scholarly journals Bioengineering Clinically Relevant Cardiomyocytes and Cardiac Tissues from Pluripotent Stem Cells

2021 ◽  
Vol 22 (6) ◽  
pp. 3005
Author(s):  
Emma Claire James ◽  
Eva Tomaskovic-Crook ◽  
Jeremy Micah Crook
Keyword(s):  
Stem Cells ◽  
Heart Disease ◽  
Electric Fields ◽  
Pluripotent Stem Cells ◽  
Heart Development ◽  
Disease Patient ◽  
Toxicity Testing ◽  
Model Systems ◽  
Patient Specific ◽  
Cardiac Tissues

The regenerative capacity of cardiomyocytes is insufficient to functionally recover damaged tissue, and as such, ischaemic heart disease forms the largest proportion of cardiovascular associated deaths. Human-induced pluripotent stem cells (hiPSCs) have enormous potential for developing patient specific cardiomyocytes for modelling heart disease, patient-based cardiac toxicity testing and potentially replacement therapy. However, traditional protocols for hiPSC-derived cardiomyocytes yield mixed populations of atrial, ventricular and nodal-like cells with immature cardiac properties. New insights gleaned from embryonic heart development have progressed the precise production of subtype-specific hiPSC-derived cardiomyocytes; however, their physiological immaturity severely limits their utility as model systems and their use for drug screening and cell therapy. The long-entrenched challenges in this field are being addressed by innovative bioengingeering technologies that incorporate biophysical, biochemical and more recently biomimetic electrical cues, with the latter having the potential to be used to both direct hiPSC differentiation and augment maturation and the function of derived cardiomyocytes and cardiac tissues by mimicking endogenous electric fields.

scholarly journals Decoding Genetics of Congenital Heart Disease Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs)

2021 ◽  
Vol 9 ◽  
Author(s):  
Hui Lin ◽  
Kim L. McBride ◽  
Vidu Garg ◽  
Ming-Tao Zhao
Keyword(s):  
Stem Cells ◽  
Congenital Heart Disease ◽  
Heart Disease ◽  
Induced Pluripotent Stem Cells ◽  
Genome Sequencing ◽  
Pluripotent Stem Cells ◽  
Congenital Heart ◽  
Model Systems ◽  
Patient Specific ◽  
Induced Pluripotent

Congenital heart disease (CHD) is the most common cause of infant death associated with birth defects. Recent next-generation genome sequencing has uncovered novel genetic etiologies of CHD, from inherited and de novo variants to non-coding genetic variants. The next phase of understanding the genetic contributors of CHD will be the functional illustration and validation of this genome sequencing data in cellular and animal model systems. Human induced pluripotent stem cells (iPSCs) have opened up new horizons to investigate genetic mechanisms of CHD using clinically relevant and patient-specific cardiac cells such as cardiomyocytes, endothelial/endocardial cells, cardiac fibroblasts and vascular smooth muscle cells. Using cutting-edge CRISPR/Cas9 genome editing tools, a given genetic variant can be corrected in diseased iPSCs and introduced to healthy iPSCs to define the pathogenicity of the variant and molecular basis of CHD. In this review, we discuss the recent progress in genetics of CHD deciphered by large-scale genome sequencing and explore how genome-edited patient iPSCs are poised to decode the genetic etiologies of CHD by coupling with single-cell genomics and organoid technologies.

Modeling Arrhythmogenic Heart Disease with Patient-Specific Induced Pluripotent Stem Cells

2013 ◽  
pp. 276-304
Author(s):  
Daniel Sinnecker ◽  
Alexander Goedel ◽  
Ralf Dirschinger ◽  
Alessandra Moretti ◽  
Karl-Ludwig Laugwitz
Keyword(s):  
Stem Cells ◽  
Heart Disease ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Induced Pluripotent

Towards the Generation of Patient-Specific Pluripotent Stem Cells for Combined Gene and Cell Therapy of Hematologic Disorders

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 17-22 ◽  
Author(s):  
George Q. Daley
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Cell Therapy ◽  
Somatic Cell ◽  
Pluripotent Stem Cells ◽  
Tissue Transplantation ◽  
Model Systems ◽  
Patient Specific ◽  
Gene Repair ◽  
Hematopoietic Stem

Abstract Hematopoietic stem cell transplantation (HSCT) has proven successful for the treatment of a host of genetic and malignant diseases of the blood, but immune barriers to allogeneic tissue transplantation have hindered wider application. Likewise, gene therapy now appears effective in the treatment of various forms of immune deficiency, and yet insertional mutagenesis from viral gene transfer has raised safety concerns. One strategy for addressing the limitations of both gene therapy and allogeneic transplantation entails the creation of pluripotent stem cells from a patient’s own somatic cells, thereby enabling precise in situ gene repair via homologous recombination in cultured cells, followed by autologous tissue transplantation. In murine model systems, the methods of somatic cell nuclear transfer, parthenogenesis, and direct somatic cell reprogramming with defined genetic factors have been used to generate pluripotent stem cells, and initial efforts at therapeutic gene repair and tissue transplantation suggest that the technology is feasible. Generating patient-specific autologous pluripotent stem cells provides an opportunity to combine gene therapy with autologous cell therapy to treat a host of human conditions. However, a number of technical hurdles must be overcome before therapies based on pluripotent human stem cells will appear in the clinic.

scholarly journals Engineering functional human gastrointestinal organoid tissues using the three primary germ layers separately derived from pluripotent stem cells

2021 ◽  
Author(s):  
Alexandra K Eicher ◽  
Daniel O Kechele ◽  
Nambirajan Sundaram ◽  
H Matthew Berns ◽  
Holly M Poling ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Clinical Care ◽  
Regional Identity ◽  
Model Systems ◽  
Gastric Epithelium ◽  
Enteric Neurons ◽  
Patient Specific ◽  
Germ Layers

The development of human organoid model systems has provided new avenues for patient-specific clinical care and disease modeling. However, all organoid systems are missing important cell types that, in the embryo, get incorporated into organ tissues during development. Based on the concept of how embryonic organs are assembled, we developed an organoid assembly approach starting with cells from the three primary germ layers; enteric neuroglial, mesenchymal, and epithelial precursors, all separately derived from human pluripotent stem cells. From these we generated human gastric tissue containing differentiated glands, surrounded by layers of smooth muscle containing functional enteric neurons that controlled contractions of the engineered tissue. We used this highly tractable system to identify essential roles for the enteric nervous system in the growth and regional identity of the gastric epithelium and mesenchyme and for glandular morphogenesis of the antral stomach. This approach of starting with separately-derived germ layer components was applied to building more complex fundic and esophageal tissue, suggesting this as a new paradigm for tissue engineering.

scholarly journals Pluripotency of human embryonic and induced pluripotent stem cells for cardiac and vascular regeneration

2010 ◽  
Vol 104 (07) ◽  
pp. 23-29 ◽  
Author(s):  
Kenneth R. Boheler
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ips Cells ◽  
Scientific Investigation ◽  
Model Systems ◽  
Patient Specific ◽  
Congenital Defects ◽  
Vascular Regeneration ◽  
The Creation ◽  
Induced Pluripotent

SummaryCardiac and vascular abnormalities and disease syndromes are major causes of death both during human development and with aging. To identify the cause of congenital defects and to combat this epidemic in the aging population, new models must be created for scientific investigation and new therapies must be developed. Recent advances in pluripotent stem cell biology offer renewed hope for tackling these problems. Of particular importance has been the creation of induced pluripotent (iPS) cells from adult tissues and organs through the forced expression of two to four transcription factors. Moreover, iPS cells, which are phenotypically indistinguishable from embryonic stem (ES) cells, can be generated from any patient. This unique capacity when coupled with samples from patients who have congenital and genetic defects of unknown aetiology should permit the creation of new model systems that foment scientific investigation. Moreover, creation of patient-specific cells should overcome many of the immunological limitations that currently impede therapeutic applications associated with other pluripotent stem cells and their derivatives. The aims of this paper will be to discuss cardiac and vascular diseases and show how iPS cells may be employed to overcome some of the most significant scientific and clinical hurdles facing this field.

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