Table 1 – Studies on the role of stem cells in leiomyoma pathology
Author	Objective	Main results	Model
Mas et al., 2015	Test the hypothesis that leiomyoma development may be due to overexpression of HMGA2 in myometrial stem cells using in vitro and in vivo approaches	Overexpression of truncated/short HMGA2 form in myometrial cells result in abnormal proliferation of the SSC niche leading to the formation of leiomyoma-like tissue.	Human and mice
Ono et al., 2014	Identify cell surface markers to isolate leiomyoma stem/progenitor cells.	Significantly elevated CD49b and CD34 gene expression in side population cells vs. main population cells	Human
Ono et al., 2013	Demonstrate the critical paracrine role of the wingless-type (WNT)/β-catenin pathway in estrogen/progesterone-dependent tumorigenesis, involving LMSP and differentiated myometrial or leiomyoma cells.	Wingless-type (WNT) acts as a paracrine signal from estrogen/progesterone receptor-rich mature cells activating the canonical β-catenin pathway in leiomyoma stem cells, suggesting a paracrine role for the canonical WNT pathway in the growth of leiomyomas.	Human
Mas et al., 2012	Obtain human leiomyoma SP cells as candidate tumor-initiating cells and establishment of two leiomyoma SP lines	SP cells from human leiomyomas were isolated, identified, and characterized. Two leiomyoma SP cell lines with a normal karyotype were established	Human and mice
Ono et al., 2012	Test the hypothesis that a distinct stem/reservoir cell-enriched population, designated as the leiomyoma-derived side population (LMSP), is responsible for cell proliferation and tumor growth	LMSP, which show stem/reservoir cell characteristics, are necessary for in vivo growth of leiomyoma xenograft tumors. Decreased estrogen and progesterone receptor levels in LMSP suggest an indirect paracrine effect of steroid hormones on stem cells via the mature neighboring cells.	Human and mice
Chang et al., 2010	Compare stem/progenitor cell characteristics in both normal myometrium and the corresponding leiomyoma of patients undergoing hysterectomies	Leiomyoma cells form fewer mesenchymal stem cell colonies and exhibit less Hoechst dye-excluding side population (SP) activity, a function associated with progenitor cells in other tissues, than cells isolated from normal myometrium	Human
Ono et al., 2007	Describe a subset of myometrial cells isolated from the myometrium of non-pregnant subjects that represents the myometrial stem cell population	When compared to the main population of myometrial cells (myoMP), myoSP remained quiescent, underexpressed or lacked myometrial cell markers; they could also proliferate and eventually differentiate into mature myometrial cells in vitro only under low oxygen concentration. myoSP produced functional human myometrial tissues efficiently when transplanted into the uteri of severely immunodeficient mice. myoSP were multipotent and could differentiate into osteocytes and adipocytes in vitro under appropriate differentiation-inducing conditions	Human and mice
SP: side-population cells; LMSP: leiomyoma-derived side population; myoSP: side population of myometrial cells