CARDIAC TRANSPLANTATION AND CARDIAC CELLULAR PROGENITOR ANALYSIS IN DYSTROPHIN CARDIOMYOPATHY | XXIV. výroční sjezd České kardiologické společnosti

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.

CARDIAC TRANSPLANTATION AND CARDIAC CELLULAR PROGENITOR ANALYSIS IN DYSTROPHIN CARDIOMYOPATHY Tématický okruh: Transplantace
Typ: Ústní sdělení - lékařské , Číslo v programu: 504


Pešl M.¹, Jelínková Š.², Holická M.³, Žampachová V.⁴, Gaillyová R.⁵, Němec P.⁶, Krejčí J.⁷, Dvořák P.⁸, Stárek Z.⁹, Rotrekl V.¹⁰ ¹ 1. Interní kardioangiologická klinika a Biologie LFMU a ICE, ICRC, Fakultní nemocnice u sv. Anny, Brno, ² Biologie, LFMU, Masarykova universita, Brno, ³ Department of Cardiology, University hospital Brno, Brno, Czech Republic, Brno, ⁴ Ist Department of Pathology, Masaryk University and St. Anne's University Hospital Brno, Brno, ⁵ Department of Clinical Genetics, Masaryk University, Faculty of Medicine, Brno, ⁶ and Transplantation, Center for Cardiovascular Surgery, Brno, ⁷ 1st Internal Cardio-Angiological Clinic, Masaryk University and St. Anne's University Hospital Brno, Brno, ⁸ Department of Biology, Masaryk University, Faculty of Medicine, Brno, ⁹ 1st Internal Cardio-Angiological Clinic, Masaryk University and St. Anne's University Hospital Brno - ICRC, Brno, ¹⁰ Department of Biology, and SCDM, Faculty of Medicine, Masaryk University, and ICRC, St. Anne ' s University Hospital, Brno
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.

PROHLÍŽENÍ ABSTRAKTA