c-kit Haploinsufficiency impairs adult cardiac stem cell growth, myogenicity and myocardial regeneration
MouseChemical/toxinC57BL/6J wild type (Jackson 000664); c-kit knock-in (c-kitKI) lines crossed with B6.Cg-Gt(ROSA)26Sor tdTomato reporter mice; Tg(Myh6-Cre/Esr1)1Jmk/J crossed with Gt(ROSA)26Sor reporter mice; R26 heterozygous littermates as controlsMalen = n = 14 per group for the 200 versus 400 mg/kg isoproterenol…Tail vein (systemic intravenous) injection; no intramyocardial delivery was usedCloned cells given by tail vein; the numerical exponent of…12 h after isoproterenol 200 mg/kg in the c-kitKI rescue experiment; after esta…
Model: Acute cardiomyocyte injury induced by a single subcutaneous interscapular overdose of isoproterenol (200 or 400 mg/kg); a chronic failing cardiomyopathy model used isoproterenol 200 mg/kg followed at 72 h by 5-fluorouracil 15 mg/kg/day for 25 days via osmotic mini-pump
Transplantation of wild-type c-kit-positive CSCs rescued the defective regenerative phenotype of c-kit knock-in mice: transplanted wild-type CSCs generated new YFP-positive cardiomyocytes reaching 4 +/- 1% of total cardiomyocytes in the apical sub-endocardium at 28 days, prevented fibrosis and norm…
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