ABSTRACT
INTRODUCTION The human endometrium is a dynamic remodeling tissue undergoing more than 400 cycles of regeneration, differentiation, and shedding during a woman’s reproductive years. The coordinated and sequential actions of estrogen and progesterone direct these major remodeling events to prepare the endometrium for blastocyst implantation. Endometrial regeneration also follows parturition, almost complete curettage and occurs in postmenopausal women taking estrogen replacement therapy. Adult stem/progenitor cells are likely responsible for endometrial regeneration. This chapter will review the evidence available to date for the existence of adult stem/progenitor cells in human endometrium. It will detail the functional approaches that have been used to identify candidate endometrial epithelial and mesenchymal stem/progenitor cells, in particular, cell cloning and side population (SP) studies. The importance of in vivo studies that demonstrate the ability to reconstruct endometrial tissue from isolated cell populations will also be emphasized. Identification of markers that distinguish endometrial epithelial and mesenchymal stem/progenitor cells from their more differentiated progeny is essential to progress this newly developing field of research. Approaches being undertaken to identify markers for endometrial mesenchymal stem/progenitor cells will be outlined, including the recent discovery that co-expression of two markers, CD146 and platelet-derived growth factor (PDGF) receptor-b, partially purifies human endometrial mesenchymal stem/progenitor cells. This CD146þPDGF-Rbþ population has a surface phenotype similar to bone marrow and fat mesenchymal stem cells (MSC), and demonstrates multipotency by their capacity to undergo multilineage differentiation into fat, cartilage, bone, and smooth muscle. They have a perivascular location in the functionalis and basalis layers of the endometrium. Application of these fundamental studies to the current knowledge on the pathophysiology of a variety of common gynecological diseases associated with abnormal endometrial proliferation, including endometrial cancer, endometriosis, and adenomyosis will also be discussed. Mention will be made of the possible use of endometrial stem/progenitor cells in autologous tissue engineering applications relevant to urogynecology. Finally, the future directions of human endometrial stem/progenitor cell research will be suggested.
