Identification and Characterization of the Human Leiomyoma Side Population as Putative Tumor-Initiating Cells

Capsule:
The side population method was used to isolate and identify putative tumor-initiating leiomyoma stem cells as demonstrated by their ability to differentiate in vitro and reconstruct leiomyoma tissue in vivo.

Authors:
Aymara Mas, Ph.D., Irene Cervelló, Ph.D., Claudia Gil-Sanchis, Ph.D., Amparo Faus, B.Sc., Jaime Ferro, M.D., Antonio Pellicer, M.D., Carlos Simón, M.D.

Volume 98, Issue 3, Pages 741-751.e6, September 2012

Abstract:

Objective:
To isolate and characterize human leiomyoma stem cells by Side
Population (SP) method.

Design:
Prospective experimental human and animal study.

Setting:
University research laboratory-affiliated infertility clinic.

Patients:
Women undergoing laparoscopic myomectomy.

Animals:
Female NOD-SCID mice.

Interventions:
Obtention of human leiomyoma SP cells as candidate tumorinitiating cells and establishment of two leiomyoma SP lines.

Main Outcome Measures:
Flow cytometry, semiquantitative polimerase chain reaction, clonogenicity assays, cDNA microarrays hybridization, cell culture, karyotype, molecular analysis, immunocytochemistry, in vitro differentiation, xenotransplantation assays, immunohistochemistry.

Results:
SP cells from human leiomyomas were isolated, identified and characterized. Two leiomyoma´s SP cell lines with a normal karyotype were thus established. Undifferentiated status was confirmed by the expression of OCT-4, NANOG, DNMT3B, GDF3. Presence of typical mesenchymal markers (CD90, CD105, CD73) and absence of hematopoietic stem cell markers (CD34, CD45) supported their mesodermal origin. Mesenchymal lineage commitment was also demonstrated by their ability to differentiate in vitro into adipogenic and osteogenic lineages. Finally, their functional capability was established in an animal model by leiomyoma tissue reconstruction.

Conclusion:
SP cells from human leiomyoma exhibit key features of tumorinitiating cells opening up new possibilities to understand the origin and develop new non-surgical approaches for leiomyomas.

  • Micah Hill

    Congratulations to Dr Mas and colleges on a thorough and
    potentially important paper. This
    research was very well conducted, with the in vitro work clearly suggesting
    that leiomyoma SP cells are putative tumor initiating cells and this was furthered by the
    xenotransplantation portion of the study. This type of study has tremendous
    “bench-to-bedside” potential, including the testing of pharmacologic
    action in an in vitro model. Given the uniqueness of the extra-cellular
    matrix in leiomyoma formation, I was wondering if the authors had comments on
    using their cell line in 2-D versus 3-D cell culture models?

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