Higher frequencies of BCRP+ cardiac resident cells in ischaemic human myocardium
Higher frequencies of BCRP+ cardiac resident cells in ischaemic human myocardium
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DOI：
10.1093/eurheartj/ehs156
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发表时间：
2013-09-01
影响因子：
39.3
通讯作者：
Gruh, Ina
中科院分区：
文献类型：
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作者：
Emmert, Maximilian Y.;Emmert, Lorenz S.;Gruh, Ina
目的已有报道成年哺乳动物心脏存在多种类型的心脏祖细胞。方法和结果我们从人的心房和脑室获得了55例活检标本，并用免疫组织学方法研究了两种类型的心脏细胞，其特征是乳腺癌耐药蛋白(BCRP)/ABCG2[旁群细胞]或c-kit的表达。BCRP+细胞在缺血区的中位数为5.40%(2.48~11.1%)，而非缺血区的中位数为4.40%(1.79~7.75%)(P<0.47)。与非缺血性脑室相比，缺血性脑室的含量显著增加，即。5.44%(3.24-9.30%)vs.0.74%(0-5.23%)(P<0.016)。少数BCRP+细胞共表达心肌标志物肌动蛋白、肌瘤α-肌动蛋白或NKX2.5；未检测到BCRP与祖细胞标志物SCA-1或多能标志物Oct-3/4、SSEA-3和SSEA-4共表达。C-kit(+)细胞在缺血心肌中的比例(1：25000+/-2500)高于非缺血心肌(1：105000+/-43000)。未见乳腺癌耐药蛋白(+)/c-kit(+)细胞。体外分化后，从人心脏活检标本中分离的BCRP+细胞(n=6)表达心肌肌钙蛋白T和α-肌球蛋白重链，但未观察到完全分化为功能性搏动心肌细胞。结论BCRP+/CD312细胞在心脏中比c-kit(+)细胞更丰富。在非缺血性心脏中，它们优先位于心房。在缺血后，它们的数量显著增加。我们的数据可能为体内急性缺血后潜在的祖细胞提供有价值的快照，而这些容易获得的细胞的图谱可能会影响未来的细胞治疗策略。
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 alpha-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 a-myosin heavy-chain, but no full differentiation into functional beating cardiomyocytes was observed.Conclusion We were able to demonstrate that BCRP+/CD312 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.