(Circulation. 2001;103:2776.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
From the Cardiovascular Research Institute and Department of Internal Medicine III, Kurume University, and the Institute of Molecular Embryology and Genetics, Kumamoto University (Y.O.), Japan.
Correspondence to Toyoaki Murohara, MD, PhD, Cardiovascular Research Institute, Kurume University, 67 Asahi, Kurume, 830-0011 Japan. E-mail toyom{at}med.kurume-u.ac.jp
| Abstract |
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Methods and ResultsFlow cytometry revealed that circulating MNCCD34+ counts significantly increased in patients with acute myocardial infarction (n=16), peaking on day 7 after onset, whereas they were unchanged in control subjects (n=8) who had no evidence of cardiac ischemia. During culture, PB-MNCs formed multiple cell clusters, and EPC-like attaching cells with endothelial cell lineage markers (CD31, vascular endothelial cadherin, and kinase insert domain receptor) sprouted from clusters. In patients with acute myocardial infarction, more cell clusters and EPCs developed from cultured PB-MNCs obtained on day 7 than those on day 1. Plasma levels of vascular endothelial growth factor significantly increased, peaking on day 7, and they positively correlated with circulating MNCCD34+ counts (r=0.35, P=0.01).
ConclusionsThis is the first clinical demonstration showing that lineage-committed EPCs and MNCCD34+, their putative precursors, are mobilized during an acute ischemic event in humans.
Key Words: angiogenesis endothelium stem cells ischemia
| Introduction |
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| Methods |
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Quantification of
MNCCD34+
The circulating MNCCD34+
count was quantified on days 1, 3, 7, 14, and 28. In brief,
peripheral white blood cells were stained with a
fluorescein isothiocyanateconjugated anti-CD34 monoclonal
antibody (Becton-Dickinson). Samples were
subjected to a 2D side scatter-fluorescence dot plot
analysis (FACScan,
Becton-Dickinson).4
After appropriate gating, the number of
MNCCD34+ with low cytoplasmic granularity
(low sideward scatter) was quantified and expressed as number of
cells per 106 white blood cells. In control
subjects, circulating PB-MNCCD34+ were
quantified on days 1 and 7.
Cell Culture Assay for Circulating EPCs
PB (20 mL) was obtained on days 1 and 7, and MNCs
were isolated by a density-gradient centrifugation
method.5 MNCs were cultured
on gelatin-coated 6-well plates in medium-199 containing 20% FBS, EC
growth supplement, antibiotics (Gibco), and heparin (10 U/mL). EPCs
were defined by the expression of EC lineage-markers (kinase insert
domain receptor [KDR], vascular endothelial [VE]-cadherin, CD31,
and
1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanineperchloratelabeled
acetylated LDL [DiI-acLDL] incorporation) and by negative CD45
antigen.2 5 Thirty
microscopic fields from 6 randomly selected wells were examined in each
sample at day 7 of culture, and numbers of EPCs and cell clusters were
expressed as number of cells or clusters per original PB (1
mL).
Biochemical Measurements
PB (5 mL) was collected from patients with AMI on
days 1, 3, 7, 14, and 28. Complete cell counts and serum creatine
kinase levels were examined as routine tests, and plasma levels of
vascular endothelial growth factor (VEGF), basic
fibroblast growth factor (bFGF), granulocyte colony-stimulating factor
(G-CSF), granulocyte macrophage colony-stimulating factor
(GM-CSF), interleukin (IL)-3, and IL-8 levels were measured
using commercially available ELISA kits. In control subjects, PB (5 mL)
was obtained on days 1 and 7 to measure plasma VEGF
levels.
Statistics
Values are expressed as mean±SE. Data were subjected
to 1-way ANOVA followed by Fishers test for comparison between any 2
means. Differences of P<0.05
were considered significant.
| Results |
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EPC Culture Assay
From cultured PB-MNCs, cell clusters developed and
spindle-shaped attaching cells sprouted from the clusters. The
morphological appearance of attaching cells resembled that of EPCs
differentiated from human PB, which we reported
previously.2 5 More
than 80% of attaching cells expressed EC lineage-markers (KDR,
VE-cadherin, and CD31) and took up DiI-acLDL.
Representative photomicrographs of KDR- and
CD31-immunostaining and DiI-acLDL incorporation are
shown in
Figure 1B
. Attaching cells, however, did not express CD45, a
common leukocyte antigen (data not shown). Attaching cells thus
expressed multiple EC antigens, and we defined attaching cells as a
major population of EPCs.
Cell culture assays revealed that more cell clusters and
EPCs developed from MNCs obtained on day 7 than those obtained on day 1
in AMI patients
(Figures 1C
and 1D
). In contrast, the numbers of EPCs and cell
clusters did not change between day 1 and day 7 in controls
(Figure 1D
).
Plasma Levels of
Cytokines
The
Table
shows the time course of circulating white blood cell counts, serum
creatine kinase, and plasma VEGF, bFGF, G-CSF, GM-CSF, IL-3, and IL-8
levels after the onset of AMI. Only plasma VEGF levels were
significantly elevated, peaking on day 7; the levels of the other 5
cytokines were unchanged. Because it was only VEGF that was
elevated in the plasma of AMI patients, we measured only plasma VEGF
levels in the control group. VEGF levels slightly but significantly
increased on day 7 compared with day 1 (100±6 versus 72±2 pg/mL) in
the control group. However, on day 7, plasma VEGF levels were
significantly greater in the AMI group than in the control group
(171±31 versus 100±6 pg/mL,
P<0.01).
|
Circulating VEGF and
MNCCD34+
We examined the potential relationship between
MNCCD34+ counts and plasma cytokine
levels in AMI. Simple regression analysis revealed that the
number of circulating MNCCD34+ positively
correlated with the plasma levels of VEGF
(r=0.35,
P=0.01;
Figure 2
). There were no significant relationships between
MNCCD34+ counts and bFGF
(P=0.06), G-CSF
(P=0.07), GM-CSF
(P=0.24), IL-3
(P=0.56), or IL-8
(P=0.09) (plots not shown). The
MNCCD34+ counts did not correlate with
maximum serum creatine kinase levels
(P=0.52). In control subjects,
plasma levels of VEGF did not correlate with
MNCCD34+ counts (plots not
shown).
|
| Discussion |
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Currently, little is known about how
MNCCD34+ are mobilized after AMI.
Inflammatory cytokines are released from ischemic
tissues and may stimulate bone marrow to release EPCs and
MNCCD34+.3
Indeed, Asahara et
al3 6 reported that
hematopoietic/angiogenic cytokines (eg, VEGF and GM-CSF)
mobilized EPCs in animals. Thus, we analyzed the time course of
plasma levels of major hematopoietic/angiogenic cytokines in
AMI patients. Among the 6 cytokines we measured, only plasma
VEGF levels were significantly elevated
(Table
).
The precise origin(s) of circulating VEGF is unknown, but
ischemic cardiac tissues likely secrete VEGF because the
promoter sequence of the VEGF
gene contains hypoxia-responsive elements. In fact, a recent
study showed that myocardial VEGF expression was enhanced in patients
with AMI.7 Interestingly,
plasma VEGF levels positively correlated with the numbers of
MNCCD34+ in AMI
(Figure 2
) in the present study, which is
consistent with a recent report showing that VEGF functions as
a mobilizer for EPCs in patients with coronary artery disease
receiving therapeutic VEGF gene
transfer.8
Because MNCCD34+ give rise to
EPCs and to hematopoietic progenitors, we analyzed the number
of circulating EPCs by PB-MNC culture assay. In our previous studies, a
subset of PB-MNCs differentiated into EPCs during
culture.2 5 In the
present study, PB-MNCs formed multiple cell clusters, and
spindle-shaped attaching cells sprouted from the clusters. The
morphological appearance of attaching cells resembled that of EPCs
originating from human PB, which we reported
recently.2 5 In
addition, >80% of attaching cells expressed EC-lineage markers and
function (KDR, VE-cadherin, CD31, and DiI-acLDL uptake). Thus, we
defined attaching cells as a major population of EPCs. A greater number
of EPCs and cell clusters developed from a culture of PB-MNCs obtained
on day 7 than those obtained on day 1 in AMI patients. Given the fact
that EPCs derive from
MNCCD34+,2 5
the results of the culture assay for circulating EPCs are
consistent with the time course of the circulating
MNCCD34+ counts
(Figure 1A
).
The present study has several limitations. First, we do not know whether EPCs participate in neovascularization after AMI. Because one cannot obtain cardiac tissues from AMI patients and because bone marrowderived ECs cannot be distinguished from native ECs due to the lack of exclusive markers, this issue may be difficult to prove. Nevertheless, a recent study showed that bone marrowderived EPCs had participated in neovascularization in patients with fatal AMI with preceding allogenic bone marrow transplantation.9 10 Also, Asahara et al3 showed that EPCs were mobilized from bone marrow and accumulated within the ischemic border zone after AMI in animals. Thus, the elevated circulating EPCs likely contribute to neovascularization (postnatal vasculogenesis), although it is unknown whether EPCs can vascularize scar tissues as well. Second, mature ECs may also circulate in the PB. However, Mutin et al11 reported that the number of circulating mature ECs was low, even in patients with AMI (10 to 100 cells/mL blood), whereas circulating EPCs ranged between 0.3 to 1x104 cells/mL.5 8 Moreover, mature ECs have a low proliferative activity and do not participate in neovascularization.9 12 13 Third, doses of medications, such as isosorbide dinitrate and aspirin, were different between the AMI and control groups. However, no study has reported that such drugs alter either hematopoiesis or MNCCD34+ mobilization. Thus, it is less likely that EPCs were mobilized in response to these drugs in AMI patients. Finally, all subjects underwent cardiac catheterization using heparin; thus, the catheterization procedure itself did not likely account for the augmented EPC mobilization.
In summary, the present study is the first to demonstrate that EPCs and their putative precursor, MNCCD34+, are mobilized into PB during an acute ischemic event in humans. The functional roles of mobilized EPCs should be determined further.
| Acknowledgments |
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Received February 12, 2001; revision received April 26, 2001; accepted April 26, 2001.
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C. Murphy, G. S. Kanaganayagam, B. Jiang, P. J. Chowienczyk, R. Zbinden, M. Saha, S. Rahman, A. M. Shah, M. S. Marber, and M. T. Kearney Vascular Dysfunction and Reduced Circulating Endothelial Progenitor Cells in Young Healthy UK South Asian Men Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 936 - 942. [Abstract] [Full Text] [PDF] |
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T. Inoue, M. Sata, Y. Hikichi, R. Sohma, D. Fukuda, T. Uchida, M. Shimizu, H. Komoda, and K. Node Mobilization of CD34-Positive Bone Marrow-Derived Cells After Coronary Stent Implantation: Impact on Restenosis Circulation, February 6, 2007; 115(5): 553 - 561. [Abstract] [Full Text] [PDF] |
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N. Roberts, Q. Xiao, G. Weir, Q. Xu, and M. Jahangiri Endothelial Progenitor Cells are Mobilized After Cardiac Surgery Ann. Thorac. Surg., February 1, 2007; 83(2): 598 - 605. [Abstract] [Full Text] [PDF] |
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A. Aicher, C. Heeschen, K.-i. Sasaki, C. Urbich, A. M. Zeiher, and S. Dimmeler Low-Energy Shock Wave for Enhancing Recruitment of Endothelial Progenitor Cells: A New Modality to Increase Efficacy of Cell Therapy in Chronic Hind Limb Ischemia Circulation, December 19, 2006; 114(25): 2823 - 2830. [Abstract] [Full Text] [PDF] |
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E. Lipsic, R. G. Schoemaker, P. van der Meer, A. A. Voors, D. J. van Veldhuisen, and W. H. van Gilst Protective Effects of Erythropoietin in Cardiac Ischemia: From Bench to Bedside J. Am. Coll. Cardiol., December 5, 2006; 48(11): 2161 - 2167. [Abstract] [Full Text] [PDF] |
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D. Zohlnhofer, I. Ott, A. Kastrati, and A. Schomig Granulocyte Colony-Stimulating Factor and Acute Myocardial Infarction--Reply JAMA, October 25, 2006; 296(16): 1968 - 1969. [Full Text] [PDF] |
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C. J. Boos, G. Y.H. Lip, and A. D. Blann Circulating Endothelial Cells in Cardiovascular Disease J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1538 - 1547. [Abstract] [Full Text] [PDF] |
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J. Leor and M. Marber Endothelial Progenitors: A New Tower of Babel? J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1588 - 1590. [Full Text] [PDF] |
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L. Postiglione, S. Montagnani, P. Ladogana, C. Castaldo, G. Di Spigna, E. M. Bruno, M. Turano, L. De Santo, G. Cudemo, S. Cocozza, et al. Granulocyte Macrophage-Colony Stimulating Factor receptor expression on human cardiomyocytes from end-stage heart failure patients Eur J Heart Fail, October 1, 2006; 8(6): 564 - 570. [Abstract] [Full Text] [PDF] |
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B. J. Capoccia, R. M. Shepherd, and D. C. Link G-CSF and AMD3100 mobilize monocytes into the blood that stimulate angiogenesis in vivo through a paracrine mechanism Blood, October 1, 2006; 108(7): 2438 - 2445. [Abstract] [Full Text] [PDF] |
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C.-H. Wang, N. Anderson, S.-H. Li, P. E. Szmitko, W.-J. Cherng, P. W.M. Fedak, S. Fazel, R.-K. Li, T. M. Yau, R. D. Weisel, et al. Stem Cell Factor Deficiency Is Vasculoprotective: Unraveling a New Therapeutic Potential of Imatinib Mesylate Circ. Res., September 15, 2006; 99(6): 617 - 625. [Abstract] [Full Text] [PDF] |
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M. Takaoka, S. Uemura, H. Kawata, K.-i. Imagawa, Y. Takeda, K. Nakatani, N. Naya, M. Horii, S. Yamano, Y. Miyamoto, et al. Inflammatory Response to Acute Myocardial Infarction Augments Neointimal Hyperplasia After Vascular Injury in a Remote Artery Arterioscler Thromb Vasc Biol, September 1, 2006; 26(9): 2083 - 2089. [Abstract] [Full Text] [PDF] |
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A. Hirata, T. Minamino, H. Asanuma, M. Fujita, M. Wakeno, M. Myoishi, O. Tsukamoto, K.-i. Okada, H. Koyama, K. Komamura, et al. Erythropoietin Enhances Neovascularization of Ischemic Myocardium and Improves Left Ventricular Dysfunction After Myocardial Infarction in Dogs J. Am. Coll. Cardiol., July 4, 2006; 48(1): 176 - 184. [Abstract] [Full Text] [PDF] |
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S. Mieno, B. Ramlawi, M. Boodhwani, R. T. Clements, K. Minamimura, T. Maki, S.-H. Xu, C. Bianchi, J. Li, and F. W. Sellke Role of Stromal-Derived Factor-1{alpha} in the Induction of Circulating CD34+CXCR4+ Progenitor Cells After Cardiac Surgery. Circulation, July 4, 2006; 114(1 Suppl): 186 - 192. [Abstract] [Full Text] [PDF] |
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Y. Numaguchi, T. Sone, K. Okumura, M. Ishii, Y. Morita, R. Kubota, K. Yokouchi, H. Imai, M. Harada, H. Osanai, et al. The Impact of the Capability of Circulating Progenitor Cell to Differentiate on Myocardial Salvage in Patients With Primary Acute Myocardial Infarction Circulation, July 4, 2006; 114(1_suppl): I-114 - I-119. [Abstract] [Full Text] [PDF] |
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J. M. DiFabio, G. R. Thomas, L. Zucco, M. A. Kuliszewski, B. M. Bennett, M. J. Kutryk, and J. D. Parker Nitroglycerin Attenuates Human Endothelial Progenitor Cell Differentiation, Function, and Survival J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 117 - 123. [Abstract] [Full Text] [PDF] |
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B. Li, E. E. Sharpe, A. B. Maupin, A. A. Teleron, A. L. Pyle, P. Carmeliet, and P. P. Young VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization FASEB J, July 1, 2006; 20(9): 1495 - 1497. [Abstract] [Full Text] [PDF] |
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Y Wang, H E Johnsen, S Mortensen, L Bindslev, R Sejersten Ripa, M Haack-Sorensen, E Jorgensen, W Fang, and J Kastrup Changes in circulating mesenchymal stem cells, stem cell homing factor, and vascular growth factors in patients with acute ST elevation myocardial infarction treated with primary percutaneous coronary intervention Heart, June 1, 2006; 92(6): 768 - 774. [Abstract] [Full Text] [PDF] |
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L. d. S. Meirelles, P. C. Chagastelles, and N. B. Nardi Mesenchymal stem cells reside in virtually all post-natal organs and tissues J. Cell Sci., June 1, 2006; 119(11): 2204 - 2213. [Abstract] [Full Text] [PDF] |
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R. Blindt, F. Vogt, I. Astafieva, C. Fach, M. Hristov, N. Krott, B. Seitz, A. Kapurniotu, C. Kwok, M. Dewor, et al. A Novel Drug-Eluting Stent Coated With an Integrin-Binding Cyclic Arg-Gly-Asp Peptide Inhibits Neointimal Hyperplasia by Recruiting Endothelial Progenitor Cells J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1786 - 1795. [Abstract] [Full Text] [PDF] |
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P. Atluri, G. P. Liao, C. M. Panlilio, V. M. Hsu, M. J. Leskowitz, K. J. Morine, J. E. Cohen, M. F. Berry, E. E. Suarez, D. A. Murphy, et al. Neovasculogenic therapy to augment perfusion and preserve viability in ischemic cardiomyopathy. Ann. Thorac. Surg., May 1, 2006; 81(5): 1728 - 1736. [Abstract] [Full Text] [PDF] |
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K. Schomig, G. Busch, B. Steppich, D. Sepp, J. Kaufmann, A. Stein, A. Schomig, and I. Ott Interleukin-8 is associated with circulating CD133+ progenitor cells in acute myocardial infarction Eur. Heart J., May 1, 2006; 27(9): 1032 - 1037. [Abstract] [Full Text] [PDF] |
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W. Wojakowski, M. Z. Ratajczak, and M. Tendera Interleukin-8: more on the mechanisms of progenitor cells mobilization in acute coronary syndromes Eur. Heart J., May 1, 2006; 27(9): 1013 - 1015. [Full Text] [PDF] |
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S. A. de Oliveira, L. H. W. Gowdak, G. Buckberg, J. E. Krieger, and the RESTORE Group Cell biology, MRI and geometry: insight into a microscopic/macroscopic marriage Eur. J. Cardiothorac. Surg., April 1, 2006; 29(Suppl_1): S259 - S265. [Abstract] [Full Text] [PDF] |
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S. R. Thom, V. M. Bhopale, O. C. Velazquez, L. J. Goldstein, L. H. Thom, and D. G. Buerk Stem cell mobilization by hyperbaric oxygen Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1378 - H1386. [Abstract] [Full Text] [PDF] |
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T. Thum, D. Fraccarollo, P. Galuppo, D. Tsikas, S. Frantz, G. Ertl, and J. Bauersachs Bone marrow molecular alterations after myocardial infarction: Impact on endothelial progenitor cells Cardiovasc Res, April 1, 2006; 70(1): 50 - 60. [Abstract] [Full Text] [PDF] |
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A. Iwakura, S. Shastry, C. Luedemann, H. Hamada, A. Kawamoto, R. Kishore, Y. Zhu, G. Qin, M. Silver, T. Thorne, et al. Estradiol Enhances Recovery After Myocardial Infarction by Augmenting Incorporation of Bone Marrow-Derived Endothelial Progenitor Cells Into Sites of Ischemia-Induced Neovascularization via Endothelial Nitric Oxide Synthase-Mediated Activation of Matrix Metalloproteinase-9 Circulation, March 28, 2006; 113(12): 1605 - 1614. [Abstract] [Full Text] [PDF] |
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F. G.P. Welt and D. W. Losordo Cell Therapy for Acute Myocardial Infarction: Curb Your Enthusiasm? Circulation, March 14, 2006; 113(10): 1272 - 1274. [Full Text] [PDF] |
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D. Zohlnhofer, I. Ott, J. Mehilli, K. Schomig, F. Michalk, T. Ibrahim, G. Meisetschlager, J. von Wedel, H. Bollwein, M. Seyfarth, et al. Stem Cell Mobilization by Granulocyte Colony-Stimulating Factor in Patients With Acute Myocardial Infarction: A Randomized Controlled Trial JAMA, March 1, 2006; 295(9): 1003 - 1010. [Abstract] [Full Text] [PDF] |
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A. Goette, K. Jentsch-Ullrich, M. Hammwohner, S. Trautmann, A. Franke, H. U. Klein, and A. Auricchio Cardiac uptake of progenitor cells in patients with moderate-to-severe left ventricular failure scheduled for cardiac resynchronization therapy. Europace, March 1, 2006; 8(3): 157 - 160. [Abstract] [Full Text] [PDF] |
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W. Wojakowski, M. Tendera, A. Zebzda, A. Michalowska, M. Majka, M. Kucia, K. Maslankiewicz, R. Wyderka, M. Krol, A. Ochala, et al. Mobilization of CD34+, CD117+, CXCR4+, c-met+ stem cells is correlated with left ventricular ejection fraction and plasma NT-proBNP levels in patients with acute myocardial infarction Eur. Heart J., February 1, 2006; 27(3): 283 - 289. [Abstract] [Full Text] [PDF] |
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J.-S. Silvestre and B. I. Levy Molecular Basis of Angiopathy in Diabetes Mellitus Circ. Res., January 6, 2006; 98(1): 4 - 6. [Full Text] [PDF] |
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L. Ye, H. K. Haider, and E. K. W. Sim Adult Stem Cells for Cardiac Repair: A Choice Between Skeletal Myoblasts and Bone Marrow Stem Cells Experimental Biology and Medicine, January 1, 2006; 231(1): 8 - 19. [Abstract] [Full Text] [PDF] |
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M. Muta, G. Matsumoto, E. Nakashima, and M. Toi Mechanical Analysis of Tumor Growth Regression by the Cyclooxygenase-2 Inhibitor, DFU, in a Walker256 Rat Tumor Model: Importance of Monocyte Chemoattractant Protein-1 Modulation Clin. Cancer Res., January 1, 2006; 12(1): 264 - 272. [Abstract] [Full Text] [PDF] |
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D. H. Kim, H.-B. Leu, J.-W. Chen, S.-J. Lin, H. C. Ott, D. A. Taylor, F. Bertolini, P. Mancuso, R. S. Kerbel, C. J. Boos, et al. Circulating Endothelial Progenitor Cells N. Engl. J. Med., December 15, 2005; 353(24): 2613 - 2616. [Full Text] [PDF] |
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J. George, A. Afek, A. Abashidze, H. Shmilovich, V. Deutsch, J. Kopolovich, H. Miller, and G. Keren Transfer of Endothelial Progenitor and Bone Marrow Cells Influences Atherosclerotic Plaque Size and Composition in Apolipoprotein E Knockout Mice Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2636 - 2641. [Abstract] [Full Text] [PDF] |
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H. Ince, M. Petzsch, H. D. Kleine, H. Schmidt, T. Rehders, T. Korber, C. Schumichen, M. Freund, and C. A. Nienaber Preservation From Left Ventricular Remodeling by Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Use of Granulocyte-Colony-Stimulating Factor (FIRSTLINE-AMI) Circulation, November 15, 2005; 112(20): 3097 - 3106. [Abstract] [Full Text] [PDF] |
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G. Garin, M. Mathews, and B. C. Berk Tissue-Resident Bone Marrow-Derived Progenitor Cells: Key Players in Hypoxia-Induced Angiogenesis Circ. Res., November 11, 2005; 97(10): 955 - 957. [Full Text] [PDF] |
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G. Kanaganayagam and M. S. Marber ADMAring Endothelial Progenitor Cells: Accident, Association, or Antecedent J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1702 - 1704. [Full Text] [PDF] |
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J. George, E. Goldstein, A. Abashidze, D. Wexler, S. Hamed, H. Shmilovich, V. Deutsch, H. Miller, G. Keren, and A. Roth Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner Cardiovasc Res, November 1, 2005; 68(2): 299 - 306. [Abstract] [Full Text] [PDF] |
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F. Limana, A. Germani, A. Zacheo, J. Kajstura, A. Di Carlo, G. Borsellino, O. Leoni, R. Palumbo, L. Battistini, R. Rastaldo, et al. Exogenous High-Mobility Group Box 1 Protein Induces Myocardial Regeneration After Infarction via Enhanced Cardiac C-Kit+ Cell Proliferation and Differentiation Circ. Res., October 14, 2005; 97(8): e73 - e83. [Abstract] [Full Text] [PDF] |
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N. Werner, S. Kosiol, T. Schiegl, P. Ahlers, K. Walenta, A. Link, M. Bohm, and G. Nickenig Circulating Endothelial Progenitor Cells and Cardiovascular Outcomes N. Engl. J. Med., September 8, 2005; 353(10): 999 - 1007. [Abstract] [Full Text] [PDF] |
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M. Valgimigli, G. M. Rigolin, C. Cittanti, P. Malagutti, S. Curello, G. Percoco, A. M. Bugli, M. D. Porta, L. Z. Bragotti, L. Ansani, et al. Use of granulocyte-colony stimulating factor during acute myocardial infarction to enhance bone marrow stem cell mobilization in humans: clinical and angiographic safety profile Eur. Heart J., September 2, 2005; 26(18): 1838 - 1845. [Abstract] [Full Text] [PDF] |
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S. Murakami, N. Nagaya, T. Itoh, T. Iwase, T. Fujisato, K. Nishioka, K. Hamada, K. Kangawa, and H. Kimura Adrenomedullin Regenerates Alveoli and Vasculature in Elastase-induced Pulmonary Emphysema in Mice Am. J. Respir. Crit. Care Med., September 1, 2005; 172(5): 581 - 589. [Abstract] [Full Text] [PDF] |
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H. Ince, M. Petzsch, H. D. Kleine, H. Eckard, T. Rehders, D. Burska, S. Kische, M. Freund, and C. A. Nienaber Prevention of Left Ventricular Remodeling With Granulocyte Colony-Stimulating Factor After Acute Myocardial Infarction: Final 1-year Results of the Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Granulocyte Colony-Stimulating Factor (FIRSTLINE-AMI) Trial Circulation, August 30, 2005; 112(9_suppl): I-73 - I-80. [Abstract] [Full Text] [PDF] |
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