CARDIAC TRANSPLANTATION AND CARDIAC CELLULAR PROGENITOR ANALYSIS IN DYSTROPHIN CARDIOMYOPATHY

We report for the first time human cardiac progenitor analysis after very rare cardiac transplantation in case of a symptomatic muscular dystrophy patient. Hypothesized was lower repair capacity, represented by fraction of reparative c-kit+ cells and their impaired migration capacity. Patient has been diagnosed with exons 16-20 deletion in the dystrophin gene. He was enrolled to heart transplantation waiting list and recently transplanted. Donor organ atrial parts (WT) were control samples, there was no significant age difference (35y vs 44y). With informed consent of patient, explanted organ was dissociated to single cells and progenitor evaluation and cultivation took place.
Methods: Histopathological evaluation was performed. Flow cytometry analysis of c-Kit+/CD45- cells was performed. The explants were propagated in vitro and evaluated for cell migration at 9 and 28 days.
Results: Dystrophy heart presented irregular fibrosis, thinned or absent myocardial layer and prevalent adipose tissue in both ventricles. Microscopy showed non-specific myocardial changes of dilated cardiomyopathy with hypertrophic cardiomyocytes and interstitial fibrosis. Samples showed mosaic pattern with subtotal absence of membranous dystrophin staining and only sporadic isolated myocytes (˂0.1‰).
Percentage of c-kit+/CD45- cells was: atria 0.28% right and 0.35% left; ventricles 0.42% right, 0.58% left and 0.12% septum. In two WT left atrial samples was c-kit percentage 0,42% and 1,69%. Outgrowths distance was 331±224µm in dystrophy and 1031±351µm in WT (p<0.001). c-Kit+ cells were detected in dystrophy at day 28 vs 9 in WT after seeding, after 6 weeks were sparse in WT, but none in dystrophin. 

Conclusion: Failing dystrophy heart has depleted pool of c-Kit+ cells with reduced mobility and outgrowth survival. This may be caused by previous increase in cardiomyocyte turnover.