7 research outputs found
Generation of an induced pluripotent stem cell line (ESi107-A) from a transthyretin amyloid cardiomyopathy (ATTR-CM) patient carrying a p.Ser43Asn mutation in the TTR gene
Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease caused by the abnormal production of misfolded TTR protein by liver cells,
which is then released systemically. Its amyloid deposition in the heart is linked to cardiac toxicity and progression toward heart failure. A human induced
pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) from a patient suffering familial transthyretin amyloid cardiomyopathy carrying a c.128G>A (p.Ser43Asn) mutation in the TTR gene. This iPSC line offers a useful resource to study the disease pathophysiology and a cell-based
model for therapeutic discovery
New strategies for echocardiographic evaluation of left ventricular function in a mouse model of long-term myocardial infarction
In summary, we have performed a complete characterization of LV post-infarction remodeling in a DBA/2J mouse model of MI, using parameters adapted to the particular characteristics of the model In the future, this well characterized model will be used in both investigative and pharmacological studies that require accurate quantitative monitoring of cardiac recovery after myocardial infarction
Analysis of the regenerative potential of the induced pluripotent stem cells in a model of acute myocardial infarction in mice
Principal limitation for generating cardiomyocytes from stem cells is that differentiated cells generally present electrophysiological immature and heterogeneous phenotype, which may hamper their in vitro and in vivo application. The purpose of this study was to examine the effect of NRG-1b and DMSO in the in vitro generation of mature working-type cardiomyocytes from induced pluripotent stem (iPS) cells and to determine their contribution to the cardiac tissue regeneration after acute myocardial infarction (AMI). iPS cells were derived from α-MHC-GFP mice fibroblasts and were in vitro differentiated towards cardiomyocytes by DMSO and/or NRG-1b treatment. iPS cardiac specification and maturation was analyzed by Q-RT-PCR, immunofluorescence, electronic microscopy and patch-clamp techniques. The iPS-derived cardiomyocytes (n=15) or culture-medium as control (n=13) were injected into the peri-infarct region of mice hearts following coronary artery ligation. Echocardiography and histology assessments were performed from 1-8 weeks post-transplantation. iPS cells showed early and robust in vitro cardiogenesis with cardiac gene and protein expression in all cases. Electrophysiological studies demonstrated a more mature ventricular-like cardiac phenotype when cells were treated with NRG-1b and DMSO than with DMSO-treatment alone. In vivo studies in the AMI mouse model demonstrated that iPS-derived CMs preserved cardiac function and induced a positive heart tissue remodeling. Moreover, iPS-CMs engrafted and electromechanically couple into the heart tissue.
The combination of NRG-1b and DMSO induced iPS cells differentiation towards mature ventricular-like cardiac cells which, when transplanted in a model of AMI, contributed to preserve the cardiac function and tissue viability
Engineering and assessing cardiac tissue complexity
Cardiac tissue engineering is very much in a current focus of regenerative medicine research as it represents a promising strategy for cardiac disease modelling, cardiotoxicity testing and cardiovascular repair. Advances in this field over the last two decades have enabled the generation of human engineered cardiac tissue constructs with progressively increased functional capabilities. However, reproducing tissue-like properties is still a pending issue, as constructs generated to date remain immature relative to native adult heart. Moreover, there is a high degree of heterogeneity in the methodologies used to assess the functionality and cardiac maturation state of engineered cardiac tissue constructs, which further complicates the comparison of constructs generated in different ways. Here, we present an overview of the general approaches developed to generate functional cardiac tissues, discussing the different cell sources, biomaterials, and types of engineering strategies utilized to date. Moreover, we discuss the main functional assays used to evaluate the cardiac maturation state of the constructs, both at the cellular and the tissue levels. We trust that researchers interested in developing engineered cardiac tissue constructs will find the information reviewed here useful. Furthermore, we believe that providing a unified framework for comparison will further the development of human engineered cardiac tissue constructs displaying the specific properties best suited for each particular application
New strategies for echocardiographic evaluation of left ventricular function in a mouse model of long-term myocardial infarction
In summary, we have performed a complete characterization of LV post-infarction remodeling in a DBA/2J mouse model of MI, using parameters adapted to the particular characteristics of the model In the future, this well characterized model will be used in both investigative and pharmacological studies that require accurate quantitative monitoring of cardiac recovery after myocardial infarction
Long-Term Engraftment of Human Cardiomyocytes Combined with Biodegradable Microparticles Induces Heart Repair
Cardiomyocytes derived from human induced pluripotent stem
cells (hiPSC-CMs) are a promising cell source for cardiac repair
after myocardial infarction (MI) because they offer several
advantages such as potential to remuscularize infarcted tissue,
integration in the host myocardium, and paracrine therapeutic
effects. However, cell delivery issues have limited their potential application in clinical practice, showing poor survival and
engraftment after transplantation. In this work, we hypothesized that the combination of hiPSC-CMs with microparticles
(MPs) could enhance long-term cell survival and retention in the
heart and consequently improve cardiac repair. CMs were
obtained by differentiation of hiPSCs by small-molecule manipulation of the Wnt pathway and adhered to biomimetic
poly(lactic-co-glycolic acid) MPs covered with collagen and
poly(D-lysine). The potential of the system to support cell
survival was analyzed in vitro, demonstrating a 1.70-fold and
1.99-fold increase in cell survival after 1 and 4 days, respectively. The efficacy of the system was tested in a mouse MI
model. Interestingly, 2 months after administration, transplanted
hiPSC-CMs could be detected in the peri-infarct area. These cells
not only maintained the cardiac phenotype but also showed
in vivo maturation and signs of electrical coupling. Importantly,
cardiac function was significantly improved, which could be
attributed to a paracrine effect of cells. These findings suggest
that MPs represent an excellent platform for cell delivery in the
field of cardiac repair, which could also be translated into an
enhancement of the potential of cell-based therapies in other
medical applications
Generation of an induced pluripotent stem cell line (ESi107-A) from a transthyretin amyloid cardiomyopathy (ATTR-CM) patient carrying a p.Ser43Asn mutation in the TTR gene
Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease caused by the abnormal production of misfolded TTR protein by liver cells,
which is then released systemically. Its amyloid deposition in the heart is linked to cardiac toxicity and progression toward heart failure. A human induced
pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) from a patient suffering familial transthyretin amyloid cardiomyopathy carrying a c.128G>A (p.Ser43Asn) mutation in the TTR gene. This iPSC line offers a useful resource to study the disease pathophysiology and a cell-based
model for therapeutic discovery