Conductive Microfibers Improve Stem Cell-Derived Cardiac Spheroid Maturation
Gisselle Gonzalez
Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, California, USA
Search for more papers by this authorThomas G. Molley
Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, California, USA
Search for more papers by this authorErin LaMontagne
Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, California, USA
Search for more papers by this authorAlis Balayan
Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA
Search for more papers by this authorAlyssa R. Holman
Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA
Search for more papers by this authorCorresponding Author
Adam J. Engler
Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, California, USA
Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA
Sanford Consortium for Regenerative Medicine, La Jolla, California, USA
Correspondence:
Adam J. Engler ([email protected])
Search for more papers by this authorGisselle Gonzalez
Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, California, USA
Search for more papers by this authorThomas G. Molley
Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, California, USA
Search for more papers by this authorErin LaMontagne
Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, California, USA
Search for more papers by this authorAlis Balayan
Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA
Search for more papers by this authorAlyssa R. Holman
Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA
Search for more papers by this authorCorresponding Author
Adam J. Engler
Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, California, USA
Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA
Sanford Consortium for Regenerative Medicine, La Jolla, California, USA
Correspondence:
Adam J. Engler ([email protected])
Search for more papers by this authorFunding: This work was supported by National Institutes of Health; California Institute for Regenerative Medicine; National Science Foundation.
ABSTRACT
Conventional two-dimensional (2D) cardiomyocyte differentiation protocols create cells with limited maturity, which impairs their predictive capacity and has driven interest in three-dimensional (3D) engineered cardiac tissue models of varying maturity and scalability. Cardiac spheroids are attractive high-throughput models that have demonstrated improved functional and transcriptional maturity over conventional 2D differentiations. However, these 3D models still tend to have limited contractile and electrical maturity compared to highly engineered cardiac tissues; hence, we incorporated a library of conductive polymer microfibers in cardiac spheroids to determine if fiber properties could accelerate maturation. Conductive microfibers improved contractility parameters of cardiac spheroids over time versus nonconductive fibers, specifically, when they were short, for example, 5 μm, and when there was moderate fiber mass per spheroid, for example, 20 μg. Spheroids with optimal conductive microfiber length and concentration developed a thicker ring-like perimeter and a less compacted cavity, improving their contractile work compared to control cardiac spheroids. Functional improvements correlated with increased expression of contractility and calcium handling-related cardiac proteins, as well as improved calcium handling abilities and drug response. Taken together, these data suggest that conductive microfibers can improve cardiac spheroid performance to improve cardiac disease modeling.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
Filename | Description |
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jbma37856-sup-0001-Supinfo.docxWord 2007 document , 658.5 KB |
Data S1. |
jbma37856-sup-0002-MovieS1.aviAVI video, 32 MB |
Movie S1. Calcium flux movie for 3D fiber-free control. Representative movie of Fluo-4 AM stained cardiac spheroid over 30 s. Intensity increases are proportional to the change in calcium concentration in cardiomyocytes. Movie intensity was adjusted for illustrative purposes, but adjustments were excluded from analysis performed in Figure 5. |
jbma37856-sup-0003-MovieS2.aviAVI video, 30.1 MB |
Movie S2. Calcium flux movie for nonconductive microfibers. Representative movie of Fluo-4 AM stained cardiac spheroid over 30 s. Intensity increases are proportional to the change in calcium concentration in cardiomyocytes. Movie intensity was adjusted for illustrative purposes, but adjustments were excluded from analysis performed in Figure 5. |
jbma37856-sup-0004-MovieS3.aviAVI video, 21.7 MB |
Movie S3. Calcium flux movie for conductive microfibers. Representative movie of Fluo-4 AM stained cardiac spheroid over 30 s. Intensity increases are proportional to the change in calcium concentration in cardiomyocytes. Movie intensity was adjusted for illustrative purposes, but adjustments were excluded from analysis performed in Figure 5. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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