Intracoronary administration of bone marrow-derived progenitor cells improves left ventricular function in patients at risk for adverse remodeling after acute ST-segment elevation myocardial infarction: Results of the Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial Infarction study (REPAIR-AMI) cardiac Magnetic Resonance Imaging substudy

Dill, Thorsten; Schächinger, Volker; Rolf, Andreas; Möllmann, Susanne; Thiele, Holger; Tillmanns, Harald; Aßmus, Birgit; Dimmeler, Stefanie; Zeiher, Andreas M.; Hamm, Christian W.

doi:10.1016/j.ahj.2008.11.011

Cited by 163 publications

(107 citation statements)

References 23 publications

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“…Details of MRI protocols and imaging analysis have been described previously 8 and were performed in identical fashion. Although MRI analysis at the offline work station in the MRI core laboratory was preformed by blinded investigators, the statistical analysis was performed by investigators being aware of the treatment assignment of the patients.…”

Section: Mri Protocolmentioning

confidence: 99%

Clinical Outcome 2 Years After Intracoronary Administration of Bone Marrow–Derived Progenitor Cells in Acute Myocardial Infarction

Aßmus

Rolf²,

Erbs³

et al. 2010

Circ: Heart Failure

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MD; for the REPAIR-AMI InvestigatorsBackground-The aim of this study was to investigate the clinical outcome 2 years after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). Methods and Results-Using a double-blind, placebo-controlled, multicenter trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone marrow-derived progenitor cells (BMC) or placebo medium into the infarct artery 3 to 7 days after successful infarct reperfusion therapy. At 2 years, the cumulative end point of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (hazard ratio, 0.58; 95% CI, 0.36 to 0.94; Pϭ0.025). Likewise, the combined end point death and recurrence of myocardial infarction and rehospitalization for heart failure, reflecting progression toward heart failure, was significantly reduced in the BMC group (hazard ratio, 0.26; 95% CI, 0.085 to 0.77; Pϭ0.015). Intracoronary administration of BMC remained a significant predictor of a favorable clinical outcome by Cox regression analysis when adjusted for classical predictors of poor outcome after AMI. There was no evidence of increased restenosis or atherosclerotic disease progression after BMC therapy nor any evidence of increased ventricular arrhythmias or neoplasms. In addition, regional left ventricular contractility of infarcted segments, as assessed by MRI in a subgroup of patients at 2-year follow-up, was significantly higher in the BMC group compared with the placebo group (PϽ0.001). Conclusions-Intracoronary administration of BMC is associated with a significant reduction of the occurrence of major adverse cardiovascular events maintained for 2 years after AMI. Moreover, functional improvements after BMC therapy may persist for at least 2 years. Larger studies focusing on clinical event rates are warranted to confirm the effects of BMC administration on mortality and progression of heart failure in patients with AMIs. Clinical Trial Registration-clinicaltrials.gov. Identifier: NCT00279175.(Circ Heart Fail. 2010;3:89-96.)

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Section: Mri Protocolmentioning

confidence: 99%

Clinical Outcome 2 Years After Intracoronary Administration of Bone Marrow–Derived Progenitor Cells in Acute Myocardial Infarction

Aßmus

Rolf²,

Erbs³

et al. 2010

Circ: Heart Failure

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260

152

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“…The presence of adult stem cells in a large variety of tissues also raises the question of which tissue sources of stem cells are best suited for applications in each of the many diseases where regenerative therapy may be possible. For example, damaged myocardium has been repaired with varying levels of success using satellite cells, bone marrow-derived and adipose-derived mesenchymal stem cells (MSC) (Beitnes et al 2009;Dill et al 2009;Hagege et al 2003;Madonna et al 2009;Menasche et al 2001). Adipose-derived MSC have several characteristics which make them well suited for regenerative medicine, they are: (1) abundant, (2) easily harvested, (3) have been shown to be multipotent, (4) possesses a degree of immunoprivilege, and (5) are amenable to good manufacturing practices (Gimble et al 2007;McIntosh et al 2006;Zuk et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Caloric restriction attenuates the age-associated increase of adipose-derived stem cells but further reduces their proliferative capacity

Schmuck

Mulligan

Saupe

2010

AGE

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White adipose tissue is a promising source of mesenchymal stem cells. Currently, little is known about the effect of age and caloric restriction (CR) on adipose-derived stem cells (ASC). This is important for three reasons: firstly, age and CR cause extensive remodeling of WAT; it is currently unknown how this remodeling affects the resident stem cell population. Secondly, stem cell senescence has been theorized as one of the causes of aging and could reduce the utility of a stem cell as a reagent. Thirdly, the mechanism by which CR extends lifespan is currently not known, one theory postulates that CR maintains the resident stem cell population in youthful "fit" state. For the purpose of this study, we define ASC as lineage negative (lin − )/CD34 +(low) /CD31 − . We show that aging increases the abundance of ASC and the expression of Cdkn2a 9.8-fold and Isl1 60.6-fold.This would suggest that aging causes an accumulation of non-replicative ASC. CR reduced the percentage of ASC in the lin − SVF while also reducing colony forming ability. Therefore, CR appears to have antiproliferative effects on ASC that may be advantageous from the perspective of cancer, but our data raises the possibility that it may be disadvantageous for regenerative medicine applications.

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“…58 In contrast, the REPAIR-AMI trial conducted by Dill et al compared autologous BM-MNC transplantation with placebo after BM aspiration in patients who had PCI after a STEMI. 59 One year after intracoronary cell infusion, the group that received BM-MNC did not show any statistically significant improvement in global EF, EDV, or ESV. However, patients who had a baseline EF of ≤ 48.9% experienced added benefit of BMC transplantation, as they had significant improvement in EF and a decrease in LVEDV and LVESV.…”

Section: -55mentioning

confidence: 99%

“…However, patients who had a baseline EF of ≤ 48.9% experienced added benefit of BMC transplantation, as they had significant improvement in EF and a decrease in LVEDV and LVESV. 59 One of the first trials to evaluate cell therapy in chronic ischemic cardiomyopathy was the phase II randomized controlled FOCUS trial by the Cardiovascular Cell Therapy…”

Section: -55mentioning

confidence: 99%

Transmyocardial Revascularization Enhances Mesenchymal Stem Cell Engraftment in Infarcted Hearts through SCF–c-Kit and SDF-1–CXCR4 Signaling Axes

Shahzad¹,

Li²,

Yau³

2013

The Journal of Heart and Lung Transplantation

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Objective:We investigated the roles of stem cell factor (SCF)-c-kit and stromal derived factor-1 (SDF-1)-CXCR4 signaling in transmyocardial revascularization (TMR)-enhanced engraftment of transplanted mesenchymal stem cells (MSCs) in infarcted hearts. His constant support and sacrifices over the years have been the reason for my motivation. I will always remember his help, guidance, and the love he gave me throughout life. ! iv! ACKNOWLEDGEMENTS

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Cited by 163 publications

References 23 publications

Clinical Outcome 2 Years After Intracoronary Administration of Bone Marrow–Derived Progenitor Cells in Acute Myocardial Infarction

Clinical Outcome 2 Years After Intracoronary Administration of Bone Marrow–Derived Progenitor Cells in Acute Myocardial Infarction

Caloric restriction attenuates the age-associated increase of adipose-derived stem cells but further reduces their proliferative capacity

Transmyocardial Revascularization Enhances Mesenchymal Stem Cell Engraftment in Infarcted Hearts through SCF–c-Kit and SDF-1–CXCR4 Signaling Axes

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