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In vitro evidence that platelet-rich plasma stimulates cellular processes involved in endometrial regeneration

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The study aims to test the hypothesis that platelet-rich plasma (PRP) stimulates cellular processes involved in endometrial regeneration relevant to clinical management of poor endometrial growth or intrauterine scarring.

Methods

Human endometrial stromal fibroblasts (eSF), endometrial mesenchymal stem cells (eMSC), bone marrow-derived mesenchymal stem cells (BM-MSC), and Ishikawa endometrial adenocarcinoma cells (IC) were cultured with/without 5% activated (a) PRP, non-activated (na) PRP, aPPP (platelet-poor-plasma), and naPPP. Treatment effects were evaluated with cell proliferation (WST-1), wound healing, and chemotaxis Transwell migration assays. Mesenchymal-to-epithelial transition (MET) was evaluated by cytokeratin and vimentin expression. Differential gene expression of various markers was analyzed by multiplex Q-PCR.

Results

Activated PRP enhanced migration of all cell types, compared to naPRP, aPPP, naPPP, and vehicle controls, in a time-dependent manner (p < 0.05). The WST-1 assay showed increased stromal and mesenchymal cell proliferation by aPRP vs. naPRP, aPPP, and naPPP (p < 0.05), while IC proliferation was enhanced by aPRP and aPPP (p < 0.05). There was no evidence of MET. Expressions of MMP1, MMP3, MMP7, and MMP26 were increased by aPRP (p < 0.05) in eMSC and eSF. Transcripts for inflammation markers/chemokines were upregulated by aPRP vs. aPPP (p < 0.05) in eMSC and eSF. No difference in estrogen or progesterone receptor mRNAs was observed.

Conclusions

This is the first study evaluating the effect of PRP on different human endometrial cells involved in tissue regeneration. These data provide an initial ex vivo proof of principle for autologous PRP to promote endometrial regeneration in clinical situations with compromised endometrial growth and scarring.

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Acknowledgments

We thank Dr. Joshua Robinson, PhD (UCSF), for his help with time-lapse microscopy.

Financial support

Funding was provided by IntegraMed Fertility 2016 Research Grant (LA), NIH NCTRI P50HD055764 (LCG).

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Authors and Affiliations

  1. Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, and Center for Reproductive Health, University of California San Francisco, 550 16th Street, 7th Floor, Box 0132, San Francisco, CA, 94158, USA

    Lusine Aghajanova, Sahar Houshdaran, Shaina Balayan, Evelina Manvelyan, Juan C. Irwin, Heather G. Huddleston & Linda C. Giudice

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  1. Lusine Aghajanova
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  2. Sahar Houshdaran
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Correspondence to Lusine Aghajanova.

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Electronic supplementary material

Supplemental Figure 1

Wound-healing assays for endometrial stromal fibroblasts (eSF, A), endometrial mesenchymal stem cells (eMSC, B), bone marrow-derived mesenchymal stem cells (BM-MSC, C) and Ishikawa cells (D). Representative images were obtained at 100× magnification. Images show the relative migration distance after incubation at different time points. aPRP = activated platelet rich plasma, naPRP = non-activated platelet rich plasma, aPPP = activated platelet poor plasma, naPPP = non-activated platelet poor plasma. (PDF 3982 kb)

Supplemental Figure 2

Transwell migration assays for endometrial stromal fibroblasts (eSF, A), endometrial mesenchymal stem cells (eMSC, B), bone marrow-derived mesenchymal stem cells (BM-MSC, C) and Ishikawa cells (D) at different time points. Representative images were obtained at 200× magnification. aPRP = activated platelet rich plasma, naPRP = non-activated platelet rich plasma, aPPP = activated platelet poor plasma, naPPP = non-activated platelet poor plasma. (PDF 2600 kb)

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Aghajanova, L., Houshdaran, S., Balayan, S. et al. In vitro evidence that platelet-rich plasma stimulates cellular processes involved in endometrial regeneration. J Assist Reprod Genet 35, 757–770 (2018). https://doi.org/10.1007/s10815-018-1130-8

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  • DOI: https://doi.org/10.1007/s10815-018-1130-8

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