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@article{Ou:2019:10.1161/CIRCRESAHA.119.314996,
author = {Ou, Q and Jacobson, Z and Abouleisa, R and Tang, X-L and Hindi, S and Kumar, A and Ivey, KN and Giridharan, GA and Al-Baz, A and Brittian, K and Rood, B and Lin, Y-H and Watson, SA and Perbellini, F and McKinsey, TA and Hill, BG and Jones, SP and Terracciano, CM and Bolli, R and Mohamed, TM},
doi = {10.1161/CIRCRESAHA.119.314996},
journal = {Circulation Research},
pages = {628--642},
title = {Physiological Biomimetic Culture System for Pig and Human Heart Slices},
url = {http://dx.doi.org/10.1161/CIRCRESAHA.119.314996},
volume = {125},
year = {2019}
}

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TY  - JOUR
AB  - 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 β-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
AU  - Ou,Q
AU  - Jacobson,Z
AU  - Abouleisa,R
AU  - Tang,X-L
AU  - Hindi,S
AU  - Kumar,A
AU  - Ivey,KN
AU  - Giridharan,GA
AU  - Al-Baz,A
AU  - Brittian,K
AU  - Rood,B
AU  - Lin,Y-H
AU  - Watson,SA
AU  - Perbellini,F
AU  - McKinsey,TA
AU  - Hill,BG
AU  - Jones,SP
AU  - Terracciano,CM
AU  - Bolli,R
AU  - Mohamed,TM
DO  - 10.1161/CIRCRESAHA.119.314996
EP  - 642
PY  - 2019///
SN  - 0009-7330
SP  - 628
TI  - Physiological Biomimetic Culture System for Pig and Human Heart Slices
T2  - Circulation Research
UR  - http://dx.doi.org/10.1161/CIRCRESAHA.119.314996
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31310161
UR  - https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.119.314996
UR  - http://hdl.handle.net/10044/1/71962
VL  - 125
ER  -

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