Reconstructing the heart using iPSCs: Engineering strategies and applications

Cho, Sang-Kyun; Lee, Chelsea; Skylar‐Scott, Mark A.; Heilshorn, Sarah C.; Wu, Joseph C.

doi:10.1016/j.yjmcc.2021.04.006

Cited by 50 publications

(44 citation statements)

References 154 publications

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“…The lack of oxygen and nutrients leads to the formation of a necrotic core [ 291 ]. However, the ever-growing field of organoid or gastruloids and artificial cardiac tissue technology, which offers a considerable number of features through the formation of small size organoids or the development of vascularization to solve this problem, will lead to a better understanding of disease pathogenesis at the tissue and organ level [ 288 , 292 , 293 ]. Recently, human cardiac organoids were used for modeling most of the cardiovascular diseases, which mimic the tissue architecture of heart, including cardiomyocytes, endothelial, stromal cells, and epicardial cells in vivo [ 122 , 294 , 295 , 296 ].…”

Section: Consideration Of Hipsc For Use In Modeling Heart Diseasementioning

confidence: 99%

Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective

Bekhite

Schulze

2021

Cells

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A comprehensive understanding of the pathophysiology and cellular responses to drugs in human heart disease is limited by species differences between humans and experimental animals. In addition, isolation of human cardiomyocytes (CMs) is complicated because cells obtained by biopsy do not proliferate to provide sufficient numbers of cells for preclinical studies in vitro. Interestingly, the discovery of human-induced pluripotent stem cell (hiPSC) has opened up the possibility of generating and studying heart disease in a culture dish. The combination of reprogramming and genome editing technologies to generate a broad spectrum of human heart diseases in vitro offers a great opportunity to elucidate gene function and mechanisms. However, to exploit the potential applications of hiPSC-derived-CMs for drug testing and studying adult-onset cardiac disease, a full functional characterization of maturation and metabolic traits is required. In this review, we focus on methods to reprogram somatic cells into hiPSC and the solutions for overcome immaturity of the hiPSC-derived-CMs to mimic the structure and physiological properties of the adult human CMs to accurately model disease and test drug safety. Finally, we discuss how to improve the culture, differentiation, and purification of CMs to obtain sufficient numbers of desired types of hiPSC-derived-CMs for disease modeling and drug development platform.

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Section: Consideration Of Hipsc For Use In Modeling Heart Diseasementioning

confidence: 99%

Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective

Bekhite

Schulze

2021

Cells

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“…Lui et al think that hiPSC-derived CMs have been bioprinted to recapitulate a vascularized cardiac tissue which can then be transplanted in a defective heart [ 52 ]. Cho et al used a 3D bioprinter to produce scaffold-free cardiac tissue grafts from hiPSC-derived CMs cell spheroids, and the results find that mechanical stretching stimulates hiPSC-derived CMs in a 3D printed, scaffold-free tissue graft to develop mature cardiac material structuring and cellular fates [ 53 ]. However, hiPSCs transplanted to lesions undergo oxidative damage and demonstrate squeeze loss as well as low cell survival and retention rates [ 54 ].…”

Section: 3d Bioprinting Of Ipscs In Tissue Engineeringmentioning

confidence: 99%

“…In-depth studies of liver regeneration and the developments in cell culture, stem cell technology, and genetic engineering should permit liver printing in the near future. One example is that researchers bioprinted hepatic tissue constructs using iPSC-derived hepatocytes, endothelial cells, and mesenchymal cells resuspended in two different bioinks: GelMA with stiffness similar to healthy liver tissues and a mix of glycidyl methacrylate-hyaluronic acid/GelMA which supported vascularization [ 63 , 64 ]. However, liver printing has two crucial bottlenecks: the need to recreate a complicated internal system of branched blood vessels and the difficulty of distributing more than three high-density functional cells in a 3D structure and making them grow into tissues.…”

Section: 3d Bioprinting Of Ipscs In Tissue Engineeringmentioning

confidence: 99%

Development and Application of 3D Bioprinted Scaffolds Supporting Induced Pluripotent Stem Cells

Liu

et al. 2021

BioMed Research International

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Three-dimensional (3D) bioprinting is a revolutionary technology that replicates 3D functional living tissue scaffolds in vitro by controlling the layer-by-layer deposition of biomaterials and enables highly precise positioning of cells. With the development of this technology, more advanced research on the mechanisms of tissue morphogenesis, clinical drug screening, and organ regeneration may be pursued. Because of their self-renewal characteristics and multidirectional differentiation potential, induced pluripotent stem cells (iPSCs) have outstanding advantages in stem cell research and applications. In this review, we discuss the advantages of different bioinks containing human iPSCs that are fabricated by using 3D bioprinting. In particular, we focus on the ability of these bioinks to support iPSCs and promote their proliferation and differentiation. In addition, we summarize the applications of 3D bioprinting with iPSC-containing bioinks and put forward new views on the current research status.

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“…In order to approve safer and more effective therapies, there is an increasing demand to develop faithful models of human heart tissue for pre-clinical research 7 . While recent technologies provide some insight into how human CVDs can be modelled in vitro, a comprehensive overview of the complexity of the human heart remains elusive due to the limited cellular heterogeneity, physiological complexity, or maturity of the constructs produced 8 . Furthermore, animal models may not always faithfully reflect the unique features of human biology and disease, and could give rise to ethical concerns [9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

Generation and Maturation of Human iPSC-derived Cardiac Organoids in Long Term Culture

Ergir

Cruz

Fernandes

et al. 2022

Preprint

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Cardiovascular diseases remain the leading cause of death worldwide; hence there is an increasing focus on developing physiologically relevant in vitro cardiovascular tissue models suitable for studying personalized medicine and pre-clinical tests. Despite recent advances, models that reproduce both tissue complexity and maturation are still limited. We have established a scaffold-free protocol to generate multicellular, beating and self-organized human cardiac organoids (hCO) in vitro from hiPSCs that can be cultured for long term. This is achieved by differentiation of hiPSC in 2D monolayer culture towards cardiovascular lineage, followed by further aggregation on low-attachment culture dishes in 3D. The generated human cardiac organoids (hCOs) containing multiple cell types that physiologically compose the heart, gradually self-organize and beat without external stimuli for more than 50 days. We have shown that 3D hCOs display improved cardiac specification, survival and maturation as compared to standard monolayer cardiac differentiation. We also confirmed the functionality of hCOs by their response to cardioactive drugs in long term culture. Furthermore, we demonstrated that hCOs can be used to study chemotherapy-induced cardiotoxicity. This study could help to develop more physiologically-relevant cardiac tissue models, and represent a powerful platform for future translational research in cardiovascular biology.

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Reconstructing the heart using iPSCs: Engineering strategies and applications

Cited by 50 publications

References 154 publications

Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective

Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective

Development and Application of 3D Bioprinted Scaffolds Supporting Induced Pluripotent Stem Cells

Generation and Maturation of Human iPSC-derived Cardiac Organoids in Long Term Culture

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