Directed Evolution of AAV9 for Efficient Gene Expression in Cardiomyocytes In Vitro and In Vivo DOI
Leonard Hüttermann,

Lena Schröder,

Prithviraj Manohar Vijaya Shetty

et al.

Human Gene Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Adeno-associated viral (AAV) vectors are increasingly used for preclinical and clinical cardiac gene therapy approaches. However, transfer to cardiomyocytes poses a challenge due differences between AAV serotypes in terms of expression efficiency vitro vivo. For example, AAV9 work well rodent heart muscle cells vivo but not cultivated neonatal rat ventricular (NRVCMs), necessitating the use AAV6 studies. Therefore, we aimed develop an that could efficiently express genes NRVCMs, human engineered tissue (hEHT), mammalian hearts. The production results lower yields compared with AAV9. Hence, random peptide libraries selected variants on NRVCMs at vector genome RNA levels parallel. enriched library were characterized using high-throughput analysis barcoded variants, followed by individual validation most promising candidates. Interestingly, found striking NRVCM transduction patterns capsid depending selection strategy. based level enabled highest outperformed AAVs efficiency. In addition, identified new variant only allowed significantly higher also similar murine hearts as wild-type after being intravenously injected into mice. Moreover, novel facilitated hEHT this streamline studies myocardial diseases eliminating need different hEHT,

Language: Английский

Challenges and opportunities for the next generation of cardiovascular tissue engineering DOI
Sang-Kyun Cho, Dennis E. Discher, Kam W. Leong

et al.

Nature Methods, Journal Year: 2022, Volume and Issue: 19(9), P. 1064 - 1071

Published: Sept. 1, 2022

Language: Английский

Citations

107
Human organoids: New strategies and methods for analyzing human development and disease DOI Creative Commons
Nina S. Corsini, Juergen A. Knoblich

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2756 - 2769

Published: July 1, 2022

For decades, insight into fundamental principles of human biology and disease has been obtained primarily by experiments in animal models. While this allowed researchers to understand many biological processes great detail, some developmental mechanisms have proven difficult study due inherent species differences. The advent organoid technology more than 10 years ago established laboratory-grown organ tissues as an additional model system recapitulate human-specific aspects biology. use 3D organoids, well other advances single-cell technologies, revealed unprecedented insights mechanisms, especially those that distinguish humans from species. This review highlights novel with a focus on how generated better understanding development disease.

Language: Английский

Citations

96
FDA Modernization Act 2.0: transitioning beyond animal models with human cells, organoids, and AI/ML-based approaches DOI Creative Commons
Peter-James H. Zushin, Souhrid Mukherjee, Joseph C. Wu

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(21)

Published: Oct. 31, 2023

Language: Английский

Citations

88
Multi-chamber cardioids unravel human heart development and cardiac defects DOI Creative Commons

Clara Schmidt,

Alison Deyett, Tobias Ilmer

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(25), P. 5587 - 5605.e27

Published: Nov. 28, 2023

The number one cause of human fetal death are defects in heart development. Because the embryonic is inaccessible and impacts mutations, drugs, environmental factors on specialized functions different compartments not captured by vitro models, determining underlying causes difficult. Here, we established a cardioid platform that recapitulates development all major compartments, including right left ventricles, atria, outflow tract, atrioventricular canal. By leveraging 2D 3D differentiation, efficiently generated progenitor subsets with distinct first, anterior, posterior second field identities. This advance enabled reproducible generation cardioids compartment-specific vivo-like gene expression profiles, morphologies, functions. We used this to unravel ontogeny signal contraction propagation between interacting chambers dissect how teratogens, drugs developing heart.

Language: Английский

Citations

78
Biomimetic Scaffolds—A Novel Approach to Three Dimensional Cell Culture Techniques for Potential Implementation in Tissue Engineering DOI Creative Commons
Tomasz Górnicki, Jakub Lambrinow, Afsaneh Golkar‐Narenji

et al.

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(6), P. 531 - 531

Published: March 16, 2024

Biomimetic scaffolds imitate native tissue and can take a multidimensional form. They are biocompatible influence cellular metabolism, making them attractive bioengineering platforms. The use of biomimetic adds complexity to traditional cell cultivation methods. most commonly used technique involves cultivating cells on flat surface in two-dimensional format due its simplicity. A three-dimensional (3D) provide microenvironment for surrounding cells. There two main techniques obtaining 3D structures based the presence scaffolding. Scaffold-free consist spheroid technologies. Meanwhile, scaffold contain organoids all constructs that various types scaffolds, ranging from decellularized extracellular matrix (dECM) through hydrogels one extensively studied forms potential culture up 4D bioprinted biomaterials. bioprinting is important create scaffolds. versatility this allows many different inks, mainly hydrogels, as well inorganic substances. Increasing amounts data evidence vast usage engineering personalized medicine, with area application being regeneration skin musculoskeletal systems. Recent papers also indicate increasing vivo tests products which further strengthen importance branch emphasize need extensive research safe humansbiomimetic tissues organs. In review article, we recent advancements field preceded by an overview technologies led development complex type culture.

Language: Английский

Citations

20
Cellular and Engineered Organoids for Cardiovascular Models DOI Open Access
Dilip Thomas, Suji Choi, Christina Alamana

et al.

Circulation Research, Journal Year: 2022, Volume and Issue: 130(12), P. 1780 - 1802

Published: June 9, 2022

An ensemble of in vitro cardiac tissue models has been developed over the past several decades to aid our understanding complex cardiovascular disorders using a reductionist approach. These approaches often rely on recapitulating single or multiple clinically relevant end points dish indicative pathophysiology. The possibility generate disease-relevant and patient-specific human induced pluripotent stem cells further leveraged utility as screening tools at large scale. To elucidate biological mechanisms models, it is critical integrate physiological cues form biochemical, biophysical, electromechanical stimuli achieve desired tissue-like maturity for robust phenotyping. Here, we review latest advances directed cell differentiation derive wide gamut types, allow customization model systems, study diseased states types. We also highlight recent progress development such organoids, microtissues, engineered heart tissues, microphysiological systems. expand discussion defining context use selection currently available models. Last, discuss limitations challenges with current state-of-the-art future directions.

Language: Английский

Citations

51
Tissue-embedded stretchable nanoelectronics reveal endothelial cell–mediated electrical maturation of human 3D cardiac microtissues DOI Creative Commons
Zuwan Lin, Jessica C. Garbern, Ren Liu

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(10)

Published: March 8, 2023

Clinical translation of stem cell therapies for heart disease requires electrical integration transplanted cardiomyocytes. Generation electrically matured human induced pluripotent cell-derived cardiomyocytes (hiPSC-CMs) is critical integration. Here, we found that hiPSC-derived endothelial cells (hiPSC-ECs) promoted the expression selected maturation markers in hiPSC-CMs. Using tissue-embedded stretchable mesh nanoelectronics, achieved a long-term stable map three-dimensional (3D) cardiac microtissue activity. The results revealed hiPSC-ECs accelerated hiPSC-CMs 3D microtissues. Machine learning-based pseudotime trajectory inference cardiomyocyte signals further phenotypic transition path during development. Guided by recording data, single-cell RNA sequencing identified subpopulations with more mature phenotype, and multiple ligand-receptor interactions were up-regulated between hiPSC-CMs, revealing coordinated multifactorial mechanism hiPSC-CM maturation. Collectively, these findings show drive via intercellular pathways.

Language: Английский

Citations

23
Complications and comorbidities associated with antineoplastic chemotherapy: Rethinking drug design and delivery for anticancer therapy DOI Creative Commons

Xiaoman Mao,

Shuang Wu, Dandan Huang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(7), P. 2901 - 2926

Published: March 11, 2024

Despite the considerable advancements in chemotherapy as a cornerstone modality cancer treatment, prevalence of complications and pre-existing diseases is on rise among patients along with prolonged survival aging population. The relationships between these disorders are intricate, bearing significant influence quality life individuals presenting challenges for prognosis outcomes malignancies. Herein, we review prevailing comorbidities that often accompany summarize lessons to learn from inadequate research management this scenario, an emphasis possible strategies reducing potential alleviating comorbidities, well overview current preclinical models practical advice establishing bio-faithful such complex context.

Language: Английский

Citations

9
Consequences of ionizing radiation exposure to the cardiovascular system DOI
James W.S. Jahng, Mark P. Little, H.J. No

et al.

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: 21(12), P. 880 - 898

Published: July 10, 2024

Language: Английский

Citations

8
Organoid, organ-on-a-chip and traditional Chinese medicine DOI Creative Commons
Jiayue Yang, Yu Jiang, Mingxing Li

et al.

Chinese Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 12, 2025

Abstract In the past few years, emergence of organoids and organ-on-a-chip (OOAC) technologies, which are complementary to animal models two-dimensional cell culture methods can better simulate internal environment human body, provides a new platform for traditional Chinese medicine (TCM) studies. Organoids OOAC techniques have been increasingly applied in fields drug screening, assessment development, personalized therapies, developmental biology, there some application cases TCM this review, we summarized current status using organoid technologies research provide key insights future study. It is believed that will play more important roles make greater contributions innovative development TCM.

Language: Английский

Citations

1