Putative human myometrial and fibroid stem-like cells have mesenchymal stem cell and endometrial stromal cell properties

Abstract

STUDY QUESTION Can endometrial stromal stem/progenitor cell markers, SUSD2 and CD146/CD140b, enrich for human myometrial and fibroid stem/progenitor cells? SUMMARY ANSWER SUSD2 enriches for myometrial and fibroid cells that have mesenchymal stem cell (MSC) characteristics and can also be induced to decidualise. WHAT IS KNOWN ALREADY Mesenchymal stem-like cells have been separately characterised in the endometrial stroma and myometrium and may contribute to diseases in their respective tissues. STUDY DESIGN, SIZE, DURATION Normal myometrium, fibroids and endometrium were collected from hysterectomies with informed consent. Primary cells or tissues were used from at least three patient samples for each experiment. PARTICIPANTS/MATERIALS, SETTING, METHODS Flow cytometry, immunohistochemistry and immunofluorescence were used to characterise tissues. In vitro colony formation in normoxic and hypoxic conditions, MSC lineage differentiation (osteogenic and adipogenic) and decidualisation were used to assess stem cell activity. Xenotransplantation into immunocompromised mice was used to determine in vivo stem-like activity. Endpoint measures included quantitative PCR, colony formation, trichrome, Oil Red O and alkaline phosphatase activity staining. MAIN RESULTS AND THE ROLE OF CHANCE CD146+CD140b+ and/or SUSD2+ myometrial and fibroid cells were located in the perivascular region and formed more colonies in vitro compared to control cells and differentiated down adipogenic and osteogenic mesenchymal lineages in vitro. SUSD2+ myometrial cells had greater in vitro decidualisation potential, and SUSD2+ fibroid cells formed larger tumours in vivo compared to control cells. LARGE-SCALE DATA N/A LIMITATIONS, REASONS FOR CAUTION Markers used in this study enrich for cells with stem/progenitor cell activity; however, they do not distinguish stem from progenitor cells. SUSD2+ myometrial cells express markers of decidualisation when treated in vitro, but in vivo assays are needed to fully demonstration their ability to decidualise. WIDER IMPLICATIONS OF THE FINDINGS These results suggest a possible common MSC for the endometrial stroma and myometrium, which could be the tumour-initiating cell for uterine fibroids. STUDY FUNDING/COMPETING INTEREST(S) These studies were supported by NIH grants to JMT (R01OD012206) and to ALP (F32HD081856). The authors certify that we have no conflicts of interest to disclose.

Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment

“…Stem cells derived from the myometrium and uterine fibroids have been isolated, and tumor-initiating cells in fibroids have been identified ( 198-201 ). Moreover, the markers used to enrich putative mesenchymal stem cells are similarly enriched for MMSCs from myometrium and uterine fibroids ( 202 ). Notably, MED12 mutations are only found in uterine fibroid stem cells and not in MMSCs ( 203 ).…”

Single-cell transcriptomics reveals the landscape of intra-tumoral heterogeneity and transcriptional activities of ECs in CC

“…In particular, most of the markers to distinguish different cell types were retrieved from the Cell Markers database (https://www.labome.com/method/Cell-Markers.html). The other marker genes were from published papers, such as the marker gene of endometrial stromal cells, SUSD2, 47 and stem-related genes SOX2 and ALDH1A1. 18…”

Endometrial stem/progenitor cells and their roles in immunity, clinical application, and endometriosis

“…However, this is switched after decidualization because these SUSD2 + cells are turned into the main source to produce chemokines and cytokines including chemokine (C–C motif) ligand 7, and the leukemia inhibitory factor [ 28 ]. SUSD2 + cells originated from myometrium and uterine fibroids are featured as MSCs and can also be induced into decidua [ 29 ]. Perivascular SUSD2 + cells isolated from postmenopausal endometrium also display the characteristics of MSCs, regardless whether the patients receive estrogen pretreatment for the regeneration of endometrium [ 30 ].…”