Published online before print October 20, 2003, doi: 10.1161/01.CIR.0000099501.52718.70
(Circulation. 2003;108:2070.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
Transdifferentiation of Human Peripheral Blood CD34+-Enriched Cell Population Into Cardiomyocytes, Endothelial Cells, and Smooth Muscle Cells In Vivo
From Departments of Cardiology (E.T.H.Y., S.Z.), Blood and Marrow Transplantation (M.K.), and Bioimmunotherapy (Z.E.), The University of Texas–M.D. Anderson Cancer Center; The University of Texas Houston Health Science Center (E.T.H.Y., H.D.W., J.T.W.); and the Texas Heart Institute, St Luke’s Episcopal Hospital (E.T.H.Y., J.T.W.), Houston, Tex.
Correspondence to Edward T.H. Yeh, MD, 1515 Holcombe Blvd, Box 449, Houston, TX 77030-4095. E-mail etyeh{at}mdanderson.org
Received April 3, 2003; de novo received July 7, 2003; revision received September 3, 2003; accepted September 8, 2003.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background— Adult human peripheral blood cells have been shown to differentiate into mature cells of nonhematopoietic tissues, such as hepatocytes and epithelial cells of the skin and gastrointestinal track. We investigated whether these cells could also transdifferentiate into human cardiomyocytes, mature endothelial cells, and smooth muscle cells in vivo.
Methods and Results— Myocardial infarction was created in SCID mice by occluding the left anterior descending coronary artery, after which adult peripheral blood CD34+ cells were injected into the tail vein. Hearts were harvested 2 months after injection and stained for human leukocyte antigen (HLA) and markers for cardiomyocytes, endothelial cells, and smooth muscle cells. Cardiomyocytes, endothelial cells, and smooth muscle cells that bear HLA were identified in the infarct and peri-infarct regions of the mouse hearts. In a separate experiment, CD34+ cells were injected intraventricularly into mice without experimental myocardial infarction. HLA-positive myocytes and smooth muscle cells could only be identified in 1 of these mice killed at different time points.
Conclusions— Adult peripheral blood CD34+ cells can transdifferentiate into cardiomyocytes, mature endothelial cells, and smooth muscle cells in vivo. However, transdifferentiation is augmented significantly by local tissue injury. The use of peripheral blood CD34+ cells for cell-based therapy should greatly simplify the procurement of cells for the regeneration of damaged myocardium.
Key Words: cells • muscle, smooth • endothelium • myocyte
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Cell-based regeneration therapy has been widely touted as a novel means of repairing damaged heart after myocardial infarction (MI), chemotherapy-induced damages, or other injuries leading to heart failure. Various cell populations, such as embryonal stem cells, cord blood cells, and mesenchymal stem cells, have been suggested as a source for replacement therapy. It will be useful to identify a readily available cell source that does not require significant manipulation. Adult human peripheral blood stem cells have been shown to differentiate into mature hepatocytes and epithelial cells of the skin and gastrointestinal track.1 In the present study, we investigated whether human peripheral blood cells could transdifferentiate into cardiomyocytes, mature endothelial cells, or smooth muscle cells using the SCID mouse as a recipient.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Animals
Female SCID mice (CB-17) weighing 16 to 23 g were used (Charles River Laboratories, Wilmington, Mass). Two and a half million human peripheral blood CD34+ cells were injected into the left ventricle of 19 mice without surgical manipulation, and the heart was harvested at 24 hours (n=3), 4 days (n=3), 12 days (n=7), 30 days (n=3), or 60 days (n=3) after cell transplantation. Another group of 6 mice receiving experimental MI (n=3) or sham surgery (n=3) was injected with the same number of CD34+ cells through the tail vein and killed at day 60 after transplantation.
Induction of MI
Mice were ventilated with 100% oxygen using a rodent ventilator (Inspira ASV, Harvard Apparatus, Inc). The chest was opened, a 7-0 silk suture (Ethicon, Inc, Johnson & Johnson Co) was passed with a tapered needle under the left anterior descending coronary artery 1 to 2 mm from the tip of the left atrium, and the 2 ends of the suture were tied to induce MI. Two million human peripheral CD34+ cells were injected into the tail vein 16 hours after MI was induced. Sham-operated mice received the same procedure except left anterior descending ligation.
Isolation of CD34+ Cells From Human Peripheral Blood
CD34+ fractionation was performed using immunomagnetic beads as previously described and contained more than 90% CD34+ cells.2
Tissue Harvesting
Hearts were removed, embedded in OCT, snap frozen in liquid nitrogen, and stored at -80°C. Mouse hearts in OCT blocks were sectioned, and 5-µm serial sections were collected on slides followed by fixation with 3.7% paraformaldehyde (pH 7.4) at 4°C for 5 minutes and stained immediately.
Immunofluorescence Staining
After rinsing slides with PBS 3 times, the slides were blocked at room temperature for 30 minutes in PBS containing 5% horse serum and incubated with primary antibodies at room temperature for 1 hour. The slides were rinsed 3 times and incubated with the secondary antibodies at room temperature for 30 minutes. Paired primary and secondary antibodies were used for double staining. The slides were rinsed again, and DAPI solution was applied for 5 minutes. Reagents used were anti–human leukocyte antigen (HLA)-ABC (BD Biosciences); anti–troponin T antibody (Santa Cruz Biotechnology) reacts against cardiomyocytes of human and mouse; anti-
-smooth muscle actin (Spring Bioscience) reacts against both human and mouse smooth muscle actin; and anti–VE-cadherin reacts against endothelial cells (Bender Medsystem). Secondary antibodies were Alexa Fluor 488-conjugated goat anti-mouse IgG (Molecular Probes) for anti-HLA and goat anti-rabbit IgG Rhodamine (Santa Cruz Biotechnology) for anti–smooth muscle actin and anti–VE-cadherin antibodies.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Transdifferentiation of Human Peripheral Blood CD34+ Cells in the Injured Heart
We first assessed the specificity and cross reactivity of the antibodies against human HLA-ABC in cultured human smooth muscle cells and endothelial cells, mouse smooth muscle cells, and peripheral blood CD34+ cells using FACS analysis. No cross-reaction to mouse cells was found (data not shown). Also, there was no cross reaction between smooth muscle–specific
-actin and VE-cadherin antibodies, confirmed by immunofluorescence staining of cultured human vascular smooth muscle cells and human endothelial cells (data not shown). Clusters of cells (Figures 1A through 1D) and single cells (Figures 1E through 1H) with the morphological appearance typical of cardiomyocytes were stained positively with both anti-human HLA-ABC and anti-cardiac troponin T in the peri-infarct area in all 3 mice that had sustained MI 60 days. However, no cardiomyocytes derived from human peripheral blood CD34+ cells were observed in the infarct zone. No transdifferentiated cardiomyocytes were found in tissue sections of sham-operated animals after cell transplantation (3 mice).
|
Blood vessels that stained with anti-HLA antibody were seen mainly in the infarct area. Double staining for HLA and smooth muscle -actin indicated that human CD34-derived smooth muscle cells had participated in the neovascularization after acute MI (Figures 1I through 1L). Double staining of the blood vessels with anti-HLA and anti–VE-cadherin confirmed that human CD34+ cells transdifferentiated into mature endothelial cells (Figures 1M through 1P).
Minimal Transdifferentiation in the Heart Without Major Injury
To investigate the transdifferentiation potential of human blood CD34+ cells in animals without MI, CD34+ cells were injected intraventricularly into the left ventricle of SCID mouse. No transdifferentiation was found in the hearts at 24 hours, 4 days, 30 days, and 60 days after injection. However, in 1 of the 7 mice examined 12 days after injection, cardiomyocytes and blood vessels double stained with anti-HLA and cardiac troponin (Figures 2A through C)/smooth muscle -actin (Figures 2D through 2F) were observed.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Attempts have been made to regenerate damaged myocardial tissue. Cells from a variety of sources have been used for the purpose.3 Many recent studies have focused on the use of embryonic stem cells and bone marrow–derived cells, including adult hematopoietic stem cells, mesenchymal stem cells, and bone marrow side population cells.4–7 CD34+ cells isolated from bone marrow and peripheral blood have been successfully used for regeneration of the blood vessels after experimental MI.8,9 A recent report described the differentiation of human CD34+ cells, when cocultured with rat cardiomyocytes, into the cardiomyocytes in vitro.10 However, there have been no reports on transdifferentiation of human peripheral blood–derived CD34+ cells into the cardiomyocytes in vivo.
Using human HLA as a marker for the donor cells, we demonstrate transdifferentiation of CD34+ cells into cardiomyocytes in vivo, although the frequency of the event is low in uninjured hearts. The cells derived from transplanted CD34+ cells demonstrate mature cardiomyocyte morphology and seem to be integrated into the myocardium of the peri-infarct area. The fact that no transdifferentiated cardiomyocytes were found inside the infarct zone is in agreement with the in vitro observation that contacts between the donor and host cells are necessary for transdifferentiation.10 CD34+ cells from the bone marrow and peripheral blood have long been recognized to contain endothelial progenitors.9 Consistent with these findings, double staining of the blood vessels with anti-HLA and anti–VE-cadherin documented the transdifferentiation of peripheral blood CD34+ cells into vascular endothelial cells. It has been reported that CD34+ cells in human blood contain a population of smooth muscle progenitor cells.11 Our data also demonstrate the potential of these cells to differentiate into vascular smooth muscle cells in vivo.
Terada et al12 demonstrated in vitro that bone marrow stem cells were able to fuse with embryonic stem cells and to adopt their phenotype. Recently, Wang et al13 and Vassilopoulos et al14 demonstrated that cell fusion was the major mechanism in regeneration of the damaged hepatocytes of mice. Because no chromosome analysis was performed in our study, we could not exclude the possibility that cell fusion is partly responsible for the phenotype conversion of the injected CD34+ cells, especially in myocytes where fusion of myotube is part of the differentiation process. However, the phenotypic conversion of the injected CD34+ cells into endothelial cells or smooth muscle cells may occur predominantly through transdifferentiation. Additional studies are in progress to differentiate between these possibilities.
In previous studies, donor cells were often labeled with the green fluorescence protein and ß-galactosidase.5,15 These labeling techniques require extensive manipulation of the donor cells. Therefore, we have chosen to use human HLA molecule as the marker for the donor cells. The monoclonal antibody (W6/32) for detection is specific for a monomorphic epitope. This method, therefore, can be used in future studies on stem cell transplantation in which human cells are used as donors.
In our study, the frequency of transdifferentiation of human blood CD34+ cells is extremely low in uninjured hearts. Apparently, severe tissue damage plays a critical role in the event. This is in concordance with the commonly accepted notion that transdifferentiation of adult stem cells in the heart is a random and rare event. The low frequency of transdifferentiation we have observed in uninjured animals might be attributable to poor homing of the transplanted cells in the absence of injury.
Our findings are clinically relevant in that adult peripheral blood stem cells may be superior to other cell sources in cell-based therapy for myocardial regeneration. Their use obviates the painful procedure of bone marrow aspiration and the attendant anesthesia risks. In addition, autologous stem cell transplantation does not require long-term immune suppressive therapy. Thus, the use of autologous peripheral blood stem cells for myocardial regeneration is a promising alternative for the treatment of heart failure.
|
Footnotes |
|---|
Guest Editor for this article was Robert A. Kloner, MD, PhD, Good Samaritan Hospital, Los Angeles, Calif.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Korbling M, Katz RL, Khanna A, et al. Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. N Engl J Med. 2002; 346: 738–746.
2. Ferrajoli A, Talpaz M, Kurzrock R, et al. Analysis of the effects of tumor necrosis factor inhibitors on human hematopoiesis. Stem Cells. 1993; 11: 112–119.[Medline] [Order article via Infotrieve]
3. Malouf NN, Coleman WB, Grisham JW, et al. Adult-derived stem cells from the liver become myocytes in the heart in vivo. Am J Pathol. 2001; 158: 1929–1935.
4. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001; 410: 701–705.[CrossRef][Medline] [Order article via Infotrieve]
5. Toma C, Pittenger MF, Cahill KS, et al. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002; 105: 93–98.
6. Jackson KA, Majka SM, Wang H, et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest. 2001; 107: 1395–1402.[CrossRef][Medline] [Order article via Infotrieve]
7. Klug MG, Soonpaa MH, Koh GY, et al. Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J Clin Invest. 1996; 98: 216–224.[Medline] [Order article via Infotrieve]
8. Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow–derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med. 2001; 7: 430–436.[CrossRef][Medline] [Order article via Infotrieve]
9. Kawamoto A, Tkebuchava T, Yamaguchi J, et al. Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation. 2003; 107: 461–468.
10. Badorff C, Brandes RP, Popp R, et al. Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes. Circulation. 2003; 107: 1024–1032.
11. Simper D, Stalboerger PG, Panetta CJ, et al. Smooth muscle progenitor cells in human blood. Circulation. 2002; 106: 1199–1204.
12. Terada N, Hamazaki T, Oka M, et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature. 2002; 416: 542–545.[CrossRef][Medline] [Order article via Infotrieve]
13. Wang X, Willenbring H, Akkari Y, et al. Cell fusion is the principal source of bone-marrow–derived hepatocytes. Nature. 2003; 422: 897–901.[CrossRef][Medline] [Order article via Infotrieve]
14. Vassilopoulos G, Wang PR, Russell DW. Transplanted bone marrow regenerates liver by cell fusion. Nature. 2003; 422: 901–904.[CrossRef][Medline] [Order article via Infotrieve]
15. Penn MS, Francis GS, Ellis SG, et al. Autologous cell transplantation for the treatment of damaged myocardium. Prog Cardiovasc Dis. 2002; 45: 21–32.[CrossRef][Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  K. V Arom, P. Ruengsakulrach, M. Belkin, and M. Tiensuwan Intramyocardial Angiogenic Cell Precursors in Nonischemic Dilated Cardiomyopathy Asian Cardiovasc Thorac Ann, August 1, 2009; 17(4): 382 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Kim, H.-N. Pak, J. H. Park, J. I. Choi, M.-H. Nam, Y. Jo, and Y.-H. Kim Non-ischaemic titrated cardiac injury caused by radiofrequency catheter ablation of atrial fibrillation mobilizes CD34-positive mononuclear cells by non-stromal cell-derived factor-1{alpha} mechanism Europace, August 1, 2009; 11(8): 1024 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Boudoulas and A. K. Hatzopoulos Cardiac repair and regeneration: the Rubik's cube of cell therapy for heart disease Dis. Model. Mech., July 1, 2009; 2(7-8): 344 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamahara and H. Itoh Potential use of endothelial progenitor cells for regeneration of the vasculature Therapeutic Advances in Cardiovascular Disease, February 1, 2009; 3(1): 17 - 27. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Valgimigli, G. G.L. Biondi-Zoccai, P. Malagutti, A. M. Leone, and A. Abbate Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after myocardial infarction Eur. Heart J. Suppl., December 1, 2008; 10(suppl_K): K27 - K34. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Murasawa and T. Asahara Review: Cardiogenic potential of endothelial progenitor cells Therapeutic Advances in Cardiovascular Disease, October 1, 2008; 2(5): 341 - 348. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Kubo, N. Jaleel, A. Kumarapeli, R. M. Berretta, G. Bratinov, X. Shan, H. Wang, S. R. Houser, and K. B. Margulies Increased Cardiac Myocyte Progenitors in Failing Human Hearts Circulation, August 5, 2008; 118(6): 649 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Stone Angioplasty Strategies in ST-Segment-Elevation Myocardial Infarction: Part II: Intervention After Fibrinolytic Therapy, Integrated Treatment Recommendations, and Future Directions Circulation, July 29, 2008; 118(5): 552 - 566. [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Zhao, A. Tseng, N. Yano, Y. Tseng, P. A. Davol, R. J. Lee, L. G. Lum, and J. F. Padbury Targeting human CD34+ hematopoietic stem cells with anti-CD45 x anti-myosin light-chain bispecific antibody preserves cardiac function in myocardial infarction J Appl Physiol, June 1, 2008; 104(6): 1793 - 1800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zampetaki, J. P. Kirton, and Q. Xu Vascular repair by endothelial progenitor cells Cardiovasc Res, June 1, 2008; 78(3): 413 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Ince, M Valgimigli, M Petzsch, J S. de Lezo, F Kuethe, S Dunkelmann, G Biondi-Zoccai, and C A Nienaber Cardiovascular events and re-stenosis following administration of G-CSF in acute myocardial infarction: systematic review and meta-analysis Heart, May 1, 2008; 94(5): 610 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. V Arom, P. Ruengsakulrach, and V. Jotisakulratana Intramyocardial Angiogenic Cell Precursor Injection for Cardiomyopathy Asian Cardiovasc Thorac Ann, April 1, 2008; 16(2): 143 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Orlandi, F. Pagani, D. Avitabile, G. Bonanno, G. Scambia, E. Vigna, F. Grassi, F. Eusebi, S. Fucile, M. Pesce, et al. Functional properties of cells obtained from human cord blood CD34+ stem cells and mouse cardiac myocytes in coculture Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1541 - H1549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Atluri, C. M. Panlilio, G. P. Liao, E. E. Suarez, R. C. McCormick, W. Hiesinger, J. E. Cohen, M. J. Smith, A. B. Patel, W. Feng, et al. Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function. J. Thorac. Cardiovasc. Surg., February 1, 2008; 135(2): 283 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. T. Gerthoffer Migration of Airway Smooth Muscle Cells Proceedings of the ATS, January 1, 2008; 5(1): 97 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Lipinski, G. G.L. Biondi-Zoccai, A. Abbate, R. Khianey, I. Sheiban, J. Bartunek, M. Vanderheyden, H.-S. Kim, H.-J. Kang, B. E. Strauer, et al. Impact of Intracoronary Cell Therapy on Left Ventricular Function in the Setting of Acute Myocardial Infarction: A Collaborative Systematic Review and Meta-Analysis of Controlled Clinical Trials J. Am. Coll. Cardiol., October 30, 2007; 50(18): 1761 - 1767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Leor, S. Gerecht, S. Cohen, L. Miller, R. Holbova, A. Ziskind, M. Shachar, M. S Feinberg, E. Guetta, and J. Itskovitz-Eldor Human embryonic stem cell transplantation to repair the infarcted myocardium Heart, October 1, 2007; 93(10): 1278 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Ferreira, S. Gerecht, H. F. Shieh, N. Watson, M. A. Rupnick, S. M. Dallabrida, G. Vunjak-Novakovic, and R. Langer Vascular Progenitor Cells Isolated From Human Embryonic Stem Cells Give Rise to Endothelial and Smooth Muscle Like Cells and Form Vascular Networks In Vivo Circ. Res., August 3, 2007; 101(3): 286 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Grote, G. Salguero, M. Ballmaier, M. Dangers, H. Drexler, and B. Schieffer The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration Blood, August 1, 2007; 110(3): 877 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. T. Gerthoffer Mechanisms of Vascular Smooth Muscle Cell Migration Circ. Res., March 16, 2007; 100(5): 607 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhang, E. Shpall, J. T. Willerson, and E. T.H. Yeh Fusion of Human Hematopoietic Progenitor Cells and Murine Cardiomyocytes Is Mediated by {alpha}4{beta}1 Integrin/Vascular Cell Adhesion Molecule-1 Interaction Circ. Res., March 16, 2007; 100(5): 693 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 K. Lunde, S. Solheim, S. Aakhus, H. Arnesen, M. Abdelnoor, T. Egeland, K. Endresen, A. Ilebekk, A. Mangschau, J. G. Fjeld, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N. Engl. J. Med., September 21, 2006; 355(12): 1199 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 G. P. Fadini, S. V. de Kreutzenberg, A. Coracina, I. Baesso, C. Agostini, A. Tiengo, and A. Avogaro Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk Eur. Heart J., September 2, 2006; 27(18): 2247 - 2255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
P. W. Serruys Fourth Annual American College of Cardiology International Lecture: A Journey in the Interventional Field J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1754 - 1768. [Full Text] [PDF]
|
|
|
|
 |
|
 O. Awad, E. I. Dedkov, C. Jiao, S. Bloomer, R. J. Tomanek, and G. C. Schatteman Differential Healing Activities of CD34+ and CD14+ Endothelial Cell Progenitors Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 758 - 764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Anghelina, P. Krishnan, L. Moldovan, and N. I. Moldovan Monocytes/Macrophages Cooperate with Progenitor Cells during Neovascularization and Tissue Repair: Conversion of Cell Columns into Fibrovascular Bundles Am. J. Pathol., February 1, 2006; 168(2): 529 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Boxall, S. T. Holgate, and D. E. Davies The contribution of transforming growth factor-{beta} and epidermal growth factor signalling to airway remodelling in chronic asthma Eur. Respir. J., January 1, 2006; 27(1): 208 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Howson, A. C. Aplin, M. Gelati, G. Alessandri, E. A. Parati, and R. F. Nicosia The postnatal rat aorta contains pericyte progenitor cells that form spheroidal colonies in suspension culture Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1396 - C1407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. T. Willerson, E. T.H. Yeh, Y.-J. Geng, and E. C. Perin Blood-Derived Progenitor Cells After Recanalization of Chronic Coronary Artery Occlusions in Humans Circ. Res., October 14, 2005; 97(8): 735 - 736. [Full Text] [PDF]
|
|
|
|
|
|
S. Erbs, A. Linke, V. Adams, K. Lenk, H. Thiele, K.-W. Diederich, F. Emmrich, R. Kluge, K. Kendziorra, O. Sabri, et al. Transplantation of Blood-Derived Progenitor Cells After Recanalization of Chronic Coronary Artery Occlusion: First Randomized and Placebo-Controlled Study Circ. Res., October 14, 2005; 97(8): 756 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Chan, S. H. Li, and S. Verma Nocturnal hemodialysis is associated with restoration of impaired endothelial progenitor cell biology in end-stage renal disease Am J Physiol Renal Physiol, October 1, 2005; 289(4): F679 - F684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
P. Roy-Chaudhury Endothelial Progenitor Cells, Neointimal Hyperplasia, and Hemodialysis Vascular Access Dysfunction: Novel Therapies for a Recalcitrant Clinical Problem Circulation, July 5, 2005; 112(1): 3 - 5. [Full Text] [PDF]
|
|
|
|
|
|
J. I. Rotmans, J. M.M. Heyligers, H. J.M. Verhagen, E. Velema, M. M. Nagtegaal, D. P.V. de Kleijn, F. G. de Groot, E. S.G. Stroes, and G. Pasterkamp In Vivo Cell Seeding With Anti-CD34 Antibodies Successfully Accelerates Endothelialization but Stimulates Intimal Hyperplasia in Porcine Arteriovenous Expanded Polytetrafluoroethylene Grafts Circulation, July 5, 2005; 112(1): 12 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
A. M. Leone, S. Rutella, G. Bonanno, A. Abbate, A. G. Rebuzzi, S. Giovannini, M. Lombardi, L. Galiuto, G. Liuzzo, F. Andreotti, et al. Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function Eur. Heart J., June 2, 2005; 26(12): 1196 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Haider and M. Ashraf Bone marrow stem cell transplantation for cardiac repair Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2557 - H2567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Koyanagi, R. P. Brandes, J. Haendeler, A. M. Zeiher, and S. Dimmeler Cell-to-Cell Connection of Endothelial Progenitor Cells With Cardiac Myocytes by Nanotubes: A Novel Mechanism for Cell Fate Changes? Circ. Res., May 27, 2005; 96(10): 1039 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Koyanagi, J. Haendeler, C. Badorff, R. P. Brandes, J. Hoffmann, P. Pandur, A. M. Zeiher, M. Kuhl, and S. Dimmeler Non-canonical Wnt Signaling Enhances Differentiation of Human Circulating Progenitor Cells to Cardiomyogenic Cells J. Biol. Chem., April 29, 2005; 280(17): 16838 - 16842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Humpert, R. Neuwirth, M. J. Battista, O. Voronko, M. von Eynatten, I. Konrade, G. Rudofsky Jr, T. Wendt, A. Hamann, M. Morcos, et al. SDF-1 Genotype Influences Insulin-Dependent Mobilization of Adult Progenitor Cells in Type 2 Diabetes Diabetes Care, April 1, 2005; 28(4): 934 - 936. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. Zhang, D. Wang, Z. Estrov, S. Raj, J. T. Willerson, and E. T.H. Yeh Both Cell Fusion and Transdifferentiation Account for the Transformation of Human Peripheral Blood CD34-Positive Cells Into Cardiomyocytes In Vivo Circulation, December 21, 2004; 110(25): 3803 - 3807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Regula, M. J. Rzeszutek, D. Baetz, C. Seneviratne, and L. A. Kirshenbaum Therapeutic opportunities for cell cycle re-entry and cardiac regeneration Cardiovasc Res, December 1, 2004; 64(3): 395 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Abbott, Y. Huang, D. Liu, R. Hickey, D. S. Krause, and F. J. Giordano Stromal Cell-Derived Factor-1{alpha} Plays a Critical Role in Stem Cell Recruitment to the Heart After Myocardial Infarction but Is Not Sufficient to Induce Homing in the Absence of Injury Circulation, November 23, 2004; 110(21): 3300 - 3305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sho, M. Sho, H. Nanjo, K. Kawamura, H. Masuda, and R. L. Dalman Hemodynamic Regulation of CD34+ Cell Localization and Differentiation in Experimental Aneurysms Arterioscler Thromb Vasc Biol, October 1, 2004; 24(10): 1916 - 1921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dimmeler and A. M. Zeiher Wanted! The best cell for cardiac regeneration J. Am. Coll. Cardiol., July 21, 2004; 44(2): 464 - 466. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||