Human umbilical cord blood cells in infarcted rats

Pinho-Ribeiro, Vanessa; Maia, A.C.V.; Werneck-de-Castro, João Pedro; Oliveira, P. M.; Goldenberg, Regina Coeli dos Santos; Carvalho, Antônio Carlos Campos de

doi:10.1590/s0100-879x2010007500007

Cited by 8 publications

(4 citation statements)

References 19 publications

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“…Preclinical studies with UCB cells have demonstrated their efficacy in various diseases, such as heatstroke, amyotrophic lateral sclerosis, post-infarct cardiac regeneration, and liver diseases [ 4 , 7 - 11 ]. Subsequently, multiple groups have demonstrated that the delivery of UCB cells has the potential to improve cardiac function in animals following acute myocardial infarction (MI) in the left ventricle [ 12 - 14 ]. Recent studies in a novel sheep model of chronic right ventricular volume overload showed that UCB cells transplanted in the right ventricle improved heart function [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Human umbilical cord blood-derived mononuclear cells improve murine ventricular function upon intramyocardial delivery in right ventricular chronic pressure overload

et al. 2015

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IntroductionStem cell therapy has emerged as potential therapeutic strategy for damaged heart muscles. Umbilical cord blood (UCB) cells are the most prevalent stem cell source available, yet have not been fully tested in cardiac regeneration. Herein, studies were performed to evaluate the cardiovascular safety and beneficial effect of mononuclear cells (MNCs) isolated from human umbilical cord blood upon intramyocardial delivery in a murine model of right ventricle (RV) heart failure due to pressure overload.MethodsUCB-derived MNCs were delivered into the myocardium of a diseased RV cardiac model. Pulmonary artery banding (PAB) was used to produce pressure overload in athymic nude mice that were then injected intramyocardially with UCB-MNCs (0.4 × 10^6 cells/heart). Cardiac functions were then monitored by telemetry, echocardiography, magnetic resonance imaging (MRI) and pathologic analysis of heart samples to determine the ability for cell-based repair.ResultsThe cardio-toxicity studies provided evidence that UCB cell transplantation has a safe therapeutic window between 0.4 to 0.8 million cells/heart without altering QT or ST-segments or the morphology of electrocardiograph waves. The PAB cohort demonstrated significant changes in RV chamber dilation and functional defects consistent with severe pressure overload. Using cardiac MRI analysis, UCB-MNC transplantation in the setting of PAB demonstrated an improvement in RV structure and function in this surgical mouse model. The RV volume load in PAB-only mice was 24.09 ± 3.9 compared to 11.05 ± 2.09 in the cell group (mm3, P-value <0.005). The analysis of pathogenic gene expression (BNP, ANP, Acta1, Myh7) in the cell-transplanted group showed a significant reversal with respect to the diseased PAB mice with a robust increase in cardiac progenitor gene expression such as GATA4, Kdr, Mef2c and Nkx2.5. Histological analysis indicated significant fibrosis in the RV in response to PAB that was reduced following UCB-MNC’s transplantation along with concomitant increased Ki-67 expression and CD31 positive vessels as a marker of angiogenesis within the myocardium.ConclusionsThese findings indicate that human UCB-derived MNCs promote an adaptive regenerative response in the right ventricle upon intramyocardial transplantation in the setting of chronic pressure overload heart failure.

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Section: Introductionmentioning

confidence: 99%

Human umbilical cord blood-derived mononuclear cells improve murine ventricular function upon intramyocardial delivery in right ventricular chronic pressure overload

et al. 2015

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“…This direct administration of cells into the damage heart muscle has proven to be more effective than indirect methods. Comparing indirect and direct delivery methods, intramyocardial injection significantly reduced the infarct size area as compared to indirect methods of HUCB cell delivery [110]. Although this method is preferred, there are some disadvantages that need to be taken into consideration before delivering the cells.…”

Section: Intramyocardial Injectionmentioning

confidence: 99%

“…Studies that are more recent further support the intramyocardial injection as an effective cell delivery system. HUCB cells were injected into one or two positions of the myocardium near the edge of the infarct area in rats [110]. Three weeks after implantation, HUCB cells were detected using nuclear staining primarily in the border of the infarct area, suggesting that the cells have the potential to survive for at least three weeks following implantation.…”

Section: Intramyocardial Injectionmentioning

confidence: 99%

Human Umbilical Cord Blood for Transplantation Therapy in Myocardial Infarction

Acosta

Franzese²,

Staples³

et al. 2012

J Stem Cell Res Ther

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Cell-based therapy is a promising therapy for myocardial infarction. Endogenous repair of the heart muscle after myocardial infarction is a challenge because adult cardiomyocytes have a limited capacity to proliferate and replace damaged cells. Pre-clinical and clinical evidence has shown that cell based therapy may promote revascularization and replacement of damaged myocytes after myocardial infarction. Adult stem cells can be harvested from different sources including bone marrow, skeletal myoblast, and human umbilical cord blood cells. The use of these cells for the repair of myocardial infarction presents various advantages over other sources of stem cells. Among these are easy harvesting, unlimited differentiation capability, and robust angiogenic potential. In this review, we discuss the milestone findings and the most recent evidence demonstrating the therapeutic efficacy and safety of the transplantation of human umbilical cord blood cells as a stand-alone therapy or in combination with gene therapy, highlighting the importance of optimizing the timing, dose and delivery methods, and a better understanding of the mechanisms of action that will guide the clinical entry of this innovative treatment for ischemic disorders, specifically myocardial infarction.

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“…UCB cells have been standardized therapeutic agents in patients suffering from major hematological disorders since 1988 [13]. Subsequently, multiple groups have been pioneering human umbilical cord blood-derived mononuclear cells (UCB-MNCs) in preclinical experimental approaches for myocardial repair and regeneration [14][15][16][17][18][19]. Collectively, these studies suggest a cellmediated improvement in the ejection fraction, wall motion, and cardiac contraction, along with a lowered left ventricular end-diastolic pressure.…”

Section: Introductionmentioning

confidence: 99%

Safety and Feasibility for Pediatric Cardiac Regeneration Using Epicardial Delivery of Autologous Umbilical Cord Blood-Derived Mononuclear Cells Established in a Porcine Model System

Peral

Burkhart²,

Oommen

et al. 2015

Stem Cells Translational Medicine

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Congenital heart diseases (CHDs) requiring surgical palliation mandate new treatment strategies to optimize long-term outcomes. Despite the mounting evidence of cardiac regeneration, there are no long-term safety studies of autologous cell-based transplantation in the pediatric setting. We aimed to establish a porcine pipeline to evaluate the feasibility and long-term safety of autologous umbilical cord blood mononuclear cells (UCB-MNCs) transplanted into the right ventricle (RV) of juvenile porcine hearts. Piglets were born by caesarean section to enable UCB collection. Upon meeting release criteria, 12 animals were randomized in a double-blinded fashion prior to surgical delivery of test article (n = 6) or placebo (n = 6). The UCB-MNC (3 3 10 6 cells per kilogram) or control (dimethyl sulfoxide, 10%) products were injected intramyocardially into the RV under direct visualization. The cohorts were monitored for 3 months after product delivery with assessments of cardiac performance, rhythm, and serial cardiac biochemical markers, followed by terminal necropsy. No mortalities were associated with intramyocardial delivery of UCB-MNCs or placebo. Two animals from the placebo group developed local skin infection after surgery that responded to antibiotic treatment. Electrophysiological assessments revealed no arrhythmias in either group throughout the 3-month study. Two animals in the cell-therapy group had transient, subclinical dysrhythmia in the perioperative period, likely because of an exaggerated response to anesthesia. Overall, this study demonstrated that autologous UCB-MNCs can be safely collected and surgically delivered in a pediatric setting. The safety profile establishes the foundation for cell-based therapy directed at the RV of juvenile hearts and aims to accelerate cell-based therapies toward clinical trials for CHD. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:195-206

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Human umbilical cord blood cells in infarcted rats

Cited by 8 publications

References 19 publications

Human umbilical cord blood-derived mononuclear cells improve murine ventricular function upon intramyocardial delivery in right ventricular chronic pressure overload

Human umbilical cord blood-derived mononuclear cells improve murine ventricular function upon intramyocardial delivery in right ventricular chronic pressure overload

Human Umbilical Cord Blood for Transplantation Therapy in Myocardial Infarction

Safety and Feasibility for Pediatric Cardiac Regeneration Using Epicardial Delivery of Autologous Umbilical Cord Blood-Derived Mononuclear Cells Established in a Porcine Model System

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