FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2122715359> ?p ?o ?g. }

• W2122715359 abstract "HomeJournal of the American Heart AssociationVol. 2, No. 5The Advancing Field of Cell‐Based Therapy: Insights and Lessons From Clinical Trials Open AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessReview ArticlePDF/EPUBThe Advancing Field of Cell‐Based Therapy: Insights and Lessons From Clinical Trials Kartik S. Telukuntla, Viky Y. Suncion, Ivonne H. Schulman and Joshua M. Hare Kartik S. TelukuntlaKartik S. Telukuntla Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL University of Miami Miller School of Medicine, Miami, FL Search for more papers by this author , Viky Y. SuncionViky Y. Suncion Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL Search for more papers by this author , Ivonne H. SchulmanIvonne H. Schulman Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL Nephrology‐Hypertension Section, Miami Veterans Affairs Healthcare System, Miami, FL Search for more papers by this author and Joshua M. HareJoshua M. Hare Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL Search for more papers by this author Originally published10 Oct 2013https://doi.org/10.1161/JAHA.113.000338Journal of the American Heart Association. 2013;2:e000338IntroductionStem cell therapy aimed at restoring organ function, notably myocardial repair and regeneration postmyocardial infarction (MI), is one of the most exciting and promising frontiers of medical research. While new pharmacotherapies and advances in interventional cardiology have significantly reduced the mortality of ischemic heart disease and heart failure, there remains an ongoing need for innovative cell‐based therapies that can prevent or reverse cardiac ventricular remodeling post‐MI. Although questions remain on how to best implement cell‐based interventions, a growing number of preclinical studies and clinical trials have demonstrated the safety of a variety of adult stem cell types. This review will focus on the collective progress in cardiovascular regenerative medicine, with particular emphasis on the findings from the most recently published or announced clinical trials: the PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis (POSEIDON),1 the Stem Cell Infusion in Patients with Ischemic cardiomyopathy (SCIPIO),2, 3, 4 Cardiosphere‐Derived aUtologous stem Cells to reverse ventricUlar dySfunction (CADUCEUS),5 the Swiss Multicenter Intracoronary Stem Cells Study in Acute Myocardial Infarction (SWISS‐AMI),6, 7 the AutoLogous Human Cardiac‐Derived Stem Cell to Treat Ischemic cArdiomyopathy (ALCADIA)8 (NCT00981006), the Cardiovascular Cell Therapy Research Network (CCTRN) trials, the Transplantation In Myocardial Infarction Evaluation (TIME),9 LateTIME,10 the First Mononuclear Cells injected in the United States conducted by the CCTRN (FOCUS‐CCTRN),11 and the Cardiopoietic stem Cell therapy in heart failURE (C‐CURE) trial.12 These trials illustrate how a novel intervention like stem cell therapy requires innovative evaluation and assessment tools that place an emphasis on clinical parameters and imaging techniques. From dosing and delivery to evaluating efficacy, stem cell therapy provides not only opportunities but also challenges in our quest to develop an effective and sustainable therapeutic intervention for cardiomyopathies.To date, researchers have experimented with multiple cell types in preclinical and clinical studies to determine which cell lines prove most safe and efficacious. At first, embryonic stem cells (ESC) and skeletal myoblasts were evaluated as viable options, but the most promising results have recently become evident from bone marrow‐derived mesenchymal stem cells, cardiac stem cells, and cardiospheres.13, 14Studies Employing Pluripotent Stem Cells and Skeletal MyoblastsInitial studies with ESCs reported surprisingly low rates of cardiac differentiation, and high rates of teratoma formation, immunologic responses, and cell rejection.13 Additionally, the ethical concerns surrounding their use have impaired their development into clinical trials. A major scientific advance that circumvented the ethical concerns was the discovery of methods to reprogram adult somatic cells (ie, fibroblast and epithelial cells) into a pluripotent state, termed inducible pluripotent stem (iPS) cells. While iPS cells may serve as an alternative to ESCs, many questions and concerns remain regarding tumorigenicity, durability, and viability of this approach.13, 14, 15Skeletal myoblasts are a cluster of quiescent stem cells found in muscle fibers that have demonstrated the ability to regenerate after muscle tissue damage. Research groups led by Taylor et al and Menashe et al demonstrated experimentally that skeletal myoblast injections into infarcted cardiac muscle resulted in improved contractility.15, 16, 17 However, it was later demonstrated that skeletal myoblasts do not express connexin 43 and cannot electrically couple with endogenous cardiac myocytes, increasing risk for ventricular tachyarrhythmias.17, 18Clinical Trials Employing Bone Marrow‐Derived Mononuclear Cells (BM‐MNCs)Acute Myocardial InfarctionAdult bone marrow is a source of heterogeneous stem cells and precursor lineage cells that are hypothesized to have the potential to differentiate into cardiac cellular elements and/or provide paracrine or miracrine support to the healing heart.14, 19, 20 Because of the easy accessibility of whole bone marrow, clinical trials began immediately in the early 2000s following provocative findings obtained in animal models that bone marrow cells could reduce infarct size and improve left ventricular (LV) function following MI. The 2 most influential early clinical trials were the BOne marrOw transfer to enhance ST‐elevation infarct regeneration (BOOST)21 and the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR‐AMI).22 Data from the BOOST and REPAIR‐AMI clinical trials demonstrated that intracoronary BM‐MNC delivery led to a 6.7% point improvement in left ventricular ejection fraction (LVEF) at 6 months and a 5.5% point improvement in LVEF at 4 months, respectively (Figure 1A and 1B). In addition, the REPAIR‐AMI showed increased event‐free survival at 12 months after treatment (Figure 1C and 1D).Download PowerPointFigure 1. Benefits of bone marrow mononuclear cell (BM‐MNC) therapy. A and B, Intracoronary BM‐MNC delivery led to a 6.7% point improvement in left ventricular ejection fraction (LVEF) at 6 months in the BOOST clinical trial and to 5.5% improvement in LVEF at 4 months in the REPAIR‐AMI clinical trial, respectively. C, Kaplan–Meier event‐free survival analysis in the REPAIR‐AMI at 12 months showed better survival from death, recurrence of myocardial infarction, or revascularization procedures and (D) death, recurrence of myocardial infarction, or rehospitalization for heart failure in the BM‐MNC group. Panel A was reproduced with permission from Wollert et al, Lancet, 2004,21 panel B from Schachinger et al, New England Journal of Medicine, 2006,22 and panels C and D from Schachinger et al, European Heart Journal, 2006.23BOOST indicates BOne marrOw transfer to enhance ST‐elevation infarct regeneration; REPAIR‐AMI, Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction.Many clinical trials explored timing of intracoronary delivery. REPAIR AMI suggested that 5 to 7 days after acute MI produced a superior improvement in global cardiac function (LVEF) when compared to an earlier delivery time.23 Several recent trials led by the National Heart, Lung, and Blood Institute (NHLBI) CCTRN, devoted major attention to the timing of intracoronary bone marrow therapy following MI. The TIME trial conducted by Traverse et al9 enrolled 120 patients with LV dysfunction (ejection fraction [EF] <45%) who had undergone a successful percutaneous coronary intervention (PCI) for anterior wall STEMI and assessed whether delivery of autologous BM‐MNC at 3 or 7 days would improve global LVEF and regional LV function. Autologous BM‐MNCs (150 million) were administered via the intracoronary route. Contrary to the REPAIR‐AMI findings, at the 6‐month time point there was no significant improvement in global or regional LV function, as measured by cardiac magnetic resonance imaging (MRI), in the BM‐MNC group when compared to the controls, regardless of which day (3 or 7) the cells were given to the patient. The recently published LateTIME trial tested whether delaying BM‐MNC delivery for 2 to 3 weeks following MI and primary PCI improves global and regional LV function.10 Similar to the TIME trial results, in LateTIME there were no significant changes between baseline and 6‐month measures in LVEF, wall motion of the infarct zone, and wall motion of the border zone, as measured by cardiac MRI, in the BM‐MNC group compared to placebo. Although the results of the TIME and LateTIME trials demonstrated that intracoronary autologous BM‐MNC delivery at the 3 or 7 day and 2 to 3 week time point after MI was not effective for improving LV function, long‐term follow‐up and designation of new endpoints may reveal previously hidden benefits of this type of cell therapy. However, it has become increasingly evident that stem cell and patient characteristics influence therapeutic effect.24, 25 In this regard, BM‐MNCs secrete lower amounts of angiogenic and antiapoptotic growth factors than other cell types.24 The percentage of CD34+ and CD133+ cells in BM‐MNCs is important because these cell populations secrete factors that recruit cells, promote cell survival, increase microvascular density, and rescue cardiomyocytes from hibernation.26, 27 Moreover, a beneficial effect of infarct‐related artery infusion of autologous CD34 cells after STEMI on perfusion and infarct size was shown in the AMR‐01 clinical trial.28 In TIME and LateTIME, the percentage of CD34+ and CD133+ cells was low, ≈2% and 1%, respectively. There is also substantial evidence that ischemic heart disease and aging negatively impact the regenerative capacity of autologous stem cells,25, 29, 30, 31 thus supporting the use of allogeneic cell therapy.1Similar results to TIME and LateTIME were seen in the SWISS‐AMI, a more recent study investigating autologous BM‐MNCs in patients with STEMI.6, 7 Sürder et al enrolled 67 patients and aimed to improve LV dysfunction after acute MI by utilizing intracoronary infusion of BM‐MNCs cells at 5 to 7 days or 3 to 4 weeks after primary PCI. At the 4‐month time point, there was no significant improvement in LVEF in either the early or late infusion times.7 Additionally, there was no evidence of significant improvement in endpoints including LV volume, scar size, and myocardial thickness in the infarct region. Although there was no demonstrated efficacy at the 4‐month time point, the researchers showed that the use of BM‐MNCs was safe, as there was no significant difference in adverse events among the groups. Patients will continue to be followed until the 12‐month time point in order to determine if there is a delayed benefit from the BM‐MNC therapeutic intervention.Chronic Ischemic CardiomyopathyBM‐MNCs have also been tested for chronic ischemic heart failure. The FOCUS‐CCTRN was a phase II trial that investigated the efficacy of transendocardial delivery of BM‐MNCs on LV performance and perfusion at 6 months in patients with chronic ischemic cardiomyopathy.11 Similar to BM‐MNC trials in AMI, this study showed no significant effect on LV end‐systolic volume, maximal oxygen consumption, or myocardial perfusion. However, exploratory analyses demonstrated significant improvement in stroke volume and LVEF that was associated with higher bone marrow CD34+ and CD133+ progenitor cell counts, suggesting the highly important concepts that the cellular composition of the bone marrow determines clinical efficacy and that certain cell populations provide greater regenerative benefit.One of the challenging aspects of stem cell efficacy is poor cell retention, especially in the chronic heart failure setting. Preclinical studies have demonstrated that extracorporeal shock wave treatment, similar to that used to treat nephrolithiasis, increases homing factors and chemokines such as stromal cell‐derived factor 1 (SDF‐1),32 which translated into a higher retention of BM‐MNCs in the myocardium.33 In the recently published phase I/II placebo‐controlled CELLWAVE (NCT NCT00326989) trial, a total of 103 patients with chronic heart failure were randomized into 5 different arms that were designed to assess dose‐responsiveness (low and high) of shock wave pretreatment with or without subsequent intracoronary BM‐MNC delivery.34 Assmus et al showed that patients receiving shock wave treatment prior to intracoronary BM‐MNC infusion had a modest but significant improvement in LVEF (absolute change of 3.2% when compared to shock wave/placebo infusion group) and improvement in wall thickening of the infarcted segments at the 4‐month time point when compared to the placebo group. This new approach to enhance homing can be translated to subpopulations of BM‐MNCs as well as other stem cells that express the SDF‐1 receptor. While these findings are promising, a larger clinical trial is necessary to thoroughly evaluate the safety of the approach and potential improvements in clinical outcomes.Future Direction of BM‐MNCsTogether the aforementioned studies support the safety profile of BM‐MNCs in acute and chronic ischemic cardiomyopathy. Some of the trials7, 9, 10 also highlight the need for more optimization studies to determine the ideal time for cell delivery after acute MI. Interestingly, 2 meta‐analyses35, 36 have provided evidence of efficacy. Indeed, their findings suggest that BM‐MNC therapy prevents remodeling by reducing infarct size and LV chamber enlargement and these benefits persisted during long‐term follow‐up. Importantly, one of these meta‐analyses confirmed a long‐observed clinical benefit that is out of proportion to increases in cardiac function: BM‐MNC therapy reduced the incidence of death, recurrent MI, and stent thrombosis in patients with ischemic heart disease.35The field of BM‐MNC cell therapy is at a crucial crossroads. The benefits of BM‐MNCs include their accessibility, ability to obtain large quantity of cells without a need for ex vivo expansion, and vast clinical experience with bone marrow transplantation.19 Additionally, multiple phase I clinical trials have established the safety profile of this cell type35, 36; however, the recent results from TIME, LateTIME, and FOCUS have not demonstrated the efficacy of BM‐MNCs.9, 10, 11 The completed phase I trials were primarily focused on establishing the safety profile of BM‐MNCs, and efficacy results were limited by the small number of patients. To address the limitations of the smaller studies, a multicenter, randomized, controlled, phase III study, The Effect of Intracoronary Reinfusion of BM‐MNC on All Cause Mortality in Acute Myocardial Infarction (BAMI) trial (NCT01569178) is underway and is adequately powered to detect evidence of efficacy. Regardless of outcome, this trial will be the first with adequate power and rigorous design that addresses clinical outcomes as opposed to surrogates for patients with acute MI. Meanwhile, investigators have placed increasing emphasis and focus on other well understood and potentially promising cell types, such as mesenchymal stem cells, cardiac stem cells, and cell combinations.Clinical Trials Employing Mesenchymal Stem CellsMesenchymal stem cells (MSCs), which were first identified over 4 decades ago, are under active investigation for their regenerative potential and are thought to be a possible lead candidate for the active constituent in bone marrow.20 MSCs, initially described as plastic‐adherent stromal cells, are a multipotent cell line capable of forming colonies and differentiating into mesodermal (bone, fat, cartilage) and nonmesodermal lineages.20 Originally thought to reside in bone marrow, they have now been isolated from diverse tissue sources.37 Results from large‐animal models demonstrate that MSCs have the ability to engraft, differentiate into myocytes, vascular smooth muscle and endothelial cells, and enhance cardiovascular hemodynamic parameters.20, 38, 39, 40, 41 The ease in preparation, immunoprivilege properties, and multipotent nature have made MSCs very promising for cardiac cell therapy,14, 15, 20, 42 as recently shown in the Transendocardial Autologous Cells in Ischemic Heart Failure (TAC‐HFT) and POSEIDON clinical trials.1, 43MSCs have immunosuppressive and immunomodulatory properties. They do not express Major Histocompatibility Class II antigens or the B7 and CD40 ligand costimulatory molecules.44, 45 Additionally, they can suppress innate immunity, making allogeneic transplantation of MSCs feasible.45MSCs for Acute Myocardial InfarctionThe ability to collect and store allogeneic stem cells from healthy donors has advantages over the harvesting and expansion of a patient's autologous cells, particularly their availability for timely transplant in the setting of acute MI.46 The first major study of allogeneic MSCs was a phase I, multi‐center, randomized, double‐blinded, placebo‐controlled study46 in patients with acute myocardial infarction. Patients (n=53) were treated 3 to 10 days post‐MI with 1 of 3 cell‐dose levels (0.5, 1.6, and 5.0 mol/L allogeneic MSCs/kg) or placebo, administered intravenously, and followed for 6 months. With regard to safety, there were no deaths, toxicity, or serious adverse events following the administration of the allogeneic MSCs. Patients in the MSC‐treated group experienced fewer arrhythmic events and an improvement in their overall clinical status at 6 months as compared to those receiving placebo. In addition, patients in the MSC group with major anterior wall MI had a significant improvement in EF at 3 months and 6 months over baseline, while similar patients receiving placebo did not have significant improvement. These provocative results led to a phase II, 220 patient study in the setting of acute MI with depressed EF. It was preliminarily reported by Osiris in July 2012 (unpublished findings) that a single intravenous infusion of either allogeneic MSCs or placebo within 7 days of an acute MI significantly reduced cardiac hypertrophy, stress‐induced ventricular arrhythmia, heart failure, and rehospitalization for cardiac complications compared to patients receiving placebo. The full impact of this study awaits publication of the data.MSCs for Chronic Ischemic CardiomyopathyMSCs are also thought to have a role for established ischemic cardiomyopathy. While allogeneic MSCs appeared safe, a direct comparison with their autologous counterparts had never been conducted. To address this, our group performed a phase I/II randomized trial to compare the safety and efficacy of allogeneic and autologous MSCs delivered via transendocardial injection in patients with chronic ischemic cardiomyopathy. In the POSEIDON trial, 30 patients were assigned to 6 subgroups based on type of MSC (allogeneic or autologous) and dose (20, 100, and 200 million).1, 47 At 13‐month follow‐up, the results showed that both allogeneic and autologous MSCs were safe and efficacious. MSC therapy was associated with reversal of LV remodeling (Figures 2 through 4), reduction in myocardial scar size (measured by CT imaging as early enhancement defect [EED] (Figures 5 and 6C),48, 49 and improvement in patient functional capacity and quality of life (Figure 7). Neither cell type showed a significant improvement in EF. Although this initial study was limited by lack of a placebo group, it validated the safety profile of allogeneic MSCs and encourages a larger phase II trial to establish efficacy of MSC therapy. Importantly, this trial provided crucial immunologic data, showing that the allogeneic cell recipients did not mount anti‐donor antibodies that could potentially limit subsequent organ transplantation options.Download PowerPointFigure 2. Reduction of left ventricular end‐diastolic volume (EDV) in the POSEIDON study. MDCT images (4 chamber and short axis view) of a patient with chronic ischemic cardiomyopathy (A) before (EDV 176.1 mL) and (B) after transendocardial stem cell injection (TESI) with 20 million autologous mesenchymal stem cells (EDV 136.8 mL). MDCT indicates multi‐detector computer tomography; POSEIDON, PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis.Download PowerPointFigure 3. Reduction of left ventricular end‐systolic volume (ESV) in the POSEIDON study. MDCT images (4 chamber and short axis view) of a patient with chronic ischemic cardiomyopathy (A) before (ESV 126.9 mL) and (B) after transendocardial stem cell injection (TESI) with 20 million autologous MSCs (ESV 77.1 mL). MDCT indicates multi‐detector computer tomography; MSCs, mesenchymal stem cells; POSEIDON, PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis.Download PowerPointFigure 4. Comparison of end‐systolic and end‐diastolic volumes in POSEIDON and CADUCEUS trials. A and B, Chamber volumes in POSEIDON trial. Mean changes from baseline to 13 months are noted by triangles and depict changes in cardiac phenotype assessed by cardiac MDCT scan. Error bars indicate 95% CIs. Individual patient changes from baseline are shown as circles. Shown are changes in cardiac volumes from baseline to 13‐month follow‐up in allogeneic, autologous, and overall patient groups. Within‐group P values are noted as a P<0.05. C and D, Chamber volumes in CADUCEUS study participants. C, Treatment effects (baseline vs 6 months) for end‐systolic volume. D, Treatment effects (baseline vs 6 months) for end‐diastolic volume. Panels A and B are reproduced with permission from Hare et al, JAMA, 2012.1 Panels C and D are reproduced with permission from Makkar et al, Lancet, 2012.5CADUCEUS indicates Cardiosphere‐Derived aUtologous stem Cells to reverse ventricUlar dySfunction; CDCs, cardiosphere‐derived cells; CIs, confidence intervals; MDCT, multi‐detector computer tomography; MSCs, mesenchymal stem cells; POSEIDON, PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis.Download PowerPointFigure 5. Reduction of scar size (POSEIDON clinical trial). (Left) MDCT 3D reconstruction image with (Right) respective (A) basal and (B) midventricular short axis images of a patient with chronic ischemic cardiomyopathy with a scar size (MDCT‐EED outlined in red) of (A and B) 40.34 g and its reduction to (A' and B') 26.35 g after transendocardial stem cell injection (TESI) with allogeneic MSCs (100 million). EED indicates early enhancement defect; MDCT, multi‐detector computer tomography; MSCs, mesenchymal stem cells; POSEIDON, PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis.Download PowerPointFigure 6. Comparison of scar size reduction in (A) SCIPIO, (B) CADUCEUS, and (C) POSEIDON trials. A, SCIPIO Trial 1‐year follow‐up shows infarct size reduction at 4 and 12 months after CSC therapy. B, CADUCEUS trial showed decreases in scar mass and increases in viable mass on MRI in patients treated with CDCs but not controls. C, Myocardial infarct (MI) size reduction shown in POSEIDON trial. Panel A reproduced with permission from Chugh et al, Circulation, 20124; panel B from Makkar et al, Lancet, 20125; and panel C from Hare et al, JAMA, 2012.1CADUCEUS indicates Cardiosphere‐Derived aUtologous stem Cells to reverse ventricUlar dySfunction; CDC, cardiosphere‐derived cell; CSCs, cardiac stem cells; EED, early enhancement defect; MRI, magnetic resonance imaging; MSCs, mesenchymal stem cells; POSEIDON, PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis; SCIPIO, Stem Cell Infusion in Patients with Ischemic cardiomyopathy.Download PowerPointFigure 7. Comparison of MLHFQ scores in POSEIDON and SCIPIO trials. A, POSEIDON trial showed improvement in MLHFQ score in the autologous MSC group at the 6‐ and 12‐month time points. B, SCIPIO trial demonstrated continuous improvement in MLHFQ score at 4 and 12 months. Panel A reproduced with permission from Hare et al, JAMA, 20121 and panel B from Chugh et al, Circulation, 2012.4CSCs indicates cardiac stem cells; MLHFQ, Minnesota Living with Heart Failure Questionnaire; MSC, mesenchymal stem cell; POSEIDON, PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis; SCIPIO, Stem Cell Infusion in Patients with Ischemic cardiomyopathy.The results from the POSEIDON study also provide a potentially attractive alternative cell source for patients who may have limited regenerative potential with their own cells. For example aging or prior chemotherapy may adversely affect the function and capabilities of MSCs,50, 51, 52 and this may contribute to impaired healing and recovery in aging populations. Thus the findings from POSEIDON supporting transplantation of allogeneic MSCs hold promise for the availability of cell‐based therapies for individuals with impaired endogenous cells.MSCs are currently among the most promising source for successful cell therapy in ischemic cardiomyopathy, but concerns have been raised regarding tumorigenicity and ectopic tissue formation. This would be a serious complication53 that was suggested by studies using murine MSCs, which after certain number of passages were at a higher risk for mutations.54, 55 However, this complication has not materialized in the POSEIDON1 population and that of other studies testing human MSCs in humans,46, 55, 56 likely due to a limited differentiation capacity, since MSCs are multipotent and not pluripotent like embryonic stem cells. Moreover, MSCs appear to have a low level of sustained engraftment in humans,56 which reduces the long‐term risks of this therapy.Bone marrow‐derived MSC precursors,57, 58, 59, 60, 61 cardiopoietic MSCs,12, 62 umbilical cord,63, 64 placenta,65 and adipose‐derived MSCs66, 67 are all currently under preclinical or clinical investigation for therapeutic potential (Table). These approaches provide additional translational opportunities for MSCs.Table 1. Future and Ongoing MSC Clinical TrialsStudy NameNCT # Clinicaltrials.govDescriptionPotential AdvantagesStatusAdipose‐Derived MSCsAPOLLO Trial: A Randomized Clinical Trial of AdiPOse‐derived Stem ceLLs in the Treatment of Patients With ST‐elevation myOcardial InfarctionNCT00442806Phase I trial to establish the safety profile of adipose‐derived stem and regenerative cells (ADRCs) in patients who have suffered ST‐elevation AMIEase of access to cellsActive Phase I, not recruitingADVANCE Study: ADRCs Delivered Via the Intracoronary Route in the Treatment of Patients With ST‐elevation Acute Myocardial InfarctionNCT01216995A double‐blind, prospective, randomized, placebo controlled safety and efficacy trial to evaluate the intracoronary delivery of ADRCs in patients with ST‐elevation AMI. Will enroll 216 patients Ease of access to cells Large patient population Multi‐center Phase II, recruitingMyStromalCell Trial: MesenchYmal STROMAL CELL Therapy in Patients With Chronic Myocardial IschemiaNCT01449032After promising pilot study that demonstrated safety of adipose‐derived MSCs, this will be a double‐blind, placebo‐controlled phase II to evaluate if adipose derived MSCs are able to improve cardiac tissue perfusion, exercise capacity and reduce symptoms in patients with CADEase of access to cellsPhase II, recruitingMSC Precursor TypesAMICI Trial: Safety Study of Allogeneic Mesenchymal Precursor Cell Infusion in MyoCardial InfarctionNCT01781390Double‐blind, randomized, placebo‐controlled trial that will enroll 225 patients with AMI due to lesion in LAD. They will undergo revascularization with PCI followed by intracoronary delivery of placebo or Stro3 MPC cells. Conducted by Angioblast systemsCell type that improves paracrine activity and engraftment rates Demonstrates multilineage potentialPhase II, not yet open for recruitingSafety Study of Allogeneic Mesenchymal Precursor Cells (MPCs) in Subjects With Recent Acute Myocardial InfarctionNCT00555828This trial will evaluate the safety and efficacy of dose‐dependent (25, 75, 150 mol/L) transendocardial injections of allogeneic stro3 MPCs using the Biosense NogaStarTM Mapping Catheter in patients with AMI. Assess optimal dose for stro3 MPCs Explore late‐term dose related tolerance at days 90, 180, 360 Phase Ib/IIa, recruitingUmbilical Cord‐Derived MSCsRandomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy (RIMECARD)NCT01739777This trial will evaluate safety and efficacy of umbilical cord derived mesenchymal stem cells (ucMSC) in patients with compensated dilated cardiomyopathy. Aims to have 30 patients with 2 arms; the first group will receive intravenous injection of ucMSC and other group will serve as control. Ease of Access to MSCs Does not require invasive procedures to isolate MSCs Phase I/II, recruitingIntracoronary Human Wharton's Jelly‐ Derived Mesenchymal Stem Cells (WJ‐MSCs) Transfer in Patients With Acute Myocardial Infarction (AMI) (WJ‐MSC‐AMI)NCT01291329This is a double‐blind, placebo‐controlled, multicenter trial that involved 160 patients with acute STEMI. Patients received intracoronary infusion of WJ‐MSCs or placebo medium into infarct artery 4 to 7 days after a successful PCI therapy.WJ‐MSCs have short doubling time which allows them to be quickly produced in large numbers.Study has been completedAllogeneic Bone Marrow‐Derived MSCsThe POSEIDON‐DCM Study PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis in Dilated CardioMyopathyNCT01392625This is a pilot study with 36 patie" @default.
• W2122715359 created "2016-06-24" @default.
• W2122715359 creator A5021152255 @default.
• W2122715359 creator A5058008648 @default.
• W2122715359 creator A5085774808 @default.
• W2122715359 creator A5089397160 @default.
• W2122715359 date "2013-09-26" @default.
• W2122715359 modified "2023-09-27" @default.
• W2122715359 title "The Advancing Field of Cell‐Based Therapy: Insights and Lessons From Clinical Trials" @default.
• W2122715359 cites W150955112 @default.
• W2122715359 cites W1525746837 @default.
• W2122715359 cites W1963716772 @default.
• W2122715359 cites W1963756072 @default.
• W2122715359 cites W1968442155 @default.
• W2122715359 cites W1969832663 @default.
• W2122715359 cites W1976127975 @default.
• W2122715359 cites W1979043688 @default.
• W2122715359 cites W1986451583 @default.
• W2122715359 cites W1987506766 @default.
• W2122715359 cites W1999631700 @default.
• W2122715359 cites W2002305938 @default.
• W2122715359 cites W2003996125 @default.
• W2122715359 cites W2008758811 @default.
• W2122715359 cites W2011518964 @default.
• W2122715359 cites W2013263214 @default.
• W2122715359 cites W2023395871 @default.
• W2122715359 cites W2027083241 @default.
• W2122715359 cites W2028036560 @default.
• W2122715359 cites W2033562173 @default.
• W2122715359 cites W2034452944 @default.
• W2122715359 cites W2035127869 @default.
• W2122715359 cites W2039665103 @default.
• W2122715359 cites W2040039411 @default.
• W2122715359 cites W2044953345 @default.
• W2122715359 cites W2045833440 @default.
• W2122715359 cites W2050974735 @default.
• W2122715359 cites W2051968888 @default.
• W2122715359 cites W2061863684 @default.
• W2122715359 cites W2063927114 @default.
• W2122715359 cites W2066630518 @default.
• W2122715359 cites W2071746224 @default.
• W2122715359 cites W2072740783 @default.
• W2122715359 cites W2075118409 @default.
• W2122715359 cites W2080539468 @default.
• W2122715359 cites W2085056729 @default.
• W2122715359 cites W2086980194 @default.
• W2122715359 cites W2087353148 @default.
• W2122715359 cites W2092746470 @default.
• W2122715359 cites W2092756213 @default.
• W2122715359 cites W2094796303 @default.
• W2122715359 cites W2103359139 @default.
• W2122715359 cites W2106111979 @default.
• W2122715359 cites W2107458043 @default.
• W2122715359 cites W2107813132 @default.
• W2122715359 cites W2108246093 @default.
• W2122715359 cites W2111486034 @default.
• W2122715359 cites W2112214249 @default.
• W2122715359 cites W2112777549 @default.
• W2122715359 cites W2114764321 @default.
• W2122715359 cites W2115370848 @default.
• W2122715359 cites W2117412164 @default.
• W2122715359 cites W2122978668 @default.
• W2122715359 cites W2129396577 @default.
• W2122715359 cites W2130794824 @default.
• W2122715359 cites W2132735690 @default.
• W2122715359 cites W2136350868 @default.
• W2122715359 cites W2142804846 @default.
• W2122715359 cites W2143298795 @default.
• W2122715359 cites W2143719911 @default.
• W2122715359 cites W2143815163 @default.
• W2122715359 cites W2144309285 @default.
• W2122715359 cites W2144327104 @default.
• W2122715359 cites W2146066235 @default.
• W2122715359 cites W2148220540 @default.
• W2122715359 cites W2151722542 @default.
• W2122715359 cites W2153899938 @default.
• W2122715359 cites W2154618513 @default.
• W2122715359 cites W2155044423 @default.
• W2122715359 cites W2159032151 @default.
• W2122715359 cites W2159869836 @default.
• W2122715359 cites W2161304727 @default.
• W2122715359 cites W2161354262 @default.
• W2122715359 cites W2162412444 @default.
• W2122715359 cites W2165697341 @default.
• W2122715359 cites W2167457707 @default.
• W2122715359 cites W2167897928 @default.
• W2122715359 cites W2170871745 @default.
• W2122715359 cites W2171926727 @default.
• W2122715359 cites W22650291 @default.
• W2122715359 cites W2315623954 @default.
• W2122715359 cites W2324772445 @default.
• W2122715359 cites W2539586383 @default.
• W2122715359 cites W4230647879 @default.
• W2122715359 cites W4251403705 @default.
• W2122715359 cites W4296747967 @default.
• W2122715359 doi "https://doi.org/10.1161/jaha.113.000338" @default.
• W2122715359 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3835242" @default.
• W2122715359 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24113326" @default.
• W2122715359 hasPublicationYear "2013" @default.
• W2122715359 type Work @default.

• next