Higher frequencies of BCRP+ cardiac resident cells in ischaemic human myocardium
| Autor: | Axel Haverich, Ina Gruh, Ulrich Martin, Issam Ismail, Maximilian Y. Emmert, Lorenz S. Emmert, Anke Gawol, Ingrid Schmidt-Richter, Andreas Martens, Burkhardt Seifert |
|---|---|
| Přispěvatelé: | University of Zurich, Gruh, Ina |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Adolescent Abcg2 Biopsy Heart Ventricles Cell Myocardial Ischemia 610 Medicine & health 2705 Cardiology and Cardiovascular Medicine Young Adult Side population In vivo medicine ATP Binding Cassette Transporter Subfamily G Member 2 Humans Myocytes Cardiac Heart Atria Progenitor cell Aged Aged 80 and over medicine.diagnostic_test biology business.industry Stem Cells Cell Differentiation 10060 Epidemiology Biostatistics and Prevention Institute (EBPI) Middle Aged medicine.disease Neoplasm Proteins 10020 Clinic for Cardiac Surgery Proto-Oncogene Proteins c-kit medicine.anatomical_structure Heart failure biology.protein ATP-Binding Cassette Transporters Female Stem cell Cardiology and Cardiovascular Medicine business |
| Zdroj: | European Heart Journal. 34:2830-2838 |
| ISSN: | 1522-9645 0195-668X |
| Popis: | Aims Several cardiac resident progenitor cell types have been reported for the adult mammalian heart. Here we characterize their frequencies and distribution pattern in non-ischaemic human myocardial tissue and after ischaemic events. Methods and results We obtained 55 biopsy samples from human atria and ventricles and used immunohistological analysis to investigate two cardiac cell types, characterized by the expression of breast cancer resistance protein (BCRP)/ABCG2 [for side population (SP) cells] or c-kit. Highest frequencies of BCRP+ cells were detected in the ischaemic right atria with a median of 5.40% (range: 2.48–11.1%) vs. 4.40% (1.79–7.75%) in the non-ischaemic right atria ( P = 0.47). Significantly higher amounts were identified in ischaemic compared with non-ischaemic ventricles, viz. 5.44% (3.24–9.30%) vs. 0.74% (0–5.23%) ( P = 0.016). Few numbers of BCRP+ cells co-expressed the cardiac markers titin, sarcomeric α-actinin, or Nkx2.5; no co-expression of BCRP and progenitor cell marker Sca-1 or pluripotency markers Oct-3/4, SSEA-3, and SSEA-4 was detected. C-kit+ cells displayed higher frequencies in ischaemic (ratio: 1:25 000 ± 2500 of cell counts) vs. non-ischaemic myocardium (1:105 000 ± 43 000). Breast cancer resistance protein+/c-kit+ cells were not identified. Following in vitro differentiation, BCRP+ cells isolated from human heart biopsy samples ( n = 6) showed expression of cardiac troponin T and α-myosin heavy-chain, but no full differentiation into functional beating cardiomyocytes was observed. Conclusion We were able to demonstrate that BCRP+/CD31− cells are more abundant in the heart than their c-kit+ counterparts. In the non-ischaemic hearts, they are preferentially located in the atria. Following ischaemia, their numbers are elevated significantly. Our data might provide a valuable snapshot at potential progenitor cells after acute ischaemia in vivo , and mapping of these easily accessible cells may influence future cell therapeutic strategies. |
| Databáze: | OpenAIRE |
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