Higher frequencies of BCRP+ cardiac resident cells in ischaemic human myocardium.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Leibniz Research Laboratories for Biotechnology and Artificial Organs, LEBAO and Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Cluster of Excellence REBIRTH, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Maximilian Y
MY
Emmert
Lorenz S
LS
Emmert
Andreas
A
Martens
Issam
I
Ismail
Ingrid
I
Schmidt-Richter
Anke
A
Gawol
Burkhardt
B
Seifert
Axel
A
Haverich
Ulrich
U
Martin
Ina
I
Gruh
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013234:Stem Cells / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit