment on days 0-4 with either 20 or 50 mg/kg/day of cyclosporin completely suppressed the skin reaction on day 10 since no redness nor swelling were observed. The inhibition caused by cyclosporin seems to affect mainly the effector cells and was achieved at well-tolerated doses. Cyclosporin has, in addition, been shown to depress not only the primary response, but also the secondary response of both IgM and IgG2a PFC, oxazolone hypersensitivity.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Peishi Yan , Atsushi Nagasawa , Hideki Uosaki ., et al.Cyclosporin-A potently induces highly cardiogenic progenitors from embryonic stem cells. BiochemsBiophys.Res.Commun. 379 (2009) 115–120.

[2]. Borel JF, Feurer C, Magnée C., et al. Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology. 1977 Jun;32(6):1017-25.