REPRODUCTIVE PHYSIOLOGY AND DISEASE
In vitro evidence that platelet-rich plasma stimulates cellular processes
involved in endometrial regeneration
Juan C. Irwin
Heather G. Huddleston
Linda C. Giudice
Received: 30 November 2017 /Accepted: 23 January 2018 /Published online: 5 February 2018
Springer Science+Business Media, LLC, part of Springer Nature 2018
Purpose The study aims to test the hypothesis that platelet-rich plasma (PRP) stimulates cellular processes involved in endome-
trial 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 regen-
eration. 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.
Keywords Platelet-rich plasma
About 13% of couples worldwide have infertility dueto
several factors, including impaired embryo quality and endo-
metrial receptivity. The latter can be affected by altered pro-
grammed responsiveness to steroid hormones [2, 3], a non-
lactobacillus dominant endometrial microbiome , or struc-
turally due to uterine anomalies, scarring and intrauterine ad-
hesions (Asherman’s syndrome (AS)), or an unexplained thin
lining. Endometrial thickness is commonly used as a clinical
marker of endometrial receptivity and a prognostic factor for
pregnancy outcome after embryo transfer . An endometrial
thickness <7–8 mm at the end of the follicular phase is asso-
ciated with reduced pregnancy rates [6, 7], poor pregnancy
outcomes , and may result in a cycle cancelation .
Unexplained thin endometrium and AS are among the most
challenging obstacles in fertility care, often resulting in pa-
tients pursuing gestational surrogacy .
The main complications of Asherman’s syndrome are in-
fertility (43%), impairment of menstrual flow (62%), and ab-
normal placentation if pregnancy is achieved , with sur-
gery (hysteroscopy) with or without oral estrogens being the
standard treatment .
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s10815-018-1130-8) contains supplementary
material, which is available to authorized users.
* Lusine Aghajanova
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
Journal of Assisted Reproduction and Genetics (2018) 35:757–770