scholarly journals Stem cell therapy in patients with nonischemic heart failure

2021 ◽  
Vol 20 (Supplement_1) ◽  
Author(s):  
Z Tomsic ◽  
V Androcec
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Treatment Options ◽  
Left Ventricular ◽  
Advanced Heart Failure ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Abstract Funding Acknowledgements None Background Advanced chronic heart failure, characterized by a functional NYHA class III/IV, low LVEF, elevated B-type natriuretic peptides and other criteria’s is a big epidemiological problem, and its prevalence is increasing every year. There are many treatment options for patients with chronic and advanced heart failure. Treatment options include optimal medical therapy, treatment with cardiac resynchronization devices, left ventricular assist devices, heart transplantation and from 2006 treatment with CD 34 + stem cells. Method Patient inclusion criteria for stem cell therapy include dilated cardiomyopathy with no valve disease, hypertension or substance abuse, with optimal medical management for 6 months and a decreased left ventricular ejection fraction of <40%. Patients are treated with autologous pluripotent CD 34+ cells, which are mobilized in the blood stream with a bone marrow stimulant Filgrastim, administered subcutaneously for 5 days. The patients are educated by the nurses to do administer the injections at home, and have a contact number of our department in case of side effects. On the day of the procedure, stem cells are collected using the apheresis technique and then delivered transendocardialy in the catheterisation laboratory using the system for electromechanical mapping. If no complications develop, the patients can go home the next day. Results During follow-up visits patients treated with stem cells have an increased left ventricular ejection fraction, lower levels of NT-proBNP, increased distance of 6-minute walk test and increased survival compared with the control group. They also report better physical performance.  Conclusion  Stem cell therapy is thus a viable option and could become a mainstream therapy for the treatment of advanced heart failure in the future.

Abstract 355: Heart Failure Impairs Bone Marrow Mesenchymal Stem Cell Renewing Capacity and Migration

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Victoria Florea ◽  
Cristina Sanina ◽  
Darcy Difede ◽  
Krystalenia Valasaki ◽  
Aisha Khan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Bone Marrow ◽  
Growth Rate ◽  
Clinical Trials ◽  
Stem Cell ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Healthy Donors

Background: Clinical trials have shown a sustained beneficial effect of bone marrow mesenchymal stem cells (MSCs) as a therapy for acute and chronic heart failure (HF). Clinical grade cell manufacturing of autologous and allogeneic MSCs is becoming a standard procedure. This study investigates the differences of bone marrow MSC isolation and expansion in favorable in vitro conditions. We compared MSC production from both healthy young donors and chronic HF patients. Methods: We analyzed MSC manufacturing records from five clinical trials: TAC-HFT (Ischemic cardiomyopathy (CMP), patient and donors), POSEIDON (Ischemic CMP, donors), POSEIDON DCM (Dilated CMP, donors), TRIDENT (Ischemic CMP, donors), and CRATUS (Frailty, donors). Results: All cells expressed CD105, CD90 and lacked hematopoietic marker CD45. The age of healthy donors (25.5 ± 0.7 y.o., N=24) and HF patients (56.1 ± 2.5, y.o., N=23), was significantly different (P<0.0001). Collectively, the number of mononuclear cells (MNCs) isolated from bone marrow (volume range 58-125ml) didn’t differ between the groups. However, plated MNCs from healthy adults generated more MSCs than MNCs from HF patients (p0: 5.9x10^6±0.5x10^6, N=23 vs 3.8x10^6±0.4x10^6, N=24, respectively, P=0.003 and p1: 15.4x10^6±2.5x10^6, N=23 vs 10.8x10^6±1.1x10^6, N=24, respectively, P=0.036). No correlation was found between stem cell growth and age (35 to 78y.o.). Left ventricular ejection fraction (LVEF) in patients with HF had a direct correlation with MSC growth rate (P=0.03), particularly, in patients with severely depressed LVEF (<30%), which had a tendency to generate less MSCs overall. Moreover, MSCs from HF patients demonstrated less migration compared to MSCs from healthy donors at 6, 10 and 24 hours (h) relative to baseline (6 h: 9.5±3.0% vs 30.7±2.1%; 10 h: 19.9±13.7% vs 53.1±2.5% and 24 h: 41.5±15.8% vs 88.9±1.6%, N=4, respectively. P=0.03). Conclusions: Despite equivalent numbers of MNCs, healthy young donors generate significantly more MSCs than HF patients, due to increased growth rate and higher number of resident stromal bone marrow stem cells. MSC migration was impaired in HF patients compared to healthy donors. HF appears to be an independent factor for MSC renewal capacity and culture phenotype.

A Systematic Review and Meta-analysis : Safety and Efficacy of Mesenchymal stem Cells Therapy for Heart Failure

2020 ◽  
Vol 15 ◽  
Author(s):  
Tiantian Shen ◽  
Lin Xia ◽  
Wenliang Dong ◽  
Jiaxue Wang ◽  
Feng Su ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Safety And Efficacy ◽  
Systolic Volume ◽  
End Diastolic Volume ◽  
End Systolic Volume

Background: Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating heart failure (HF). However, the effects of stem cell therapy in patients with heart failure is an ongoing debate and the safety and efficacy of MSCs therapy is not well-known. We conducted a systematic review of clinical trials that evaluated the safety and efficacy of MSCs for HF. This study aimed to assess the safety and efficacy of MSCs therapy compared to the placebo in heart failure patients. Methods: We searched PubMed, Embase, Cochrane library systematically, with no language restrictions. Randomized controlled trials(RCTs) assessing the influence of MSCs treatment function controlled with placebo in heart failure were included in this analysis. We included RCTs with data on safety and efficacy in patients with heart failure after mesenchymal stem cell transplantation. Two investigators independently searched the articles, extracted data, and assessed the quality of the included studies. Pooled data was performed using the fixed-effect model or random-effect model when it appropriate by use of Review Manager 5.3. The Cochrane risk of bias tool was used to assess bias of included studies. The primary outcome was safety assessed by death and rehospitalization and the secondary outcome was efficacy which was assessed by six-minute walk distance and left ventricular ejection fraction (LVEF)，left ventricular end-systolic volume（LVESV），left ventricular end-diastolic volume（LVEDV） and brain natriuretic peptide（BNP） Results: A total of twelve studies were included, involving 823 patients who underwent MSCs or placebo treatment. The overall rate of death showed a trend of reduction of 27% (RR [CI]=0.73 [0.49, 1.09], p=0.12) in the MSCs treatment group. The incidence of rehospitalization was reduced by 47% (RR [CI]=0.53[0.38, 0.75], p=0.0004). The patients in the MSCs treatment group realised an average of 117.01m (MD [95% CI]=117.01m [94.87, 139.14], p<0.00001) improvement in 6MWT.MSCs transplantation significantly improved left ventricular ejection fraction (LVEF) by 5.66 % (MD [95% CI]=5.66 [4.39, 6.92], p<0.00001), decreased left ventricular end-systolic volume (LVESV) by 14.75 ml (MD [95% CI]=-14.75 [-16.18, -12.83], p<0.00001 ) and left ventricular end-diastolic volume (LVEDV) by 5.78 ml (MD [95% CI]=-5.78[-12.00, 0.43], p=0.07 ) ,in the MSCs group , BNP was decreased by 133.51 pg/ml MD [95% CI]= -133.51 [-228.17,-38.85], p=0.54, I2= 0.0%) than did in the placebo group. Conclusions: Our results suggested that mesenchymal stem cells as a regenerative therapeutic approach for heart failure is safe and effective by virtue of their self-renewal potential, vast differentiation capacity and immune modulating properties. Allogenic MSCs have superior therapeutic effects and intracoronary injection is the optimum delivery approach. In the tissue origin, patients who received treatment with umbilical cord MSCs seem more effective than bone marrow MSCs. As to dosage injected, (1-10)*10^8 cells were of better effect.

scholarly journals Differences in the prognoses of patients referred to an advanced heart failure center from hospitals with different bed volumes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Koichi Narita ◽  
Eisuke Amiya ◽  
Masaru Hatano ◽  
Junichi Ishida ◽  
Hisataka Maki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Primary Outcome ◽  
Left Ventricular ◽  
Cox Proportional Hazards ◽  
Advanced Heart Failure ◽  
Ventricular Assist Devices ◽  
Left Ventricular Ejection ◽  
Left Ventricular Assist Devices ◽  
Ventricular Ejection Fraction

AbstractFew reports have discussed appropriate strategies for patient referrals to advanced heart failure (HF) centers with available left ventricular assist devices (LVADs). We examined the association between the characteristics and prognoses of referred patients with advanced HF and the bed volume of the referring hospitals. This retrospective analysis evaluated 186 patients with advanced HF referred to our center for consultation about the indication of LVAD between January 1, 2015, and August 31, 2018. We divided the patients into two groups according to the bed volume of their referring hospital (high bed volume hospitals (HBHs): ≥ 500 beds in the hospital; low bed volume hospitals (LBHs): < 500 beds). We compared the primary outcome measure, a composite of LVAD implantation and all-cause death, between the patients referred from HBHs and patients referred from LBHs. The 186 patients with advanced HF referred to our hospital, who were referred from 130 hospitals (87 from LBHs and 99 from HBHs), had a mean age of 43.0 ± 12.6 years and a median left ventricular ejection fraction of 22% [15–33%]. The median follow-up duration of the patients was 583 days (119–965 days), and the primary outcome occurred during follow-up in 42 patients (43%) in the HBH group and 20 patients (23%) in the LBH group. Patients referred from HBHs tended to require catecholamine infusion on transfer more often than those referred from LBLs (36.5% (HBH), 20.2% (LBL), P = 0.021). Kaplan–Meier analysis indicates that the occurrence of the primary outcome was significantly higher in the HBH patients than in the LBH patients (log-rank P = 0.0022). Multivariate Cox proportional hazards analysis revealed that catecholamine support on transfer and long disease duration were statistically significant predictors of the primary outcome. Patients from HBHs had a greater risk of the primary outcome. However, the multivariate analysis did not indicate an association between referral from an HBH and the primary outcome. In contrast, catecholamine support on transfer, long duration of disease, and low blood pressure were independent predictors of the primary outcome. Therefore, these should be considered when determining the timing of a referral to an advanced HF center, irrespective of the bed volume of the referring hospital.

scholarly journals Regenerative Cardiovascular Therapies: Stem Cells and Beyond

2019 ◽  
Vol 20 (6) ◽  
pp. 1420 ◽  
Author(s):  
Bernhard Wernly ◽  
Moritz Mirna ◽  
Richard Rezar ◽  
Christine Prodinger ◽  
Christian Jung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Basic Science ◽  
Left Ventricular ◽  
Specific Cell ◽  
Therapeutic Effects ◽  
Cell Processing

Although reperfusion therapy has improved outcomes, acute myocardial infarction (AMI) is still associated with both significant mortality and morbidity. Once irreversible myocardial cell death due to ischemia and reperfusion sets in, scarring leads to reduction in left ventricular function and subsequent heart failure. Regenerative cardiovascular medicine experienced a boost in the early 2000s when regenerative effects of bone marrow stem cells in a murine model of AMI were described. Translation from an animal model to stem cell application in a clinical setting was rapid and the first large trials in humans suffering from AMI were conducted. However, high initial hopes were early shattered by inconsistent results of randomized clinical trials in patients suffering from AMI treated with stem cells. Hence, we provide an overview of both basic science and clinical trials carried out in regenerative cardiovascular therapies. Possible pitfalls in specific cell processing techniques and trial design are discussed as these factors influence both basic science and clinical outcomes. We address possible solutions. Alternative mechanisms and explanations for effects seen in both basic science and some clinical trials are discussed here, with special emphasis on paracrine mechanisms via growth factors, exosomes, and microRNAs. Based on these findings, we propose an outlook in which stem cell therapy, or therapeutic effects associated with stem cell therapy, such as paracrine mechanisms, might play an important role in the future. Optimizing stem cell processing and a better understanding of paracrine signaling as well as its effect on cardioprotection and remodeling after AMI might improve not only AMI research, but also our patients’ outcomes.

scholarly journals An overview of stem cell therapy for paediatric heart failure

2020 ◽  
Vol 58 (5) ◽  
pp. 881-887
Author(s):  
Shuta Ishigami ◽  
Toshikazu Sano ◽  
Sunaya Krishnapura ◽  
Tatsuo Ito ◽  
Shunji Sano
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Developed Countries ◽  
Medical Community ◽  
Circulatory Support ◽  
Persistent Problem ◽  
Regenerative Therapies

Abstract Significant achievements in paediatric cardiology, surgical treatment and intensive care of congenital heart disease have drastically changed clinical outcomes for paediatric patients. Nevertheless, late-onset heart failure in children after staged surgeries still remains a serious concern in the medical community. Heart transplantation is an option for treatment; however, the shortage of available organs is a persistent problem in many developed countries. In order to resolve these issues, advanced technologies, such as innovative mechanical circulatory support devices and regenerative therapies, are strongly desired. Accumulated evidence regarding cell-based cardiac regenerative therapies has suggested their safety and efficacy in treating adult heart failure. Given that young children seem to have a higher regenerative capacity than adults, stem cell-based therapies appear a promising treatment option for paediatric heart failure as well. Based on the findings from past trials and studies, we present the potential of various different types of stem cells, ranging from bone marrow mononuclear cells to cardiosphere-derived stem cells for use in paediatric cell-based therapies. Here, we assess both the current challenges associated with cell-based therapies and novel strategies that may be implemented in the future to advance stem cell therapy in the paediatric population.

Circulatory support and stem cell therapy in the management of advanced heart failure: a concise review of available evidence

2019 ◽  
Vol 14 (6) ◽  
pp. 585-593
Author(s):  
Mohsin A Hussain ◽  
Martina Colicchia ◽  
Jessry Veerapen ◽  
Deshan Weeraman ◽  
Mihai-Nicolae Podaru ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Advanced Heart Failure ◽  
Circulatory Support ◽  
Concise Review

scholarly journals Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured Myocardium

2017 ◽  
Vol 121 (6) ◽  
Author(s):  
Atsushi Tachibana ◽  
Michelle R. Santoso ◽  
Morteza Mahmoudi ◽  
Praveen Shukla ◽  
Lei Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Left Ventricular Ejection Fraction ◽  
Cardiac Myocytes ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Paracrine Effects

Rationale: Cardiac myocytes derived from pluripotent stem cells have demonstrated the potential to mitigate damage of the infarcted myocardium and improve left ventricular ejection fraction. However, the mechanism underlying the functional benefit is unclear. Objective: To evaluate whether the transplantation of cardiac-lineage differentiated derivatives enhance myocardial viability and restore left ventricular ejection fraction more effectively than undifferentiated pluripotent stem cells after a myocardial injury. Herein, we utilize novel multimodality evaluation of human embryonic stem cells (hESCs), hESC-derived cardiac myocytes (hCMs), human induced pluripotent stem cells (iPSCs), and iPSC-derived cardiac myocytes (iCMs) in a murine myocardial injury model. Methods and Results: Permanent ligation of the left anterior descending coronary artery was induced in immunosuppressed mice. Intramyocardial injection was performed with (1) hESCs (n=9), (2) iPSCs (n=8), (3) hCMs (n=9), (4) iCMs (n=14), and (5) PBS control (n=10). Left ventricular ejection fraction and myocardial viability, measured by cardiac magnetic resonance imaging and manganese-enhanced magnetic resonance imaging, respectively, was significantly improved in hCM- and iCM-treated mice compared with pluripotent stem cell- or control-treated mice. Bioluminescence imaging revealed limited cell engraftment in all treated groups, suggesting that the cell secretions may underlie the repair mechanism. To determine the paracrine effects of the transplanted cells, cytokines from supernatants from all groups were assessed in vitro. Gene expression and immunohistochemistry analyses of the murine myocardium demonstrated significant upregulation of the promigratory, proangiogenic, and antiapoptotic targets in groups treated with cardiac lineage cells compared with pluripotent stem cell and control groups. Conclusions: This study demonstrates that the cardiac phenotype of hCMs and iCMs salvages the injured myocardium effectively than undifferentiated stem cells through their differential paracrine effects.

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