scholarly journals Human iPSCs and Genome Editing Technologies for Precision Cardiovascular Tissue Engineering

2021 ◽  
Vol 9 ◽  
Author(s):  
Eric K. N. Gähwiler ◽  
Sarah E. Motta ◽  
Marcy Martin ◽  
Bramasta Nugraha ◽  
Simon P. Hoerstrup ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Lines ◽  
Drug Screening ◽  
Genome Engineering ◽  
Molecular Mechanisms ◽  
Disease Modeling ◽  
Cell Types ◽  
Cardiovascular Tissue ◽  
Human Ipscs ◽  
Cardiovascular Tissue Engineering

Induced pluripotent stem cells (iPSCs) originate from the reprogramming of adult somatic cells using four Yamanaka transcription factors. Since their discovery, the stem cell (SC) field achieved significant milestones and opened several gateways in the area of disease modeling, drug discovery, and regenerative medicine. In parallel, the emergence of clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR-Cas9) revolutionized the field of genome engineering, allowing the generation of genetically modified cell lines and achieving a precise genome recombination or random insertions/deletions, usefully translated for wider applications. Cardiovascular diseases represent a constantly increasing societal concern, with limited understanding of the underlying cellular and molecular mechanisms. The ability of iPSCs to differentiate into multiple cell types combined with CRISPR-Cas9 technology could enable the systematic investigation of pathophysiological mechanisms or drug screening for potential therapeutics. Furthermore, these technologies can provide a cellular platform for cardiovascular tissue engineering (TE) approaches by modulating the expression or inhibition of targeted proteins, thereby creating the possibility to engineer new cell lines and/or fine-tune biomimetic scaffolds. This review will focus on the application of iPSCs, CRISPR-Cas9, and a combination thereof to the field of cardiovascular TE. In particular, the clinical translatability of such technologies will be discussed ranging from disease modeling to drug screening and TE applications.

scholarly journals Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting

2016 ◽  
Vol 113 (8) ◽  
pp. 2206-2211 ◽  
Author(s):  
Xuanyi Ma ◽  
Xin Qu ◽  
Wei Zhu ◽  
Yi-Shuan Li ◽  
Suli Yuan ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Drug Screening ◽  
Disease Modeling ◽  
Umbilical Vein ◽  
Cell Types ◽  
Supporting Cell ◽  
Specific Gene ◽  
3D Bioprinting

The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.

The cardiotomy reservoir – a preliminary evaluation of a new cell source for cardiovascular tissue engineering

2017 ◽  
Vol 41 (2) ◽  
pp. 115-123
Author(s):  
Sophie von Nathusius ◽  
Fabian König ◽  
Ralf Sodian ◽  
Frank Born ◽  
Christian Hagl ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Lines ◽  
Easy Access ◽  
Control Group ◽  
Positive Staining ◽  
Widespread Application ◽  
Blood Samples ◽  
Cardiovascular Tissue ◽  
Cell Source ◽  
Cardiovascular Tissue Engineering

Objectives: Cell sources for cardiovascular tissue engineering (TE) are scant. However, the need for an ideal TE cardiovascular implant persists. We investigated the cardiotomy reservoir (CR) as a potential cell source that is more accessible and less ethically problematic. Methods: CR (n = 10) were removed from the bypass system after surgery. Isolation was performed using different isolation methods: blood samples were taken from the cardiopulmonary bypass and centrifuged at low density. The venous filter screen was cut out and placed into petri dishes for cultivation. The spongelike filter was removed, washed and treated in the same way as the blood samples. After cultivation, cell lines of fibroblasts (FB) and endothelial cells (EC) were obtained for analysis. The cells were seeded on polyurethane patches and analyzed via scanning electron microscopy (SEM), Life/Dead assay and immunohistochemistry. Results: No correlation between age, time of surgery and quality of cells was observed. The successful extraction of FB and was proven by positive staining results for TE-7, CD31 and vWF. Cell morphology, cytoskeleton staining and quantification of proliferation using WST-1 assay resembled the cells of the control group in all ways. The topography of a confluent and vital cell layer after cell seeding was displayed by SEM analysis, Life/Dead Assay and immunohistochemistry. The establishment of an extracellular matrix (ECM) was proven by positive staining for collagen IV, laminin, fibronectin and elastin. Conclusions: Viable FB and EC cell lines were extracted from the CR after surgery. Easy access and high availability make this cell source destined for widespread application in cardiovascular tissue engineering.

Cryopreserved prenatal progenitor cells as cell source for cardiovascular tissue engineering

2007 ◽  
Vol 55 (S 1) ◽  
Author(s):  
D Schmidt ◽  
C Breymann ◽  
J Achermann ◽  
B Odermatt ◽  
M Genoni ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Progenitor Cells ◽  
Cardiovascular Tissue ◽  
Cell Source ◽  
Cardiovascular Tissue Engineering

scholarly journals Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery

2021 ◽  
Vol 22 (3) ◽  
pp. 1203
Author(s):  
Lu Qian ◽  
Julia TCW
Keyword(s):  
Drug Discovery ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Structural Complexity ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Central Nerve System ◽  
Human Ipscs ◽  
Nerve System

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients’ CNS and serve as a platform for therapeutic development and personalized precision medicine.

Regenerative implants for cardiovascular tissue engineering

2014 ◽  
Vol 163 (4) ◽  
pp. 321-341 ◽  
Author(s):  
Avione Y. Lee ◽  
Nathan Mahler ◽  
Cameron Best ◽  
Yong-Ung Lee ◽  
Christopher K. Breuer
Keyword(s):  
Tissue Engineering ◽  
Cardiovascular Tissue ◽  
Cardiovascular Tissue Engineering
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