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Bone marrow mononuclear cells and acute myocardial infarction.Stem Cell Research & Therapy 2012, 3:2

Review
Bone marrow mononuclear cells and acute myocardial infarction

Samer Arnous1, Abdul Mozid1, John Martin1 and Anthony Mathur2*

* Corresponding author: Anthony Mathur a.mathur@qmul.ac.uk

Author Affiliations

1 Department of Cardiology, London Chest Hospital, Bonner Road, London E2 9JX, UK

2 Department of Cardiology, London Chest Hospital, Queen Mary University of London, Barts and the London NHS Trust, Bonner Road, London E2 9JX, UK

For all author emails, please log on.

Stem Cell Research & Therapy 2012, 3:2 doi:10.1186/scrt93

The electronic version of this article is the complete one and can be found online at: http://stemcellres.com/content/3/1/2

Published: 17 January 2012

© 2012 BioMed Central Ltd

Abstract

Stem cell transplantation is emerging as a potential therapy to treat heart diseases. Promising results from early animal studies led to an explosion of small, non-controlled clinical trials that created even further excitement by showing that stem cell transplantation improved left ventricular systolic function and enhanced remodelling. However, the specific mechanisms by which these cells improve heart function remain largely unknown. A large variety of cell types have been considered to possess the regenerative ability needed to repair the damaged heart. One of the most studied cell types is the bone marrow-derived mononuclear cells and these form the focus of this review. This review article aims to provide an overview of their use in the setting of acute myocardial infarction, the challenges it faces and the future of stem cell therapy in heart disease.
Introduction

Despite the recent advances in percutaneous intervention, drug and device therapy, patients with acute myocardial infarction (AMI) and resulting left ventricular impairment have 13% mortality at 1 year [1]. Following the loss of over one billion cardiomyocytes in a functionally significant MI, the overloaded surviving cardiomyocytes undergo abnormal remodelling, eventually leading to heart failure. This condition, a leading cause of death and disability in the developed world, is associated with 5-year mortality rates of up to 70% in symptomatic patients [2]. Current conventional therapies do not correct underlying defects in cardiac muscle cell number [3].

The only therapeutic option that currently addresses cardiomyocyte loss is heart transplantation. However, due to stringent selection criteria and chronic shortage of donor hearts, the vast majority of patients are deemed unsuitable or never receive a transplant. Therefore, preventing this progression post-MI is a major challenge requiring novel therapeutic strategies such as stem cell transplantation to improve the prognosis and quality of life for these patients.

The traditional view that the heart is a terminally differentiated organ has been challenged by the discovery of differentiation of stem cells into cardiomyocytes in animal and human hearts [4-7]. This in turn has led to the exciting possibility for regenerative therapy for cardiomyocyte loss after a MI. The demonstration of functional recovery of myocardium through cardiomyogenesis and neoangiogenesis in AMI in murine models by Orlic and colleagues [8] generated tremendous interest in the potential of bone marrow-derived stem cells. Since then, the cardiomyogenic ability of these cells has been challenged. However, studies continue to demonstrate improvement in cardiac function and reduction in infarct size. It should be noted that progenitor cells also contribute to cardiac repair by mechanisms beyond the growth of new cardiomyocytes and as such may offer an 'indirect' benefit.
Animal and human trials

The most promising and obvious cell type for the growth of new cardiomyocytes is the embryonic stem cell; however, considerable technical and ethical issues exist with these cells, which must be overcome before their successful use in humans. Adult stem cells are an attractive option to explore for transplantation as they are autologous, but their differentiation potential is more restricted than embryonic stem cells. Currently, the major sources of adult cells used for basic research and in clinical trials originate from the bone marrow. The bone marrow mononuclear subset is heterogeneous and comprises mesenchymal stem cells, haematopoietic progenitor cells and endothelial progenitor cells. The differentiation capacity of different populations of bone marrow-derived stem cells into cardiomyocytes has been studied intensively. The results are rather confusing and difficult to compare, since different isolation and identification methods have been used to determine the cell population studied. To date, only mesenchymal stem cells seem to form cardiomyocytes, and only a small percentage of this population will do so in vitro or in vivo. Pragmatically, the translation of the basic science into clinical research has followed a common pathway: injection of bone marrow-derived mononuclear cells (BMMNCs) as a source of stem cells into the heart. Table 1 provides a summary of clinical trials using BMMNCs in patients with acute MI.

Table 1. Clinical trials using autologous bone marrow mononuclear cells in patients with acute myocardial infarction
Trials with no sham bone marrow harvest or intracoronary re-infusion in the control group

In the first human trial, Strauer and colleagues [9] re-infused intracoronary BMMNCs 7 days after myocardial infarction (MI). The mean number of mononuclear cells was 2.8 × 107. There was a significant improvement in myocardial perfusion and a reduction in the infarct region in the cell therapy group. The Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI) investigators randomised patients into intracoronary infusion of BMMNCs or ex vivo expanded circulating progenitor cells 4 days after MI [10]. There was a significant improvement in global and regional left ventricular (LV) function in both groups and a beneficial effect on the post-infarction remodelling process manifest by a profound improvement in wall motion abnormalities in the infarct area and a significant reduction in end-systolic LV volume at 4 months post-MI. The LV ejection fraction (LVEF) further improved at 12 months, resulting in a total increase of 9.3% at 1 year [11]. Of interest, there was no difference between the two active treatment groups. The mean number of infused cells was 245 × 106, which contained haematopoietic progenitor, mesenchymal and stromal cells. However, a major limitation of both of these trials was the lack of a control group receiving sham bone marrow harvest or intracoronary re-infusion.

Another trial in which there was no sham procedure is the Autologous Stem-Cell Transplantation in Acute Myocardial Infarction (ASTAMI) trial, which included only patients with acute anterior MI. The intracoronary re-infusion of BMMNCs 4 to 8 days after infarction did not have a beneficial effect on LVEF compared to percutaneous coronary intervention (PCI) alone at 6 months [12]. This lack of beneficial effect may be explained by the different cell processing protocols used in this trial. Cell processing protocols may have a significant impact on the functional capacity of bone marrow-derived stem cells [13]. Comparison of different isolation protocols revealed a vastly reduced recovery of mononuclear cells and nullification of the neovascularisation capacity when the ASTAMI cell isolation and storage protocol was used [13].

The Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration (BOOST) trial, a slightly larger trial, included 60 patients that were randomised to receive intracoronary BMMNCs or standard therapy 4.8 days after successful PCI following AMI. There was a significant improvement in global LVEF in the cell treatment group at 6 months without an effect on LV remodelling [14]. However, this improvement was not maintained at 18 months. The mean number of bone marrow cells that were infused contained 9.5 × 106 CD34+ and 3.6 × 106 haematopoietic colony-forming cells. The improvement in LVEF did not correlate with the number of CD34+ cells or haematopoietic colony forming cells. Again, a major limitation of the BOOST trial is that the control group did not undergo a sham bone marrow harvest or intracoronary infusion.

The first long-term study involving 62 patients who underwent intracoronary BMMNC transplantation 7 days post-AMI not only resulted in an early significant improvement in ejection fraction (EF) and infarct size, but there was also a significant reduction in mortality and improvement in exercise capacity compared to controls at 5 years [15].
Randomised controlled trials

The Transcatheter Transplantation of Stem Cells for Treatment of Acute Myocardial Infarction (TCT-STAMI) trial, which included a control group receiving a placebo infusion, showed a significant (approximately 5%) improvement in LVEF of patients receiving intracoronary BMMNCs at 6 months [16].

Intracoronary bone marrow derived progenitor cells in acute infarction (REPAIR-AMI), a large randomized double-blind controlled trial that included over 200 patients, showed an improvement in the primary endpoint in the treatment group that was an absolute change in global LVEF from baseline to 4 months, as measured by quantitative left ventricular angiography [17]. Furthermore, the pre-specified cumulative endpoint of death, MI, or revascularisation was significantly reduced, and this benefit was maintained at one year follow-up [18]. The mean increase in LVEF in the BMMNC group was 2.5% and there was an inverse relationship between the baseline EF and the degree of improvement. For example, patients with a baseline EF below the median value (48.9%) had an absolute increase in global EF that was three times higher than that in the placebo group. In contrast, the improvement in LVEF in patients with a baseline EF that was above the median value was non-significant (0.3%). The timing of cell infusion post-PCI also had an effect on the primary endpoint. Patients in whom the cells were infused ?5 days post-PCI were the only ones who derived benefit.

By contrast, the LEUVEN-AMI study by Janssens and colleagues [19] showed that intracoronary re-infusion of BMMNCs within 24 hours of reperfusion was associated with a greater reduction in infarct size and improved regional systolic function, but no overall improvement in global left ventricular function compared to controls.
Trials that used two different cell populations

More recently, the Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) trial, which included patients with anterior MI, uniquely compared two cell types. Patients were randomized to receive intracoronary infusion of unselected (n = 80) or selected CD34+CXCR4+ (n = 80) BMMNCs, or to the control group (n = 40) [20]. Although patients in the treatment group had a 3% improvement in LVEF, this did not reach statistical significance. However, the primary endpoint analysis included 5 hours) may be more likely to have significant improvement of LVEF following the BMMNC infusion [20].

The timing of cell infusion may also play a role on the derived benefit. Although the REPAIR-AMI trial suggests that the enhanced improvement of the LVEF was confined to patients who were treated ?5 days after primary PCI, the investigators of the HEBE and REGENT trials showed no interaction between the timing of cell infusion and derived benefit. The meta-analysis by Martin-Rendon and colleagues [22], however, showed that the benefit of stem cell therapy was even greater when the BMMNCs were infused >7 days after MI. The effect of timing on the beneficial effects of BMMNC administration is further supported by the study by Lai and colleagues [31] that showed that intracoronary BMMNC administration provided cardio-protection in a fashion similar to ishaemic preconditioning. This benefit was only seen when the myocardium had not been preconditioned by other means. An ongoing study at our centre, the REGENERATE-AMI (ClinicalTrial.gov NCT00765453), is designed to study the delivery of BMMNCs at very early time points (within 6 hours of PCI). The purpose of this design is to replicate the animal models where very early interventions lead to a significant (40%) improvement in cardiac function [8].

The dose of infused BMMNCs has varied between different trials with variable results. There appears to be a dose-dependent improvement in EF, with the benefit of BMMNCs only seen when doses higher than 108 are administered [22].
Direct (transdifferentiation) and indirect (paracrine and angiogenesis) effects of stem cells

To date, there is no direct clinical evidence that cellular cardiomyogenesis in fact occurs in the human heart after transplantation of progenitor cells, and over the past few years, various experiments using different types of stem cells have shown that 4 days after reperfusion (based on available evidence). Furthermore, given the seemingly small improvements that these trials have shown, the cost-effectiveness of cell therapy will also need to be addressed.

Two ongoing randomised controlled trials (TIME and late TIME studies) may help us understand whether the timing of cell administration plays an important role. The TIME study (Clinicaltrials.gov NCT00684021) is a trial designed to assess the effect of timing (3 versus 7 days) of BMMNC administration versus placebo in patients with acute MI. The LATE TIME study (Clinicaltrials.gov NCT00684060) will assess the effect of BMMNC administration 2 to 3 weeks after a MI.
Future cells

Animal and human studies have clearly shown that stem cell engraftment into the myocardium is associated with improvement in cardiac function; however, the quest for the optimal population of cells remains a challenge [85,86]. Embryonic stem cells are able to transform into cardiomyocytes and can replicate indefinitely, although ethical issues - their potential to form teratomas and the need for immunosuppressive therapy - have hindered their use in clinical trials. Furthermore, one of the major limitations of adult stem cells, including skeletal myoblasts and bone marrow-derived stem cells, is their limited ability to cross their lineage boundaries.

Fat tissue-derived multipotent stem cells [87], multi-potential cells from bone marrow or skeletal muscle [88,89], somatic stem cells from placental cord blood [90], and cardiac-resident progenitor cells [32,91] all show promising pre-clinical and some clinical applications.

Ultimately, cells that more closely resemble embryonic stem cells in their regenerative potential without the ethical issues provide an important future direction. A cell type that comes close, and is on the horizon of being tested for potential clinical application, is the inducible pluripotent stem cell (iPSC). iPSCs can be generated from adult human somatic cells by retroviral transduction [92], have similar differentiation potential and may provide an alternative to pluripotent embryonic stem cells.
The future of bone marrow stem cells

For the time being, it is important to establish whether the simple unfractionated bone marrow cell approach has clinical benefit, given the large number of studies that have been performed using this cell type without providing a clear answer. Meta-analysis suggests a positive effect on surrogate cardiac end-points in studies using BMMNCs to treat AMI. There is now a need to perform a large scale clinical trial using clinical hard end-points such as mortality to establish whether the positive effects seen on surrogate end-points can indeed translate to meaningful clinical benefits.
Abbreviations

AMI: acute myocardial infarction; ASTAMI: Autologous Stem-Cell Transplantation in Acute Myocardial Infarction; BMMNC: bone marrow-derived mononuclear cell; BOOST: Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration; EF: ejection fraction; LV: left ventricular; LVEF: left ventricular ejection fraction; MI: myocardial infarction; PCI: percutaneous coronary intervention; REPAIR-AMI: Intracoronary bone marrow derived progenitor cells in acute infarction; SDF: stromal-cell-derived factor.
Competing interests

The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
Acknowledgements

This work forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit, which is supported and funded by the National Institute of Health Research.
References

1.

Pfeffer M, John J, McMurray M, Velazquez E, Rouleau J: Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.

N Engl J Med 2003, 349:1893-1906. PubMed Abstract | Publisher Full Text OpenURL

Return to text
2.

Braunwald E: Cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities.

N Engl J Med 1997, 337:1360-1369. PubMed Abstract | Publisher Full Text OpenURL

Return to text
3.

Mathur A, Martin JF: Stem cells and repair of the heart.

Lancet 2004, 364:183-192. PubMed Abstract | Publisher Full Text OpenURL

Return to text
4.

Yeh TH, Zhang S, Wu H: Transdifferentiation of human peripheral blood CD34+ enriched cell population into cardiomyocytes, endothelial cell and smooth muscle cells in vivo.

Circulation 2003, 108:2070-2073. PubMed Abstract | Publisher Full Text OpenURL

Return to text
5.

Badorff C: Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes.

Circulation 2003, 107:1024-1032. PubMed Abstract | Publisher Full Text OpenURL

Return to text
6.

Kawada H, Fujita J, Kinjo K: Non-haematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction.

Blood 2004, 104:3581-3587. PubMed Abstract | Publisher Full Text OpenURL

Return to text
7.

Orlic D: Mobilized bone marrow cells repair the infarcted heart, improving function and survival.

Proc Natl Acad Sci USA 2001, 98:10344-10349. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

Return to text
8.

Orlic D, Kajstrua J, Chimenti S: Bone marrow cells regenerate infarcted myocardium.

Nature 2001, 410:701-705. PubMed Abstract | Publisher Full Text OpenURL

Return to text
9.

Strauer B, Brehm M, Zeus T: Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans.

Circulation 2002, 106:1913-1918. PubMed Abstract | Publisher Full Text OpenURL

Return to text
10.

Assmus B, Schächinger V, Teupe C: Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI).

Circulation 2002, 106:3009-3017. PubMed Abstract | Publisher Full Text OpenURL

Return to text
11.

Schächinger V, Assmus B, Britten M: Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: Final one year results of the TOPCARE-AMI trial.

J Am Coll Cardiol 2004, 44:1690-1699. PubMed Abstract | Publisher Full Text OpenURL

Return to text
12.

Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, Endresen K, Ilebekk A, Mangschau A, Fjeld JG, Smith HJ, Taraldsrud E, Grøgaard HK, Bjørnerheim R, Brekke M, Müller C, Hopp E, Ragnarsson A, Brinchmann JE, Forfang K: Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction.

N Engl J Med 2006, 355:1199-1209. PubMed Abstract | Publisher Full Text OpenURL

Return to text
13.

Seeger FH, Tonn T, Krzossok N, Zeiher AM, Dimmeler S: Cell isolation procedures matter: a comparison of different isolation protocols of bone marrow mononuclear cells used for cell therapy in patients with acute myocardial infarction.

Eur Heart J 2007, 28:766-772. PubMed Abstract | Publisher Full Text OpenURL

Return to text
14.

Wollert K, Meyer G, Joachim L: Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial.

Lancet 2004, 364:141-148. PubMed Abstract | Publisher Full Text OpenURL

Return to text
15.

Yousef M, Schannwell CM, Kostering M, Zeus T, Brehm M, Strauer BE: The BALANCE Study: clinical benefit and long-term outcome after intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction.

J Am Coll Cardiol 2009, 53:2262-2269. PubMed Abstract | Publisher Full Text OpenURL

Return to text
16.

Ge J, Qian J: Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI).

Heart 2006, 92:1764-1767. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

Return to text
17.

Schächinger V, Erbs S, Elsässer A, REPAIR-AMI investigators: Intracoronary bone marrow derived progenitor cells in acute infarction.

N Engl J Med 2006, 355:1210-1221. PubMed Abstract | Publisher Full Text OpenURL

Return to text
18.

Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Hölschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Süselbeck T, Werner N, Haase J, Neuzner J, Germing A, Mark B, Assmus B, Tonn T, Dimmeler S, Zeiher AM, REPAIR-AMI Investigators: Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial.

Eur Heart J 2006, 27:2775-2783. PubMed Abstract | Publisher Full Text OpenURL

Return to text
19.

Janssens S, Dubois C, Bogaert J: Autologous bone marrow derived stem cell transfer in patients with ST-segment elevation myocardial infarction: double blind randomised controlled trial.

Lancet 2006, 367:113-121. PubMed Abstract | Publisher Full Text OpenURL

Return to text
20.

Tendera M, Wojakowski W, Ruzy??o W, Chojnowska L, Kepka C, Tracz W, Musia?ek P, Piwowarska W, Nessler J, Buszman P, Grajek S, Breborowicz P, Majka M, Ratajczak MZ, REGENT Investigators: Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial.

Eur Heart J 2009, 30:1313-1321. PubMed Abstract | Publisher Full Text OpenURL

Return to text
21.

Hirsch A, Nijveldt R, van der Vleuten PA, Tijssen JG, van der Giessen WJ, Tio RA, Waltenberger J, ten Berg JM, Doevendans PA, Aengevaeren WR, Zwaginga JJ, Biemond BJ, van Rossum AC, Piek JJ, Zijlstra F, HEBE Investigators: Intracoronary infusion of mononuclear cells from bone marrow or peripheral blood compared with standard therapy in patients after acute myocardial infarction treated by primary percutaneous coronary intervention: results of the randomized controlled HEBE trial.

Eur Heart J 2011, 32:1736-1747. PubMed Abstract | Publisher Full Text OpenURL

Return to text
22.

Martin-Rendon E, Brunskill SJ, Hyde CJ, Stanworth SJ, Mathur A, Watt SM: Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review.

Eur Heart J 2008, 29:1807-1818. PubMed Abstract | Publisher Full Text OpenURL

Return to text
23.

Lipinski JM, Giuseppe GL, Zoccai B, Abbate A, Khianey R: Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction.

J Am Coll Cardiol 2007, 50:1761-1767. PubMed Abstract | Publisher Full Text OpenURL

Return to text
24.

Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B: Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis.

Arch Intern Med 2007, 167:989-997. PubMed Abstract | Publisher Full Text OpenURL

Return to text
25.

Reffelmann T, Konemann S, Kloner RA: Promise of blood- and bone marrow-derived stem cell transplantation for functional cardiac repair: putting it in perspective with existing therapy.

J Am Coll Cardiol 2009, 53:305-308. PubMed Abstract | Publisher Full Text OpenURL

Return to text
26.

Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Guagliumi G, Stuckey T, Turco M, Carroll JD, Rutherford BD, Lansky AJ, Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Investigators: Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction.

N Engl J Med 2002, 346:957-966. PubMed Abstract | Publisher Full Text OpenURL

Return to text
27.

Montalescot G, Barragan P, Wittenberg O, Ecollan P, Elhadad S, Villain P, Boulenc JM, Morice MC, Maillard L, Pansiéri M, Choussat R, Pinton P, ADMIRAL Investigators. Abciximab before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long-Term Follow-up: Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction.

N Engl J Med 2001, 344:1895-1903. PubMed Abstract | Publisher Full Text OpenURL

Return to text
28.

Curtis JP, Sokol SI, Wang Y, Rathore SS, Ko DT, Jadbabaie F, Portnay EL, Marshalko SJ, Radford MJ, Krumholz HM: The association of left ventricular ejection fraction, mortality, and cause of death in stable outpatients with heart failure.

J Am Coll Cardiol 2003, 42:736-742. PubMed Abstract | Publisher Full Text OpenURL

Return to text
29.

Tribouilloy C, Rusinaru D, Mahjoub H, Soulière V, Lévy F, Peltier M, Slama M, Massy Z: Prognosis of heart failure with preserved ejection fraction: a 5 year prospective population-based study.

Eur Heart J 2008, 29:339-347. PubMed Abstract | Publisher Full Text OpenURL

Return to text
30.

Sharif F, Bartunek J, Vanderheyden M: Adult stem cells in the treatment of acute myocardial infarction.

Catheter Cardiovasc Interv 2011, 77:72-83. PubMed Abstract | Publisher Full Text OpenURL

Return to text
31.

Lai VK, Ang KL, Rathbone W, Harvey NJ, Galinanes M: Randomized controlled trial on the cardioprotective effect of bone marrow cells in patients undergoing coronary bypass graft surgery.

Eur Heart J 2009, 30:2354-2359. PubMed Abstract | Publisher Full Text OpenURL

Return to text
32.

Oh H: Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction.

Proc Natl Acad Sci USA 2003, 100:12313-12318. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

Return to text
33.

Murry C, Soonpaa M, Reinecke H: Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts.

Nature 2004, 428:664-668. PubMed Abstract | Publisher Full Text OpenURL

Return to text
34.

Balsam L, Wagers A, Christensen J: Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium.

Nature 2004, 428:668-673. PubMed Abstract | Publisher Full Text OpenURL

Return to text
35.

Caplan AI, Dennis JE: Mesenchymal stem cells as trophic mediators.

J Cell Biochem 2006, 98:1076-1084. PubMed Abstract | Publisher Full Text OpenURL

Return to text
36.

Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, Epstein SE: Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms.

Circ Res 2004, 94:678-685. PubMed Abstract | Publisher Full Text OpenURL

Return to text
37.

Takahashi M, Li TS, Suzuki R, Kobayashi T, Ito H, Ikeda Y, Matsuzaki M, Hamano K: 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. PubMed Abstract | Publisher Full Text OpenURL

Return to text
38.

Kubal C, Sheth K, Nadal-Ginard B, Galinanes M: Bone marrow cells have a potent anti-ischemic effect against myocardial cell death in humans.

J Thorac Cardiovasc Surg 2006, 132:1112-1118. PubMed Abstract | Publisher Full Text OpenURL

Return to text
39.

Nelissen-Vrancken H, Debets J, Snoeckx L, Daemen M, Smits J: Time-related normalization of maximal coronary flow in isolated perfused hearts of rats with myocardial infarction.

Circulation 1996, 93:349-355. PubMed Abstract | Publisher Full Text OpenURL

Return to text
40.

Takahashi T, Kalka C, Masuda H: Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization.

Nat Med 1999, 5:434-438. PubMed Abstract | Publisher Full Text OpenURL

Return to text
41.

Kalka C, Masuda H, Takahashi T: Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization.

Proc Natl Acad Sci USA 2000, 97:3422-3427. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

Return to text
42.

Folkman J: Therapeutic angiogenesis in ischemic limbs.

Circulation 1998, 97:1108-1110. PubMed Abstract | Publisher Full Text OpenURL

Return to text
43.

Asahara T: Isolation of putative progenitor cells for endothelial angiogenesis.

Science 1997, 275:964-967. PubMed Abstract | Publisher Full Text OpenURL

Return to text
44.

Isner J, Asahara T: Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization.

J Clin Invest 1999, 103:1231-1236. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

Return to text
45.

Dowell JD, Rubart M, Pasumarthi KBS, Soonpaa MH, Field LJ: Myocyte and myogenic stem cell transplantation in the heart.

Cardiovasc Res 2003, 58:336-350. PubMed Abstract | Publisher Full Text OpenURL

Return to text
46.

Kocher A: Neovascularization of ischemic myocardium by human bonemarrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function.

Nat Med 2001, 7:430-436. PubMed Abstract | Publisher Full Text OpenURL

Return to text
47.

Kawamoto A, Gwon HC, Iwaguro H, Yamaguchi JI, Uchida S, Masuda H, Silver M, Ma H, Kearney M, Isner JM, Asahara T: Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia.

Circulation 2001, 103:634-637. PubMed Abstract | Publisher Full Text OpenURL

Return to text
48.

Urbich C, Heeschen C, Aicher A, Dembach E, Zeiher AM, Dimmeler S: Relevance of monocytic features for neovascularization capacity of circulating endothelial progenitor cells.

Circulation 2003, 108:2511-2516. PubMed Abstract | Publisher Full Text OpenURL

Return to text
49.

Aicher A, Heeschen C, Mildner-Rihm C, Urbich C, Ihling C, Technau-Ihling K, Zeiher AM, Dimmeler S: Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells.

Nat Med 2003, 9:1370-1376. PubMed Abstract | Publisher Full Text OpenURL

Return to text
50.

Fuchs S, Baffour R, Zhou Y: Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischaemia.

J Am Coll Cardiol 2001, 37:1726-1732. PubMed Abstract | Publisher Full Text OpenURL

Return to text
51.

Hamano K, Li TS, Kobayashi T, Hirata K, Yano M, Kohno M, Matsuzaki M: Therapeutic angiogenesis induced by local autologous bone marrow cell implantation.

Ann Thorac Surg 2002, 73:1210-1215. PubMed Abstract | Publisher Full Text OpenURL

Return to text
52.

Kamihata H, Matsubara H, Nishiue T: Improvement of collateral perfusion and regional function by implantation of peripheral blood mononuclear cells into ischemic hibernating myocardium.

Arterioscler Thromb Vasc Biol 2002, 22:1804-1810. PubMed Abstract | Publisher Full Text OpenURL

Return to text
53.

Kamihata H, Matsubara H, Nishiue T: 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. PubMed Abstract | Publisher Full Text OpenURL

Return to text
54.

Jackson K: Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells.

J Clin Invest 2001, 107:1395-1402. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

Return to text
55.

Rehman J, Li J, Orschell CM, March KL: Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors.

Circulation 2003, 107:1164-1169. PubMed Abstract | Publisher Full Text OpenURL

Return to text
56.

Shintani S, Murohara T, Ikeda H: Mobilization of endothelial progenitor cells in patients with acute myocardial infarction.

Circulation 2001, 103:2776-2779. PubMed Abstract | Publisher Full Text OpenURL

Return to text
57.

Iwaguro H, Yamaguchi J, Kalka C: Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration.

Circulation 2002, 105:732-738. PubMed Abstract | Publisher Full Text OpenURL

Return to text
58.

Perin E: Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure.

Circulation 2003, 107:2294-2302. PubMed Abstract | Publisher Full Text OpenURL

Return to text
59.

Beauchamp J, Morgan J, Pagel C, Partridge T: Dynamics of myoblast transplantation reveal a discrete minority of precursors with stem cell-like properties as the myogenic source.

J Cell Biol 1999, 144:1113-1122. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

Return to text
60.

Papayannopoulou T: Bone marrow homing: the players, the playfield, and their evolving roles.

Curr Opin Hematol 2003, 10:214-219. PubMed Abstract | Publisher Full Text OpenURL

Return to text
61.

Aicher A: Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling.

Circulation 2003, 107:2134-2139. PubMed Abstract | Publisher Full Text OpenURL

Return to text
62.

De Falco E: Sdf-1 involvement in endothelial phenotype and ischemiainduced recruitment of bone marrow progenitor cells.

Blood 2004, 104:3472-3482. PubMed Abstract | Publisher Full Text OpenURL

Return to text
63.

Chavakis E: Role of b2-integrins for homing and neovascularization capacity of endothelial progenitor cells.

J Exp Med 2005, 201:63-72. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

Return to text
64.

Vajkoczy P: Multistep nature of microvascular recruitment of ex vivoexpanded embryonic endothelial progenitor cells during tumor angiogenesis.

J Exp Med 2003, 197:1755-1765. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

Return to text
65.

Askari A: Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy.

Lancet 2003, 362:697-703. PubMed Abstract | Publisher Full Text OpenURL

Return to text
66.

Yamaguchi J: Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization.

Circulation 2003, 107:1322-1328. PubMed Abstract | Publisher Full Text OpenURL

Return to text
67.

Scaffidi P, Misteli T, Bianchi M: Release of chromatin protein hmgb1 by necrotic cells triggers inflammation.

Nature 2002, 418:191-195. PubMed Abstract | Publisher Full Text OpenURL

Return to text
68.

Hristov M, Zernecke A, Bidzhekov K, Liehn EA, Shagdarsuren E, Ludwig A, Weber C: Importance of CXC chemokine receptor 2 in the homing of human peripheral blood endothelial progenitor cells to sites of arterial injury.

Circ Res 2007, 100:590-597. PubMed Abstract | Publisher Full Text OpenURL

Return to text
69.

Levesque JP, Hendy J, Takamatsu Y, Simmons PJ, Bendall LJ: Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide.

J Clin Invest 2003, 111:187-196. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

Return to text
70.

Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, Ponomaryov T, Taichman RS, Arenzana-Seisdedos F, Fujii N, Sandbank J, Zipori D, Lapidot T: G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4.

Nat Immunol 2002, 3:687-694. PubMed Abstract | Publisher Full Text OpenURL

Return to text
71.

Yamaguchi J, Kusano KF, Masuo O, Kawamoto A, Silver M, Murasawa S, Bosch-Marce M, Masuda H, Losordo DW, Isner JM, Asahara T: Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization.

Circulation 2003, 107:1322-1328. PubMed Abstract | Publisher Full Text OpenURL

Return to text
72.

Bartunek J, Dimmeler S, Drexler H, Fernández-Avilés F, Galinanes M, Janssens S, Martin J, Mathur A, Menasche P, Priori S, Strauer B, Tendera M, Wijns W, Zeiher A, task force of the European Society of Cardiology: The consensus of the task force of the European Society of Cardiology concerning the clinical investigation of the use of autologous adult stem cells for repair of the heart.

Eur Heart J 2006, 27:1338-1340. PubMed Abstract | Publisher Full Text OpenURL

Return to text
73.

Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan R, Melton D: "Stemness": transcriptional profiling of embryonic and adult stem cells.

Science 2002, 298:597-600. PubMed Abstract | Publisher Full Text OpenURL

Return to text
74.

Jiang S, Haider HK, Idris NM, Salim A, Ashraf M: Supportive interaction between cell survival signaling and angiocompetent factors enhances donor cell survival and promotes angiomyogenesis for cardiac repair.

Circ Res 2006, 99:776-784. PubMed Abstract | Publisher Full Text OpenURL

Return to text
75.

Norol F, Bonnet N, Peinnequin A, Chretien F, Legrand R, Isnard R, Herodin F, Baillou C, Delache B, Negre D, Klatzmann D, Vernant JP, Lemoine FM: GFP-transduced CD34+ and Lin- CD34- hematopoietic stem cells did not adopt a cardiac phenotype in a nonhuman primate model of myocardial infarct.

Exp Hematol 2007, 35:653-661. PubMed Abstract | Publisher Full Text OpenURL

Return to text
76.

Nakamura Y, Wang X, Xu C, Asakura A, Yoshiyama M, From AH, Zhang J: Xenotransplantation of long-term-cultured swine bone marrow-derived mesenchymal stem cells.

Stem Cells 2007, 25:612-620. PubMed Abstract | Publisher Full Text OpenURL

Return to text
77.

Heeschen C: Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease.

Circulation 2004, 109:1615-1622. PubMed Abstract | Publisher Full Text OpenURL

Return to text
78.

Vasa M: Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease.

Circ Res 2001, 89:E1-E7. PubMed Abstract | Publisher Full Text OpenURL

Return to text
79.

Hill J: Circulating endothelial progenitor cells, vascular function, and cardiovascular risk.

N Engl J Med 2003, 348:593-600. PubMed Abstract | Publisher Full Text OpenURL

Return to text
80.

Edelberg J, Tang L, Hattori K, Lyden D, Rafii S: Young adult bone marrow-derived endothelial precursor cells restore aging-impaired cardiac angiogenic function.

Circ Res 2002, 90:E89-E93. PubMed Abstract | Publisher Full Text OpenURL

Return to text
81.

Torella D: Cardiac stem cell and myocyte aging, heart failure, and insulinlike growth factor-1 overexpression.

Circ Res 2004, 94:514-524. PubMed Abstract | Publisher Full Text OpenURL

Return to text
82.

Assmus B: Hmg-coa reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes.

Circ Res 2003, 92:1049-1055. PubMed Abstract | Publisher Full Text OpenURL

Return to text
83.

Spyridopoulos I: Statins enhance migratory capacity by upregulation of the telomere repeat-binding factor trf2 in endothelial progenitor cells.

Circulation 2004, 110:3136-3142. PubMed Abstract | Publisher Full Text OpenURL

Return to text
84.

Hong SJ, Choi SC, Kim JS, Shim WJ, Park SM, Ahn CM, Park JH, Kim YH, Lim DS: Low-dose versus moderate-dose atorvastatin after acute myocardial infarction: 8-month effects on coronary flow reserve and angiogenic cell mobilisation.

Heart 2010, 96:756-764. PubMed Abstract | Publisher Full Text OpenURL

Return to text
85.

Smits AM, van VP, Hassink RJ, Goumans MJ, Doevendans PA: The role of stem cells in cardiac regeneration.

J Cell Mol Med 2005, 9:25-36. PubMed Abstract | Publisher Full Text OpenURL

Return to text
86.

Davani S, Deschaseaux F, Chalmers D, Tiberghien P, Kantelip JP: Can stem cells mend a broken heart?

Cardiovasc Res 2005, 65:305-316. PubMed Abstract | Publisher Full Text OpenURL

Return to text
87.

Planat-Benard V: Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells.

Circ Res 2004, 94:223-229. PubMed Abstract | Publisher Full Text OpenURL

Return to text
88.

Jiang Y: Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain.

Exp Hematol 2002, 30:896-904. PubMed Abstract | Publisher Full Text OpenURL

Return to text
89.

Jiang Y: Pluripotency of mesenchymal stem cells derived from adult marrow.

Nature 2002, 418:41-49. PubMed Abstract | Publisher Full Text OpenURL

Return to text
90.

Kogler G: A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential.

J Exp Med 2004, 200:123-135. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

Return to text
91.

Beltrami A: Adult cardiac stem cells are multipotent and support myocardial regeneration.

Cell 2003, 114:763-776. PubMed Abstract | Publisher Full Text OpenURL

Return to text
92.

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S: Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

Cell 2007, 131:861-872. PubMed Abstract | Publisher Full Text OpenURL

Return to text
93.

Meluzin J, Mayer J, Groch L: Autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction: The effect of the dose of transplanted cells on myocardial function.

Am Heart J 2006, 152:975.e9-975.e15. PubMed Abstract | Publisher Full Text OpenURL

Return to text
94.

Fernández-Avilés F, San Román JA, García-Frade J, Fernández ME, Peñarrubia MJ, de la Fuente L, Gómez-Bueno M, Cantalapiedra A, Fernández J, Gutierrez O, Sánchez PL, Hernández C, Sanz R, García-Sancho J, Sánchez A: Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction.

Circ Res 2004, 95:742-748. PubMed Abstract | Publisher Full Text OpenURL

Return to text
95.

De Lezo J, Herrera C, Pan M: Regenerative therapy in patients with a revascularized acute anterior myocardial infarction and depressed ventricular function.

Rev Esp Cardiol 2007, 60:357-365. PubMed Abstract | Publisher Full Text OpenURL

Return to text
96.

Zhan-quan L, Ming Z: The clinical study of autologous peripheral blood stem cell transplantation by intracoronary infusion in patients with acute myocardial infarction.

Int J Cardiol 2007, 115:52-56. PubMed Abstract | Publisher Full Text OpenURL

Return to text
97.

Lipiec P, Pakula M, Plewka M: Impact of intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction on left ventricular perfusion and function: a 6-month follow-up gated mTc-MIBI single-photon emission computed tomography study.

Eur J Nucl Mol Imaging 2009, 36:587-593. Publisher Full Text OpenURL

Return to text
98.

Huikuri H, Kervinen K, Niemelä M: Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restonosis after thrombolytic therapy of acute myocardial infarction.

Eur Heart J 2008, 29:2723-2732. PubMed Abstract | Publisher Full Text OpenURL

Return to text
99.

Kang H, Kim H, Zhang S, Park K, Cho H, Koo B: Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocytecolony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial.

Lancet 2004, 363:751-756. PubMed Abstract | Publisher Full Text OpenURL

Return to text
100.

Bartunek J, Vanderheyden M, Vandekerckhove B: Intracoronary injection of CD133 positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety.

Circulation 2005, 112 (Suppl 9):I178-I183. OpenURL

Return to text
101.

Chen SL, Fang WW, Ye F, Liu YH, Qian J, Shan SJ, Zhang JJ, Chunhua RZ, Liao LM, Lin S, Sun JP: Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction.

Am J Cardiol 2004, 94:92-95. PubMed Abstract | Publisher Full Text OpenURL

Return to text

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