(Circulation. 2001;103:634.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
From the Division of Cardiovascular Research, St Elizabeths Medical Center, Tufts University School of Medicine, Boston, Mass.
Correspondence to Takayuki Asahara, MD, or Jeffrey M. Isner, MD, St Elizabeths Medical Center, 736 Cambridge Street, Boston, MA 02135. E-mail VeJeff{at}aol.com
| Abstract |
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Methods and ResultsPeripheral blood mononuclear cells obtained from healthy human adults were cultured in EPC medium and harvested 7 days later. Myocardial ischemia was induced by ligating the left anterior descending coronary artery in male Hsd:RH-rnu (athymic nude) rats. A total of 106 EPCs labeled with 1,1'-dioctadecyl-1 to 3,3,3',3'-tetramethylindocarbocyanine perchlorate were injected intravenously 3 hours after the induction of myocardial ischemia. Seven days later, fluorescence-conjugated Bandeiraea simplicifolia lectin I was administered intravenously, and the rats were immediately killed. Fluorescence microscopy revealed that transplanted EPCs accumulated in the ischemic area and incorporated into foci of myocardial neovascularization. To determine the impact on left ventricular function, 5 rats (EPC group) were injected intravenously with 106 EPCs 3 hours after ischemia; 5 other rats (control group) received culture media. Echocardiography, performed just before and 28 days after ischemia, disclosed ventricular dimensions that were significantly smaller and fractional shortening that was significantly greater in the EPC group than in the control group by day 28. Regional wall motion was better preserved in the EPC group. After euthanization on day 28, necropsy examination disclosed that capillary density was significantly greater in the EPC group than in the control group. Moreover, the extent of left ventricular scarring was significantly less in rats receiving EPCs than in controls. Immunohistochemistry revealed capillaries that were positive for human-specific endothelial cells.
ConclusionsEx vivo expanded EPCs incorporate into foci of myocardial neovascularization and have a favorable impact on the preservation of left ventricular function.
Key Words: endothelium stem cells ischemia regeneration neovascularization
| Introduction |
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| Methods |
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Animal Model of Myocardial Ischemia
All procedures were performed in accordance
with St Elizabeths Institutional Animal Care and Use Committee. Male
athymic nude rats (Hsd:RH-rnu rats, Harlan Sprague Dawley,
Indianapolis, Ind) aged 6 to 8 weeks were anesthetized with sodium
pentobarbital (50 mg/kg IP). Myocardial ischemia was induced by
ligating the left anterior descending (LAD) coronary
artery.11 Immediately before
euthanization, rats were injected with an overdose of
pentobarbital.
Transplantation of Ex Vivo Expanded
EPCs
Three hours after inducing myocardial ischemia, rats
received intravenous injections of 106
culture-expanded human EPCs resuspended with 200 µL of EBM-2 (n=5) or
the same volume of EBM-2 without cells (n=5). These rats were killed 28
days after myocardial ischemia.
To evaluate the incorporation of EPCs into ischemic myocardium, cells were labeled with fluorescent carbocyanine 1,1'-dioctadecyl-1 to 3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) dye (Molecular Probes).10 Athymic nude rats (n=2) received DiI-labeled EPCs (106 cells) by intravenous injection 3 hours after myocardial ischemia. This subgroup of rats was killed on day 7 after myocardial ischemia. Thirty minutes before euthanization, 500 µg of Bandeiraea simplicifolia lectin I (Vector Laboratories), the murine-specific EC marker, was administered intravenously.
Histological Assessment of Transplanted
Animals
At necropsy, hearts were sliced in a bread-loaf
fashion into 8 transverse sections from apex to base and fixed with 4%
paraformaldehyde. In 2 rats injected with DiI-labeled EPCs, fixed
tissues were embedded in OCT compound (Miles Scientific) and
snap-frozen in liquid nitrogen for fluorescence microscopy. In the
remaining 10 rats, paraffin-embedded tissues were used to measure the
average ratio of fibrosis area to LV area. Immunohistochemical staining
was performed using antibodies prepared against the murine-specific EC
marker isolectin B4 (Vector Laboratories), as well as antibodies
against the human-specific EC markers CD31 (DAKO) and ulex europaeus
lectin type 1 (Vector
Laboratories).10
Capillary density was evaluated morphometrically by histological examination of 5 randomly selected fields of tissue sections recovered from segments of LV myocardium, subserved by the occluded LAD. Capillaries were recognized as tubular structures positive for isolectin B4. All morphometric studies were performed by 2 examiners (H.M., H.I.) who were blinded to treatment.
Physiological Assessment of LV Function
Transthoracic echocardiography (SONOS 5500, Hewlett
Packard) was performed just before (baseline) and 28 days after
myocardial ischemia. LV diastolic (LVDd) and systolic (LVDs) dimensions
and fractional shortening were measured at the midpapillary muscle
level. Regional wall motion score was examined per published
criteria.12 All procedures
and analyses were performed by an experienced researcher (H.-C.G.) who
was blinded to treatment.
Statistical Analysis
All values were expressed as mean±SE. Unpaired
t tests were performed to
compare values between treated and control rats. Paired
t tests were used to compare
echocardiographic parameters between baseline and day 28.
P<0.05 was considered
statistically significant.
| Results |
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Exogenous Human EPCs Differentiate to Mature
ECs in the Rat Heart
Human CD31-positive and ulex europaeus lectin type
1positive mature ECs were identified in the vasculature of that
portion of myocardium subserved by the occluded LAD
(Figure 1d
and 1e
). Thus, ex vivo expanded and intravenously
administered human EPCs differentiated to mature ECs in rat ischemic
myocardium.
Morphometric Evaluation of Capillary Density
and Infarct Size
Capillary density 28 days after the development of
myocardial ischemia was significantly greater in rats receiving
human EPCs than in control rats (290.1±21.5 versus
191.1±17.8/mm2,
P=0.0009;
Figure 2a
through 2c). The ratio of percent fibrosis
area/entire LV area was significantly lower in rats receiving EPCs than
in rats in the control group (8.9±0.9 versus 17.8±1.4%,
P=0.0007;
Figure 2d
through 2f).
|
Ex Vivo Expanded EPCs Preserve LV Function
After Myocardial Ischemia
LVDd, LVDs, fractional shortening, and regional wall
motion scores at baseline were not significantly different between rats
receiving EPCs versus control rats. In rats receiving EPCs and in
control rats, LVDd and LVDs increased significantly during the 28 days
after myocardial ischemia
(P<0.01 in both groups),
whereas fractional shortening significantly decreased and regional wall
motion scores significantly worsened
(P<0.01 in both
groups).
By day 28, however, LVDd and LVDs were significantly lower
in rats receiving EPCs than in control rats (LVDd: 0.87±0.03 versus
0.93±0.01 cm, P=0.032; LVDs:
0.68±0.03 versus 0.79±0.02 cm,
P=0.005). Fractional shortening
on day 28 was significantly higher in rats receiving EPCs than in
controls (21.3±0.6% versus 15.3±2.2%,
P=0.0004). Regional wall motion
was also better preserved in rats receiving EPCs than in those in the
control group (25.3±0.8 versus 30.6±1.0,
P=0.0021;
Figure 2g
).
Thus, echocardiographic examination performed before and after myocardial ischemia suggests that the intravenous administration of ex vivo expanded EPCs had a favorable impact on the preservation of LV function in rats with myocardial ischemia.
| Discussion |
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The recent demonstration that the bone marrowderived EC precursors present in peripheral blood may home to and incorporate into sites of neovascularization4 7 8 has prompted an investigation of cell-based approaches. In certain cases, this has involved the use of total bone marrow cells that were transplanted intramyocardially and were shown to enhance neovascularization at sites of myocardial injury.13 14 These approaches not only merit but require further investigation. Parenteral harvest and administration of cultured EPCs is clearly less invasive than bone marrow aspiration with direct myocardial transplantation. However, the safety of ex vivo culture expansion of the cells for clinical applications remains to be demonstrated. Also implicit in the use of the total bone marrow mononuclear cell populations is the potential for differentiation into nonendothelial lineage cells, including osteoblasts, chondroblasts, and fibroblasts. To avoid this potential problem, we transplanted ex vivo cultured EPCs that were expanded and enriched in a prespecified culture system.
The strategy of therapeutic neovascularization used here contrasts with those approaches in which genes, growth factors, or cells are delivered by local administration to optimize activity in the target region. Previous studies performed in our laboratory4 indicated that intravenously injected EPCs may specifically home to the sites of nascent neovascularization and differentiate into mature ECs. Indeed, this finding was the basis for studies that established proof of the concept that exogenously administered EPCs could accelerate revascularization and promote limb salvage in mice with hindlimb ischemia.10 The current study extends these previous findings by documenting that exogenously administered EPCs home to foci of myocardial neovascularization, augment vascularity, and exert a favorable impact on the preservation of LV function.
Capillary density, a direct anatomic reflection of neovascularization, was significantly greater in rats transplanted with EPCs than in control rats in this study. Enhanced neovascularization after the administration of ex vivo expanded EPCs led to a reduction in LV dilatation and a preservation of contractile performance after myocardial ischemia. The precise mechanism of these favorable effects of EPCs on cardiac function requires further elucidation. Rescue of hibernating myocardium, recently documented in human subjects after therapeutic angiogenesis,3 may have contributed to this improved physiology. The statistically significant reduction in the extent of myocardial fibrosis may also be a factor; previous clinical and experimental studies demonstrated that late reperfusion of the infarct vascular bed attenuates left ventricular remodeling, including infarct expansion.15 16 EPC transplantation may thus inhibit LV remodeling after myocardial infarction via an improvement in myocardial blood flow.
| Acknowledgments |
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Received September 27, 2000; revision received December 13, 2000; accepted December 20, 2000.
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T. Matsumoto, A. Kawamoto, R. Kuroda, M. Ishikawa, Y. Mifune, H. Iwasaki, M. Miwa, M. Horii, S. Hayashi, A. Oyamada, et al. Therapeutic Potential of Vasculogenesis and Osteogenesis Promoted by Peripheral Blood CD34-Positive Cells for Functional Bone Healing Am. J. Pathol., October 1, 2006; 169(4): 1440 - 1457. [Abstract] [Full Text] [PDF] |
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J. Li, J. A. Deane, N. V. Campanale, J. F. Bertram, and S. D. Ricardo Blockade of p38 Mitogen-Activated Protein Kinase and TGF-beta1/Smad Signaling Pathways Rescues Bone Marrow-Derived Peritubular Capillary Endothelial Cells in Adriamycin-Induced Nephrosis J. Am. Soc. Nephrol., October 1, 2006; 17(10): 2799 - 2811. [Abstract] [Full Text] [PDF] |
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V. Schachinger, S. Erbs, A. Elsasser, W. Haberbosch, R. Hambrecht, H. Holschermann, J. Yu, R. Corti, D. G. Mathey, C. W. Hamm, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N. Engl. J. Med., September 21, 2006; 355(12): 1210 - 1221. [Abstract] [Full Text] [PDF] |
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B. Assmus, J. Honold, V. Schachinger, M. B. Britten, U. Fischer-Rasokat, R. Lehmann, C. Teupe, K. Pistorius, H. Martin, N. D. Abolmaali, et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N. Engl. J. Med., September 21, 2006; 355(12): 1222 - 1232. [Abstract] [Full Text] [PDF] |
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T. Ishikawa, M. Eguchi, M. Wada, Y. Iwami, K. Tono, H. Iwaguro, H. Masuda, T. Tamaki, and T. Asahara Establishment of a Functionally Active Collagen-Binding Vascular Endothelial Growth Factor Fusion Protein In Situ Arterioscler Thromb Vasc Biol, September 1, 2006; 26(9): 1998 - 2004. [Abstract] [Full Text] [PDF] |
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R. S. Ripa, Y. Wang, E. Jorgensen, H. E. Johnsen, B. Hesse, and J. Kastrup Intramyocardial injection of vascular endothelial growth factor-A165 plasmid followed by granulocyte-colony stimulating factor to induce angiogenesis in patients with severe chronic ischaemic heart disease Eur. Heart J., August 1, 2006; 27(15): 1785 - 1792. [Abstract] [Full Text] [PDF] |
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Y. Misao, G. Takemura, M. Arai, T. Ohno, H. Onogi, T. Takahashi, S. Minatoguchi, T. Fujiwara, and H. Fujiwara Importance of recruitment of bone marrow-derived CXCR4+ cells in post-infarct cardiac repair mediated by G-CSF Cardiovasc Res, August 1, 2006; 71(3): 455 - 465. [Abstract] [Full Text] [PDF] |
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D. You, L. Waeckel, T. G. Ebrahimian, O. Blanc-Brude, P. Foubert, V. Barateau, M. Duriez, S. LeRicousse-Roussanne, J. Vilar, E. Dejana, et al. Increase in Vascular Permeability and Vasodilation Are Critical for Proangiogenic Effects of Stem Cell Therapy Circulation, July 25, 2006; 114(4): 328 - 338. [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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H.-J. Kang, H.-Y. Lee, S.-H. Na, S.-A Chang, K.-W. Park, H.-K. Kim, S.-Y. Kim, H.-J. Chang, W. Lee, W. J. Kang, et al. Differential Effect of Intracoronary Infusion of Mobilized Peripheral Blood Stem Cells by Granulocyte Colony-Stimulating Factor on Left Ventricular Function and Remodeling in Patients With Acute Myocardial Infarction Versus Old Myocardial Infarction: The MAGIC Cell-3-DES Randomized, Controlled Trial Circulation, July 4, 2006; 114(1_suppl): I-145 - I-151. [Abstract] [Full Text] [PDF] |
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R. Uemura, M. Xu, N. Ahmad, and M. Ashraf Bone Marrow Stem Cells Prevent Left Ventricular Remodeling of Ischemic Heart Through Paracrine Signaling Circ. Res., June 9, 2006; 98(11): 1414 - 1421. [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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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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C.-H. Yoon, J. Hur, I.-Y. Oh, K.-W. Park, T.-Y. Kim, J.-H. Shin, J.-H. Kim, C.-S. Lee, J.-K. Chung, Y.-B. Park, et al. Intercellular Adhesion Molecule-1 Is Upregulated in Ischemic Muscle, Which Mediates Trafficking of Endothelial Progenitor Cells Arterioscler Thromb Vasc Biol, May 1, 2006; 26(5): 1066 - 1072. [Abstract] [Full Text] [PDF] |
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T. Yoshioka, M. Takahashi, Y. Shiba, C. Suzuki, H. Morimoto, A. Izawa, H. Ise, and U. Ikeda Granulocyte colony-stimulating factor (G-CSF) accelerates reendothelialization and reduces neointimal formation after vascular injury in mice Cardiovasc Res, April 1, 2006; 70(1): 61 - 69. [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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H. Iwasaki, A. Kawamoto, M. Ishikawa, A. Oyamada, S. Nakamori, H. Nishimura, K. Sadamoto, M. Horii, T. Matsumoto, S. Murasawa, et al. Dose-Dependent Contribution of CD34-Positive Cell Transplantation to Concurrent Vasculogenesis and Cardiomyogenesis for Functional Regenerative Recovery After Myocardial Infarction Circulation, March 14, 2006; 113(10): 1311 - 1325. [Abstract] [Full Text] [PDF] |
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H. Jin, J. Su, B. Garmy-Susini, J. Kleeman, and J. Varner Integrin {alpha}4{beta}1 Promotes Monocyte Trafficking and Angiogenesis in Tumors Cancer Res., February 15, 2006; 66(4): 2146 - 2152. [Abstract] [Full Text] [PDF] |
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N. Werner and G. Nickenig Influence of Cardiovascular Risk Factors on Endothelial Progenitor Cells: Limitations for Therapy? Arterioscler Thromb Vasc Biol, February 1, 2006; 26(2): 257 - 266. [Abstract] [Full Text] [PDF] |
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Y. Misao, G. Takemura, M. Arai, S. Sato, K. Suzuki, S. Miyata, K.-i. Kosai, S. Minatoguchi, T. Fujiwara, and H. Fujiwara Bone marrow-derived myocyte-like cells and regulation of repair-related cytokines after bone marrow cell transplantation Cardiovasc Res, February 1, 2006; 69(2): 476 - 490. [Abstract] [Full Text] [PDF] |
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G. Qin, M. Ii, M. Silver, A. Wecker, E. Bord, H. Ma, M. Gavin, D. A. Goukassian, Y.-s. Yoon, T. Papayannopoulou, et al. Functional disruption of {alpha}4 integrin mobilizes bone marrow-derived endothelial progenitors and augments ischemic neovascularization J. Exp. Med., January 23, 2006; 203(1): 153 - 163. [Abstract] [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. Nakagami, K. Maeda, R. Morishita, S. Iguchi, T. Nishikawa, Y. Takami, Y. Kikuchi, Y. Saito, K. Tamai, T. Ogihara, et al. Novel Autologous Cell Therapy in Ischemic Limb Disease Through Growth Factor Secretion by Cultured Adipose Tissue-Derived Stromal Cells Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2542 - 2547. [Abstract] [Full Text] [PDF] |
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D. H. Walter, J. Haendeler, J. Reinhold, U. Rochwalsky, F. Seeger, J. Honold, J. Hoffmann, C. Urbich, R. Lehmann, F. Arenzana-Seisdesdos, et al. Impaired CXCR4 Signaling Contributes to the Reduced Neovascularization Capacity of Endothelial Progenitor Cells From Patients With Coronary Artery Disease Circ. Res., November 25, 2005; 97(11): 1142 - 1151. [Abstract] [Full Text] [PDF] |
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C. E. Murry, L. J. Field, and P. Menasche Cell-Based Cardiac Repair: Reflections at the 10-Year Point Circulation, November 15, 2005; 112(20): 3174 - 3183. [Full Text] [PDF] |
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R. R. Makkar, M. J. Price, M. Lill, M. Frantzen, K. Takizawa, T. Kleisli, J. Zheng, S. Kar, R. McClelan, T. Miyamota, et al. Intramyocardial Injection of Allogenic Bone Marrow-Derived Mesenchymal Stem Cells Without Immunosuppression Preserves Cardiac Function in a Porcine Model of Myocardial Infarction Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 2005; 10(4): 225 - 233. [Abstract] [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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C. Kupatt, R. Hinkel, M. Lamparter, M.-L. von Bruhl, T. Pohl, J. Horstkotte, H. Beck, S. Muller, S. Delker, F.-J. Gildehaus, et al. Retroinfusion of Embryonic Endothelial Progenitor Cells Attenuates Ischemia-Reperfusion Injury in Pigs: Role of Phosphatidylinositol 3-Kinase/AKT Kinase Circulation, August 30, 2005; 112(9_suppl): I-117 - I-122. [Abstract] [Full Text] [PDF] |
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M. Siepe, C. Heilmann, P. von Samson, P. Menasche, and F. Beyersdorf Stem cell research and cell transplantation for myocardial regeneration Eur. J. Cardiothorac. Surg., August 1, 2005; 28(2): 318 - 324. [Abstract] [Full Text] [PDF] |
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S. Murasawa, A. Kawamoto, M. Horii, S. Nakamori, and T. Asahara Niche-Dependent Translineage Commitment of Endothelial Progenitor Cells, Not Cell Fusion in General, Into Myocardial Lineage Cells Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1388 - 1394. [Abstract] [Full Text] [PDF] |
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V. J. Dzau, M. Gnecchi, A. S. Pachori, F. Morello, and L. G. Melo Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases Hypertension, July 1, 2005; 46(1): 7 - 18. [Abstract] [Full Text] [PDF] |
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N. Nagaya, H. Mori, S. Murakami, K. Kangawa, and S. Kitamura Adrenomedullin: angiogenesis and gene therapy Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1432 - R1437. [Abstract] [Full Text] [PDF] |
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U. Landmesser, F. Bahlmann, M. Mueller, S. Spiekermann, N. Kirchhoff, S. Schulz, C. Manes, D. Fischer, K. de Groot, D. Fliser, et al. Simvastatin Versus Ezetimibe: Pleiotropic and Lipid-Lowering Effects on Endothelial Function in Humans Circulation, May 10, 2005; 111(18): 2356 - 2363. [Abstract] [Full Text] [PDF] |
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M. A. Costa and D. I. Simon Molecular Basis of Restenosis and Drug-Eluting Stents Circulation, May 3, 2005; 111(17): 2257 - 2273. [Full Text] [PDF] |
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D. Schmidt, A. Mol, S. Neuenschwander, C. Breymann, M. Gossi, G. Zund, M. Turina, and S. P. Hoerstrup Living patches engineered from human umbilical cord derived fibroblasts and endothelial progenitor cells Eur. J. Cardiothorac. Surg., May 1, 2005; 27(5): 795 - 800. [Abstract] [Full Text] [PDF] |
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P. Madeddu Therapeutic angiogenesis and vasculogenesis for tissue regeneration Exp Physiol, May 1, 2005; 90(3): 315 - 326. [Abstract] [Full Text] [PDF] |
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D. A. Ingram, L. E. Mead, D. B. Moore, W. Woodard, A. Fenoglio, and M. C. Yoder Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells Blood, April 1, 2005; 105(7): 2783 - 2786. [Abstract] [Full Text] [PDF] |
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M. Ii, H. Nishimura, A. Iwakura, A. Wecker, E. Eaton, T. Asahara, and D. W. Losordo Endothelial Progenitor Cells Are Rapidly Recruited to Myocardium and Mediate Protective Effect of Ischemic Preconditioning via "Imported" Nitric Oxide Synthase Activity Circulation, March 8, 2005; 111(9): 1114 - 1120. [Abstract] [Full Text] [PDF] |
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J. Sugawara, M. Mitsui-Saito, T. Hoshiai, C. Hayashi, Y. Kimura, and K. Okamura Circulating Endothelial Progenitor Cells during Human Pregnancy J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1845 - 1848. [Abstract] [Full Text] [PDF] |
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V. Schachinger and A. M. Zeiher Stem Cells and Cardiovascular and Renal Disease: Today and Tomorrow J. Am. Soc. Nephrol., March 1, 2005; 16(3_suppl_1): S2 - S6. [Abstract] [Full Text] [PDF] |
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K. C. Wollert and H. Drexler Clinical Applications of Stem Cells for the Heart Circ. Res., February 4, 2005; 96(2): 151 - 163. [Abstract] [Full Text] [PDF] |
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S. Murasawa and T. Asahara Endothelial Progenitor Cells for Vasculogenesis Physiology, February 1, 2005; 20(1): 36 - 42. [Abstract] [Full Text] [PDF] |
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M. S. Goligorsky Whispers and shouts in the pathogenesis of acute renal ischaemia Nephrol. Dial. Transplant., February 1, 2005; 20(2): 261 - 266. [Full Text] [PDF] |
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B. Dawn and R. Bolli Bone marrow cells for cardiac regeneration: the quest for the protagonist continues Cardiovasc Res, February 1, 2005; 65(2): 293 - 295. [Full Text] [PDF] |
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S. Davani, F. Deschaseaux, D. Chalmers, P. Tiberghien, and J.-P. Kantelip Can stem cells mend a broken heart? Cardiovasc Res, February 1, 2005; 65(2): 305 - 316. [Abstract] [Full Text] [PDF] |
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O. M. Tepper, J. M. Capla, R. D. Galiano, D. J. Ceradini, M. J. Callaghan, M. E. Kleinman, and G. C. Gurtner Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells Blood, February 1, 2005; 105(3): 1068 - 1077. [Abstract] [Full Text] [PDF] |
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E. Chavakis, A. Aicher, C. Heeschen, K.-i. Sasaki, R. Kaiser, N. El Makhfi, C. Urbich, T. Peters, K. Scharffetter-Kochanek, A. M. Zeiher, et al. Role of {beta}2-integrins for homing and neovascularization capacity of endothelial progenitor cells J. Exp. Med., January 3, 2005; 201(1): 63 - 72. [Abstract] [Full Text] [PDF] |
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N. Sengupta, S. Caballero, R. N. Mames, A. M. Timmers, D. Saban, and M. B. Grant Preventing Stem Cell Incorporation into Choroidal Neovascularization by Targeting Homing and Attachment Factors Invest. Ophthalmol. Vis. Sci., January 1, 2005; 46(1): 343 - 348. [Abstract] [Full Text] [PDF] |
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U. Ghani, A. Shuaib, A. Salam, A. Nasir, U. Shuaib, T. Jeerakathil, F. Sher, F. O'Rourke, A. M. Nasser, B. Schwindt, et al. Endothelial Progenitor Cells During Cerebrovascular Disease Stroke, January 1, 2005; 36(1): 151 - 153. [Abstract] [Full Text] [PDF] |
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D. Fliser, K. de Groot, F. H. Bahlmann, and H. Haller Cardiovascular disease in renal patients--a matter of stem cells? Nephrol. Dial. Transplant., December 1, 2004; 19(12): 2952 - 2954. [Full Text] [PDF] |
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