Mesenchymal Stem Cells from Cervix and Age: New Insights into CIN Regression Rate.

Monia Orciani,Roberto Di Primio,Miriam Caffarini,Andrea Ciavattini,Giovanni Delli Carpini,Raffaella Lazzarini,Dimitrios Tsiroglou

doi:10.1155/2018/1545784

Abstract

Cervical intraepithelial neoplasia (CIN) is a precancerous lesion of the uterine cervix that can regress or progress to cervical cancer; interestingly, it has been noted that young women generally seem to have higher rates of spontaneous regression and remission, suggesting a correlation between the patient's age and regression/progression rates of CIN. Even if the underlying mechanisms are still unclear, inflammation seems to play a pivotal role in CIN fate and inflammatory processes are often driven by mesenchymal stem cells (MSCs). This study was aimed at evaluating if age affects the behavior of MSCs from the cervix (C-MSCs) that in turn may modulate inflammation and, finally, regression rate. Fourteen samples of the human cervix were recovered from two groups of patients, “young” (mean age 28 ± 2) and “old” (mean age 45 ± 3), during treatment using the loop electrosurgical excision procedure (LEEP) technique. Progenitor cells were isolated, deeply characterized, and divided into young (yC-MSCs) and old cervixes (oC-MSCs); the senescence, expression/secretion of selected cytokines related to inflammation, and the effects of indirect cocultures with HeLa cells were analyzed. Our results show that isolated cells satisfy the fixed criteria for stemness and display age-related properties; yC-MSCs express a higher level of cytokines related to acute inflammation than oC-MSCs. Finally, in the crosstalk with HeLa cells, MSCs derived from the cervixes of young patients play a stronger antitumoral role than oC-MSCs. In conclusion, the immunobiology of MSCs derived from the cervix is affected by the age of donors and this can correlate with the regression rate of CIN by influencing their paracrine effect. In addition, MSCs from a young cervix drives an antitumoral effect by sustaining an acute inflammatory environment.

Highlights

High-grade cervical intraepithelial neoplasia (CIN2–3) is a precancerous lesion of the uterine cervix with an incidence of 250,000–1 million annually in the USA
It was possible to isolate an undifferentiated cellular population able to satisfy all the minimal yC-MSCs oC-MSCs (a) criteria to qualify as mesenchymal stem cells
Cells isolated from young cervixes were named yC-MSCs and those from old cervixes oC-MSCs

Summary

Introduction

High-grade cervical intraepithelial neoplasia (CIN2–3) is a precancerous lesion of the uterine cervix with an incidence of 250,000–1 million annually in the USA. High-grade CIN are typically treated with cervical excision; since this procedure may correlate with an increased risk for prematurity and adverse pregnancy outcomes [2,3,4], each patient needs an individual evaluation, especially in the case of young women with a desire for future pregnancy, with a careful selection of patients who can be treated surgically and those who can be managed conservatively, as well as with the consideration of the possibility of a regression of the lesions [5]. Several researches [1, 6, 7] have evaluated the possible correlation between a patient’s age and regression/progression rates of CIN, finding that younger women generally seem to have higher rates of spontaneous regression and remission. The hypothesis of an involvement of inflammation in CIN progression is enforced by studies aimed at evaluating the use of anti-inflammatory drugs in the treatment of CIN [9]

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