key: cord-0299654-7z07eqr1
authors: Perez-Bermejo, Juan A.; Reisman, Samuel J.; Ma, Joyce; Cerrito, Chris; Conklin, Bruce R.; Yu, Kristina
title: Synchronization of iPS-derived cardiomyocytes to visitor heartbeat in an interactive museum exhibit
date: 2021-04-19
journal: bioRxiv
DOI: 10.1101/2021.04.19.440451
sha: ab67d47686482ae24a406e3a3c208c19a682b4c5
doc_id: 299654
cord_uid: 7z07eqr1

Science museums play an important role in science education, both engaging the public with science concepts and building support for scientific research. Designing museum exhibits to meet increasing public interests in the life sciences is particularly important, yet remains challenging. In this report we describe Give Heart Cells a Beat, a permanent interactive science exhibit that allows museum visitors to synchronize the beating of live stem cell-derived cardiomyocytes to their own heart rate in real-time. Evaluation with museum visitors reveals that the exhibit engaged the public with the specimen and prompted curiosity in heart biology and, to a lesser degree, stem cells and electrophysiology. Give Heart Cells a Beat is the product of a close collaboration between a museum and a research laboratory, and, to our knowledge, the first example of the use of live human heart cells in an interactive exhibit. We hope this exhibit will serve as an example for the implementation of stem cell technology in the field of informal science education and encourage others to pursue close working relationships between academia and public science venues such as museums.

Important cell biology advances, such as the development of stem cell 31 technologies, have led to breakthroughs in basic and translational biology 1 and are 32 increasingly relevant to public life 2-5 . This scientific and societal prominence has created 33 an opportunity for scientists and educators to bring these technologies to the public in an 34 engaging and relatable way, and to use them to create new types of educational 35 experiences. Museums and science centers are key components of the science 36 education landscape 6-8 , and provide rich opportunities for reaching a wide and diverse 37 audience 6 . In addition, there is a growing appreciation for interactive museum exhibits 6,9-38 11 and the use of real living samples, rather than recordings or simulations 11 , to promote 39 visitors' interest, engagement and understanding of the content. However, the 40 development of interactive biology exhibits featuring live human cells has been 41 significantly limited by cost and availability of reagents, capabilities needed for museums 42 to maintain and display cell lines, and lack of mechanisms that let visitors interact with 43 microscopic specimens. As a result, human cell biology at science museums has 44 traditionally been limited to non-interactive models, fixed samples, or simulations. 45 Academic research laboratories have been called on to expand their involvement in 46 science education 12 and represent a promising partner in overcoming these challenges 13 . 47

Here we report our development and assessment of Give Heart Cells a Beat 48 (GHCB), an exhibit that allows visitors to interact with living human induced pluripotent 49 stem (iPS) cell-derived cardiomyocytes (iPS-CMs) by synchronizing the beating of the 50 cells to their own heart rate. Created via a close and continuing partnership between an 51 academic laboratory and a science museum, GHCB employs human stem cell-derived 52 tissue and demonstrates that stem cell technology can be used to create innovative 53 educational experiences engaging to museum visitors. The exhibit was available to 54 visitors in its current form from January to March 2020 at the Exploratorium, an interactive 55 museum of science, art and human perception in San Francisco. Although the 56 Exploratorium temporarily closed in March of 2020 due to the COVID-19 pandemic, the 3 conducted visitor evaluation to gauge visitor interest and understanding and assess if the 59 GHCB exhibit prompted visitors to think further about important scientific topics. 60

Results and Discussion 61 We designed Give Heart Cells a Beat (GHCB) as a way to allow museum visitors 62 to interact dynamically with cells in culture, (Fig 1a- handlebar, the electrode synchronizes the beating of the cells in culture to their heart rate 67 in real-time. A live feed from the microscope is projected on a large screen for the visitors 68 to observe, and an interpretive text overlay encourages them to interact dynamically, for 69 instance by performing activities that increase or lower their heart rate (Supplementary 70 Table 1 ). The microscope, with cells in an environmental control chamber, is inside the 71 museum's laboratory facility. It is visible through a large glass window to help visitors 72 appreciate the scale and authenticity of the specimen 14 (Supplementary Figure 2c) . 73

To test the functioning principle of GHCB, we asked a set of volunteers to interact 75 with the exhibit before and after performing a short exercise routine. In all cases, we were 76 able to observe a significant increase in the displayed beat rate after exercise ( Figure 1c) . 77

In addition, we observed a near perfect correlation between the actual heart rate of users 78 and the beat rate of the cells in the projected video ( Figure 1d ). This allowed us to 79 conclude that GHCB accurately and sensitively synchronizes the beat rate of iPS-CMs to 80 the heart rate of the user in real time. 

To assess visitors' reactions to GHCB, we observed unprompted museum visitors 97 as they interacted with the exhibit, then approached and interviewed a subset of those 98 visitors (for detailed results and discussion, see Supplementary Information 2). The technology behind the exhibit (e.g., "how did they do that? How much electricity can you 112 use?"), and 20% talked about stem cells (e.g., "I was just interested in the fact that they 113 were able to recreate human heart cells with stem cells"). Taken together, these findings 114 suggest that GHCB provided an engaging, relatable experience and sparked thought 115 about the heart and, to a lesser extent, advanced biology concepts such as stem cells or 116 electrophysiology. In this study we have reported the development of Give Heart Cells a Beat, the 166 first science museum exhibit to allow dynamic, real-time interaction between museum 167 visitors and cultured human stem-cell derived cells. Our evaluation study with visitors 168 highlights the importance of interactive design to foster engagement with biology content, 169

and also suggests that the use of heart cells provides a relatable hook for visitors that hours after plating (day 0). Media was changed to RPMI/B27 without insulin a day later, 208 and then RPMI/B27 (without insulin) containing 5 μM IWP2 (Tocris). After another 48 209 hours, the media was changed to RPMI/B27 containing insulin. Fresh RPMI/B27 was CryoStor media (BioLife Solutions). Cells were stored in Liquid Nitrogen tanks until 213 transferred to museum facilities for thawing. 214

Frozen vials of differentiated cells were transferred from the Gladstone Institutes to the 216 Exploratorium on dry ice. Cells were thawed in 6-well plates and, if they had not been 217 purified, cardiomyocytes were enriched using a metabolic selection method 20 . Briefly, 218 three days after plating, media was replaced with DMEM without glucose (Gibco) 219 supplemented with 4mM lactate (Sigma). Lactate media was exchanged every other day 220 to a total of 3 times. Cells were then maintained in RPMI/B27 with 0.5% Penicillin- annotated and classified. The term "cells-unspecified" refers to answers that 248 acknowledged seeing cells without any other descriptor, while "other" was used for 249 answers that didn't fit in previous categories ("an image", "blood", or simply "weird stuff"). 250

Data for Likert scores and key terms was plotted using R (version 3.5.3). 

Induced pluripotent stem cell technology: a decade of 293 progress

Communicating Risks and Benefits About Ethically 295

Controversial Topics: the Case of Induced Pluripotent Stem (iPS) Cells

The impact of commercialisation on public perceptions 298 of stem cell research: exploring differences across the use of induced pluripotent cells, 299 human and animal embryos

Translation of Human-Induced Pluripotent Stem Cells

From Dish to Bedside: Lessons 304

Learned While Translating Findings from a Stem Cell Model of Disease to a Clinical Trial

Learning Science in Informal Environments: People, Places, and Pursuits

Informal STEM education: resources for outreach, 309 engagement and broader impacts

Prepare and Inspire

Impact of interactive technologies on stimulating learning experiences in a 313 museum

Interactives and Visitor Learning

Designs for learning: Studying science museum exhibits that do more than 317 entertain

Finding the key -cell biology and science education

A guide to building partnerships between science museums and university-based 321 research centers

First-hand, immersive full-body experiences with living cells 323 through interactive museum exhibits

Planning for People in Museum Exhibitions. Association of Science-Technology 326 Centers

Interconnections: The IMLS national study on the use 328 of libraries, museums and the Internet

Americans' knowledge of climate change

SARS-CoV-2 Infection of Human IPSC-332

Derived Cardiac Cells Predicts Novel Cytopathic Features in Hearts of COVID-19 Patients

A BAG3 chaperone complex maintains 335 cardiomyocyte function during proteotoxic stress

Purification of Mouse and Human Pluripotent Stem Cell-Derived Cardiomyocytes

Methods for in vitro functional analysis of 341 iPSC derived cardiomyocytes -Special focus on analyzing the mechanical beating 342 behavior

A non-invasive platform for functional 345 characterization of stem-cell-derived cardiomyocytes with applications in cardiotoxicity 346 testing

Before Exercise After

Exhibit Keep in incubator Rotation system Transport to the Museum

Cardiomyocyte production from stem cells (15d)Liquid nitrogen storage