Striated muscle function, regeneration, and repair

Abstract

As the only striated muscle tissues in the body, skeletal and cardiac muscle share numerous structural and functional characteristics, while exhibiting vastly different size and regenerative potential. Healthy skeletal muscle harbors a robust regenerative response that becomes inadequate after large muscle loss or in degenerative pathologies and aging. In contrast, the mammalian heart loses its regenerative capacity shortly after birth, leaving it susceptible to permanent damage by acute injury or chronic disease. In this review, we compare and contrast the physiology and regenerative potential of native skeletal and cardiac muscles, mechanisms underlying striated muscle dysfunction, and bioengineering strategies to treat muscle disorders. We focus on different sources for cellular therapy, biomaterials to augment the endogenous regenerative response, and progress in engineering and application of mature striated muscle tissues in vitro and in vivo. Finally, we discuss the challenges and perspectives in translating muscle bioengineering strategies to clinical practice.

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Abbreviations

CM:

Cardiomyocyte

CSC:

Cardiac stem cell

CV:

Conduction velocity

CHD:

Congenital heart defect

DGC:

Dystrophin-associated glycoprotein complex

ECM:

Extracellular matrix

FAP:

Fibroadipogenic progenitors

hESC:

Human embryonic stem cell

hiPSC:

Human induced pluripotent stem cell

mESC-CM:

Mouse embryonic stem cell-derived cardiomyocyte

MHC:

Myosin heavy chain

MMP:

Matrix metalloproteinase

MSC:

Mesenchymal stem cells

NRVM:

Neonatal rat ventricular myocyte

PIC:

Pw1 interstitial cell

RyR:

Ryanodine receptor

SR:

Sarcoplasmic reticulum

SERCA:

Sarcoplasmic reticulum Ca2+ ATPase

SC:

Satellite cell

SIS:

Small intestine submucosa

T-tubule:

Transverse tubule

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Acknowledgments

This work was supported by the NIH Grants AR055226 and AR065873 from National Institute of Arthritis and Musculoskeletal and Skin Disease, NIH Grants HL104326 and HL122079 from National Heart, Lung, and Blood Institute, NIH Grant T32 GM007171-Medical Scientist Training Program, UH3TR000505 Grant from the NIH Common Fund for the Microphysiological Systems Initiative, and a Grant from the Fondation Leducq. The content of the manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

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Correspondence to N. Bursac.

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I. Y. Shadrin and A. Khodabukus equally contributing authors.

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Shadrin, I.Y., Khodabukus, A. & Bursac, N. Striated muscle function, regeneration, and repair. Cell. Mol. Life Sci. 73, 4175–4202 (2016). https://doi.org/10.1007/s00018-016-2285-z

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Keywords

  • Muscle
  • Cardiac
  • Skeletal
  • Tissue engineering
  • Stem cells
  • iPS