Transmyocardial Laser Revascularization Combined with Intramyocardial Endothelial Progenitor Cell Transplantation in Patients with Intractable Ischemic Heart Disease Ineligible for Conventional Revascularization: Preliminary Results in a Highly Selected Small Patient Cohort

Babin‐Ebell, Jörg; Sievers, Hans‐Hinrich; Charitos, EI; Klein, Hans-Martin; Jung, F; Hellberg, Anders; Depping, Reinhard; Sier, Holger; Marxsen, Jan H.; Stoelting, Stephanie; Kraatz, E. G.; Wagner, Kim

doi:10.1055/s-0029-1186199

Cited by 28 publications

(19 citation statements)

References 20 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: 95%

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: 95%

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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“…The presence of different numbers or impaired function of pro-angiogenic hematopoietic cells in different disease states supports their role as mediators of vascular health. They have, for instance, been demonstrated to correlate with degree of cardiovascular disease, severity of pulmonary hypertension, cancer, and diabetes [44,45] [6–12,15,32]. They have been demonstrated to be derived from the marrow and home in to sites of vascular remodeling [6–12].…”

Section: Origin and Function Of Pro-angiogenic Hematopoietic Cells Anmentioning

confidence: 99%

“…They have, for instance, been demonstrated to correlate with degree of cardiovascular disease, severity of pulmonary hypertension, cancer, and diabetes [44,45] [6–12,15,32]. They have been demonstrated to be derived from the marrow and home in to sites of vascular remodeling [6–12]. Furthermore, preliminary trials have demonstrated a possible therapeutic role for these cells in cardiovascular disease [6–12].…”

Section: Origin and Function Of Pro-angiogenic Hematopoietic Cells Anmentioning

confidence: 99%

“…Vascular degenerative disorders such as ischemic cardiovascular disease[6–12], cerebrovascular disease[13,14] and diabetes[15–17] are associated with reduced function of circulating pro-angiogenic hematopoietic cells, which are believed to have protective effects on the vasculature in these diseases. In conditions of pathological vascularization, such as, tumor proliferation[1,18] and macular degeneration[19–22], increased numbers of pro-angiogenic progenitors in the blood contribute to the angiogenic remodeling.…”

Section: Introductionmentioning

confidence: 99%

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Pro-angiogenic hematopoietic progenitor cells and endothelial colony-forming cells in pathological angiogenesis of bronchial and pulmonary circulation

2011

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Dysregulation of angiogenesis is a common feature of many disease processes. Vascular remodeling is believed to depend on the participation of endothelial progenitor cells, but the identification of endothelial progenitors in postnatal neovascularization remains elusive. Current understanding posits a role for circulating pro-angiogenic hematopoietic cells, which interact with local endothelial cells to establish an environment that favors angiogenesis in physiologic and pathophysiologic responses. In the lung, increased and dysregulated angiogenesis is a hallmark of diseases of the bronchial and pulmonary circulations, manifested by asthma and pulmonary arterial hypertension (PAH), respectively. In asthma THelper-2 immune cells produce angiogenic factors that mobilize and recruit pro-inflammatory and pro-angiogenic precursors from the bone marrow into the airway wall where they induce angiogenesis and fuel inflammation. In contrast, in PAH, upregulation of hypoxia-inducible factor (HIF) in vascular cells leads to the production of bone marrow-mobilizing factors that recruit pro-angiogenic progenitor cells to the pulmonary circulation where they contribute to angiogenic remodeling of the vessel wall. This review focuses on current knowledge of pro-angiogenic progenitor cells in the pathogenesis of asthma and PAH.

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“…Albeit using a time-optimized accelerated procedure protocol, the procedure resulted in a high-quality cell product in terms of purity as well as vitality. This approach was presented for the first time in a small cohort study in patients with intractable ischemic heart disease who received laser treatment and CD133+ cell transplantation [11].…”

Section: Discussionmentioning

confidence: 99%

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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Transmyocardial Laser Revascularization Combined with Intramyocardial Endothelial Progenitor Cell Transplantation in Patients with Intractable Ischemic Heart Disease Ineligible for Conventional Revascularization: Preliminary Results in a Highly Selected Small Patient Cohort

Cited by 28 publications

References 20 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

Pro-angiogenic hematopoietic progenitor cells and endothelial colony-forming cells in pathological angiogenesis of bronchial and pulmonary circulation

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

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