Designing multicellular cardiac tissue engineering technologies for clinical translation DOI Creative Commons
Andrew Laskary, James E. Hudson, Enzo R. Porrello

et al.

Seminars in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 171, P. 103612 - 103612

Published: April 29, 2025

Cardiovascular diseases remain the leading cause of death worldwide-claiming one-third all deaths every year. Current two-dimensional in vitro cell culture systems and animal models cannot completely recapitulate clinical complexity these humans. Therefore, there is a dire need for higher fidelity biological capable replicating phenotypes to inform outcomes therapeutic development. Cardiac tissue engineering (CTE) strategies have emerged fulfill this by design three-dimensional myocardial from human pluripotent stem cells. In way, CTE serve as highly controllable variety applications-including physiological pathological modeling, drug discovery preclinical testing platforms, even direct interventions clinic. Although significant progress has been made development technologies, critical challenges necessary refinements are required derive more advanced heart technologies. review, we distill three focus areas field address: I) Generating cardiac muscle types scalable manufacturing methods, II) Engineering structure, function, analyses, III) Curating system specific application. each our areas, emphasize importance designing mimicking intricate intercellular connectivity discuss fundamental considerations that subsequently arise. We conclude highlighting cutting-edge applications use technologies modeling repair damaged diseased hearts.

Language: Английский

Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms DOI
Shira Landau, Yimu Zhao, Homaira Hamidzada

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(8), P. 1222 - 1238.e10

Published: June 21, 2024

Language: Английский

Citations

20
Generation of human vascularized and chambered cardiac organoids for cardiac disease modelling and drug evaluation DOI Creative Commons

Jingsi Yang,

Wei Lei,

Yang Xiao

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(8)

Published: March 7, 2024

Abstract Human induced pluripotent stem cell (hiPSC)‐derived cardiac organoids (COs) have shown great potential in modelling human heart development and cardiovascular diseases, a leading cause of global death. However, several limitations such as low reproducibility, limited vascularization difficulty formation chamber were yet to be overcome. We established new method for robust generation COs, via combination methodologies hiPSC‐derived vascular spheres directly differentiated cardiomyocytes from hiPSCs, investigated the application COs injury drug evaluation. The we built displayed vascularized chamber‐like structure, hence named vaschamcardioids (vcCOs). These vcCOs exhibited approximately 90% spontaneous beating ratio. Single‐cell transcriptomics identified total six types vcCOs, including cardiomyocytes, precursor cells, endothelial fibroblasts, etc. successfully recaptured processes fibrosis vivo on showed that FDA‐approved medication captopril significantly attenuated injury‐induced functional disorders. In addition, an obvious toxicity reaction doxorubicin dose‐dependent manner. developed three‐step complex our data suggested might become useful model understanding pathophysiological mechanisms developing intervention strategies screening drugs.

Language: Английский

Citations

18
Dissecting endothelial cell heterogeneity with new tools DOI Creative Commons
Jing Zhong,

Rongrong Gao,

Xin Zhang

et al.

Cell Regeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 23, 2025

Abstract The formation of a blood vessel network is crucial for organ development and regeneration. Over the past three decades, central molecular mechanisms governing growth have been extensively studied. Recent evidence indicates that vascular endothelial cells—the specialized cells lining inner surface vessels—exhibit significant heterogeneity to meet specific needs different organs. This review focuses on current understanding cell heterogeneity, which includes both intra-organ inter-organ heterogeneity. Intra-organ encompasses arterio-venous tip-stalk specialization, while refers organ-specific transcriptomic profiles functions. Advances in single-cell RNA sequencing (scRNA-seq) enabled identification new subpopulations comparison gene expression patterns across subsets cells. Integrating scRNA-seq with other high-throughput technologies promises deepen our at epigenetic level spatially resolved context. To further explore human organoids offer powerful tools studying function three-dimensional culture systems investigating endothelial-tissue interactions using Developing presents unique opportunities unravel its implications disease. Emerging technologies, such as organoids, are poised transform pave way innovative therapeutic strategies address diseases. Graphical

Language: Английский

Citations

1
Advances in cardiac tissue engineering and heart‐on‐a‐chip DOI Creative Commons
Jennifer Kieda, Amid Shakeri, Shira Landau

et al.

Journal of Biomedical Materials Research Part A, Journal Year: 2023, Volume and Issue: 112(4), P. 492 - 511

Published: Nov. 1, 2023

Abstract Recent advances in both cardiac tissue engineering and hearts‐on‐a‐chip are grounded new biomaterial development as well the employment of innovative fabrication techniques that enable precise control mechanical, electrical, structural properties tissues being modelled. The elongated structure cardiomyocytes requires tuning substrate application biophysical stimuli to drive its mature phenotype. Landmark have already been achieved with induced pluripotent stem cell‐derived patches advanced human testing. Heart‐on‐a‐chip platforms now commonly used by a number pharmaceutical biotechnology companies. Here, we provide an overview physiology order better define requirements for functional recapitulation. We then discuss biomaterials most heart‐on‐a‐chip, followed discussion recent representative studies fields. outline significant challenges common fields, specifically: scalable platform standardization, improving cellular fidelity through effective vascularization, achieving adult maturation, ultimately developing cryopreservation protocols so available off shelf.

Language: Английский

Citations

19
Engineering Organ-on-a-Chip Systems for Vascular Diseases DOI Open Access
Amid Shakeri, Ying Wang, Yimu Zhao

et al.

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2023, Volume and Issue: 43(12), P. 2241 - 2255

Published: Oct. 12, 2023

Vascular diseases, such as atherosclerosis and thrombosis, are major causes of morbidity mortality worldwide. Traditional in vitro models for studying vascular diseases have limitations, they do not fully recapitulate the complexity vivo microenvironment. Organ-on-a-chip systems emerged a promising approach modeling by incorporating multiple cell types, mechanical biochemical cues, fluid flow microscale platform. This review provides an overview recent advancements engineering organ-on-a-chip including use microfluidic channels, ECM (extracellular matrix) scaffolds, patient-specific cells. We also discuss limitations future perspectives diseases.

Language: Английский

Citations

18
Clinical trials in-a-dish for cardiovascular medicine DOI
Xuekun Wu, Kyle Swanson, Zehra Yıldırım

et al.

European Heart Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Abstract Cardiovascular diseases persist as a global health challenge that requires methodological innovation for effective drug development. Conventional pipelines relying on animal models suffer from high failure rates due to significant interspecies variation between humans and models. In response, the recently enacted Food Drug Administration Modernization Act 2.0 encourages alternative approaches including induced pluripotent stem cells (iPSCs). Human iPSCs provide patient-specific, precise, screenable platform testing, paving way cardiovascular precision medicine. This review discusses milestones in iPSC differentiation their applications disease modelling discovery It then explores challenges emerging opportunities implementation of ‘clinical trials in-a-dish’. Concluding, this proposes framework future clinical trial design with strategic incorporations technology, microphysiological systems, pan-omics, artificial intelligence improve success advance healthcare.

Language: Английский

Citations

7
Advances in the Generation of Constructed Cardiac Tissue Derived from Induced Pluripotent Stem Cells for Disease Modeling and Therapeutic Discovery DOI Creative Commons
Truman J. Roland, Kunhua Song

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 250 - 250

Published: Jan. 29, 2024

The human heart lacks significant regenerative capacity; thus, the solution to failure (HF) remains organ donation, requiring surgery and immunosuppression. demand for constructed cardiac tissues (CCTs) model treat disease continues grow. Recent advances in induced pluripotent stem cell (iPSC) manipulation, CRISPR gene editing, 3D tissue culture have enabled a boom iPSC-derived CCTs (iPSC-CCTs) with diverse types architecture. Compared 2D-cultured cells, iPSC-CCTs better recapitulate biology, demonstrating potential advance modeling, drug discovery, medicine, though could benefit from methods faithfully mimic physiology electrophysiology. Here, we summarize future developments vascularization, immunization, maturation of study therapy.

Language: Английский

Citations

6
Progress of organoid platform in cardiovascular research DOI Creative Commons

Xingchao Du,

Hao Jia,

Yuan Chang

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 40, P. 88 - 103

Published: June 9, 2024

Language: Английский

Citations

6
Recent advances in regulating the proliferation or maturation of human-induced pluripotent stem cell-derived cardiomyocytes DOI Creative Commons
Hao Yang, Yuan Yang, Fedir N. Kiskin

et al.

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 30, 2023

Abstract In the last decade, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM)-based cell therapy has drawn broad attention as a potential for treating injured hearts. However, mass production of hiPSC-CMs remains challenging, limiting their translational in regenerative medicine. Therefore, multiple strategies including cycle regulators, small molecules, co-culture systems, and epigenetic modifiers have been used to improve proliferation hiPSC-CMs. On other hand, immaturity these proliferative could lead lethal arrhythmias due limited ability functionally couple with resident cardiomyocytes. To achieve functional maturity, numerous methods such prolonged culture, biochemical or biophysical stimulation, vivo transplantation, 3D culture approaches employed. this review, we summarize recent promote hiPSC-CM proliferation, thoroughly review advances promoting maturation, which will serve foundation large-scale mature future clinical applications.

Language: Английский

Citations

14
The crosstalks between vascular endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts in vascular remodeling DOI

Ming Xie,

Xiandeng Li,

L Chen

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 361, P. 123319 - 123319

Published: Dec. 17, 2024

Language: Английский

Citations

5