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Differential Response to Mechanical Cues in Uterine Fibroid Versus Paired Myometrial Cells

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Abstract

Uterine leiomyomas, or fibroids, are common, benign tumors for which hysterectomy is the only definitive treatment. The extracellular matrix of fibroids is disorganized and stiffer than the surrounding myometrial tissue. To understand how stiffness affects fibroid cells, patient-matched fibroid and myometrial cells were cultured on substrates with stiffnesses varying from 0.2 to 150 kPa. Fibroid cells grew more slowly than myometrial cells overall, and only the myometrial cells altered their growth rate in response to stiffness. In both cell types, cell proliferation decreased with inhibition of PI3K and increased with inhibition of IGF-1. The cellular area was greater for the fibroid cells. The only significant effect of stiffness on the cell area was between the 0.2 and 64 kPa substrates, and this was true for both cell types. To investigate intracellular stiffness, intracellular particle tracking microrheology was used. Fibroid cells exhibited a more than 100-fold increase in elastic modulus at a frequency of 1 Hz in response to the addition of external stress, while myometrial cells showed little change in elastic modulus. Overall, the responses of both cells followed similar trends in response to stiffness and inhibitors, although the response was attenuated in the fibroid cells. The changes that were demonstrated by the change in intracellular stiffness with response to compression suggest that other mechanical forces may provide insight into differences in the two cell types.

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Data Availability

Images that support the findings of this study are openly available at scholar@UC at https://scholar.uc.edu/collections/sn00b034n. All other data is available upon request.

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Acknowledgements

We would like to thank Dr. Suruchi Thakore and Dr. Paul Lee for their assistance in obtaining the tissues used for this work.

Funding

The microrheology work was funded by a Regenerative Engineering and Medicine Research Center Seed Grant. The substrate stiffness work was funded in part by University of Cincinnati University Research Council Faculty Costs Support Award.

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Correspondence to S. C. Schutte or M. R. Dawson.

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This study was approved by the Institutional Review Boards of Emory University and the University of Cincinnati, where the surgeries were performed.

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Schutte, S.C., Ghosh, D., Moset Zupan, A. et al. Differential Response to Mechanical Cues in Uterine Fibroid Versus Paired Myometrial Cells. Reprod. Sci. 30, 3305–3314 (2023). https://doi.org/10.1007/s43032-023-01267-z

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  • DOI: https://doi.org/10.1007/s43032-023-01267-z

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