Micropatterned substrates with physiological stiffness promote cell maturation and Pompe disease phenotype in human induced pluripotent stem cell-derived skeletal myocytes

Nunnapas Jiwlawat, Eileen M. Lynch, Brett N. Napiwocki, Alana Stempien, Randolph S. Ashton, Timothy J. Kamp, Wendy C. Crone, Masatoshi Suzuki

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Recent advances in bioengineering have enabled cell culture systems that more closely mimic the native cellular environment. Here, we demonstrated that human induced pluripotent stem cell (iPSC)-derived myogenic progenitors formed highly-aligned myotubes and contracted when seeded on two-dimensional micropatterned platforms. The differentiated cells showed clear nuclear alignment and formed elongated myotubes dependent on the width of the micropatterned lanes. Topographical cues from micropatterning and physiological substrate stiffness improved the formation of well-aligned and multinucleated myotubes similar to myofibers. These aligned myotubes exhibited spontaneous contractions specifically along the long axis of the pattern. Notably, the micropatterned platforms developed bundle-like myotubes using patient-derived iPSCs with a background of Pompe disease (glycogen storage disease type II) and even enhanced the disease phenotype as shown through the specific pathology of abnormal lysosome accumulations. A highly-aligned formation of matured myotubes holds great potential in further understanding the process of human muscle development, as well as advancing in vitro pharmacological studies for skeletal muscle diseases.

Original languageEnglish (US)
Pages (from-to)2377-2392
Number of pages16
JournalBiotechnology and bioengineering
Volume116
Issue number9
DOIs
StatePublished - 2019
Externally publishedYes

Bibliographical note

Funding Information:
The first author (N. J.) would like to thank the financial support from the Royal Thai Government Scholarship. This work was supported by grants from the ALS Association (15-IIP-201, M. S.), NIH/NINDS (R01NS091540, M. S.), the University of Wisconsin Stem Cell and Regenerative Medicine Center (M. S. and E. M. L.), and the University of Wisconsin Foundation (M. S). B. N. N., A. S., and W. C. C. were supported by the Karen Thompson Medhi Professorship, Graduate School, and Office of the Vice Chancellor for Research and Graduate Education at the University of Wisconsin-Madison. The antibodies for Pax7, myogenin (F5D), titin (9D10), and myosin heavy chain (MF20) were obtained from the DSHB developed under the NICHD and maintained by the University of Iowa.

Publisher Copyright:
© 2019 Wiley Periodicals, Inc.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

  • human induced pluripotent stem cells
  • in vitro modeling
  • micropattern
  • Pompe disease
  • skeletal myocytes
  • substrate stiffness

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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