First-trimester human decidua contains a population of mesenchymal stem cells

Dimitrov, Rumen; Kyurkchiev, Dobroslav; Timeva, Tanya; Yunakova, Maria; Stamenova, Maria; Shterev, A; Kyurkchiev, Stanimir

doi:10.1016/j.fertnstert.2008.09.061

Cited by 34 publications

(36 citation statements)

References 28 publications

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“…Hence, we conclude that the absence of cAMP and progesterone promotes de-differentiation of HDSC, although the presence of residual progenitor cells in isolated cultures cannot be excluded. Indeed, recent evidence suggested that first trimester decidua contains spindle-shaped, multipotent decidual stromal cells capable of differentiating into diverse cell types including PRL-producing, differentiated decidual cells [35]. …”

Section: Discussionmentioning

confidence: 99%

Evaluation of human first trimester decidual and telomerase-transformed endometrial stromal cells as model systems of in vitro decidualization

Saleh

Otti

Fiala³

et al. 2011

Reprod Biol Endocrinol

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BackgroundDecidualization, the differentiation process of maternal uterine stromal cells into secretory decidual cells, is a prerequisite for successful implantation and progression of pregnancy. For in vitro differentiation mostly primary human endometrial stromal cells (HESC) isolated from uterine samples after hysterectomy for benign gynaecological diseases are utilised. However, a continuous supply of endometrial tissue is often lacking. Hence, we analysed whether cultivated human decidual stromal cells (HDSC) prepared from first trimester pregnancy terminations may represent an alternative model system for in vitro decidualization. Moreover, based on the expression of critical marker genes these cells were compared to a previously established endometrial stromal cell line during in vitro differentiation.MethodsHDSC isolated from decidual tissue attached to first trimester placentae, and telomerase-transformed human endometrial stromal cells (THESC) were characterised by immunofluorescence and differentiated in vitro using either cyclic adenosine monophosphate (cAMP) and/or estrogen (E2)/progesterone (P4). Proliferation was measured by analyzing cumulative cell numbers. Expression of mRNAs encoding progesterone receptor (PR), prolactin (PRL), insulin-like growth factor binding protein-1 (IGFBP1), and Dickkopf-1 (DKK1) was evaluated using quantitative PCR after 3, 6, 9 and 12 days of in vitro differentiation. PRL and IGFBP-1 protein expression was investigated by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively. Furthermore, forkhead box O1A (FOXO1A), a critical transcription factor in decidualization, was analysed by immunofluorescence and Western blotting at two different time points of differentiation.ResultsTreatment with cAMP provoked morphological changes and growth arrest of THESC and HDSC, the latter showing loss of cells after 6 days of treatment. E2P4 stimulation did neither affect cell morphology nor proliferation of THESC and HDSC. Upon cAMP stimulation PR mRNA was suppressed in HDSC but not in THESC, whereas E2P4 did not alter transcript levels in both cell types. Protein expression of PR-A and PR-B was detectable in HDSC and diminished under cAMP, whereas THESC failed to produce the nuclear receptors. Supplementation of cAMP induced mRNA and protein expression of PRL and IGFBP-1 in both cell types at day 3, 6, 9, and 12 of treatment. In HDSC stimulation with E2P4 increased PRL and IGFBP-1 mRNA and protein production, whereas hormone treatment did not induce the two factors in THESC. E2P4 increased DKK1 mRNA at all time points in HDSC and cAMP provoked induction at day 9 and 12 of differentiation. In contrast, cAMP suppressed DKK1 mRNA in THESC, whereas E2P4 was ineffective. In both cell types combined treatments with cAMP and E2P4 provoked higher expression levels of PRL and IGFBP1 mRNA and protein as compared to cAMP stimulation alone. FOXO1A protein and its nuclear abundance were increased by cAMP in both cell types. However, reduction of its nuclear localisation upo...

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Section: Discussionmentioning

confidence: 99%

Evaluation of human first trimester decidual and telomerase-transformed endometrial stromal cells as model systems of in vitro decidualization

Saleh

Otti

Fiala³

et al. 2011

Reprod Biol Endocrinol

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“…This method has been used for the identification of putative somatic stem cells in several human tissues, including human endometrium [15,19,21]–[23]. There is increasing evidence of multilineage differentiation of tissue SP cells including human endometrial SP cells [15,16,24,25]. Cervello et al .…”

Section: Resultsmentioning

confidence: 99%

Vasculogenesis of decidua side population cells of first-trimester pregnancy

et al. 2013

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IntroductionSufficient uterine blood supply is essential for the fetus to develop normally in the uterus. Several mechanisms are involved in the process of vessel development in deciduas and villus. We focus on whether first-trimester decidua side population (SP) cells contain cells capable of differentiating into endothelial cells.MethodsEight decidua samples were collected from healthy women, 22- to 30-years old, undergoing elective terminations of early pregnancy (six to eight gestational weeks). The cell suspensions from human deciduas were stained by Hoechst 33342 and sorted by flow cytometry, further cultured under differentiation conditions and analyzed for specific markers. These cells were implanted into ischemic limbs of nude mice to test the capacity of angiogenesis in vivo by DiI tracers and immunohistochemistry.ResultsDecidua CD31-CD146- SP cells of first-trimester human pregnancy can differentiate into endothelial cells, express the corresponding specific markers of endothelial cells, such as CD31 and CD146, and form tube-like structures on Matrigel and part of newly formed vessels in the ischemic limbs of nude mice. Vascular endothelial growth factor was more effective in promoting proliferation of CD31-CD146-SP cells compared with other growth factors, and estrogen and progesterone at a final concentration of 10 μmol/L and 30 μmol/L, respectively, promoted the migration of CD31-CD146-SP cells in a dose-dependent manner.ConclusionsCD31-CD146- SP cells may be involved in the formation of new vessels in the maternal aspect of the placenta in the first trimester.

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“…Therefore, the presence of a network has been concluded, in which hormones, together with cytokines, regulate the expression of HLA-G by DSC, which may support maintenance of maternal-fetal tolerance. 89,163 PreD-MSC expressed higher amounts of intracellular HLA-G in the presence of progesterone compared with BM-MSC and AT-MSC. 166,167 Exposure of primary cultures of cytotrophoblasts and JEG-3 choriocarcinoma cells to progesterone led to increased HLA-G production.…”

Section: Msc and Immunogenicitymentioning

confidence: 93%

“…89 So far, multipotent stromal cells have been isolated from both the basal and the surface (functional) layer of human endometrium, from early and term decidua (transformed endometrium), and from menstrual blood. DSC at 4th-5th passage were cultured in low-serum medium containing estradiol, medroxyprogesterone acetate, and 8-bromo-cAMP.…”

Section: Decidual Stem Cells Have Immunophenotype and Differentiationmentioning

confidence: 99%

“…164,165 HLA-G expression, although weak, was up-modulated by IL-10, INF-c, and progesterone plus cAMP, but not by IL-2. 168 MSC have been isolated from human adipose tissue (AT-MSC), bone marrow (BM-MSC), 169 or human decidua (preD-MSC) 89 and have been cultured in presence or absence of progesterone concentrations typical of the feto-maternal interface. 163 In recent reports, MSC were used as targets to assess the influence of progesterone on the expression of proteins known to exert immunomodulatory activity, such as HLA-G and the progesteroneinduced blocking factor (PIBF).…”

Section: Msc and Immunogenicitymentioning

confidence: 99%

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Stem Cells in the Reproductive System

Kyurkchiev

Gandolfi

Hayrabedyan

et al. 2012

American J Rep Immunol

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This review article summarizes current knowledge on regulation, functions, and capacities of stem cells in the female and male reproductive tract. Major locations in which pluripotent cells reside and from where they can be isolated are the ovaries, the endometrium, the decidua, and the testis. They include oocytes, embryonic stem cells, trophoblast stem cells, and spermatogonial stem cells, but also several side populations, which can be obtained after certain isolation and culture procedures. The potential of pluripotent cells in the reproductive tract to differentiate is manifold, but heterogenous, depending upon their respective origin. As stem cells have a potential for future application in transplantation and regenerative medicine, this article also reviews the literature on major histocompatibility complex expression on stem cells of the reproductive tract, because of its immunogenic effects, but also because of its potential expression of HLA-G, a potent immunomodulator mainly associated with trophoblast cells.

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First-trimester human decidua contains a population of mesenchymal stem cells

Cited by 34 publications

References 28 publications

Evaluation of human first trimester decidual and telomerase-transformed endometrial stromal cells as model systems of in vitro decidualization

Evaluation of human first trimester decidual and telomerase-transformed endometrial stromal cells as model systems of in vitro decidualization

Vasculogenesis of decidua side population cells of first-trimester pregnancy

Stem Cells in the Reproductive System

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