In-vivo measurement of vascular repair: EPCs, OCT and beyond
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sion, potentiated reparative neovascularization and continuously attenuated cardiomyocyte apoptosis. Whole mount immunohistochem- istry demonstrated the association of transplanted SVPs, some positive for proliferating cell nuclear antigen, to vessels sprouting toward the infarct area. Expressional studies showed the activation of a pro- angiogenic mechanism involving VEGF-B 186 and Angiopoietin 1 and of a pro-survival signaling centered on Akt/eNOS/Bcl2. Conclusion: SVPs therapy of MI produces long-term improvement of cardiac function through implementation of neovascularization and activation of pro-survival mechanisms. doi:10.1016/j.vph.2011.08.050 L.7.2 In-vivo measurement of vascular repair: EPCs, OCT and beyond Jonathan Hill King's College Hospital NHS Foundation Trust, London, UK E-mail address: [email protected] This would be a talk about the evolution of EPC measurement technology and using OCT for assessing stent strut coverage as a surrogate for reendothelialisation and then to finish with a brief look to the future about integration of OCT or intravascular imaging with molecular imaging strategies. doi:10.1016/j.vph.2011.08.051 L.7.3 Bone marrow cell therapy: Current status and future directions? Buddhadeb Dawn Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of Kansas Medical Center, 3901 Rainbow Blvd, Rm.1001 Eaton, MS 3006, Kansas City, KS, 66160, UK E-mail address: [email protected] A new therapy for cardiac repair has gained momentum in the recent years ? transplantation of bone marrow cells. On the basis of strong evidence from animal studies, numerous clinical trials of cardiac repair with adult bone marrow-derived cells (BMC) have been completed. These relatively smaller studies employed different BMC types with highly variable numbers, routes, and timings of transplantation, and included patients with acute myocardial infarction (MI), as well as chronic ischemic heart disease (IHD). Although the outcomes have been predictably disparate, analysis of pooled data indicates that BMC therapy in patients with acute MI and chronic IHD results in modest improvements in LV function and infarct scar size without any increase in untoward effects. However, a number of hurdles remain to be overcome in order to make cell therapy for infarct repair a routine clinical practice. While the search for an optimal cell continues, efforts are being made to modify cells to make them more suitable for cardiac repair. During this talk, the available clinical evidence regarding the efficacy and safety of therapeutic cardiac repair with adult BMCs will be summarized, and future directions in the field will be discussed with particular reference to Wnt11 signaling. doi:10.1016/j.vph.2011.08.052 L.7.4 Mobilization of stem and progenitor cells in acute cardiovascular syndromes and heart failure Wojciech Wojakowski Third Division of Cardiology, Medical University of Silesia, Katowice, Poland E-mail address: [email protected] In the last decade the concept of myocardial regeneration was rapidly translated from basic science and animal experiments to application of bone marrow (BM)-derived stem and progenitor cells in multiple clinical trials. Meta-analyses and systematic reviews of these trials suggest that this form of cellular therapy leads to modest improvement of left ventricular ejection fraction (LVEF) and reduces LV remodeling in patients with acute myocardial infarction (MI). The primary goal of all studies using stem and progenitor cells was to improve the myocardial function and reduce remodeling by replace- ment of the fibrotic scar tissue by the viable cardiac myocytes. Recently the possibility of myocardial regeneration in humans has been challenged. Most probably the benefits observed with BM cell therapy can be attributed to the paracrine and proangiogenic effects of injected cells. So far, in the majority of clinical trials heterogenous population of non-selected bone marrow-derived mononuclear cells was used and currently there is no proof that any particular type of cells might be superior to others for myocardial repair in patients with AMI and ischemic cardiomyopathy. Parallel to ongoing clinical trials with BM cells, investigating the optimal cell delivery route, dose and target population of patients, new concepts emerged which aim to enhance the capability of BM cells to induce the functional recovery of the myocardium or identifying new, more potent cell populations. This lecture reviews the recent progress in experimental stem cell therapy in patients with acute myocardial infarction. Results of Polish multicenter trial (REGENT) using autologous CD34+ CXCR4+ cells and non-selected BM-derived mononuclear cells will be discussed. doi:10.1016/j.vph.2011.08.053 O.7.1 Heme oxygenase-1 is crucial for proangiogenic progenitor cells and facilitates cell-free strategy for therapeutic angiogenesis of ischemic limbs in diabetes Anna Grochot-Przeczek, Jerzy Kotlinowski, Katarzyna Starowicz, Jolanta Jagodzinska, Anna Stachurska, Magdalena Kozakowska, Agnieszka Jazwa, Ewa Zuba-Surma, Krzysztof Szade, Jozef Dulak, Alicja Jozkowicz Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland E-mail addresses: [email protected] (A. Grochot-Przeczek), [email protected] (J. Dulak), [email protected] (A. Jozkowicz) Heme oxygenase-1 (HO-1) has proangiogenic and cytoprotective effects, which may play a pivotal role in proangiogenic progenitor cells (PPCs) function and influence their therapeutic efficiency. PPCs were identified as heterogenic population of bone marrow- derived mononuclear cells, expressing both endothelial markers, such as KDR, eNOS, vWF and VE-cadherin, as well as hematopoietic markers, such as CD45 and Sca-1, up-taking acLDLs and binding BS1 lectin. The cells with targeted deletion of HO-1 gene were less viable upon stimulation with H 2 O 2 or hemin then wild type cells. Moreover, HO-1 -/- PPCs proliferated slower in response to VEGF treatment, did not migrate to SDF-1 neither to 10% FBS medium and produced lower amounts of proangiogenic factors VEGF, SDF-1 and KC in comparison to HO-1 +/+ . In vitro angiogenesis assay revealed impaired ability of HO-1 -/- cells to form tubes on matrigel and conditioned media from these cells were less potent in stimulation of tube formation by human umbilical vein endothelial cells in comparison to HO-1 +/+ cell media. In vivo matrigel plug assay demonstrated PPCs of both genotypes to form vessels, however they were non-functional. Importantly, in vivo studies showed that restoration of perfusion in Abstracts 323
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Transcript of In-vivo measurement of vascular repair: EPCs, OCT and beyond
sion, potentiated reparative neovascularization and continuouslyattenuated cardiomyocyte apoptosis.Wholemount immunohistochem-istry demonstrated the association of transplanted SVPs, some positivefor proliferating cell nuclear antigen, to vessels sprouting toward theinfarct area. Expressional studies showed the activation of a pro-angiogenicmechanism involving VEGF-B186 and Angiopoietin 1 and of apro-survival signaling centered on Akt/eNOS/Bcl2.
Conclusion: SVPs therapy of MI produces long-term improvementof cardiac function through implementation of neovascularizationand activation of pro-survival mechanisms.
doi:10.1016/j.vph.2011.08.050
L.7.2In-vivo measurement of vascular repair: EPCs, OCT and beyondJonathan HillKing's College Hospital NHS Foundation Trust, London, UKE-mail address: [email protected]
This would be a talk about the evolution of EPC measurementtechnology and using OCT for assessing stent strut coverage as asurrogate for reendothelialisation and then to finish with a brief lookto the future about integration of OCT or intravascular imaging withmolecular imaging strategies.
doi:10.1016/j.vph.2011.08.051
L.7.3Bone marrow cell therapy: Current status and future directions?Buddhadeb DawnDivision of Cardiovascular Diseases, Cardiovascular Research Institute,University of Kansas Medical Center, 3901 Rainbow Blvd,Rm. 1001 Eaton, MS 3006, Kansas City, KS, 66160, UKE-mail address: [email protected]
Anew therapy for cardiac repair has gainedmomentum in the recentyears ? transplantation of bone marrow cells. On the basis of strongevidence from animal studies, numerous clinical trials of cardiac repairwith adult bone marrow-derived cells (BMC) have been completed.These relatively smaller studies employed different BMC types withhighly variable numbers, routes, and timings of transplantation, andincluded patients with acute myocardial infarction (MI), as well aschronic ischemic heart disease (IHD). Although the outcomes have beenpredictably disparate, analysis of pooleddata indicates thatBMC therapyin patients with acute MI and chronic IHD results in modestimprovements in LV function and infarct scar size without any increasein untoward effects. However, a number of hurdles remain to beovercome in order to make cell therapy for infarct repair a routineclinical practice. While the search for an optimal cell continues, effortsare being made to modify cells to make them more suitable for cardiacrepair. During this talk, the available clinical evidence regarding theefficacy and safety of therapeutic cardiac repair with adult BMCs will besummarized, and future directions in the field will be discussed withparticular reference to Wnt11 signaling.
doi:10.1016/j.vph.2011.08.052
L.7.4Mobilization of stem and progenitor cells in acute cardiovascularsyndromes and heart failureWojciech Wojakowski
Third Division of Cardiology, Medical University of Silesia,Katowice, PolandE-mail address: [email protected]
In the last decade the concept of myocardial regeneration wasrapidly translated from basic science and animal experiments toapplication of bone marrow (BM)-derived stem and progenitor cellsin multiple clinical trials. Meta-analyses and systematic reviews ofthese trials suggest that this form of cellular therapy leads to modestimprovement of left ventricular ejection fraction (LVEF) and reducesLV remodeling in patients with acute myocardial infarction (MI). Theprimary goal of all studies using stem and progenitor cells was toimprove the myocardial function and reduce remodeling by replace-ment of the fibrotic scar tissue by the viable cardiac myocytes.Recently the possibility of myocardial regeneration in humans hasbeen challenged. Most probably the benefits observed with BM celltherapy can be attributed to the paracrine and proangiogenic effectsof injected cells. So far, in the majority of clinical trials heterogenouspopulation of non-selected bone marrow-derived mononuclear cellswas used and currently there is no proof that any particular type ofcells might be superior to others for myocardial repair in patientswith AMI and ischemic cardiomyopathy. Parallel to ongoing clinicaltrials with BM cells, investigating the optimal cell delivery route, doseand target population of patients, new concepts emerged which aimto enhance the capability of BM cells to induce the functionalrecovery of the myocardium or identifying new, more potent cellpopulations. This lecture reviews the recent progress in experimentalstem cell therapy in patients with acute myocardial infarction. Resultsof Polish multicenter trial (REGENT) using autologous CD34+ CXCR4+cells and non-selected BM-derivedmononuclear cells will be discussed.
doi:10.1016/j.vph.2011.08.053
O.7.1Heme oxygenase-1 is crucial for proangiogenic progenitor cellsand facilitates cell-free strategy for therapeutic angiogenesis ofischemic limbs in diabetesAnna Grochot-Przeczek, Jerzy Kotlinowski, Katarzyna Starowicz, JolantaJagodzinska, Anna Stachurska, Magdalena Kozakowska, AgnieszkaJazwa, Ewa Zuba-Surma, Krzysztof Szade, Jozef Dulak, Alicja JozkowiczDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysicsand Biotechnology, Jagiellonian University, Krakow, PolandE-mail addresses:[email protected] (A.Grochot-Przeczek),[email protected] (J. Dulak), [email protected] (A. Jozkowicz)
Heme oxygenase-1 (HO-1) has proangiogenic and cytoprotectiveeffects, which may play a pivotal role in proangiogenic progenitor cells(PPCs) function and influence their therapeutic efficiency.
PPCs were identified as heterogenic population of bone marrow-derived mononuclear cells, expressing both endothelial markers, suchas KDR, eNOS, vWF and VE-cadherin, as well as hematopoieticmarkers, such as CD45 and Sca-1, up-taking acLDLs and binding BS1lectin. The cells with targeted deletion of HO-1 gene were less viableupon stimulation with H2O2 or hemin then wild type cells. Moreover,HO-1−/− PPCs proliferated slower in response to VEGF treatment, didnot migrate to SDF-1 neither to 10% FBS medium and produced loweramounts of proangiogenic factors VEGF, SDF-1 and KC in comparisonto HO-1+/+. In vitro angiogenesis assay revealed impaired ability ofHO-1−/− cells to form tubes on matrigel and conditioned media fromthese cells were less potent in stimulation of tube formation byhuman umbilical vein endothelial cells in comparison to HO-1+/+ cellmedia. In vivo matrigel plug assay demonstrated PPCs of bothgenotypes to form vessels, however they were non-functional.Importantly, in vivo studies showed that restoration of perfusion in
Abstracts 323
