Multiparametric slice culture platform for the investigation of human cardiac tissue physiology

Qiao, Yun; Dong, Quan; Li, Baichen; Obaid, Sofian N.; Miccile, Christian; Yin, Rose T.; Talapatra, Trisha; Lin, Zexu; Li, Sihui; Li, Zhenyu; Efimov, Igor R.

doi:10.1016/j.pbiomolbio.2018.06.001

Cited by 30 publications

(27 citation statements)

References 42 publications

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“…Therefore, we tested the effect of mimicking the biological conditions in the heart. First, similar to recent studies [13][14][15] we provided continuous electrical stimulation to pig heart slices at the physiological rate (1.2 Hz) ( Figure 1E-G). To provide adequate oxygen supply to the slices, the medium was changed every 8 hours with oxygenated medium.…”

Section: Development and Optimization Of A Biomimetic Culture System mentioning

confidence: 70%

“…14 Three recent studies have demonstrated the importance of continuous electromechanical stimulation in maintaining slices in culture [13][14][15] . However, all of these studies used the basal M199/ITS medium, which is not sufficient to maintain the metabolic needs of heart slices.…”

Section: F O R C I R C U L a T I O N R E S E A R C H P E E R R E V I mentioning

confidence: 99%

“…However, all of these studies used the basal M199/ITS medium, which is not sufficient to maintain the metabolic needs of heart slices. This led to several compromises in the slice contractility and calcium homeostasis early during culture [13][14][15] . Qiao et al, 13 have shown that using a highly sophisticated bioengineering chips, they can maintain the electrophysiological properties of the heart slices for 4 days, but no assessment of the contractile function was provided.…”

Section: F O R C I R C U L a T I O N R E S E A R C H P E E R R E V I mentioning

confidence: 99%

“…This led to several compromises in the slice contractility and calcium homeostasis early during culture [13][14][15] . Qiao et al, 13 have shown that using a highly sophisticated bioengineering chips, they can maintain the electrophysiological properties of the heart slices for 4 days, but no assessment of the contractile function was provided. Fischer et al, 14 Our rigorous assessments show that our biomimetic stimulated culture system maintains viability and functionality of human and pig heart slices for 6 days of culture.…”

Section: F O R C I R C U L a T I O N R E S E A R C H P E E R R E V I mentioning

confidence: 99%

“…This culture system has been used by others to culture heart slices for up to 24 hours [10][11][12] . Three recent studies have shown that electromechanical stimulation is paramount for maintaining heart slices in culture [13][14][15] .…”

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confidence: 99%

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Physiological Biomimetic Culture System for Pig and Human Heart Slices

Jacobson²,

Abouleisa

et al. 2019

Circulation Research

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Rationale: Preclinical testing of cardiotoxicity and efficacy of novel heart failure therapies faces a major limitation: the lack of an in situ culture system that emulates the complexity of human heart tissue and maintains viability and functionality for a prolonged time. Objective: To develop a reliable, easily reproducible, medium-throughput method to culture pig and human heart slices under physiological conditions for a prolonged period of time. Methods and Results: Here, we describe a novel, medium-throughput biomimetic culture system that maintains viability and functionality of human and pig heart slices (300 µm thickness) for 6 days in culture. We optimized the medium and culture conditions with continuous electrical stimulation at 1.2 Hz and oxygenation of the medium. Functional viability of these slices over 6 days was confirmed by assessing their calcium homeostasis, twitch force generation, and response to -adrenergic stimulation. Temporal transcriptome analysis using RNAseq at day 2, 6, and 10 in culture confirmed overall maintenance of normal gene expression for up to 6 days, while over 500 transcripts were differentially regulated after 10 days. Electron microscopy demonstrated intact mitochondria and Z-disc ultra-structures after 6 days in culture under our optimized conditions. This biomimetic culture system was successful in keeping human heart slices completely viable and functionally and structurally intact for 6 days in culture. We also used this system to demonstrate the effects of a novel gene therapy approach in human heart slices. Furthermore, this culture system enabled the assessment of contraction and relaxation kinetics on isolated single myofibrils from heart slices after culture. Conclusions: We have developed and optimized a reliable medium-throughput culture system for pig and human heart slices as a platform for testing the efficacy of novel heart failure therapeutics and reliable testing of cardiotoxicity in a 3D heart model.

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Section: Development and Optimization Of A Biomimetic Culture System mentioning

confidence: 70%

Section: F O R C I R C U L a T I O N R E S E A R C H P E E R R E V I mentioning

confidence: 99%

Section: F O R C I R C U L a T I O N R E S E A R C H P E E R R E V I mentioning

confidence: 99%

Section: F O R C I R C U L a T I O N R E S E A R C H P E E R R E V I mentioning

confidence: 99%

mentioning

confidence: 99%

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Physiological Biomimetic Culture System for Pig and Human Heart Slices

Jacobson²,

Abouleisa

et al. 2019

Circulation Research

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Advancing Intelligent Organ‐on‐a‐Chip Systems with Comprehensive In Situ Bioanalysis

Li,

Zhu,

et al. 2024

Advanced Materials

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In vitro biological models are essential to a broad range of biomedical research, including drug development, pathological studies, and personalized medicine. As a potentially transformative paradigm of in vitro 3D biological models, organs‐on‐a‐chip (OOC) devices have been extensively developed to recapitulate sophisticated architectures and dynamic microenvironments of organs by applying the principles of life sciences and leveraging micro‐ and nanoscale engineering capabilities. A pivotal function of OOC devices is to support multifaceted and timely analysis of living tissues and their microenvironments. However, in‐depth analysis of OOC models typically requires biomedical assay procedures that are labor‐intensive and interruptive. This article examines the latest advances toward intelligent OOC (iOOC) systems where sensors integrated with OOC devices continuously report cellular and microenvironmental information for comprehensive in situ bioanalysis. It is envisioned that the multimodal data in iOOC systems can support closed‐loop control of iOOC models and offer holistic biomedical insights for diverse applications. Essential techniques for establishing iOOC systems are surveyed, encompassing in situ sensing, data processing, and dynamic modulation. Eventually, the future development of iOOC systems featuring cross‐disciplinary strategies is discussed.This article is protected by copyright. All rights reserved

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Cryopreservation of Human Adult Ventricular Tissue for the Preparation of Viable Myocardial Slices

Lodrini,

Groeneveld,

Palmen

et al. 2024

Current Protocols

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Living myocardial slices (LMS) are ultrathin sections of adult myocardium that can be maintained in culture. These slices provide a unique platform for studying interactions between cardiomyocytes (CMs), other cardiac cell types, and the extracellular matrix while maintaining the cytoarchitecture and electrical phenotype of CMs over extended periods. Despite their advantages over other cardiac models, LMS have limitations, particularly their reliance on slice quality. The primary factor influencing the quality of the slices is the method used to process the cardiac tissue block. Current methods typically require immediate slice preparation following the excision of the tissue block, which restricts the timing of experiments. To address this limitation, we developed a simple procedure for cryopreserving human adult myocardium, allowing the preparation of LMS at a later stage. The protocol provides a list of required equipment and reagents, as well as a detailed description of the methodology for processing the myocardium and slice preparation. We present typical results demonstrating that cryopreserved human cardiac tissue retains biomass and structural integrity comparable to freshly obtained myocardium. Furthermore, we assessed the LMS derived from both fresh and cryopreserved samples. Histological analysis confirmed the preservation of viability, normal cytomorphology, and gap junctions between CMs in all LMS after 24 h and up to 5 days of culture in the absence of electrical stimulation. Cryopreservation extends the interval between tissue collection and LMS preparation, facilitating longer‐term and more complex experiments. Further research into the impact of cryopreservation on various cardiac cell types will promote better donor organ management and efficient banking of cardiac samples from a multitude of donors and disease states. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Preparation and preservation of human adult myocardiumBasic Protocol 2: Preparation of adult living myocardial slices from cryopreserved blocks

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Multiparametric slice culture platform for the investigation of human cardiac tissue physiology

Cited by 30 publications

References 42 publications

Physiological Biomimetic Culture System for Pig and Human Heart Slices

Physiological Biomimetic Culture System for Pig and Human Heart Slices

Advancing Intelligent Organ‐on‐a‐Chip Systems with Comprehensive In Situ Bioanalysis

Cryopreservation of Human Adult Ventricular Tissue for the Preparation of Viable Myocardial Slices

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