Sca1+/CD31−/PDGFRa+ Cardiac Stem Cells are from an Epicardial/Mesodermal but not Neural-crest,...
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ABSTRACTS Heart, Lung and Circulation S3 2009;18S:S1–S286 Abstracts 3 SCA1+/CD31−/PDGFRA+ CARDIAC STEM CELLS ARE FROM AN EPICARDIAL/MESODERMAL BUT NOT NEURAL-CREST, CARDIOMYOCYTE OR BONE-MARROW ORIGIN James Chong 1,2 , Owen Prall 1 , Vashe Chandrakanthan 1 , Munira Xaymardan 1 , Ishtiaq Ahmed 1 , Chris Scarlett 2 , Emily Colvin 2 , Mark Pinese 2 , Andrew Biankin 2 , Richard Harvey 1 1 Victor Chang Cardiac Research Institute, Sydney, Australia 2 Garvan Institute of Medical Research, Sydney, Australia Background: Support for the ambitious goal of ther- apeutic cardiac regeneration has come from the recent discovery of endogenous cardiac stem cells in the post- natal heart. The biological origin of these cells remains a fundamental, yet unanswered question. Methods: By employing the colony forming unit fibrob- last (CFU-F) assay, we have previously shown that a subpopulation (cCFU-F) of Sca1+/CD31−/PDGFRa+ cells from the adult murine heart are clonogenic, long term self renewing and multi-potent (properties of true stem cells). Using state-of-the-art Cre-Lox technology, dou- ble transgenic (Cre/ZEG-Reporter) mice were created to conduct lineage tracing of cCFU-F. A possible epicar- dial, mesodermal, neural-crest or cardiomyocyte origin was investigated by placing Cre-recombinase under the control of GATA5, Mesp1, Wnt1 and Nkx2.5 promoters, respectively. To investigate a possible bone-marrow (BM) origin, BM was transplanted from transgenic mice ubiq- uitously expressing enhanced green fluorescent protein (-actin-EGFP) into lethally irradiated wild-type recipi- ents. Results: Percentage of cCFU-F colonies from respective lineage origins (n = 3) were 70 ± 9% epicardial, 81 ± 11% mesodermal, 2 ± 2% cardiomyocyte, 0 ± 0% neural-crest. Few Sca1+/CD31−/PDGFRa+ cardiac cells were BM derived at 3 months (5.1 ± 1%) and 6 months (0.5 ± 0.4%) post-transplantation. Colony forming ability of cCFU-F in irradiated mice was lost and not rescued by the trans- plantation of non-irradiated donor BM either after normal aging or myocardial infarction to stimulate BM stem cell homing. Conclusions/significance: cCFU-F endogenous cardiac stem cells are derived from an epicardial and mesoder- mal origin but not from the neural-crest, dedifferentiated cardiomyocytes or adult BM. Knowledge of stem cell ori- gins will aid progress toward successful translation of cell/regenerative strategies. doi:10.1016/j.hlc.2009.05.005 Ralph Reader Finalists – Clinical 4 CARDIOVASCULAR MORTALITY DURING LONG- TERM FOLLOW-UP OF 1112 PATIENTS WITH ACUTE PULMONARY EMBOLISM A.C.C. Ng , H. Wong, T. Chung, L. Kritharides Concord Hospital, The University of Sydney, Sydney, Australia Background: While previous studies have explored acute outcome after pulmonary embolism (PE), there are no guidelines advising long-term surveillance as long- term outcome studies are rare. We investigated long-term cardiovascular and non-cardiovascular mortality after PE. Methods: The outcomes of all patients presenting with acute PE to a tertiary referral hospital from 2000 to 2007 were tracked using the NSW Death Registry Database. Age-specific death-rates were obtained from the Aus- tralian Bureau of Statistics (ABS). Analysis of outcome according to age quintiles was performed using Chi- square statistic. Results: There were 1230 presentations of acute PE in 1112 patients, mean age 68 ± 16 years, 499 (45%) males. Mean length of hospital stay was 8 ± 7 days. During a mean follow-up of 4 ± 3 years, total mortality was 36% (399 deaths) and only 54 (5%) deaths occurred during the initial hospitalisation. The cumulative mortality was 13%, 19%, 23% and 35% at 6 months, 1 year, 2 year, 3 year and 5 year, respectively, and did not improve over the 7-year period. The overall annual mortality of 9.5% was 11-fold that of the age- and sex-matched general population (ABS data). After PE, annual mortality by age group was 2% (15–54 years), 7% (55–64 years), 9% (65–74 years), 12% (75–84 years) and 23% (>85 years). Of the 345 deaths occurring post-discharge, 155 (45%) were cardiovascular, 143 (41%) non-cardiovascular, and 47 (14%) undefined. Of cardio- vascular deaths, 66 (19%) were cardiac arrests, 31 (9%) acute myocardial infarction, 23 (7%) heart failure-related, 20 (6%) strokes and 15 (4%) PE-related. Conclusion: In contemporary adult populations, acute PE is associated with a substantially increased long-term mortality, of which nearly half is cardiovascular. Long- term surveillance may be warranted. doi:10.1016/j.hlc.2009.05.006
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Transcript of Sca1+/CD31−/PDGFRa+ Cardiac Stem Cells are from an Epicardial/Mesodermal but not Neural-crest,...
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Heart, Lung and Circulation S32009;18S:S1–S286 Abstracts
3SCA1+/CD31−/PDGFRA+ CARDIAC STEM CELLSARE FROM AN EPICARDIAL/MESODERMALBUT NOT NEURAL-CREST, CARDIOMYOCYTEOR BONE-MARROW ORIGIN
James Chong 1,2, Owen Prall 1, Vashe Chandrakanthan 1,Munira Xaymardan 1, Ishtiaq Ahmed 1, Chris Scarlett 2,Emily Colvin 2, Mark Pinese 2, Andrew Biankin 2, RichardHarvey 1
1 Victor Chang Cardiac Research Institute, Sydney, Australia2 Garvan Institute of Medical Research, Sydney, Australia
Background: Support for the ambitious goal of ther-apeutic cardiac regeneration has come from the recentdiscovery of endogenous cardiac stem cells in the post-natal heart. The biological origin of these cells remains afundamental, yet unanswered question.
Methods: By employing the colony forming unit fibrob-last (CFU-F) assay, we have previously shown that asubpopulation (cCFU-F) of Sca1+/CD31−/PDGFRa+ cellsfrom the adult murine heart are clonogenic, long termself renewing and multi-potent (properties of true stemcells). Using state-of-the-art Cre-Lox technology, dou-ble transgenic (Cre/ZEG-Reporter) mice were created toconduct lineage tracing of cCFU-F. A possible epicar-dial, mesodermal, neural-crest or cardiomyocyte originwas investigated by placing Cre-recombinase under thecontrol of GATA5, Mesp1, Wnt1 and Nkx2.5 promoters,respectively. To investigate a possible bone-marrow (BM)origin, BM was transplanted from transgenic mice ubiq-uitously expressing enhanced green fluorescent protein(�-actin-EGFP) into lethally irradiated wild-type recipi-ents.
Results: Percentage of cCFU-F colonies from respectivelineage origins (n = 3) were 70 ± 9% epicardial, 81 ± 11%mesodermal, 2 ± 2% cardiomyocyte, 0 ± 0% neural-crest.Few Sca1+/CD31−/PDGFRa+ cardiac cells were BMderived at 3 months (5.1 ± 1%) and 6 months (0.5 ± 0.4%)post-transplantation. Colony forming ability of cCFU-F inirradiated mice was lost and not rescued by the trans-plantation of non-irradiated donor BM either after normalaging or myocardial infarction to stimulate BM stem cellhoming.
Conclusions/significance: cCFU-F endogenous cardiacstem cells are derived from an epicardial and mesoder-mal origin but not from the neural-crest, dedifferentiatedcardiomyocytes or adult BM. Knowledge of stem cell ori-gins will aid progress toward successful translation ofcell/regenerative strategies.
doi:10.1016/j.hlc.2009.05.005
Ralph Reader Finalists – Clinical
4CARDIOVASCULAR MORTALITY DURING LONG-TERM FOLLOW-UP OF 1112 PATIENTS WITH ACUTEPULMONARY EMBOLISM
A.C.C. Ng, H. Wong, T. Chung, L. Kritharides
Concord Hospital, The University of Sydney, Sydney, Australia
Background: While previous studies have exploredacute outcome after pulmonary embolism (PE), there areno guidelines advising long-term surveillance as long-term outcome studies are rare. We investigated long-termcardiovascular and non-cardiovascular mortality after PE.
Methods: The outcomes of all patients presenting withacute PE to a tertiary referral hospital from 2000 to 2007were tracked using the NSW Death Registry Database.Age-specific death-rates were obtained from the Aus-tralian Bureau of Statistics (ABS). Analysis of outcomeaccording to age quintiles was performed using Chi-square statistic.
Results: There were 1230 presentations of acute PE in1112 patients, mean age 68 ± 16 years, 499 (45%) males.Mean length of hospital stay was 8 ± 7 days. During amean follow-up of 4 ± 3 years, total mortality was 36% (399deaths) and only 54 (5%) deaths occurred during the initialhospitalisation. The cumulative mortality was 13%, 19%,23% and 35% at 6 months, 1 year, 2 year, 3 year and 5 year,respectively, and did not improve over the 7-year period.The overall annual mortality of 9.5% was 11-fold that ofthe age- and sex-matched general population (ABS data).After PE, annual mortality by age group was 2% (15–54years), 7% (55–64 years), 9% (65–74 years), 12% (75–84years) and 23% (>85 years). Of the 345 deaths occurringpost-discharge, 155 (45%) were cardiovascular, 143 (41%)non-cardiovascular, and 47 (14%) undefined. Of cardio-vascular deaths, 66 (19%) were cardiac arrests, 31 (9%)acute myocardial infarction, 23 (7%) heart failure-related,20 (6%) strokes and 15 (4%) PE-related.
Conclusion: In contemporary adult populations, acutePE is associated with a substantially increased long-termmortality, of which nearly half is cardiovascular. Long-term surveillance may be warranted.
doi:10.1016/j.hlc.2009.05.006
