Differentiation of Intrafusal Fibers from Human Induced Pluripotent Stem Cells

ACS Chem Neurosci. 2020 Apr 1;11(7):1085-1092. doi: 10.1021/acschemneuro.0c00055. Epub 2020 Mar 19.


Human-based "body-on-a-chip" technology provides powerful platforms in developing models for drug evaluation and disease evaluations in phenotypic models. Induced pluripotent stem cells (iPSCs) are ideal cell sources for generating different cell types for these in vitro functional systems and recapitulation of the neuromuscular reflex arc would allow for the study of patient specific neuromuscular diseases. Regarding relevant afferent (intrafusal fibers, sensory neurons) and efferent (extrafusal fibers, motoneurons) cells, in vitro differentiation of intrafusal fiber from human iPSCs has not been established. This work demonstrates a protocol for inducing an enrichment of intrafusal bag fibers from iPSCs using morphological analysis and immunocytochemistry. Phosphorylation of the ErbB2 receptors and S46 staining indicated a 3-fold increase of total intrafusal fibers further confirming the efficiency of the protocol. Integration of induced intrafusal fibers would enable more accurate reflex arc models and application of this protocol on patient iPSCs would allow for patient-specific disease modeling.

Keywords: Intrafusal fibers; induced pluripotent stem cells; muscle spindle; neuregulin; neuromuscular reflex arc.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Differentiation / physiology*
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Motor Neurons / cytology*
  • Muscle Spindles / cytology
  • Muscle, Skeletal / cytology
  • Sensory Receptor Cells / cytology*