ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Ann Thorac Surg 2008;86:1833-1840. doi:10.1016/j.athoracsur.2008.08.068
© 2008 The Society of Thoracic Surgeons
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Qiang Zhao
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhao, Q.
Right arrow Articles by Wang, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, Q.
Right arrow Articles by Wang, Z.
Related Collections
Right arrow Molecular biology

Original Articles: Adult Cardiac

Randomized Study of Mononuclear Bone Marrow Cell Transplantation in Patients With Coronary Surgery

Qiang Zhao, MD*, Yongxin Sun, MD, Limin Xia, MD, Anqing Chen, MD, Zhe Wang, MD

Department of Cardiac Surgery, Zhongshan Hospital Fudan University, Shanghai, China

Accepted for publication August 29, 2008.

Abbreviations and Acronyms AF = atrial fibrillation; CABG = coronary artery bypass grafting; CCU = cardiac care unit; COPD = chronic obstructive pulmonary disease; CPB = cardiac pulmonary bypass; CPR = cardiac-pulmonary rescue; DVD = double-vessel disease; EPCs = endothelial progenitor cells; IABP = intra-aortic balloon pulsation; IWMV = infarction wall motion velocity; IWT = infarction wall thickness; LM = left main disease; LV = left ventricle; LVEDd = left ventricle end-diastolic diameter; LVEDs = left ventricle end-systolic diameter; LVEF = left ventricular ejection fraction; LVFS = left ventricle shortening fraction; MI = myocardial infarction; MN-BMC = mononuclear bone marrow cells; MR = mitral valve regurgitation; MVP = mitrial valve plasty; OPCAB = off-pump coronary artery bypass grafting; PCI = percutaneous coronary intervention; SPECT = single-photon emission computed tomography; SRS = segmental resting score; SVD = single-vessel disease; SVR = surgical left ventricle repair; TVD = triple-vessel disease; VF = ventricular fibrillation; VPBs = ventricular premature beats; VT = ventricular tachycardia

* Address correspondence to Dr Zhao, Department of Cardiac Surgery, Zhongshan Hospital Fudan University, 180 Fenglin Road, Shanghai, 200032, China (Email: zhao.qiang{at}zs-hospital.sh.cn).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Background: Mononuclear bone marrow cell (MN-BMC) transplantation has great clinical potential to promote myocardiogenesis and angiogenesis. This randomized study was designed to assess the feasibility and safety of MN-BMC transplantation during coronary artery bypass grafting (CABG) in patients with ischemic heart failure.

Methods: Thirty-six patients were prospectively enrolled and randomized to a MN-BMC group (n = 18) and a control group (n = 18). A mean number of 6.59 x 108 ± 5.12 x 108 MN-BMC were injected into the infarcted and marginal areas during CABG in the MN-BMC group. The patients in the control group underwent CABG alone. All patients were followed up to 6 months.

Results: There was one death in the MN-BMC group and no death in the control group. Two patients developed ventricular arrhythmia in the MN-BMC group. Compared with baseline and the control group, therapeutic effects of MN-BMC transplantation were observed over time. Heart function (New York Heart Association) was significantly improved and angina pectoris was alleviated in the MN-BMC group. Left ventricular ejection fraction in the MN-BMC group was greater than the control group. The thickness and motion velocity of the infarcted wall were significantly increased in the MN-BMC group. More pronounced perfusion improvements of ischemic regions and LV were observed in the MN-BMC group. There was one late death in the MN-BMC group. No procedure-related complications occurred.

Conclusions: MN-BMC transplantation improves cardiac function and regional perfusion in ischemic heart failure patients during CABG. A large cohort with long-term follow-up is needed to further evaluate the safety of MN-BMC transplantation.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Myocardial regeneration and angiogenesis by bone marrow-derived cells (BMC) has been suggested to have therapeutic potential in ischemic heart disease [1–3]. Many early phase clinical trials of direct injection of BMC into the coronary arteries and the myocardium have also reported to improve postinfarction left ventricular (LV) function [4–8]. Some randomized studies have proved that MN-BMC and myoblast transplantation during coronary artery bypass grafting (CABG) are safe and feasible with different results [9–13]. Therefore, we tested the hypothesis that MN-BMC transplantation concomitant with CABG would result in better improvement of cardiac function than CABG alone in patients with ischemic heart failure.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Acknowledgments
 References
 
Study Population and Protocol
From February 2003 to December 2006, 36 ischemic heart failure patients admitted for elective CABG were prospectively enrolled and randomized into two groups; MN-BMC group and control group, with 18 patients in each group. Randomization was achieved by using a sequence of random numbers generated by a computer. All patients provided informed consent and signed a form approved by the local Ethics Committee. The enrollment criteria were the following: (1) age between 18 and 75 years; (2) history of transmural old myocardial infarction with akinesis or dyskinesis of the left ventricle (LV) shown by echocardiography; (3) multivessel disease with a reversible perfusion defect detected by single-photon emission computed tomography (SPECT); (4) left ventricular ejection fraction (LVEF) less than 0.40. The exclusion criteria were the following: (1) primary hematologic disease; (2) previous history of neoplasia or malignancy that could impact the patient's survival; (3) unexplained abnormal baseline laboratory values; (4) any condition judged by the investigator would place the patients at undue risk.

All patients underwent baseline investigations. Echocardiography and Holter monitoring were taken at baseline, 1, 3, and 6 months postoperatively. Technetium-99m sestamibi SPECT was tested at baseline and 6 months postoperatively.

Harvest and Transplantation of MN-BMC
After heparinization and median sternotomy, bone marrow (about 30 mL) was aspirated from the sternum by a special suction appliance in both groups. The MN-BMC were immediately isolated by density gradient centrifugation using Ficoll (Phamarcia, Piscataway, NJ). Isolated cells were washed twice with heparinized saline and subsequently resuspended in 5 mL saline. The cells were counted and the viability was assessed by rypan blue dye exclusion. The cell suspension was filtered by a 70-micron cell strainer (Gibico, Grand Island, NY) before transplantation. In the MN-BMC group, an average of 6.59 x 108 ± 5.12 x 108 MN-BMC (cell viability 96.48% ± 3.10%) in 5 mL were injected in and around the infarcted area for 10 points (about 0. 5mL per injection) with a 29-gauge syringe after CABG was finished. In the control group, an equivalent volume of heparinized saline was injected in the same areas. A regular dose of amiodarone was administered in both groups for 6 months to prevent ventricular arrhythmias.

Echocardiography
All echocardiography were tested by IE33 Ultrasound System (Philip's Ultrasound systems, Andover, MA), comprising a 2 to 4 MHz transducer (Philip's Ultrasound systems). The parameters of regional function included infarction wall thickness (IWT) and infarction wall motion velocity (IWMV). The LV end-systolic diameter (LVEDs) and LV end-diastolic diameter (LVEDd) were measured by M-mode echocardiography. The global heart function was evaluated as LVEF and LV shortening fraction (LVFS). Mitral valve regurgitation (MR) was measured according to the recommendation of the American Society of Echocardiography [14]. The results were analyzed by two independent, blinded, experienced observers.

Single-Photon Emission Computed Tomography
Patients received an injection of technetium-99m sestamibi (740 MBq) at rest followed by gated-SPECT using a 90° double-detector camera (Vertex, Philips) within 2 hours. All measurements were conducted in the nuclear medicine core laboratory by investigators blind to the randomization scheme. The methods for quantitative analysis have been described previously [15, 16].

Follow-Up
All patients were followed up with outpatient visit and telephone communication every month up to 6 months. The completion of follow-up was 100%. The endpoints of the observation were death, myocardial infarction, and reoccurrence of heart failure.

Statistical Analysis
Continuous variables were presented as mean ± standard deviation. Categoric data were presented as frequencies and percentages. For time varying analysis of variance, generalized linear mixed effect models were fitted to the repeated measures data to determine how these echocardiographic characteristics and SPECT scans varied during a set of follow-up and by MN-BMC transplantation [17]. Normally distributed random effects were fitted to the interindividual differences in change over time point (slope) and starting point (intercept). Within-patient correlation over time was fitted using a continuous autoregressive function. An extended Mantel-Haenszel statistic was used to determine the difference of MR, New York Heart Association (NYHA), and Canadian Cardiovascular Society (CCS) classification between the two groups during a four repeated measurement. All statistical tests were two-sided and used a p value of 0.05 as the nominal level of significance.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Acknowledgments
 References
 
Baseline Demographic Characteristics
The demographics of the studied population at baseline are shown in Table 1. The two groups were well-matched for age, sex, and presentation profile. There were no differences in the use of nitrates, β-blockers, angiotensin-converting enzyme inhibitors, digitalis, or diuretics between the two groups.


View this table:
[in this window]
[in a new window]

  		Table 1 Patient Demographics
 
Operative and Perioperative Data
There were no significant differences in the operative procedures, average number of bypass grafts, cardiopulmonary bypass time, aortic cross-clamping time, cardiac care unit stay, chest drainage in the first 24 hours after operation, and postoperative treatment between the two groups (Table 2). All bacterial cultures of the MN-BMC samples were negative. In the perioperative period, sporadic ventricular premature beats and self-terminating bouts of rapid atrial fibrillation were observed in both groups. However, two patients developed ventricular fibrillation (VF) and one died in the MN-BMC group. One patient who had undertaken on-pump CABG with 3 grafts and left ventricular aneurysm resection (Dor's procedure) developed VF on the fifth day postoperatively. He was successfully resuscitated and then VF was well-controlled by amiodarone without reoccurrences during follow-up. The other patient, whose LV function was severely depressed (LVEF 22%) and received off-pump CABG with 4 grafts, developed VF 5 hours postoperatively. Although amiodarone was administrated and cardioversion was repeated, the VF was refractory and the patient died on the third day postoperatively. There were no ventricular arrhythmias in the control group.


View this table:
[in this window]
[in a new window]

  		Table 2 Operative and Perioperative Data of MN-BMC Transplantation
 
Follow-Up Evaluation
There was one late death of cerebral vessel accident in the MN-BMC group during follow-up. The NYHA classification improved in both groups compared with baseline, but the improvement was greater in the MN-BMC group. Angina pectoris was significantly alleviated in the MN-BMC group. The Holter analysis showed no significant difference of arrhythmia between the two groups (Table 3).


View this table:
[in this window]
[in a new window]

  		Table 3 Clinical Characteristics After MN-BMC Transplantation
 
Compared with the baseline and control group, LVEDs and LVEDd were significantly decreased by MN-BMC transplantation and over time. The IWT and IWMV in the MN-BMC group were significantly improved, as well as LVEF and LVFS (Table 4 and Fig 1). The segmental resting scores (SRS) of LV and the infarcted area detected by technetium-99m sestamibi SPECT were significantly decreased over the time in the MN-BMC group, compared with the baseline and control group (Table 5; and Fig 2; Fig 3).


View this table:
[in this window]
[in a new window]

  		Table 4 Echocardiographic Results After MN-BMC Transplantation
 

Figure 1
View larger version (75K):
[in this window]
[in a new window]

  		Fig 1. Regional and global heart function over time points. (Black line = MN-BMC group; gray line = control group; IWMV = infarction wall motion velocity; IWT = infarction wall thickness; LVEDd = left ventricle end-diastolic diameter; LVEDs = left ventricle end-systolic diameter; LVEF = left ventricular ejection fraction; LVFS = left ventricle shortening fraction; MN-BMC = mononuclear bone marrow cells.)

 

View this table:
[in this window]
[in a new window]

  		Table 5 SPECT Study Results After MN-BMC Transplantation
 

Figure 2
View larger version (36K):
[in this window]
[in a new window]

  		Fig 2. Sample of Technetium-99m sestamibi single-photon emission computed tomography scan at baseline and 6 months. (MN-BMC = mononuclear bone marrow cells.)

 

Figure 3
View larger version (45K):
[in this window]
[in a new window]

  		Fig 3. Segmental resting score at baseline and 6 months. (LV = left ventricle; MN-BMC = mononuclear bone marrow cells; SRS = segmental resting score.)

 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Acknowledgments
 References
 
Stem cell transplantation has been implied clinically to treat ischemic heart disease in the last decade [18–20]. It is reported that the transplant route by catheter to the coronary artery cannot localize the cells in the infarcted area and may result in microembolism by cell clumps [21, 22]. The stem cells can be injected into the infarcted and marginal area under direct visualization during CABG; however, the number of source cells limits the clinical use of cell transplantation for surgical patients. Harvesting MN-BMC from the sternotomy surgical field is a new approach. The rationale of MN-BMC transplantation during CABG are that the pain caused by additional bone marrow puncture is avoided, an adequate number of MN-BMC can be harvested, there is no waiting for in vitro culture, and the risks of cell degeneration, adverse transdifferentiation, and bacterial contamination is reduced.

Similar to other studies, we found that MN-BMC transplantation significantly reduces LV remodeling and improves both regional and global heart function in ischemic heart failure patients [11, 12, 23]. Although the mechanisms of this beneficial effect need to be elucidated, animal experimental studies have shown that MN-BMC contained multipotent adult stem cells that show a high capacity for differentiation [24]. In addition, paracrine, antiinflammatory effect, and extracellular matrix in LV remodeling induced by bone marrow stem cells may also be important [25, 26]. In this study, the improvement of regional cardiac performance is associated with the increasing of IWT and IWMV induced by MN-BMC transplantation. Consequently, the global geometry and function were significantly improved.

Although the angiogenic mechanism is complicated, the angiogenesis induced by MN-BMC transplantation plays an important role in the regional cardiac performance improvement. The significant improvement of perfusion in and around the infarcted region was demonstrated with SPECT scan in this study. The promotion of angiogenesis could be caused by angiogenic cytokines paracrined from multipotent cells and transdifferentiation of endothelial progenitor cells as reported in the literature [27, 28].

Ventricular arrhythmia occurred in few patients in the MN-BMC group of this study, as other stem cell transplantation studies reported [29–31]. Although the mechanism of arrhythmia remains unknown, several studies have demonstrated the arrhythmogenic property of autologous skeletal myoblasts or bone marrow-derived cells [32–34]. Myocardial injury caused by the injection may play an important role [35]. It may slow zigzag conduction caused by electrical insulation of transplanted cells, and reentry can be induced. Ischemia-reperfusion injury may also cause myocardial damage and ventricular arrhythmias. Moreover, in vitro study showed that factors predisposing to reentrant arrhythmias included heterogeneous distribution and electrical coupling of inexcitable bone marrow mesenchymal cells with cardiomyocytes [36]. Although these studies do not confirm a relationship between cell injection and ventricular arrhythmia, a large cohort with long-term follow-up is needed to further evaluate the safety of cell transplantation.

Several limitations of this study have to be addressed. First, the trial was not double-blinded although it was prospective and randomized. The physicians responsible for clinical follow-up evaluation knew the detailed protocol of the study. Second, although there was a significant increase in perfusion, and regional and global contractility, the patient population was too small to reach the definitive conclusion in short-term follow-up. Third, techniques with higher sensitivity and specificity to evaluate the heart function and myocardial perfusion still need to be found. Fourth, MN-BMC are unfractionated. The availability of techniques which permit quick separation of more potent stem cells in the operating room could be employed in the future.


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
References
 
This work was sponsored by a Shanghai Medical Development Research Fund, Grant Number 2000I-2D002.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Li TS, Hayashi M, Ito H, et al. Regeneration of infarcted myocardium by intramyocardial implantation of ex vivo transforming growth factor-beta-preprogrammed bone marrow stem cells Circulation 2005;111:2438-2445.[Abstract/Free Full Text]
  2. Imada T, Tatsumi T, Mori Y, et al. Targeted delivery of bone marrow mononuclear cells by ultrasound destruction of microbubbles induces both angiogenesis and arteriogenesis response Arterioscler Thromb Vasc Biol 2005;25:2128-2134.[Abstract/Free Full Text]
  3. Zeng L, Hu Q, Wang X, et al. Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling Circulation 2007;115:1866-1875.[Abstract/Free Full Text]
  4. Britten MB, Abolmaali ND, Assmus B, et al. Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging Circulation 2003;108:2212-2218.[Abstract/Free Full Text]
  5. Fuchs S, Satler LF, Kornowski R, et al. Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study J Am Coll Cardiol 2003;41:1721-1724.[Abstract/Free Full Text]
  6. Perin EC, Dohmann HF, Borojevic R, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure Circulation 2003;107:2294-2302.[Abstract/Free Full Text]
  7. Gavira JJ, Herreros J, Perez A, et al. Autologous skeletal myoblast transplantation in patients with nonacute myocardial infarction: 1-year follow-up J Thorac Cardiovasc Surg 2006;131:799-804.[Abstract/Free Full Text]
  8. Lunde K, Solheim S, Aakhus S, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction N Engl J Med 2006;355:1199-1209.[Medline]
  9. Menasché P, Alfieri O, Janssens S, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation Circulation 2008;117:1189-1200.[Abstract/Free Full Text]
  10. Hendrikx M, Hensen K, Clijsters C, et al. Recovery of regional but not global contractile function by the direct intramyocardial autologous bone marrow transplantation: results from a randomized controlled clinical trial Circulation 2006;114(1 suppl):I101-I107.[Medline]
  11. Stamm C, Kleine HD, Choi YH, et al. Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies J Thorac Cardiovasc Surg 2007;133:717-725.[Abstract/Free Full Text]
  12. Dib N, McCarthy P, Campbell A, et al. Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy Cell Transplant 2005;14:11-19.[Medline]
  13. Hagège AA, Marolleau JP, Vilquin JT, et al. Skeletal myoblast transplantation in ischemic heart failure: long-term follow-up of the first phase 1 cohort of patients Circulation 2006;114(1 suppl):I108-I113.[Medline]
  14. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358-367.[Medline]
  15. Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association Circulation 2002;105:539-542.[Free Full Text]
  16. Sharir T, Berman DS, Waechter PB, et al. Quantitative analysis of regional motion and thickening by gated myocardial perfusion SPECT: normal heterogeneity and criteria for abnormality J Nucl Med 2001;42:1630-1638.[Abstract/Free Full Text]
  17. Evans BA, Feng Z, Peterson AV. A comparison of generalized linear mixed model procedures with estimating equations for variance and covariance parameter estimation in longitudinal studies and group randomized trials Stat Med 2001;20:3353-3373.[Medline]
  18. Menasché P, Hagège A, Scorsin M, et al. Autologous skeletal myoblast transplantation for cardiac insufficiency. First clinical case. Arch Mal Coeur Vaiss 2001;94:180-182.[Medline]
  19. Lunde K, Solheim S, Forfang K, et al. Anterior myocardial infarction with acute percutaneous coronary intervention and intracoronary injection of autologous mononuclear bone marrow cells: safety, clinical outcome, and serial changes in left ventricular function during 12-months' follow-up J Am Coll Cardiol 2008;51:674-676.[Free Full Text]
  20. Beeres SL, Bax JJ, Dibbets-Schneider P, et al. Intramyocardial injection of autologous bone marrow mononuclear cells in patients with chronic myocardial infarction and severe left ventricular dysfunction Am J Cardiol 2007;100:1094-1098.[Medline]
  21. Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson, MD. Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs Lancet 2004;363:783-784.[Medline]
  22. Goussetis E, Manginas A, Koutelou M, et al. Intracoronary infusion of CD133+ and CD133-CD34+ selected autologous bone marrow progenitor cells in patients with chronic ischemic cardiomyopathy: cell isolation, adherence to the infarcted area, and body distribution Stem Cells 2006;24:2279-2283.[Medline]
  23. Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP. Angiogenesis in ischemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation Lancet 2003;361:47-49.[Medline]
  24. Zhang S, Guo J, Zhang P, et al. Long-term effects of bone marrow mononuclear cell transplantation on left ventricular function and remodeling in rats Life Sci 2004;74:2853-2864.[Medline]
  25. Tse HF, Siu CW, Zhu SG, et al. Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischemic myocardium Eur J Heart Fail 2007;9:747-753.[Abstract/Free Full Text]
  26. Atoui R, Shum-Tim D, Chiu RC. Myocardial regenerative therapy: immunologic basis for the potential "universal donor cells" Ann Thorac Surg 2008;86:327-334.[Abstract/Free Full Text]
  27. Takahashi M, Li TS, Suzuki R, et al. Cytokines produced by bone marrow cells can contribute to functional improvement of the infarcted heart by protecting cardiomyocytes from ischemic injury Am J Physiol Heart Circ Physiol 2006;291:H886-H893.[Abstract/Free Full Text]
  28. Kamihata H, Matsubara H, Nishiue T, et al. Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines Circulation 2001;104:1046-1052.[Abstract/Free Full Text]
  29. Smits PC, van Geuns RJ, Poldermans D, et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up J Am Coll Cardiol 2003;42:2063-2069.[Abstract/Free Full Text]
  30. Pompilio G, Cannata A, Peccatori F, et al. Autologous peripheral blood stem cell transplantation for myocardial regeneration: a novel strategy for cell collection and surgical injection Ann Thorac Surg 2004;78:1808-1812.[Abstract/Free Full Text]
  31. Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans Circulation 2002;106:1913-1918.[Abstract/Free Full Text]
  32. Leobon B, Garcin I, Menasche P, Vilquin JT, Audinat E, Charpak S. Myoblasts transplanted into rat infracted myocardium are functionally isolated from their host Proc Natl Acad Sci USA 2003;100:7808-7811.[Abstract/Free Full Text]
  33. Kuhlmann MT, Kirchhof P, Klocke R, et al. G-CSF/SCF reduces inducible arrhythmias in the infarcted heart potentially via increased connexin43 expression and arteriogenesis J Exp Med 2006;203:87-97.[Abstract/Free Full Text]
  34. Fernandes S, Amirault JC, Lande G, et al. Autologous myoblast transplantation after myocardial infarction increases the inducibility of ventricular arrhythmias Cardiovasc Res 2006;69:348-358.[Abstract/Free Full Text]
  35. Fukushima S, Varela-Carver A, Coppen SR, et al. Direct intramyocardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model Circulation 2007;115:2254-2261.[Abstract/Free Full Text]
  36. Chang MG, Tung L, Sekar RB, et al. Proarrhythmic potential of mesenchymal stem cell transplantation revealed in an in vitro coculture model Circulation 2006;113:1832-1841.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
K. H. Wu, X. M. Mo, Z. C. Han, and B. Zhou
Stem Cell Engraftment and Survival in the Ischemic Heart
Ann. Thorac. Surg., November 1, 2011; 92(5): 1917 - 1925.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
P. Donndorf, G. Kundt, A. Kaminski, C. Yerebakan, A. Liebold, G. Steinhoff, and A. Glass
Intramyocardial bone marrow stem cell transplantation during coronary artery bypass surgery: A meta-analysis
J. Thorac. Cardiovasc. Surg., October 1, 2011; 142(4): 911 - 920.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
B.-E. Strauer and G. Steinhoff
10 Years of Intracoronary and Intramyocardial Bone Marrow Stem Cell Therapy of the Heart: From the Methodological Origin to Clinical Practice
J. Am. Coll. Cardiol., September 6, 2011; 58(11): 1095 - 1104.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
S. Hu, S. Liu, Z. Zheng, X. Yuan, L. Li, M. Lu, R. Shen, F. Duan, X. Zhang, J. Li, et al.
Isolated Coronary Artery Bypass Graft Combined With Bone Marrow Mononuclear Cells Delivered Through a Graft Vessel for Patients With Previous Myocardial Infarction and Chronic Heart Failure: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial
J. Am. Coll. Cardiol., June 14, 2011; 57(24): 2409 - 2415.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
J. L. Herrmann, A. M. Abarbanell, B. R. Weil, Y. Wang, M. Wang, J. Tan, and D. R. Meldrum
Cell-Based Therapy for Ischemic Heart Disease: A Clinical Update
Ann. Thorac. Surg., November 1, 2009; 88(5): 1714 - 1722.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
P. Menasche
Stem Cell Therapy for Heart Failure: Are Arrhythmias a Real Safety Concern?
Circulation, May 26, 2009; 119(20): 2735 - 2740.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Qiang Zhao
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhao, Q.
Right arrow Articles by Wang, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, Q.
Right arrow Articles by Wang, Z.
Related Collections
Right arrow Molecular biology

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS