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In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
Bioengineering Clinically Relevant Cardiomyocytes and Cardiac Tissues from Pluripotent Stem Cells
Emma Claire James1, Eva Tomaskovic-Crook1,2, Jeremy Micah Crook1,2,3
1ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, University of Wollongong, Wollongong 2500, Australia.
Insights
Human-induced pluripotent stem cells (hiPSCs) offer potential for heart repair, but derived cardiomyocytes are immature. Biomimetic electrical cues show promise for directing differentiation and improving cardiomyocyte function for cardiac therapies.
Area of Science:
- Biomedical Engineering
- Stem Cell Biology
- Cardiovascular Research
Background:
- Cardiomyocyte regeneration is limited, leading to high mortality from ischemic heart disease.
- Human-induced pluripotent stem cells (hiPSCs) are promising for patient-specific cardiac applications.
- Current hiPSC-derived cardiomyocytes exhibit immaturity and mixed subtypes, hindering their therapeutic and modeling utility.
Purpose of the Study:
- To explore advanced bioengineering strategies for improving hiPSC-derived cardiomyocyte development.
- To investigate the role of biomimetic electrical cues in directing hiPSC differentiation and maturation.
- To enhance the functional properties of cardiomyocytes for cardiac disease modeling and regenerative therapy.
Main Methods:
- Utilizing insights from embryonic heart development to refine hiPSC differentiation protocols.
- Incorporating biophysical, biochemical, and biomimetic electrical cues in bioengineering approaches.
- Investigating the impact of mimicking endogenous electric fields on cardiomyocyte development and function.
Main Results:
- New bioengineering technologies are addressing challenges in hiPSC-derived cardiomyocyte production.
- Biomimetic electrical cues demonstrate potential in directing hiPSC differentiation.
- Electrical cues can augment the maturation and function of derived cardiomyocytes and cardiac tissues.
Conclusions:
- Innovative bioengineering, particularly biomimetic electrical cues, is crucial for overcoming the limitations of hiPSC-derived cardiomyocytes.
- This approach holds significant potential for advancing cardiac disease modeling, drug screening, and cell-based regenerative therapies.
- Mimicking endogenous electric fields offers a novel strategy to improve the physiological relevance and therapeutic efficacy of engineered cardiac tissues.
Abstract:
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.

