Stro-1/CD44 as putative human myometrial and fibroid stem cell markers

Aymara Mas, Sangeeta Nair, Archana Laknaur, Carlos Simón, Michael Peter Diamond, Ayman Al-Hendy

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective To identify and characterize myometrial/fibroid stem cells by specific stem cell markers in human myometrium, and to better understand the stem cell contribution in the development of uterine fibroids. Design Prospective, experimental human and animal study. Setting University research laboratory. Patient(s)/Animal(s) Women undergoing hysterectomy for treatment of symptomatic uterine fibroids and female NOD/SCID/IL-2Rγnull mice. Intervention(s) Identification and isolation of stem cells from human fibroids and adjacent myometrium tissues using Stro-1/CD44-specific surface markers. Main Outcome Measure(s) Flow cytometry, semiquantitative polymerase chain reaction, clonogenicity assays, cell culture, molecular analysis, immunocyto-histochemistry, in vitro differentiation, and xenotransplantation assays. Result(s) Using Stro-1/CD44 surface markers, we were able to isolate stem cells from adjacent myometrium and human fibroid tissues. The undifferentiated status of isolated cells was confirmed by the expression of ABCG2 transporter, as well as additional stem cell markers OCT4, NANOG, and GDB3, and the low expression of steroid receptors ERα and PR-A/PR-B. Mesodermal cell origin was established by the presence of typical mesenchymal markers (CD90, CD105, and CD73) and absence of hematopoietic stem cell markers (CD34, CD45), and confirmed by the ability of these cells to differentiate in vitro into adipocytes, osteocytes, and chondrocytes. Finally, their functional capability to form fibroid-like lesions was established in a xenotransplantation mouse model. The injected cells labeled with superparamagnetic iron oxide were tracked by both magnetic resonance imaging and fluorescence imaging, thus demonstrating the regenerative potential of putative fibroid stem cells in vivo. Conclusion(s) We have demonstrated that Stro-1/CD44 can be used as specific surface markers to enrich a subpopulation of myometrial/fibroids cells, exhibiting key features of stem/progenitor cells. These findings offer a useful tool to better understand the initiation of uterine fibroids, and may lead to the establishment of effective therapeutic options.

Original languageEnglish (US)
Pages (from-to)225-234.e3
JournalFertility and sterility
Volume104
Issue number1
DOIs
StatePublished - Jul 1 2015

Fingerprint

Leiomyoma
Stem Cells
Myometrium
Heterologous Transplantation
Osteocytes
Steroid Receptors
Optical Imaging
Chondrocytes
Hematopoietic Stem Cells
Hysterectomy
Adipocytes
Flow Cytometry
Research Design
Cell Culture Techniques
Magnetic Resonance Imaging
Outcome Assessment (Health Care)
Polymerase Chain Reaction
Therapeutics
Research

Keywords

  • CD44/Stro-1
  • Human myometrium
  • stem cells
  • uterine fibroids/leiomyomas

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Stro-1/CD44 as putative human myometrial and fibroid stem cell markers. / Mas, Aymara; Nair, Sangeeta; Laknaur, Archana; Simón, Carlos; Diamond, Michael Peter; Al-Hendy, Ayman.

In: Fertility and sterility, Vol. 104, No. 1, 01.07.2015, p. 225-234.e3.

Research output: Contribution to journalArticle

Mas, Aymara ; Nair, Sangeeta ; Laknaur, Archana ; Simón, Carlos ; Diamond, Michael Peter ; Al-Hendy, Ayman. / Stro-1/CD44 as putative human myometrial and fibroid stem cell markers. In: Fertility and sterility. 2015 ; Vol. 104, No. 1. pp. 225-234.e3.
@article{4c5eb00517c14301a1807a25c4ed5d56,
title = "Stro-1/CD44 as putative human myometrial and fibroid stem cell markers",
abstract = "Objective To identify and characterize myometrial/fibroid stem cells by specific stem cell markers in human myometrium, and to better understand the stem cell contribution in the development of uterine fibroids. Design Prospective, experimental human and animal study. Setting University research laboratory. Patient(s)/Animal(s) Women undergoing hysterectomy for treatment of symptomatic uterine fibroids and female NOD/SCID/IL-2Rγnull mice. Intervention(s) Identification and isolation of stem cells from human fibroids and adjacent myometrium tissues using Stro-1/CD44-specific surface markers. Main Outcome Measure(s) Flow cytometry, semiquantitative polymerase chain reaction, clonogenicity assays, cell culture, molecular analysis, immunocyto-histochemistry, in vitro differentiation, and xenotransplantation assays. Result(s) Using Stro-1/CD44 surface markers, we were able to isolate stem cells from adjacent myometrium and human fibroid tissues. The undifferentiated status of isolated cells was confirmed by the expression of ABCG2 transporter, as well as additional stem cell markers OCT4, NANOG, and GDB3, and the low expression of steroid receptors ERα and PR-A/PR-B. Mesodermal cell origin was established by the presence of typical mesenchymal markers (CD90, CD105, and CD73) and absence of hematopoietic stem cell markers (CD34, CD45), and confirmed by the ability of these cells to differentiate in vitro into adipocytes, osteocytes, and chondrocytes. Finally, their functional capability to form fibroid-like lesions was established in a xenotransplantation mouse model. The injected cells labeled with superparamagnetic iron oxide were tracked by both magnetic resonance imaging and fluorescence imaging, thus demonstrating the regenerative potential of putative fibroid stem cells in vivo. Conclusion(s) We have demonstrated that Stro-1/CD44 can be used as specific surface markers to enrich a subpopulation of myometrial/fibroids cells, exhibiting key features of stem/progenitor cells. These findings offer a useful tool to better understand the initiation of uterine fibroids, and may lead to the establishment of effective therapeutic options.",
keywords = "CD44/Stro-1, Human myometrium, stem cells, uterine fibroids/leiomyomas",
author = "Aymara Mas and Sangeeta Nair and Archana Laknaur and Carlos Sim{\'o}n and Diamond, {Michael Peter} and Ayman Al-Hendy",
year = "2015",
month = "7",
day = "1",
doi = "10.1016/j.fertnstert.2015.04.021",
language = "English (US)",
volume = "104",
pages = "225--234.e3",
journal = "Fertility and Sterility",
issn = "0015-0282",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Stro-1/CD44 as putative human myometrial and fibroid stem cell markers

AU - Mas, Aymara

AU - Nair, Sangeeta

AU - Laknaur, Archana

AU - Simón, Carlos

AU - Diamond, Michael Peter

AU - Al-Hendy, Ayman

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Objective To identify and characterize myometrial/fibroid stem cells by specific stem cell markers in human myometrium, and to better understand the stem cell contribution in the development of uterine fibroids. Design Prospective, experimental human and animal study. Setting University research laboratory. Patient(s)/Animal(s) Women undergoing hysterectomy for treatment of symptomatic uterine fibroids and female NOD/SCID/IL-2Rγnull mice. Intervention(s) Identification and isolation of stem cells from human fibroids and adjacent myometrium tissues using Stro-1/CD44-specific surface markers. Main Outcome Measure(s) Flow cytometry, semiquantitative polymerase chain reaction, clonogenicity assays, cell culture, molecular analysis, immunocyto-histochemistry, in vitro differentiation, and xenotransplantation assays. Result(s) Using Stro-1/CD44 surface markers, we were able to isolate stem cells from adjacent myometrium and human fibroid tissues. The undifferentiated status of isolated cells was confirmed by the expression of ABCG2 transporter, as well as additional stem cell markers OCT4, NANOG, and GDB3, and the low expression of steroid receptors ERα and PR-A/PR-B. Mesodermal cell origin was established by the presence of typical mesenchymal markers (CD90, CD105, and CD73) and absence of hematopoietic stem cell markers (CD34, CD45), and confirmed by the ability of these cells to differentiate in vitro into adipocytes, osteocytes, and chondrocytes. Finally, their functional capability to form fibroid-like lesions was established in a xenotransplantation mouse model. The injected cells labeled with superparamagnetic iron oxide were tracked by both magnetic resonance imaging and fluorescence imaging, thus demonstrating the regenerative potential of putative fibroid stem cells in vivo. Conclusion(s) We have demonstrated that Stro-1/CD44 can be used as specific surface markers to enrich a subpopulation of myometrial/fibroids cells, exhibiting key features of stem/progenitor cells. These findings offer a useful tool to better understand the initiation of uterine fibroids, and may lead to the establishment of effective therapeutic options.

AB - Objective To identify and characterize myometrial/fibroid stem cells by specific stem cell markers in human myometrium, and to better understand the stem cell contribution in the development of uterine fibroids. Design Prospective, experimental human and animal study. Setting University research laboratory. Patient(s)/Animal(s) Women undergoing hysterectomy for treatment of symptomatic uterine fibroids and female NOD/SCID/IL-2Rγnull mice. Intervention(s) Identification and isolation of stem cells from human fibroids and adjacent myometrium tissues using Stro-1/CD44-specific surface markers. Main Outcome Measure(s) Flow cytometry, semiquantitative polymerase chain reaction, clonogenicity assays, cell culture, molecular analysis, immunocyto-histochemistry, in vitro differentiation, and xenotransplantation assays. Result(s) Using Stro-1/CD44 surface markers, we were able to isolate stem cells from adjacent myometrium and human fibroid tissues. The undifferentiated status of isolated cells was confirmed by the expression of ABCG2 transporter, as well as additional stem cell markers OCT4, NANOG, and GDB3, and the low expression of steroid receptors ERα and PR-A/PR-B. Mesodermal cell origin was established by the presence of typical mesenchymal markers (CD90, CD105, and CD73) and absence of hematopoietic stem cell markers (CD34, CD45), and confirmed by the ability of these cells to differentiate in vitro into adipocytes, osteocytes, and chondrocytes. Finally, their functional capability to form fibroid-like lesions was established in a xenotransplantation mouse model. The injected cells labeled with superparamagnetic iron oxide were tracked by both magnetic resonance imaging and fluorescence imaging, thus demonstrating the regenerative potential of putative fibroid stem cells in vivo. Conclusion(s) We have demonstrated that Stro-1/CD44 can be used as specific surface markers to enrich a subpopulation of myometrial/fibroids cells, exhibiting key features of stem/progenitor cells. These findings offer a useful tool to better understand the initiation of uterine fibroids, and may lead to the establishment of effective therapeutic options.

KW - CD44/Stro-1

KW - Human myometrium

KW - stem cells

KW - uterine fibroids/leiomyomas

UR - http://www.scopus.com/inward/record.url?scp=84937521566&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937521566&partnerID=8YFLogxK

U2 - 10.1016/j.fertnstert.2015.04.021

DO - 10.1016/j.fertnstert.2015.04.021

M3 - Article

VL - 104

SP - 225-234.e3

JO - Fertility and Sterility

JF - Fertility and Sterility

SN - 0015-0282

IS - 1

ER -