Impact of preoperative left ventricular function and time from infarction on the long-term benefits after intramyocardial CD133+ bone marrow stem cell transplant

Yerebakan, Can; Kaminski, Alexander; Westphal, Bernd; Donndorf, Peter; Glass, Äenne; Liebold, Andreas; Stamm, Christof; Steinhoff, Gustav

doi:10.1016/j.jtcvs.2011.05.002

Cited by 52 publications

(32 citation statements)

References 33 publications

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“…According to Davy et al [16] enrichment of autologous bone marrow CD34 + stem cells could increase the efficacy of treatments in clinical settings. Despite the fact that CD34 + cells have been the selected option for heart repair, there are also some reports of CD133 + cells applied in clinical trials showing improvement of myocardial viability and local perfusion of the infarcted zone [17][18][19][20][21][22]. However, none of these studies have shown de novo formation of cardiac muscle.…”

Section: Introductionmentioning

confidence: 99%

Engraftment of pre-differentiated stem cells into cardiomyocytes in an animal model of ischemic cardiopathy

González‐Garza

Alcaraz²,

Gonzalez-Jara³

et al. 2014

SCD

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Stem cell therapy for cardiac infarct regeneration has been widely used in clinical research. Despite the fact that important advances in this field have been reached, the observed recovery does not demonstrate new cardiac muscle formation. Benefits have been observed due to an improvement in neovascularisation. The main objective of this study was to determine if predifferentiated stem cells into cells of myocardic lineage are capable of engraftment in animal models with induced cardiac infarct and are capable of truly differentiating into myocardiocytes. Bone marrow rat stem cells were predifferentiated with 5-AZ. After 4 weeks, pre-differentiated stem cells express muscarinic 1, 2 and β adrenergic 2 receptors. Also, proteins such as sarcomeric α-actin, cardiac myosin heavy chain, desmin and vimentin were detected by immunocytochemistry. Cells were transplanted intracardialy in an ischemic cardiac rat model. Pre-differentiated or non differentiated cells were transplanted after 4 weeks post infarct induction. Histopathology of the hearts was made 2 weeks after cell transplantation. Typical granulated tissue, scare formation and neovascularisation were observed in both groups. However, in those hearts from rats inoculated with pre-differentiated cells many appeared atypical and were α-actin sarcomeric positive. These events suggest that pre-differentiated cells conserve some muscle characteristic traits in situ that at least last for two weeks after transplantation.

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Section: Introductionmentioning

confidence: 99%

Engraftment of pre-differentiated stem cells into cardiomyocytes in an animal model of ischemic cardiopathy

González‐Garza

Alcaraz²,

Gonzalez-Jara³

et al. 2014

SCD

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“…In a previous study, Stamm et al described a significant postoperative improvement of the LVEF 6 months after CD133+ cell transplantation in CABG patients with moderately reduced LVEF [10]. However, the same group reported that with regard to the LVEF, combined CABG and cell therapy were not superior to single CABG beyond 6 months after surgery [22]. In fact, they found a LVEF <40% and a time period of 7 to 12 weeks between myocardial infarction and surgery to be predictors of an improvement of the LVEF of at least 5%.…”

Section: Discussionmentioning

confidence: 96%

Laser-Supported CD133+ Cell Therapy in Patients with Ischemic Cardiomyopathy: Initial Results from a Prospective Phase I Multicenter Trial

et al. 2014

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ObjectivesThis study evaluates the safety, principal feasibility and restoration potential of laser-supported CD133+ intramyocardial cell transplantation in patients with ischemic cardiomyopathy.MethodsForty-two patients with severe ischemic cardiomyopathy (left ventricular ejection fraction (LVEF) >15% and <35%) were included in this prospective multicenter phase I trial. They underwent coronary artery bypass grafting (CABG) with subsequent transepicardial low-energy laser treatment and autologous CD133+ cell transplantation, and were followed up for 12 months. To evaluate segmental myocardial contractility as well as perfusion and to identify the areas of scar tissue, cardiac MRI was performed at 6 months and compared to the preoperative baseline. In addition, clinical assessment comprising of CCS scoring, blood and physical examination was performed at 3, 6 and 12 months, respectively.ResultsIntraoperative cell isolation resulted in a mean cell count of 9.7±1.2×106. Laser treatment and subsequent CD133+ cell therapy were successfully and safely carried out in all patients and no procedure-related complications occurred. At 6 months, the LVEF was significantly increased (29.7±1.9% versus 24.6±1.5% with p = 0.004). In addition, freedom from angina was achieved, and quality of life significantly improved after therapy (p<0.0001). Interestingly, an extended area of transmural delayed enhancement (>3 myocardial segments) determined in the preoperative MRI was inversely correlated with a LVEF increase after laser-supported cell therapy (p = 0.024).ConclusionsThis multicenter trial demonstrates that laser-supported CD133+ cell transplantation is safe and feasible in patients with ischemic cardiomyopathy undergoing CABG, and in most cases, it appears to significantly improve the myocardial function. Importantly, our data show that the beneficial effect was significantly related to the extent of transmural delayed enhancement, suggesting that MRI-guided selection of patients is mandatory to ensure the effectiveness of the therapy.Trial Registration:EudraCT 2005-004051-35) Controlled-Trials.com ISRCTN49998633

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“…Currently the Multicenter Phase III clinical randomized placebo-control study is carried out [2], following terminated clinical studies Phase I and Phase II [10]. After studies closure all participants of mentioned trials are observed yearly lifelong within the registry program established in our center.…”

Section: Methodsmentioning

confidence: 99%

Long-term results of intramyocardial CD133+ bone marrow stem cell therapy for myocardial ischemia: experience with stem cell register

Nesteruk¹,

Steinhoff²

2016

CTT

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Standardization of stem cell therapy requires application of appropriate methods to evaluate safety and efficacy, including long-term pharmacovigilance. To accomplish this objective, a long-term registry program was installed in the Regeneration and Translation Center for cardiac stem cell therapy in Rostock, Germany 14 years ago. The registry program in RTC contains parameters for the evaluation of functional outcomes and safety including major adverse cardiovascular and cerebral events (MACCEs). The register follows 223 patients with a total of 1152 patient years, who are observed yearly lifelong after stem cell application or as a control groups. The present study was done in 96 patients (n=73 cell therapy, n=23 control group) with coronary arterial disease and heart failure, treated with coronary artery bypass operation with or without stem cells injections. The analysis revealed, that owing to yearly MACCE registrations, register allow that late probable complications are carefully followed as well as unexpected complication reported, which is required to ensure patient's safety as the main aspect of Good Clinical Practice. Nevertheless, the registry by itself cannot substitute randomized clinical trials, as patient's cohort is heterogeneous. However, registry data can be used for long term efficiency and safety evaluation in standardized patient groups. Furthermore, registry program could help to improve patient selection revealing predictors of good response and define patients who did not respond to the stem cell therapy. It is expedient to establish an obligatory common registry program for all centers, carrying stem cell studies.

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Impact of preoperative left ventricular function and time from infarction on the long-term benefits after intramyocardial CD133+ bone marrow stem cell transplant

Cited by 52 publications

References 33 publications

Engraftment of pre-differentiated stem cells into cardiomyocytes in an animal model of ischemic cardiopathy

Engraftment of pre-differentiated stem cells into cardiomyocytes in an animal model of ischemic cardiopathy

Laser-Supported CD133+ Cell Therapy in Patients with Ischemic Cardiomyopathy: Initial Results from a Prospective Phase I Multicenter Trial

Long-term results of intramyocardial CD133+ bone marrow stem cell therapy for myocardial ischemia: experience with stem cell register

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