**2. Histology of human uterus**

The inner layer of uterus (Endometrium) comprises the mucosal lining which is highly regenerative tissue during menstrual cycle. The human endometrium undergoes more than 400 cycles of shedding and regeneration during a woman's reproductive years (McLennan and Rydell 1965). This layer is backed by a thick muscular myometrium which consists of muscular cells. There is no submucosal tissue to separate endometrial glandular tissue from

Endometrial Stem Cells and Endometriosis 299

Stem cells are undifferentiated cells which are defined by their functional properties such as; high proliferative potential, substantial self-renewal capacity and ability to differentiate to other organ/tissue-specific cell types. Cellular self- renewal is a capacity that parental stem cells are able to divide into two daughter cells which can happen through symmetrical or asymmetrical division. The symmetrical division produces two identical daughter stem cells or transit amplifying (TA) cells. TA cells undergo repetitive cell division cycles and progressively acquire differentiation marker and lose their self-renewal capacity. Asymmetrical division leads to an identical daughter cell as well as a more differentiated

Although stem cells are potentially capable to proliferation, they remain mostly in a

Adult stem cells present in all organs and tissues and are responsible for tissue regeneration

Rarity and lack of distinguishable morphological features and specific molecular markers of

Broadly they can be divided into two categories, embryonic and adult stem cells. Stem cells can also be divided into various groups according to their differentiation capacity. For example, the zygote can be considered as a totipotent stem cell, which means it is able to differentiate into all other cell types in embryo and extraembryonic tissue. Other stem cells with decreased levels of potency can be named as; pluripotent, which can differentiate into nearly all cell types (e.g., inner cell mass of the blastocyst), multipotent, which can differentiate into a number of cells that are closely related family of cell (e.g., Hematopoetic stem cells), oligopotent which differentiate into a few cell types (e.g., myeloid or lymphoid stem cells) and unipotent, which differentiate into only one cell type with self-renewal

Anatomic structure surrounding stem cells which have profound effect on cell function is called niche. Signaling elements and various cellular and molecular interactions inside the niche can determine the fate of cell to stay in undifferentiated state until tissue regeneration

Adult stem cells present throughout whole body and responsible for replenishment and regeneration of damaged tissues and contribute to the structural and functional maintenance of tissues and organs. Human endometrium undergoes periodical process of regeneration during menstrual cycle. The growth rate may vary between 0.5 -7mm in thickness. Menstruation is a phenomenon consisted of various cellular and tissue functions from cell proliferation and differentiation to shedding and regeneration. During each menstrual cycle, the functionalis and a part of basalis layer of endometrium undergo shedding. After shedding, the endometrium regrows under the influence of estrogen.

stem cells have hindered their isolation, purification and studies for several years.

quiescent state until an inductive factor to induce them to proliferation.

and repair after damage and trauma encountered during life time.

**5. Stem cell-based theory** 

capacity(e.g., muscle stem cell ).

**5.2.1 Indirect evidences** 

or repair to motivate stem cell differentiation.

**5.2 Evidences for existence of endometrial stem cells** 

**5.1 Stem cells** 

cell.

underlying smooth muscle. The endometrium is composed of single columnar epithelial layer, resting on a layer of connective tissue, the stroma. Tubular glands reach through the endometrial surface to the base of stroma. In a woman of reproductive age, the endometrium itself is structurally and functionally divided into two relatively distinct layers of upper functionalis and lower basalis. The functionalis zone is adjacent to uterine cavity and contains glands and supportive stroma for optimal implantation and growth condition of embryo. Basalis (basal layer), adjacent to myometrium, provides basal region of glands, dense stroma and lymphoid aggregates and from it functional layer develops. During menstrual cycle only the functional layer is regenerated and the basal layer is not affected.

Both endometrium and subendometrial myometrium originate from the Müllerian ducts during embryonic life. However, outer myometrial layer is formed during fetal life and from non- Müllerian origin (Ferenczy and Bergeron 1991).

The cellular components of human endometrium can be primarily divided into two cell types; the epithelial cells (luminal and glandular) and the supporting mesenchymal cells (stromal cells) as well as vascular (endothelial) cells and leukocytes.
